Generation of Induced Pluripotent Stem Cells from CD34+ Cells across Blood Drawn from Multiple Donors with Non-Integrating Episomal Vectors

The methodology to create induced pluripotent stem cells (iPSCs) affords the opportunity to generate cells specific to the individual providing the host tissue. However, existing methods of reprogramming as well as the types of source tissue have significant limitations that preclude the ability to generate iPSCs in a scalable manner from a readily available tissue source. We present the first study whereby iPSCs are derived in parallel from multiple donors using episomal, non-integrating, oriP/EBNA1-based plasmids from freshly drawn blood. Specifically, successful reprogramming was demonstrated from a single vial of blood or less using cells expressing the early lineage marker CD34 as well as from unpurified peripheral blood mononuclear cells. From these experiments, we also show that proliferation and cell identity play a role in the number of iPSCs per input cell number. Resulting iPSCs were further characterized and deemed free of transfected DNA, integrated transgene DNA, and lack detectable gene rearrangements such as those within the immunoglobulin heavy chain and T cell receptor loci of more differentiated cell types. Furthermore, additional improvements were made to incorporate completely defined media and matrices in an effort to facilitate a scalable transition for the production of clinic-grade iPSCs

Coordination of Cell Polarity during Xenopus Gastrulation

Cell polarity is an essential feature of animal cells contributing to morphogenesis. During Xenopus gastrulation, it is known that chordamesoderm cells are polarized and intercalate each other allowing anterior-posterior elongation of the embryo proper by convergent extension (CE). Although it is well known that the cellular protrusions at both ends of polarized cells exert tractive force for intercalation and that PCP pathway is known to be essential for the cell polarity, little is known about what triggers the cell polarization and what the polarization causes to control intracellular events enabling the intercalation that leads to the CE. In our research, we used EB3 (end-binding 3), a member of +TIPs that bind to the plus end of microtubule (MT), to visualize the intracellular polarity of chordamesoderm cells during CE to investigate the trigger of the establishment of cell polarity. We found that EB3 movement is polarized in chordamesoderm cells and that the notochord-somite tissue boundary plays an essential role in generating the cell polarity. This polarity was generated before the change of cell morphology and the polarized movement of EB3 in chordamesoderm cells was also observed near the boundary between the chordamesoderm tissue and naïve ectoderm tissue or lateral mesoderm tissues induced by a low concentration of nodal mRNA. These suggest that definitive tissue separation established by the distinct levels of nodal signaling is essential for the chordamesodermal cells to acquire mediolateral cell polarity

Psychophysiological effects of a web-based stress management system: A prospective, randomized controlled intervention study of IT and media workers [ISRCTN54254861]

BACKGROUND: The aim of the present study was to assess possible effects on mental and physical well-being and stress-related biological markers of a web-based health promotion tool. METHODS: A randomized, prospectively controlled study was conducted with before and after measurements, involving 303 employees (187 men and 116 women, age 23–64) from four information technology and two media companies. Half of the participants were offered web-based health promotion and stress management training (intervention) lasting for six months. All other participants constituted the reference group. Different biological markers were measured to detect possible physiological changes. RESULTS: After six months the intervention group had improved statistically significantly compared to the reference group on ratings of ability to manage stress, sleep quality, mental energy, concentration ability and social support. The anabolic hormone dehydroepiandosterone sulphate (DHEA-S) decreased significantly in the reference group as compared to unchanged levels in the intervention group. Neuropeptide Y (NPY) increased significantly in the intervention group compared to the reference group. Chromogranin A (CgA) decreased significantly in the intervention group as compared to the reference group. Tumour necrosis factor α (TNFα) decreased significantly in the reference group compared to the intervention group. Logistic regression analysis revealed that group (intervention vs. reference) remained a significant factor in five out of nine predictive models. CONCLUSION: The results indicate that an automatic web-based system might have short-term beneficial physiological and psychological effects and thus might be an opportunity in counteracting some clinically relevant and common stress and health issues of today

Seroprevalence of SARS-CoV-2 Antibody in Echocardiography and Stress Laboratory

Purpose: Transesophageal echocardiography is an aerosol-generating procedure, and exercise stress testing is a potentially aerosol-generating activity. Concern has been raised about heightened risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among health care personnel participating in these procedures. We aimed to investigate the prevalence of past coronavirus disease 2019 (COVID-19) infection in echocardiography and stress laboratory staff. Methods: All staff who worked in the echocardiography and stress laboratories of one high-traffic urban hospital from March 15, 2020, to June 15, 2020, were asked to voluntarily participate. Those willing to participate were consented, and past COVID-19 infection was confirmed by a SARS-CoV-2 IgG antibody test (ARCHITECT, Abbott Laboratories) from June 15, 2020, to July 3, 2020. Clinical data were collected from the electronic medical record, and self-reported symptoms were documented with a participant survey. Results: A total of 43 staff members (86.0% of 50 total laboratory staff) participated. A majority of participants were less than 40 years old (69.8%), were White (86.0%), and were women (79.1%); mean body mass index was 24.9 ± 4.7 kg/m2. Of the 43 staff members tested for past COVID-19 infection, 3 (7.0%) had a positive SARS-CoV-2 IgG antibody result. There were no unique features in the 3 SARS-CoV-2 antibody-positive subjects; of these, 2 had known prior COVID-19 infection and 1 was asymptomatic. Conclusions: This study provides clinical data on the seroprevalence of SARS-CoV-2 antibody in echocardiography and stress laboratory staff who regularly participate in a variety of procedures that are or may be aerosol-generating

Seroprevalence of SARS-CoV-2 Antibody in Echocardiography and Stress Laboratory

Purpose: Transesophageal echocardiography is an aerosol-generating procedure, and exercise stress testing is a potentially aerosol-generating activity. Concern has been raised about heightened risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among health care personnel participating in these procedures. We aimed to investigate the prevalence of past coronavirus disease 2019 (COVID-19) infection in echocardiography and stress laboratory staff. Methods: All staff who worked in the echocardiography and stress laboratories of one high-traffic urban hospital from March 15, 2020, to June 15, 2020, were asked to voluntarily participate. Those willing to participate were consented, and past COVID-19 infection was confirmed by a SARS-CoV-2 IgG antibody test (ARCHITECT, Abbott Laboratories) from June 15, 2020, to July 3, 2020. Clinical data were collected from the electronic medical record, and self-reported symptoms were documented with a participant survey. Results: A total of 43 staff members (86.0% of 50 total laboratory staff) participated. A majority of participants were less than 40 years old (69.8%), were White (86.0%), and were women (79.1%); mean body mass index was 24.9 ± 4.7 kg/m2. Of the 43 staff members tested for past COVID-19 infection, 3 (7.0%) had a positive SARS-CoV-2 IgG antibody result. There were no unique features in the 3 SARS-CoV-2 antibody-positive subjects; of these, 2 had known prior COVID-19 infection and 1 was asymptomatic. Conclusions: This study provides clinical data on the seroprevalence of SARS-CoV-2 antibody in echocardiography and stress laboratory staff who regularly participate in a variety of procedures that are or may be aerosol-generating

On the ultimate shimming performance in the human brain

Purpose/Introduction: Improved shimming the human brain has attracted increasing interest in the recent years, using both conventional spherical harmonics (SH) of higher orders1 and multiple local coils2-8. Currently, the exact trade-off between the shim coil dimensions, the current and power requirements and the achievable shimming performance remains unclear. In this study we explore the impact of these factors on shimming the human brain. Subjects and Methods: B0 field map of the whole brain of one healthy volunteer was shimmed to the second order to account for the currently available shimming and define a valid starting point. The resultant field map was used as a target magnetic field. A stream function9 on a cylindrical surface of certain dimensions was then optimized to minimize the standard deviation of the residual magnetic field over the whole brain. During the optimization procedure, dissipated power of the coil was constrained by Pmax. All optimization problems were solved with the regularization tools10 for MATLAB (The MathWorks. Natick, USA). Considering the dimensions of a typical RF-shimming array, multicoil 7,8 and whole-body gradient coil, the radii of three cylindrical current-carrying surfaces were selected to be 105, 180 and 309 mm, with the lengths of 230, 300 and 503 mm, respectively. Results: Figure 1 shows the variation of standard deviations (SD) of the residual magnetic field inhomogeneity with regard to Pmax. In order to compare different shimming strategies, SDs achieved with global SH shimming are also marked by horizontal dotted lines. As seen, the variation of SDs for different shim coils present a similar tendency. Discussion/Conclusion: As seen in Fig. 1, for coils of smaller radius less power is required to achieve a certain shimming fideliy. Alternatively, given the power limit, a decision on the coil geometry can be made. The presented coil layouts demonstrate the importance of the certain areas of the current carrying surface, e.g. in the low face region or areas close to ears, which may guide future designs of shim arrays with irregularly-shaped coil elements or combined RF-shimming arrays

Preprocedure COVID-19 Testing in Early Phase of Pandemic

The COVID-19 pandemic led to a nationwide shutdown of elective medical procedures. Upon resumption of services, preprocedure nasopharyngeal swab testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was introduced for all patients requiring surgical or other aerosol-generating procedures. We investigated preprocedure COVID-19 testing in one of the largest U.S. health systems. Patients included in this retrospective, observational study were asymptomatic and scheduled for a procedure or surgery. All patients underwent a nasopharyngeal swab test for SARS-CoV-2 performed 24–72 hours prior to a planned procedure. Clinical demographics, type of procedure, test results, and subsequent procedure status were evaluated. Of 38,608 total patients, there were 277 COVID-19–positive patients (positivity rate: 0.72%). Of those 277, 244 (88%) had procedural delays or cancellations. Of the COVID-19–negative patients, 50 (0.13%) required later hospitalization for COVID-19. Median time from preprocedure negative test to admission was 46.3 ± 27.2 days. In the largest series published on preprocedure COVID-19 testing in the early phase of the pandemic, preprocedure COVID-19 positivity was low. Preprocedure COVID-19 testing had a significant impact on clinical management. Rate of COVID-19 cases requiring hospitalization in the months following the procedure was negligible, suggesting health system policies adequately protected patient safety

Preprocedure COVID-19 Testing in Early Phase of Pandemic

The COVID-19 pandemic led to a nationwide shutdown of elective medical procedures. Upon resumption of services, preprocedure nasopharyngeal swab testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was introduced for all patients requiring surgical or other aerosol-generating procedures. We investigated preprocedure COVID-19 testing in one of the largest U.S. health systems. Patients included in this retrospective, observational study were asymptomatic and scheduled for a procedure or surgery. All patients underwent a nasopharyngeal swab test for SARS-CoV-2 performed 24–72 hours prior to a planned procedure. Clinical demographics, type of procedure, test results, and subsequent procedure status were evaluated. Of 38,608 total patients, there were 277 COVID-19–positive patients (positivity rate: 0.72%). Of those 277, 244 (88%) had procedural delays or cancellations. Of the COVID-19–negative patients, 50 (0.13%) required later hospitalization for COVID-19. Median time from preprocedure negative test to admission was 46.3 ± 27.2 days. In the largest series published on preprocedure COVID-19 testing in the early phase of the pandemic, preprocedure COVID-19 positivity was low. Preprocedure COVID-19 testing had a significant impact on clinical management. Rate of COVID-19 cases requiring hospitalization in the months following the procedure was negligible, suggesting health system policies adequately protected patient safety