Effects of a Respiratory Resistance Mask on Forced Expiratory Volume at 1s (FEV1), Forced Vital Capacity (FVC) and the Ratio of FEV1/FVC Lung Function following High Intensity Training (HIT)

Training masks (TMs), marketed as simulated altitude training devices, suggest increased workout capacity, intensity tolerance and recovery. The claim is that the training mask improves respiratory power and breathing mechanics by strengthening the respiratory muscles through breathing resistance provided by the TM. The aim of this study was to compare the effects of a commercially manufactured TM in conjunction with bicycle ergometry, high intensity training (HIT) on selected lung function parameters. Volunteers (N=16) participated in this study and were randomly assigned to an experimental or control group. The experimental group wore the TM with progressive increased respiratory resistance and the control group wore the TM with no respiratory resistance. To determine lung function, pre- and post-test assessments consisted of forced expiratory volume at 1s (FEV1), forced vital capacity (FVC), the ratio of FEV1/FVC. Additionally, to determine the TMs effectiveness of maximal oxygen consumption pre- and post-time to failure during a maximum treadmill test was performed. Training was completed on a cycle ergometer on 3d/wk for 4 wks. Participants exercised at 85% of HRmax with a pedal rate of 100-120 rpm at individually set resistance levels. Training sessions consisted of 10 bouts of 30s exercise followed by 30s of active recovery for a total time of 10 minutes. The respiratory resistance for the experimental group progressively increased over the training period. Repeated measures ANOVAs yielded significant between group difference in FVC (p = 0.02) but not for FEV1 or maximum treadmill time. In conclusion, TMs in combination with HIT failed to improve lung function but created sufficient resistance to strengthen the muscles in respiratory ventilation

Comparison of Physiological Responses and Perceived Respiratory Resistance Among Mask Usage During Exercise

Since the beginning of the COVID-19 pandemic, the use of a face mask in public is recommended when social distancing cannot be maintained to decrease the spread of the virus with many fitness facilities requiring their patrons to wear a face mask during exercise. The physiological response of wearing a face mask during exercise is relatively unknown and is speculated among the media resulting in contradicting messages conveyed to the public PURPOSE: The purpose of this study was to determine if a face mask influenced performance (time to exhaustion), physiological responses (heart rate, oxyhemoglobin saturation and temperature) and subjective measurements such as dyspnea, perceived respiratory resistance, and rating of perceived exertion (RPE) during exercise. METHODS: Fifteen healthy males (n =8) and females (n=7) completed three graded exercise treadmill tests with (1) a surgical face mask, (2) a cloth face mask, and (3) no mask randomly with at least 48hrs apart. Heart rate (HR), oxyhemoglobin saturation (SpO2), temperature, RPE, dyspnea, was measured throughout exercise. Participants rated their perceived respiratory resistance for each condition at rest, beginning of exercise, and at fatigue using a 100 mm visual analog scale. RESULTS: Significant differences (p \u3c 0.05) were observed in perceived respiratory resistance between no mask and both surgical and cloth conditions at rest (1.55 ± 2.34mm; 6.33 ± 6.11mm; 9.67 ± 10.77mm respectively) and at the beginning of exercise (5.93 ± 6.64mm; 15.47 ± 12.56mm; 21.07± 15.04mm respectively). During stage 3 of the exercise test, the no mask condition had a significantly lower RPE compared to the cloth mask condition (13.22 ± 2.14;14.60 ± 2.13 respectively). Time to exhaustion was similar for all conditions (mask: 11:51 ± 2:31min; cloth: 11:16 ± 2:24min; surgical: 11:32 ± 2:23min). At all times points, there was no significant (p \u3e 0.05) difference between the conditions for HR, SpO2, temperature, and dyspnea. CONCLUSION: Wearing either a surgical or cloth face mask is safe during exercise in healthy adults and has no effect on HR, SpO2, or body temperature. It appears that wearing a face mask may have a minor influence on subjective measurements such as perceived respiratory resistance or RPE during exercise

Bat-associated Rabies Virus in Skunks

Rabies was undetected in terrestrial wildlife of northern Arizona until 2001, when rabies was diagnosed in 19 rabid skunks in Flagstaff. Laboratory analyses showed causative rabies viruses associated with bats, which indicated cross-species transmission of unprecedented magnitude. Public health infrastructure must be maintained to address emerging zoonotic diseases

TigerPlace, a State-Academic-Private Project to Revolutionize Traditional Long Term Care

This is a preprint of an article whose final and definitive form has been published in the Journal of Housing for the Elderly 2008, copyright Taylor & Francis. Journal of Housing for the Elderly is available online at: http://www.informaworld.com/openurl?genre=article&issn=0276-3893&volume=22&issue=1&spage=66 DOI:10.1080/02763890802097045The Aging in Place Project at the University of Missouri (MU) required legislation in 1999 and 2001 to be fully realized. An innovative home health agency was initiated by the Sinclair School of Nursing specifically to help older adults age in place in the environment of their choice. In 2004, an innovative independent living environment was built and is operated by a private long term care company, as a special facility where residents can truly age in place and never fear being moved to a traditional nursing home unless they choose to do so. With care provided by the home care agency with registered nurse care coordination services, residents receive preventative and early illness recognition assistance that have markedly improved their lives. Evaluation of aging in place reveal registered nurse care coordination improves outcomes of cognition, depression, activities of daily living, incontinence, pain, and shortness of breath as well as delaying or preventing nursing home placement. Links with MU students, faculty, and nearly every school or college on campus enrich the lives of the students and residents of the housing environment. Research projects are encouraged and residents who choose to participate are enjoying helping with developing cutting technology to help other seniors age in place.The authors wish to acknowledge the organizations and staff who made the AIP project possible: Americare of Sikeston, MO; TigerPlace staff; Sinclair Home Care staff; MU Sinclair School of Nursing faculty and deans; MU administration; Missouri Department of Health and Senior Services staff; Missouri state legislature (in particular, Tim Harlan of Columbia, MO); and all the friends and families who have supported those who implemented this pioneering effort

Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU

Stem cells are proposed to segregate chromosomes asymmetrically during self-renewing divisions so that older ('immortal') DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells(1-6). Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridine (BrdU), either because they segregate chromosomes asymmetrically or because they divide slowly(5,7-9). However, the purity of stem cells among BrdU-label-retaining cells has not been documented in any tissue, and the 'immortal strand hypothesis' has not been tested in a system with definitive stem cell markers. Here we tested these hypotheses in haematopoietic stem cells (HSCs), which can be highly purified using well characterized markers. We administered BrdU to newborn mice, mice treated with cyclophosphamide and granulocyte colony-stimulating factor, and normal adult mice for 4 to 10 days, followed by 70 days without BrdU. In each case, less than 6% of HSCs retained BrdU and less than 0.5% of all BrdU-retaining haematopoietic cells were HSCs, revealing that BrdU has poor specificity and poor sensitivity as an HSC marker. Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly. Division of individual HSCs in culture revealed no asymmetric segregation of the label. Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62821/1/nature06115.pd

Publisher Correction: Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma.

The original version of this Article omitted Suzana A. Kahn, Siddhartha S. Mitra & Samuel H. Cheshier as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article

Radiomic signatures of posterior fossa ependymoma: Molecular subgroups and risk profiles

BACKGROUND: The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB. METHODS: We extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers. RESULTS: For all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (p < 0.0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (p = 0.002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86. CONCLUSIONS: We present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy

A Novel Assay to Trace Proliferation History In Vivo Reveals that Enhanced Divisional Kinetics Accompany Loss of Hematopoietic Stem Cell Self-Renewal

BACKGROUND: The maintenance of lifelong blood cell production ultimately rests on rare hematopoietic stem cells (HSCs) that reside in the bone marrow microenvironment. HSCs are traditionally viewed as mitotically quiescent relative to their committed progeny. However, traditional techniques for assessing proliferation activity in vivo, such as measurement of BrdU uptake, are incompatible with preservation of cellular viability. Previous studies of HSC proliferation kinetics in vivo have therefore precluded direct functional evaluation of multi-potency and self-renewal, the hallmark properties of HSCs. METHODOLOGY/PRINCIPAL FINDINGS: We developed a non-invasive labeling technique that allowed us to identify and isolate candidate HSCs and early hematopoietic progenitor cells based on their differential in vivo proliferation kinetics. Such cells were functionally evaluated for their abilities to multi-lineage reconstitute myeloablated hosts. CONCLUSIONS: Although at least a few HSC divisions per se did not influence HSC function, enhanced kinetics of divisional activity in steady state preceded the phenotypic changes that accompanied loss of HSC self-renewal. Therefore, mitotic quiescence of HSCs, relative to their committed progeny, is key to maintain the unique functional and molecular properties of HSCs

A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival

YesGlioblastoma (GBM) has a dismal prognosis. Evidence from preclinical tumor models and human trials indicates the role of GBM initiating cells (GIC) in GBM drug resistance. Here, we propose a new treatment option with tumor enzyme-activatable, combined therapeutic and diagnostic (theranostic) nanoparticles, which caused specific toxicity against GBM tumor cells and GICs. The theranostic cross-linked iron oxide nanoparticles (CLIO) were conjugated to a highly potent vascular disrupting agent (ICT) and secured with a matrix-metalloproteinase (MMP-14) cleavable peptide. Treatment with CLIO-ICT disrupted tumor vasculature of MMP-14 expressing GBM, induced GIC apoptosis and significantly impaired tumor growth. In addition, the iron core of CLIO-ICT enabled in vivo drug tracking with MR imaging. Treatment with CLIO-ICT plus temozolomide achieved tumor remission and significantly increased survival of human GBM bearing mice by more than 2 fold compared to treatment with temozolomide alone. Thus, we present a novel therapeutic strategy with significant impact on survival and great potential for clinical translation.Heike E Daldrup-Link, NIH, R21CA176519 and R21CA190196; Sanjiv Sam Gambhir, NIH, 1U54CA199075; Jessica Klockow, NCI training grant, T32CA118681, Robert A. Falconer, University of Bradford, UoB-6603

Effect of Cellular Quiescence on the Success of Targeted CML Therapy

Similar to tissue stem cells, primitive tumor cells in chronic myelogenous leukemia have been observed to undergo quiescence; that is, the cells can temporarily stop dividing. Using mathematical models, we investigate the effect of cellular quiescence on the outcome of therapy with targeted small molecule inhibitors.According to the models, the initiation of treatment can result in different patterns of tumor cell decline: a biphasic decline, a one-phase decline, and a reverse biphasic decline. A biphasic decline involves a fast initial phase (which roughly corresponds to the eradication of cycling cells by the drug), followed by a second and slower phase of exponential decline (corresponding to awakening and death of quiescent cells), which helps explain clinical data. We define the time when the switch to the second phase occurs, and identify parameters that determine whether therapy can drive the tumor extinct in a reasonable period of time or not. We further ask how cellular quiescence affects the evolution of drug resistance. We find that it has no effect on the probability that resistant mutants exist before therapy if treatment occurs with a single drug, but that quiescence increases the probability of having resistant mutants if patients are treated with a combination of two or more drugs with different targets. Interestingly, while quiescence prolongs the time until therapy reduces the number of cells to low levels or extinction, the therapy phase is irrelevant for the evolution of drug resistant mutants. If treatment fails as a result of resistance, the mutants will have evolved during the tumor growth phase, before the start of therapy. Thus, prevention of resistance is not promoted by reducing the quiescent cell population during therapy (e.g., by a combination of cell activation and drug-mediated killing).The mathematical models provide insights into the effect of quiescence on the basic kinetics of the response to targeted treatment of CML. They identify determinants of success in the absence of drug resistant mutants, and elucidate how quiescence influences the emergence of drug resistant mutants