Mitigation of SARS-CoV-2 transmission at a large public university.

In Fall 2020, universities saw extensive transmission of SARS-CoV-2 among their populations, threatening health of the university and surrounding communities, and viability of in-person instruction. Here we report a case study at the University of Illinois at Urbana-Champaign, where a multimodal "SHIELD: Target, Test, and Tell" program, with other non-pharmaceutical interventions, was employed to keep classrooms and laboratories open. The program included epidemiological modeling and surveillance, fast/frequent testing using a novel low-cost and scalable saliva-based RT-qPCR assay for SARS-CoV-2 that bypasses RNA extraction, called covidSHIELD, and digital tools for communication and compliance. In Fall 2020, we performed >1,000,000 covidSHIELD tests, positivity rates remained low, we had zero COVID-19-related hospitalizations or deaths amongst our university community, and mortality in the surrounding Champaign County was reduced more than 4-fold relative to expected. This case study shows that fast/frequent testing and other interventions mitigated transmission of SARS-CoV-2 at a large public university.

Objectively measured sedentary behavior and brain volumetric measurements in multiple sclerosis.

AIM: This study examined the association between sedentary behavior patterns and whole brain gray matter (GM), white matter (WM) and subcortical GM structures in persons with multiple sclerosis (MS). METHODS: 36 persons with MS wore an accelerometer and underwent a brain MRI. Whole brain GM and WM and deep GM structures were calculated from 3D T1-weighted structural brain images. RESULTS: There were statistically significant (p < 0.01) and moderate or large associations between number of sedentary bouts/day and brain volume measures. The primary result was a consistent negative association between number of sedentary bouts/day and whole brain GM and WM, and deep GM structures. CONCLUSION: We provide novel evidence for decreased brain volume as a correlate of a sedentary behavior pattern in persons with MS.

Diffusion tensor imaging of the corticospinal tract and walking performance in multiple sclerosis.

Research has identified a significant relationship between DTI (Diffusion Tensor Imaging) indices in the Corticospinal Tract (CST) and disability status in persons with multiple sclerosis (MS). To date, there is little known about the association between DTI indices of the CST with walking and gait outcomes in MS. This study examined the associations among DTI indices [fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD)] of the CST with walking and gait outcomes in persons with MS. We enrolled 69 persons with MS who underwent 3T brain magnetic resonance imaging (MRI) and examined white matter structural integrity in the CST in the brain with DTI. Participants completed three walking performance assessments: 6-minute walk (6MW), timed 25-foot walk (T25FW), and gait testing. We examined associations using Spearman (r(s)) and partial Spearman correlation (pr(s)) analyses, using the entire sample and stratifying by disability status after controlling for age and sex. After controlling for age, sex, and disease duration, RD was significantly correlated (p<0.05) with step time (pr(s)=0.30). AD was significantly correlated (p<0.05) with step length (pr(s)=-0.32). MD was significantly associated (p<0.05) with 6MW (pr(s)=-0.35), T25FW (pr(s)=-0.34), gait velocity (pr(s)=-0.31), step time (pr(s)=0.29), and step length (pr(s)=-0.36). FA was not significantly correlated with any of the walking parameters (p>0.05). We provide novel evidence of possible motor pathway damage involved in walking performance in MS. There may be subtle differences in associations between MD, AD, and RD with walking outcomes, and these could be assessed in future longitudinal examinations and clinical trials of motor rehabilitation.

Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.

Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.

Fully automated open-source lesion mapping of T2-FLAIR images with FSL correlates with clinical disability in MS.

BACKGROUND: T2 Lesion Volume (T2LV) has been an important biomarker for multiple sclerosis (MS). Current methods available to quantify lesions from MR images generally require manual adjustments or multiple images with different contrasts. Further, implementations are often not easily or openly accessible. OBJECTIVE: We created a fully unsupervised, single T2 FLAIR image T2LV quantification package based on the popular open-source imaging toolkit FSL. METHODS: By scripting various processing tools in FSL, we developed an image processing pipeline that distinguishes normal brain tissue from CSF and lesions. We validated our method by hierarchical multiple regression (HMR) with a preliminary study to see if our T2LVs correlate with clinical disability measures in MS when controlled for other variables. RESULTS: Pearson correlations between T2LV and Expanded Disability Status Scale (EDSS: r = 0.344, P = 0.013), Six-Minute Walk (6MW: r = -0.513, P = 0.000), Timed 25-Foot Walk (T25FW: r = -0.438, P = .000), and Symbol Digit Modalities Test (SDMT: r = -0.499, P = 0.000) were all significant. Partial correlations controlling for age were significant between T2LV and 6MW (r = -0.433, P = 0.002), T25FW (r = -0.392, P = 0.004), and SDMT (r = -0.450, P = 0.001). In HMR, T2LV explained significant additional variance in 6MW (R(2) change = 0.082, P = 0.020), after controlling for confounding variables such as age, white matter volume (WMV), and gray matter volume (GMV). CONCLUSION: Our T2LV quantification software produces T2LVs from a single FLAIR image that correlate with physical disability in MS and is freely available as open-source software.

Transplantation of an LGR6+ Epithelial Stem Cell-Enriched Scaffold for Repair of Full-Thickness Soft-Tissue Defects: The In Vitro Development of Polarized Hair-Bearing Skin.

BACKGROUND: Recent literature has shown that full-thickness wounds, devoid of the stem cell niche, can subsequently be reconstructed with functional skin elements following migration of the LGR6 epithelial stem cell into the wound bed. In this study, the authors use a variety of LGR6 epithelial stem cell-seeded scaffolds to determine therapeutic utility and regenerative potential in the immediate reconstruction of full-thickness wounds. METHODS: Isolated LGR6 epithelial stem cells were seeded onto a spectrum of acellular matrices and monitored in both in vitro and in vivo settings to determine their relative capacity to regenerate tissues and heal wounds. RESULTS: Wound beds containing LGR6 stem cell-seeded scaffolds showed significantly augmented rates of healing, epithelialization, and hair growth compared with controls. Gene and proteomic expression studies indicate that LGR6 stem cell-seeded constructs up-regulate WNT, epidermal growth factor, and angiogenesis pathways. Finally, the addition of stromal vascular fraction to LGR6 stem cell-seeded constructs induces polarized tissue formation, nascent hair growth, and angiogenesis within wounds. CONCLUSIONS: LGR6 stem cells are able to undergo proliferation, differentiation, and migration following seeding onto a variety of collagen-based scaffolding. In addition, deployment of these constructs induces epithelialization, hair growth, and angiogenesis within wound beds. The addition of stromal vascular fraction to LGR6 stem cell-containing scaffolds initiated an early form of tissue polarization, providing for the first time a clinically applicable stem cell-based construct that is capable of the repair of full-thickness wounds and hair regeneration. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Objectively Measured Physical Activity Is Associated with Brain Volumetric Measurements in Multiple Sclerosis.

BACKGROUND: Little is known about physical activity and its association with volumes of whole brain gray matter and white matter and deep gray matter structures in persons with multiple sclerosis (MS). PURPOSE: This study examined the association between levels of physical activity and brain volumetric measures from magnetic resonance imaging (MRI) in MS. METHOD: 39 persons with MS wore an accelerometer for a 7-day period and underwent a brain MRI. Normalized GM volume (NGMV), normalized WM volume (NWMV), and deep GM structures were calculated from 3D T1-weighted structural brain images. We conducted partial correlations (pr) controlling for demographic and clinical variables. RESULTS: Moderate-to-vigorous physical activity (MVPA) was significantly associated with NGMV (pr = 0.370, p < 0.05), NWMV (pr = 0.433, p < 0.01), hippocampus (pr = 0.499, p < 0.01), thalamus (pr = 0.380, p < 0.05), caudate (pr = 0.539, p < 0.01), putamen (pr = 0.369, p < 0.05), and pallidum (pr = 0.498, p < 0.01) volumes, when controlling for sex, age, clinical course of MS, and Expanded Disability Status Scale score. There were no associations between sedentary and light physical activity with MRI outcomes. CONCLUSION: Our results provide the first evidence that MVPA is associated with volumes of whole brain GM and WM and deep GM structures that are involved in motor and cognitive functions in MS.

Pallidal and caudate volumes correlate with walking function in multiple sclerosis.

BACKGROUND: Walking dysfunction is common in multiple sclerosis (MS). The thalamus and basal ganglia seemingly have important associations with walking performance. The contribution of these subcortical gray matter (SGM) structures for walking dysfunction is poorly understood in MS. PURPOSE: This study examined associations among volumes of the thalamus and basal ganglia with walking outcomes in MS. METHOD: We enrolled 61 MS patients who underwent brain MRI and completed the 6-minute walk (6MW) and timed 25-foot walk (T25FW). Volumes of the thalamus, caudate, putamen, and pallidum as well as whole-brain white matter (WM) and gray matter (GM) were calculated from 3D T1-weighted structural brain images. We examined associations using bivariate correlations (r) and partial correlations (pr) that controlled for age, MS clinical course, and whole-brain WM and GM volumes. We further performed hierarchical linear regression (HLR) for identifying the strongest SGM correlate of walking performance. RESULTS: The 6MW and T25FW correlated significantly with volumes of the thalamus (r's=.382 & .383), caudate (r's=.388 & .416), pallidum (r's=.457 & .457), and putamen (r's=.258 & .293) in bivariate correlations. The 6MW and T25FW remained significantly correlated with caudate (pr's=.243 & .312) and pallidum (pr's=.321 & .345) volumes in partial correlations. Pallidum volume was the strongest SGM correlate of 6MW (ß=.39) and T25FW (ß=.40) performance in HLR. CONCLUSION: We provide novel evidence of possible SGM structures, particularly the pallidum and perhaps caudate, as correlates of walking performance in MS.

Cardiorespiratory fitness and its association with thalamic, hippocampal, and basal ganglia volumes in multiple sclerosis.

BACKGROUND: There is little known about cardiorespiratory fitness and its association with volumes of the thalamus, hippocampus, and basal ganglia in multiple sclerosis (MS). Such inquiry is important for identifying a possible behavioral approach (e.g., aerobic exercise training) that might change volumes of deep gray matter (DGM) structures associated with cognitive and motor functions in MS. PURPOSE: This study examined the association between cardiorespiratory fitness and volumes of the thalamus, hippocampus, and basal ganglia in MS. METHOD: We enrolled 35 persons with MS who underwent a maximal exercise test for measuring cardiorespiratory fitness as peak oxygen consumption (VO2peak) and brain MRI. Volumes of the thalamus, hippocampus, caudate, putamen, and pallidum were calculated from 3D T1-weighted structural brain images. We examined associations using partial (pr) correlations controlling for demographic and clinical variables. RESULTS: VO2peak was significantly associated with composite scaled volumes of the caudate(pr = .47, p < .01), putamen (pr = .44, p < .05), pallidum (pr = .40, p < .05), and hippocampus (pr = .42, p < .05), but not thalamus (pr = .31, p = .09), when controlling for sex, age, disability, and duration of MS. CONCLUSION: Our results provide novel evidence that cardiorespiratory fitness is associated with volumes of DGM structures that are involved in motor and cognitive functions in MS.

Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes.

BACKGROUND: The recently discovered leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6+) epithelial stem cell located within the follicular bulge of the adnexal compartment is capable of producing all cellular lineages of the skin. In this study, the authors sought to determine whether these cells can be transplanted for use as a type of cellular therapy for the repair of full-thickness wounds in which the native stem cell niche has been obliterated. METHODS: Full-thickness murine skin was harvested and LGR6(+GFP) epithelial stem cells were isolated using fluorescence-activated cell sorting. This enriched epithelial stem cell population was then transplanted by means of local injection into wound beds on the dorsum of nude mice. Viability, migration, healing, the development of nascent hair follicles, and gene and proteomic expression studies were performed to determine whether the engraftment of LGR6(+GFP) epithelial stem cells enhanced healing when compared with controls. RESULTS: Wound beds receiving LGR6(+GFP) epithelial stem cells showed enhanced healing; nascent follicle growth; and augmentation of the Wnt, vascular endothelial growth factor, epidermal growth factor, and platelet-derived growth factor pathways when compared with controls. CONCLUSIONS: The LGR6+ epithelial stem cells appear to hold great promise for the development of a clinically useful stem cell­based therapy for the repair of full-thickness wounds and hair regeneration. These results indicate that transplantation of LGR6+ epithelial stem cells promotes epithelialization, hair growth, and angiogenesis in tissues destined for scar formation.

Medical students' online learning technology needs.

PURPOSE: This study investigated medical students' online learning technology needs at a medical school. The study aimed to provide evidence-based guidance for technology selection and online learning design in medical education. METHODS: The authors developed a 120-item survey in collaboration with the New Technology in Medical Education (NTIME) committee at the Southern Illinois University School of Medicine (SIUSOM). Overall, 123 of 290 medical students (42%) at the medical school participated in the survey. The survey focused on five major areas: students' hardware and software use; perception of educational technology (ET) in general; online behaviours; perception of ET use at the school; and demographic information. RESULTS: Students perceived multimedia tools, scheduling tools, communication tools, collaborative authoring tools, learning management systems and electronic health records useful educational technologies for their learning. They did not consider social networking tools useful for their learning, despite their frequent use. Third-year students were less satisfied with current technology integration in the curriculum, information sharing and collaborative learning than other years. Students in clerkships perceived mobile devices as useful for their learning. Students using a mobile device (i.e. a smartphone) go online, text message, visit social networking sites and are online during classes more frequently than non-users. CONCLUSIONS: Medical students' ET needs differ between preclinical and clinical years. Technology supporting ubiquitous mobile learning and health information technology (HIT) systems at hospitals and out-patient clinics can be integrated into clerkship curricula.

The impact of brief team communication, leadership and team behavior training on ad hoc team performance in trauma care settings.

BACKGROUND: Communication breakdowns and care coordination problems often cause preventable adverse patient care events, which can be especially acute in the trauma setting, in which ad hoc teams have little time for advanced planning. Existing teamwork curricula do not address the particular issues associated with ad hoc emergency teams providing trauma care. METHODS: Ad hoc trauma teams completed a preinstruction simulated trauma encounter and were provided with instruction on appropriate team behaviors and team communication. Teams completed a postinstruction simulated trauma encounter immediately afterward and 3 weeks later, then completed a questionnaire. Blinded raters rated videotapes of the simulations. RESULTS: Participants expressed high levels of satisfaction and intent to change practice after the intervention. Participants changed teamwork and communication behavior on the posttest, and changes were sustained after a 3-week interval, though there was some loss of retention. CONCLUSIONS: Brief training exercises can change teamwork and communication behaviors on ad hoc trauma teams.

Expression of inducible nitric oxide synthase in muscle flaps treated with ischemic postconditioning.

BACKGROUND/OBJECTIVE: Preconditioning has been considered promising for the treatment of ischemic flaps. In this study, the therapeutic effect of postconditioning was compared with that of preconditioning during ischemia/reperfusion (I/R) injury, and a role of inducible nitric oxide synthase (iNOS) in postconditioning treatment was also explored. METHODS: Sixty rats were randomly divided into four groups with 15 rats in each group. Ischemic injury was induced in a rat's gracilis muscle flap model. Preconditioning and postconditioning were performed respectively on the flaps in the pre-con group and the post-con group. No treatment was given to the flaps in the control group, and flaps without I/R injury were used as a sham control. Muscle viability ratio, histology, and gene expression of iNOS were examined at different time intervals (3, 12, and 18 h). RESULTS: A significantly higher survival ratio was observed in both the pre-con group (78.98 ± 3.39, 62.74 ± 3.7, and 54.42 ± 4.45 %) and the post-con group (77.42 ± 4.14, 59.74 ± 6.67, and 49.52 ± 4.13 %) than the control group (45.22 ± 3.69, 42.44 ± 3.76, and 33.2 ± 3.29 %) at 3, 12, and 18 h postoperatively (P < 0.05). There was no statistical difference between the pre-con group and the post-con group (P > 0.05). Histological examination showed delayed and attenuated tissue damage in both the pre-con group and the post-con group when compared to that of the control group. A higher expression of iNOS was observed in both the pre-con group and the post-con group than the control group and the sham group (P < 0.05). CONCLUSIONS: Significant improvement of flap survival could be achieved by both preconditioning and postconditioning treatments; however, better protection could be provided by preconditioning. The higher expression of iNOS may play an important role in the therapeutic effect of postconditioning during I/R injury.