Glycemic Variability Is Associated With All-Cause Mortality In COVID-19 Patients With ARDSFindings From The COVAS Cohort

There is high mortality among intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS) caused by coronavirus disease 19 (COVID-19). Important factors for COVID-19 mortality are diabetes status and elevated fasting plasma glucose (FPG). However, the effect of glycemic variability on survival has not been explored in patients with COVID-19 and ARDS. This single-centre cohort-study compared several metrics of daily glycemic variability (DGV) for goodness-of-fit in patients requiring mechanical ventilation due to COVID-19 ARDS in the ICU at University Hospital Aachen, Germany. 106 patients had moderate to severe ARDS (P/F ratio median [IQR]: 112 [87-148] mmHg). Continuous HRs showed a proportional increase in mortality risk with DGV. Multivariable unadjusted and adjusted Cox-models showed a statistically significant difference in mortality for DGV (HR: 1.02, (P)<0.001, LR(P)<0.001; HR: 1.016, (P)=0.001, LR(P)<0.001, respectively). Kaplan-Meier estimators yielded a shorter median survival (25 vs. 87 days) and higher likelihood of death (75% vs. 31%) in patients with DGV ≥ 25.5mg/dl (P<0.0001). High glycemic variability during ICU admission is associated with significant increase in all-cause mortality for patients admitted with COVID-19 ARDS to the ICU. This effect persisted even after adjustment for clinically predetermined confounders, including diabetes, procalcitonin and FPG levels at baseline.

Impacts of an EMS Hospital Liaison Program on Ambulance Offload Times: A Preliminary Analysis

Introduction: Ambulance patients who are unable to be quickly transferred to an emergency department (ED) bed represent a key contributing factor to ambulance offload delay (AOD). Emergency department crowding and associated AOD are exacerbated by multiple factors, including infectious disease outbreaks such as the coronavirus disease 2019 (COVID-19) pandemic. Initiatives to address AOD present an opportunity to streamline ambulance offload procedures while improving patient outcomes. Study Objective: The goal of this study was to evaluate the initial outcomes and impact of a novel Emergency Medical Service (EMS)-based Hospital Liaison Program (HLP) on ambulance offload times (AOTs). Methods: Ambulance offload times associated with EMS patients transported to a community hospital six months before and after HLP implementation were retrospectively analyzed using proportional significance tests, t-tests, and multiple regression analysis. Results: A proportional increase in incidents in the zero to <30 minutes time category after program implementation (+2.96%; P <.01) and a commensurate decrease in the proportion of incidents in the 30 to <60 minutes category (−2.65%; P <.01) were seen. The fully adjusted regression model showed AOT was 16.31% lower (P <.001) after HLP program implementation, holding all other variables constant. Conclusion: The HLP is an innovative initiative that constitutes a novel pathway for EMS and hospital systems to synergistically enhance ambulance offload procedures. The greatest effect was demonstrated in patients exhibiting potentially life-threatening symptoms, with a reduction of approximately three minutes. While small, this outcome was a statistically significant decrease from the pre-intervention period. Ultimately, the HLP represents an additional strategy to complement existing approaches to mitigate AOD.

Pharmacokinetics, Pharmacodynamics, and Safety of Etrolizumab in Children With Moderately to Severely Active Ulcerative Colitis or Crohn’s Disease: Results from a Phase 1 Randomized Trial

Background Etrolizumab, a humanized anti-β7 antibody, has not been studied in children. Here, we evaluate the pharmacokinetics, pharmacodynamics, and safety of etrolizumab in children with inflammatory bowel disease. Methods Patients age 4 to 17 years with moderately to severely active ulcerative colitis or Crohn’s disease were randomized 1:1 to receive 1.5mg/kg of etrolizumab subcutaneously every 4 weeks (q4w) or 3.0mg/kg every 8 weeks (q8w) for 16 weeks in this open-label phase 1 trial. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed. Results Of the 24 patients treated, 21 completed the study. In the groups of 1.5mg/kg q4w and 3.0mg/kg q8w, respectively, mean (SD) maximum concentration (Cmax) was 9.8 (4.86) µg/mL and 18.1 (6.25) µg/mL; and mean (SD) area under the curve within a dosing interval (AUCtau) was 167 (86.9) and 521 (306) μg·day/mL after the last dose. The Cmax increased dose proportionally. The AUC over an 8-week period was slightly higher in the 3.0mg/kg q8w dose group. Median half-life was similar for both dosing regimens. Median numbers of free β7high gut-homing T and B cell subsets declined below 10% of baseline, confirming β7 target engagement and complete/near-complete receptor occupancy. Adverse events were consistent with the safety profile in adults. Approximately 60% of patients achieved a clinical response. Conclusions Etrolizumab showed a dose-proportional increase in Cmax and a slightly greater than dose-proportional increase in AUCtau. Both regimens achieved complete/near-complete β7 receptor occupancy, with a similar relationship to concentration as adults. Etrolizumab was well tolerated and demonstrated clinical activity in children.

The Impact of the COVID-19 Pandemic on the Composition of Dietary Supplements and Functional Foods Notified in Poland

The COVID-19 pandemic has exerted a strong impact on numerous areas of everyday life. The aim of this study was to check how the pandemic influenced the composition of dietary supplements and other functional food products placed on the market till March 2021, compared to 2019. For this purpose, data concerning the registered products and reports of popularity of online searches of terms connected with vitamins and minerals were used. The results of the study made it possible to determine the group of ingredients especially popular during the pandemic. Their use in products after the announcement of the pandemic was significantly higher than in the preceding period. In conclusion, it can be shown that the pandemic changed the ingredients used in functional foods—mainly as far as vitamins and minerals are concerned. The highest proportional increase in its use in dietary supplements was noted for potassium. Personalized therapy has also become more popular, promoted by one of the manufacturers of dietary supplements active during the pandemic. Moreover, different phases of the pandemic were characterized by the popularity of different ingredients among the consumers—first, these were immunity-boosting ingredients, then those that improved psychological functions, and finally mixtures with universal health effects.

Effect of the COVID-19 Pandemic on Residential Water Use Behavior in Japan

To investigate the effect of the COVID-19 (coronavirus) pandemic on residential water use behavior in Japan, we conducted a web-based survey of 1310 people throughout Japan in March 2021, one year after the initial spread of coronavirus. The survey was designed to provide an average picture of Japan. The survey revealed that the time respondents spent at home increased during the pandemic for both men and women in all age groups by an average of 1 h, an increase of 9%. Changes in water use behavior increased almost in proportion to the increase in time spent at home, except for the frequency of defecation, which was limited to once a day. The amount of time spent in the washroom increased by 13%, an increase of more than 1.4 times the increase in the amount of time spent at home. The additional 40% increase could be considered an effect of the awareness of disease prevention. The coronavirus pandemic is expected to end in the near future. In Japan, the pandemic has led to a strong push for the reform of work styles. Therefore, even in a post-coronavirus-pandemic society, changes in work styles may normalize the increased time spent at home and the proportional increase in water use. However, because the change in water use behavior caused by quarantine awareness is a result of the fear of coronavirus infection, it is possible that water use will gradually return to pre-pandemic levels once the source of the fear is removed. To reflect the changes in water use behavior in the design of facilities in the post-coronavirus-pandemic society, it is necessary to continue this survey even once the pandemic has ended.

Structure of the secondary xylem and development of a cambial variant in Serjania mexicana (Sapindaceae)

The lianas in the family Sapindaceae are known for their unique secondary growth which differs from climbing species in other plant families in terms of their cambial variants. The present study deals with the stem anatomy of self-supporting and lianescent habit, development of phloem wedges, the ontogeny of cambial variants and structure of the secondary xylem in the stems of Serjania mexicana (L.) Willd. Thick stems (15–20 mm) were characterized by the presence of distinct phloem wedges and tangentially wide neo-formed cambial cylinders. As the stem diameter increases, there is a proportional increase in the number of phloem wedges and neo-formed vascular cylinders. The parenchymatous (pericyclic) cells external to phloem wedges that are located on the inner margin of the pericyclic fibres undergo dedifferentiation, become meristematic and form small segments of cambial cylinders. These cambia extend tangentially into wide and large segments of neoformations. Structurally, the secondary xylem and phloem of the neo-formed vascular cylinders remain similar to the derivatives produced by the regular vascular cambium. The secondary xylem is composed of vessels (wide and narrow), fibres, axial and ray parenchyma cells. The occurrence of perforated ray cells is a common feature in both regular and variant xylem.

LB10. Impact of SARS-CoV-2 Delta Variant on the Spectrum of Pediatric COVID-19 Disease in Arkansas

Background Pediatric SARS-CoV-2 infection is generally thought to be asymptomatic or result in mild COVID-19 disease, with a paucity of severe outcomes. However, SARS-CoV-2 variants, notably B.1.617.2 (WHO Delta), have changed the clinical landscape of COVID-19 in the United States. Delta became the dominant variant in Arkansas (AR) the 1st week of July 2021. Schools contributed to pediatric infections during the January 2021 surge in COVID-19 infections even with physical mitigation measures (PMM) that were removed in March 2021. We present preliminary data suggesting a shift in the clinical presentation of children with Delta variant infection. Methods Pediatric (ages ≤ 18 years) case records for the 3 months representing key inflection points of the COVID-19 Pandemic in AR were reviewed. Outcomes (hospitalizations, ICU admission, mechanical ventilation, death) were recorded by the Arkansas Department of Health (ADH) in a statewide database. Fisher’s Exact Test was used with p-values &lt; 0.05 indicating statistical significance. Results During July 2020, 3,268 pediatric cases were reported to ADH with 55 hospitalizations, 6 ICU admissions, 2 mechanical ventilations, and no deaths. A second peak in January 2021 included 11,735 pediatric cases, a 259.1% increase. Increases were also seen in hospitalizations (n=74), ICU admissions (n= 11), and mechanical ventilations (n=2). No deaths reported. The beginning of an exponential growth in cases during July 2021, before the opening of schools, included 8,031 pediatric cases. Despite 31.6% fewer cases than the previous peak, hospitalizations increased 41.9% (n=105) (p &lt; 0.0001) and included increases in ICU and ventilator use of 68.6% (n=18) (p 0.0016) and 300% (n=8) (p 0.0034), respectively. One pediatric death was reported. (Tbl 1) Conclusion In the absence of PMM and despite the summer closure of schools, pediatric COVID-19 cases and severe outcomes increased significantly. Initial analysis of the AR July 2021 Delta variant surge indicates a statistically significant increase in pediatric COVID-19 disease and severity as indicated by a proportional increase in hospitalizations, ICU, and ventilator use. Further studies are warranted to better define Delta related childhood disease. Our findings also have implications for school PMM efforts. Disclosures All Authors: No reported disclosures

PROPORTION OF NAIVE CD45RA+ AND CD31+T-CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS UNDER STIMULATION WITH HOMEOSTATIC FACTORS IN VITRO

Much attention of researchers is directed to study the role of factors of homeostatic proliferation in the pathogenesis of autoimmune diseases, however, the effect of IL-7 and IL-15 on the phenotype of naive T cells has not yet been sufficiently investigated in the pathology. The aim of this study was to investigate the proportion of CD45RA+ and CD31+ naive cells among CD4+ and CD8+ lymphocytes from healthy individuals and patients with rheumatoid arthritis (RA) upon stimulation with IL-7, IL-15 in vitro. In peripheral blood, we did not find any differences in the number of CD45RA+ and CD31+ cells between the group of donors and group of RA patients. In donors, stimulation by a combination of IL-7 with IL-15 promoted an increase in the proportion of CD4+CD45RA+ and CD8+CD45RA+ relative to their level in the peripheral blood. Whereas in RA patients the number of CD8+CD45RA+ cells decreased under IL-15 and the combination of IL-15 with IL-7 compared to the control without stimulation, and it, as a proportion of CD4+CD45RA+ cells, significantly differed from the content of these cells under the same conditions in donors. There were no significant differences in the content of CD31+ cells and the number of CD31+ cells proliferating to cytokines, both between the groups of donors and patients with RA, and between different culture conditions. Thus, we can say that under the factors of homeostatic proliferation, there is a proportional increase in CD31+ T cells number, both in donors and in patients with RA. At the same time, naive T cells from donors retain the expression of CD45RA during cultivation, while naive T cells from patients partially lose it. The obtained data indicate that in RA, under factors of homeostatic proliferation the phenotype of naive T cells is converted into the phenotype of memory T cells.

Shifts in learning assistants’ self-determination due to COVID-19 disruptions in Calculus II course delivery

Background The Learning Assistant (LA) model with its subsequent support and training has evidenced significant gains for undergraduate STEM learning and persistence, especially in high-stakes courses like Calculus. Yet, when a swift and unexpected transition occurs from face-to-face to online, remote learning of the LA environment, it is unknown how LAs are able to maintain their motivation (competence, autonomy, and relatedness), adapt to these new challenges, and sustain their student-centered efforts. This study used Self-Determination Theory (SDT) to model theoretical aspects of LAs’ motivations (persistence and performance) both before and after changes were made in delivery of a Calculus II course at Texas Tech University due to COVID-19 interruptions. Results Analysis of weekly written reflections, a focus group session, and a post-course questionnaire of 13 Calculus II LAs throughout Spring semester of 2020 showed that LAs’ reports of competence proportionally decreased when they transitioned online, which was followed by a moderate proportional increase in reports of autonomy (actions they took to adapt to distance instruction) and a dramatic proportional increase in reports of relatedness (to build structures for maintaining communication and building community with undergraduate students). Conclusions Relatedness emerged as the most salient factor from SDT to maintain LA self-determination due to the COVID-19 facilitated interruption to course delivery in a high-stakes undergraduate STEM course. Given that online learning continues during the pandemic and is likely to continue after, this research provides an understanding to how LAs responded to this event and the mounting importance of relatedness when LAs are working with undergraduate STEM learners. Programmatic recommendations are given for enhancing LA preparation including selecting LAs for autonomy and relatedness factors (in addition to competence), modeling mentoring for remote learners, and coaching in best practices for online instruction.

Counting actin in contractile rings reveals novel contributions of cofilin and type II myosins to fission yeast cytokinesis

Cytokinesis by animals, fungi and amoebas depends on actomyosin contractile rings, which are stabilized by continuous turnover of actin filaments. Remarkably little is known about the amount of polymerized actin in contractile rings, so we used low concentration of GFP-Lifeact to count total polymerized actin molecules in the contractile rings of live fission yeast cells. Contractile rings of wild-type cells accumulated polymerized actin molecules at 4,900/min to a peak number of ∼198,000 followed by a loss of actin at 5,400/min throughout ring constriction. In adf1-M3 mutant cells with cofilin that severs actin filaments poorly, contractile rings accumulated polymerized actin at twice the normal rate and eventually had almost two-fold more actin along with a proportional increase in type II myosins Myo2, Myp2 and formin Cdc12. Although 30% of adf1-M3 mutant cells failed to constrict their rings fully, the rest lost actin from the rings at the wild-type rates. Mutations of type II myosins Myo2 and Myp2 reduced contractile ring actin filaments by half and slowed the rate of actin loss from the rings.