Baylor Research Institute

Driver, S., Reynolds, M., Brown, K., Vingren, J.L., Hill, D.W., Bennett, M., Gilliland, T., McShan, E., Callender, L., Reynolds, E., Borunda, N., Mosolf, J., Cates, C. and Jones, A. (2021). “Effects of wearing a cloth face mask on performance, physiological and perceptual responses during a graded treadmill running exercise test.” Br J Sports Med.

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OBJECTIVES: To (1) determine if wearing a cloth face mask significantly affected exercise performance and associated physiological responses, and (2) describe perceptual measures of effort and participants’ experiences while wearing a face mask during a maximal treadmill test. METHODS: Randomised controlled trial of healthy adults aged 18-29 years. Participants completed two (with and without a cloth face mask) maximal cardiopulmonary exercise tests (CPETs) on a treadmill following the Bruce protocol. Blood pressure, heart rate, oxygen saturation, exertion and shortness of breath were measured. Descriptive data and physical activity history were collected pretrial; perceptions of wearing face masks and experiential data were gathered immediately following the masked trial. RESULTS: The final sample included 31 adults (age=23.2±3.1 years; 14 women/17 men). Data indicated that wearing a cloth face mask led to a significant reduction in exercise time (-01:39±01:19 min/sec, p<0.001), maximal oxygen consumption (VO(2)max) (-818±552 mL/min, p<0.001), minute ventilation (-45.2±20.3 L/min), maximal heart rate (-8.4±17.0 beats per minute, p<0.01) and increased dyspnoea (1.7±2.9, p<0.001). Our data also suggest that differences in SpO(2) and rating of perceived exertion existed between the different stages of the CPET as participant's exercise intensity increased. No significant differences were found between conditions after the 7-minute recovery period. CONCLUSION: Cloth face masks led to a 14% reduction in exercise time and 29% decrease in VO(2)max, attributed to perceived discomfort associated with mask-wearing. Compared with no mask, participants reported feeling increasingly short of breath and claustrophobic at higher exercise intensities while wearing a cloth face mask. Coaches, trainers and athletes should consider modifying the frequency, intensity, time and type of exercise when wearing a cloth face mask.

Beebe, K.E., Reynolds, E. and Driver, S. (2021). “One size fits none: neurobiologic-specific modifications for the assessment, diagnosis, and treatment of sport-related concussion (SRC).” Brain Inj 35(5): 505-510.

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PRIMARY OBJECTIVE: – To discuss how the underlying neuroanatomy and neurobiology of five sport-related concussion (SRC) clinical profiles impacts assessment and treatment. RESEARCH DESIGN: – Narrative review. METHODS AND PROCEDURES: – Based on the current literature and clinical experience, arguments against the traditional SRC protocol and for a clinical profiles-based SRC protocol are made. MAIN OUTCOMES AND RESULTS: – While the clinical profiles-based SRC protocol is widely used and accepted, there has been little published regarding the link to the underlying neuropathology. Our narrative review describes the five SRC clinical profiles: vestibular, ocular, mood, post-traumatic migraine, and cognitive/fatigue. For these profiles, the underlying neuroanatomy and neurobiology is outlined, as well as how that anatomy and biology impact the profiles’ etiology, assessment, and treatment. The cervical and sleep modifiers are also briefly covered. CONCLUSIONS: – Utilizing this model, clinicians are able to provide an individualized assessment, conceptualization, and treatment plan for SRC, leading to improved outcomes and clinical experiences for athletes.

Markus, H., Zhao, J., Contente-Cuomo, T., Stephens, M.D., Raupach, E., Odenheimer-Bergman, A., Connor, S., McDonald, B.R., Moore, B., Hutchins, E., McGilvrey, M., de la Maza, M.C., Van Keuren-Jensen, K., Pirrotte, P., Goel, A., Becerra, C., Von Hoff, D.D., Celinski, S.A., Hingorani, P. and Murtaza, M. (2021). “Analysis of recurrently protected genomic regions in cell-free DNA found in urine.” Sci Transl Med 13(581).

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Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, urine cfDNA is highly fragmented. Whether characteristics of these fragments reflect underlying genomic architecture is unknown. Here, we characterized fragmentation patterns in urine cfDNA using whole-genome sequencing. Size distribution of urine cfDNA fragments showed multiple strong peaks between 40 and 120 base pairs (bp) with a modal size of 81- and sharp 10-bp periodicity, suggesting transient protection from complete degradation. These properties were robust to preanalytical perturbations, such as at-home collection and delay in processing. Genome-wide sequencing coverage of urine cfDNA fragments revealed recurrently protected regions (RPRs) conserved across individuals, with partial overlap with nucleosome positioning maps inferred from plasma cfDNA. The ends of cfDNA fragments clustered upstream and downstream of RPRs, and nucleotide frequencies of fragment ends indicated enzymatic digestion of urine cfDNA. Compared to plasma, fragmentation patterns in urine cfDNA showed greater correlation with gene expression and chromatin accessibility in epithelial cells of the urinary tract. We determined that tumor-derived urine cfDNA exhibits a higher frequency of aberrant fragments that end within RPRs. By comparing the fraction of aberrant fragments and nucleotide frequencies of fragment ends, we identified urine samples from cancer patients with an area under the curve of 0.89. Our results revealed nonrandom genomic positioning of urine cfDNA fragments and suggested that analysis of fragmentation patterns across recurrently protected genomic loci may serve as a cancer diagnostic.

Li, J., Qi, D., Hsieh, T.C., Huang, J.H., Wu, J.M. and Wu, E. (2021). “Trailblazing perspectives on targeting breast cancer stem cells.” Pharmacol Ther Jan 7;223:107800. [Epub ahead of print]. 107800.

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Breast cancer (BCa) is one of the most prevalent malignant tumors affecting women’s health worldwide. The recurrence and metastasis of BCa have made it a long-standing challenge to achieve remission-persistent or disease-undetectable clinical outcomes. Cancer stem cells (CSCs) possess the ability to self-renew and generate heterogeneous tumor bulk. The existence of CSCs has been found to be vital in the initiation, metastasis, therapy resistance, and recurrence of tumors across cancer types. Because CSCs grow slowly in their dormant state, they are insensitive to conventional chemotherapies; however, when CSCs emerge from their dormant state and become clinically evident, they usually acquire genetic traits that make them resistant to existing therapies. Moreover, CSCs also show evidence of acquired drug resistance in synchrony with tumor relapses. The concept of CSCs provides a new treatment strategy for BCa. In this review, we highlight the recent advances in research on breast CSCs and their association with epithelial-mesenchymal transition (EMT), circulating tumor cells (CTCs), plasticity of tumor cells, tumor microenvironment (TME), T-cell modulatory protein PD-L1, and non-coding RNAs. On the basis that CSCs are associated with multiple dysregulated biological processes, we envisage that increased understanding of disease sub-classification, selected combination of conventional treatment, molecular aberration directed therapy, immunotherapy, and CSC targeting/sensitizing strategy might improve the treatment outcome of patients with advanced BCa. We also discuss novel perspectives on new drugs and therapeutics purposing the potent and selective expunging of CSCs.

Srivastava, S., Cirrincione, K.N., Deshpande, D. and Gumbo, T. (2020). “Tedizolid, Faropenem, and Moxifloxacin Combination With Potential Activity Against Nonreplicating Mycobacterium tuberculosis.” Front Pharmacol 11: 616294.

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Background: Mycobacterium tuberculosis [Mtb] could be present in different metabolic population in the lung lesions, and nonreplicating persisters [NRP], associated with latent tuberculosis [TB], are the most difficult to kill. Objective: Test the combination of tedizolid, moxifloxacin, and faropenem for activity against NRP using Mtb SS18b in the hollow fiber model [HFS-TB]. Methods: Tedizolid and moxifloxacin were tested as, first, two-drug combination against log-phase growth [LPG] and, second, slowly replicating bacilli [SRB] under acidic condition and with faropenem to create a three-drug combination regimen. Finally, standard regimen [isoniazid-rifampin-pyrazinamide] was used as comparator in the HFS-TB experiment with NRP Mtb. HFS-TB units were sampled for drug-concentration measurement as well as for estimation of bacterial burden using solid agar and mycobacterial growth indicator tube [MGIT] method. Linear regression was used to calculate the kill slopes with each treatment regimen and analysis of variance (ANOVA) to compare the regimen. Results: Tedizolid at standard dose in combination with high-dose moxifloxacin killed 3.05 log(10) CFU/ml LPG Mtb and 7.37 log(10) CFU/ml SRB in the bactericidal and sterilizing activity HFS-TB experiments, respectively. There was no statistical difference between tedizolid-moxifloxacin-faropenem combination and the standard regimen as both killed 7.35 log(10) CFU/ml NRP Mtb in 21 days. There was no emergence of resistance to any of the drugs studied in the three HFS-TB experiments. Conclusion: The experimental regimen of tedizolid, moxifloxacin, and faropenem could effectively kill NRP population of Mtb, and given the efficacy against different metabolic population of Mtb could serve as a pan-TB regimen. Clinical studies are warranted to validate the in vitro findings.