Physiology Commons^™

The Value Of Using Validated Competency-Based Assessments Across The Career Span Of An Athletic Trainer, Matthew Drescher, Lindsey Eberman

Clinical Practice in Athletic Training

No abstract provided.

The Development, Implementation, And Value Of The Athletic Training Milestones For Assessing Progressive Clinical Behaviors, Hollie Walusz, Eric Sauers, Mark Laursen, Forrest Pecha

Clinical Practice in Athletic Training

No abstract provided.

Perceptions And Use Of The Athletic Training Milestones In Education: A Report From The Aate Research Network, Cailee E. Welch Bacon, Barton E. Anderson, Julie M. Cavallario, Bonnie L. Van Lunen, Lindsey E. Eberman

Clinical Practice in Athletic Training

The Athletic Training Milestones (AT Milestones) were developed as an evaluation tool to capture the breadth and depth of athletic training knowledge, skills, and behavior. However, it is unclear whether athletic training programs are implementing this tool or how they are implementing it to gauge the clinical progression of students or residents in athletic training. We aimed to explore the perceptions and use of the AT Milestones among educators in athletic training programs. We used a cross-sectional, web- based survey with open-ended questions to collect data from athletic training programs on if and how they implement the AT Milestones at …

Seasonal Climate And Environmental Conditions Associated With Physiological Variations Of Southwestern United States Pines, Taylor Brewer

UNLV Theses, Dissertations, Professional Papers, and Capstones

Juvenile and adult conifers in the southwestern United States are vulnerable to a range of different abiotic and biotic factors, yet it is unclear how their stress tolerance varies across environments. Predicted increases in the frequency and intensity of disturbance as well as greater climate and weather variability across the region highlight the potential for differential physiological responses across tree species and populations. This thesis focuses on two physiologic mechanisms, hydraulic vulnerability and mortality, that could be altered by climate change in two broadly distributed southwestern United States conifers: ponderosa pine and pinyon pine.

In chapter 2, I measured the …

Formulation Of Preservation Solutions For Model Generation With In Vivo Tissue Morphology, Holly Pickett

The Journal of Purdue Undergraduate Research

No abstract provided.

Innate And Adaptive Immune System Consequences Of Post-Traumatic Stress Disorder, Tatlock H. Lauten, Tamara Natour, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

In the field of psychiatry, biological markers are rarely, if ever, used in the diagnosis of mental health disorders. Clinicians rely primarily on patient histories and behavioral symptoms to identify specific psychopathologies, which makes diagnosis highly subjective. Moreover, therapies for mental health disorders are aimed specifically at attenuating behavioral manifestations, which overlooks the pathophysiological indices of the disease. This is highly evident in posttraumatic stress disorder (PTSD) where inflammation and immune system perturbations are becoming increasingly described. Further, patients with PTSD possess significantly elevated risks of developing comorbid inflammatory diseases such as autoimmune and cardiovascular diseases, which are likely linked …

Activation Of Renal Epithelial Na+ Channels (Enac) In Infants With Congenital Heart Disease, Laura Ortmann, Shyam Sundar Nandi, Yulong Li, Hong Zheng, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

INTRODUCTION: This study was designed to measure the concentration and activity of urinary proteases that activate renal epithelial sodium channel (ENaC) mediated Na

METHODS: Urine samples from infants undergoing cardiac surgery were collected at three time points: T1) pre-operatively, T2) 6-8 h after surgery, and T3) 24 h after diuretics. Urine was collected from five heathy infant controls. The urine was tested for four proteases and whole-cell patch-clamp testing was conducted in renal collecting duct M-1 cells to test whether patient urine increased Na

RESULTS: Heavy chain of plasminogen, furin, and prostasin were significantly higher in cardiac patients prior to …

Chemoreflex Sensitization Occurs In Both Male And Female Rats During Recovery From Acute Lung Injury, Kajal Kamra, Irving H. Zucker, Harold D. Schultz, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

Introduction: Sex-specific patterns in respiratory conditions, such as asthma, COPD, cystic fibrosis, obstructive sleep apnea, and idiopathic pulmonary fibrosis, have been previously documented. Animal models of acute lung injury (ALI) have offered insights into sex differences, with male mice exhibiting distinct lung edema and vascular leakage compared to female mice. Our lab has provided evidence that the chemoreflex is sensitized in male rats during the recovery from bleomycin-induced ALI, but whether sex-based chemoreflex changes occur post-ALI is not known. To bridge this gap, the current study employed the bleomycin-induced ALI animal model to investigate sex-based differences in chemoreflex activation during …

Physiological And Biomechanical Response To Indoor Cycling With And Without The Ability To Sway, Alina P. Swafford

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: Bicycles have been around since the early 19th century. Since the invention of the bicycle, it has taken on several purposes. People have used bicycles as a means of transportation, leisure, exercise, and sport. The number of individuals who participate in a cycling event per year has increased. With the increase in popularity, research related to cycling has also increased. Research related to the physiology and biomechanics of cycling are of particular areas of interest. Balance is a crucial component of understanding why we cycle a certain way. Some research has labeled balancing on a bicycle as cycling sway. …

Elongation Of Very Long Chain Fatty Acids-3 (Elovl3) Is Activated By Zhx2 And Is A Regulator Of Cell Cycle Progression, Kate Townsend Creasy, Hui Ren, Jieyun Jiang, Martha L. Peterson, Brett T. Spear

Markey Cancer Center Faculty Publications

Zinc fingers and homeoboxes 2 (Zhx2) are transcriptional regulators of liver gene expression with key functions in embryonic development as well as tissue regeneration in response to damage and disease, presumably through its control of target genes. Previous microarray data suggested that elongation of very long chain fatty acids-3 (Elovl3), a member of the ELOVL family of enzymes that synthesize very long chain fatty acids (VLCFAs), is a putative Zhx2 target gene. VLCFAs are core component of ceramides and other bioactive sphingolipids that are often dysregulated in diseases and regulate key cellular processes including proliferation. Since several previously identified Zhx2 …

Survey Of How Irregularities In The Electrical System Of The Human Heart Link To Different Heart Arrhythmias, Jazmine Boloor

UNLV Theses, Dissertations, Professional Papers, and Capstones

This thesis explores the circuital pathway that a signal takes within the heart throughout a full heartbeat and provides a timing analysis. It then surveys the different pathways that could arise in the electrical system of the heart, and the associated heart diseases linked to the location of each pathway. Common heart arrhythmias such as atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, atrial flutter, and atrial fibrillation are surveyed, and their pathways are analyzed. Electrocardiograms are presented to aid in understanding of the timing analysis associated with irregularity in heart function. Finally, this thesis explores an avenue of the heartbeat …

Sexual Dimorphism Of Glomerular Capillary Morphology In Rats, Zackarias Coker

Undergraduate Honors Theses

Chronic kidney disease (CKD) progresses faster in males than females; however, the underlying mechanisms remain poorly understood. Sex differences in glomerular capillary morphology has been hypothesized to contribute, in part, to the increased susceptibility to hypertension-induced renal injury and CKD progression in males, but this has not been investigated. The goal of the present study was to assess glomerular capillary morphology in male vs. female rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (R_CAP) and length (L_CAP) would be greater in male rats.

Male (n=4) and female (n=4) with intact …

Oxygen Consumption In Highly Skilled Baseball Pitchers, Jesse Clingman

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to describe the physiological demands of highly skilled baseball pitchers during pitching, along with pitch metrics. Three junior college and three professional (n = 6) baseball pitchers participated in this study. Participants completed a graded exercise test (GXT) to volitional exhaustion to determine maximal oxygen consumption (VO2 max) and estimated body fat percentage, height, and body mass were measured on day one of testing. Next, participants faced live batters on a baseball field while wearing a portable metabolic analyzer (Cosmed K5) to measure respiratory gases including oxygen consumption (VO2) and carbon dioxide produced (VCO2) …

Chronic Environmental Circadian Disruption Increases Atherosclerosis And Dyslipidemia In Female, But Not Male, Apolipoproteine-Deficient Mice, Jeffrey M. Chalfant, Deborah A. Howatt, Victoria B. Johnson, Lisa R. Tannock, Alan Daugherty, Julie S. Pendergast

Saha Cardiovascular Research Center Faculty Publications

Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD) cycle, which models the disordered exposure to light that may occur during shift work, on atherosclerosis. Atherosclerosis is the progressive accumulation of lipid-filled lesions within the artery wall and is the leading cause of cardiovascular disease. We studied ApolipoproteinE-deficient (ApoE−/−) mice that are a well-established model of atherosclerosis. Male and female ApoE−/− mice were housed in control 12L:12D …

Repeated Social Defeat Stress Leads To Immunometabolic Shifts In Innate Immune Cells Of The Spleen, Mandakh Bekhbat, John Drake, Emily C. Reed, Tatlock H. Lauten, Tamara Natour, Vladimir I. Vladimirov, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Psychosocial stress has been shown to prime peripheral innate immune cells, which take on hyper-inflammatory phenotypes and are implicated in depressive-like behavior in mouse models. However, the impact of stress on cellular metabolic states that are thought to fuel inflammatory phenotypes in immune cells are unknown. Using single cell RNA-sequencing, we investigated mRNA enrichment of immunometabolic pathways in innate immune cells of the spleen in mice subjected to repeated social defeat stress (RSDS) or no stress (NS). RSDS mice displayed a significant increase in the number of splenic macrophages and granulocytes (p < 0.05) compared to NS littermates. RSDS-upregulated genes in macrophages, monocytes, and granulocytes significantly enriched immunometabolic pathways thought to play a role in myeloid-driven inflammation (glycolysis, HIF-1 signaling, MTORC1 signaling) as well as pathways related to oxidative phosphorylation (OXPHOS) and oxidative stress (p < 0.05 and FDR<0.1). These results suggest that the metabolic enhancement reflected by upregulation of glycolytic and OXPHOS pathways may be important for cellular proliferation of splenic macrophages and granulocytes following repeated stress exposure. A better understanding of these intracellular metabolic mechanisms may ultimately help develop novel strategies to reverse the impact of stress and associated peripheral immune changes on the brain and behavior.

Defining The Nuanced Nature Of Redox Biology In Post-Traumatic Stress Disorder, Emily C. Reed, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Post-traumatic stress disorder (PTSD) is a mental health disorder that arises after experiencing or witnessing a traumatic event. Despite affecting around 7% of the population, there are currently no definitive biological signatures or biomarkers used in the diagnosis of PTSD. Thus, the search for clinically relevant and reproducible biomarkers has been a major focus of the field. With significant advances of large-scale multi-omic studies that include genomic, proteomic, and metabolomic data, promising findings have been made, but the field still has fallen short. Amongst the possible biomarkers examined, one area is often overlooked, understudied, or inappropriately investigated: the field of …

Potential Of Synthetic And Natural Compounds As Novel Histone Deacetylase Inhibitors For The Treatment Of Hematological Malignancies, Dilipkumar Pal, Khushboo Raj, Shyam Sundar Nandi, Surajit Sinha, Abhishek Mishra, Arijit Mondal, Ricardo Lagoa, Jack T. Burcher, Anupam Bishayee

Journal Articles: Cellular & Integrative Physiology

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor …

Repeated Social Defeat Stress Induces An Inflammatory Gut Milieu By Altering The Mucosal Barrier Integrity And Gut Microbiota Homeostasis, Santosh K. Yadav, Rizwan Ahmad, Cassandra M. Moshfegh, Jagadesan Sankarasubramanian, Vineet A. Joshi, Safwan K. Elkhatib, Yashpal S. Chhonker, Goeffrey A. Talmon, Chittibabu Guda, Adam Case, Amar B. Singh

Journal Articles: Cellular & Integrative Physiology

Background

Posttraumatic stress disorder (PTSD) is a mental health condition triggered by exposure to traumatic events in an individual’s life. Patients with PTSD are also at a higher risk for comorbidities. However, it is not well understood how PTSD affects human health and/or promotes the risk for comorbidities. Nevertheless, patients with PTSD harbor a proinflammatory milieu and dysbiotic gut microbiota. Gut barrier integrity helps to maintain normal gut homeostasis and its dysregulation promotes gut dysbiosis and inflammation.

Methods

We used a mouse model of repeated social defeat stress (RSDS), a preclinical model of PTSD. Behavioral studies, metagenomics analysis of the …

Enhanced Central Sympathetic Tone Induces Heart Failure With Preserved Ejection Fraction (Hfpef) In Rats, Shyam S. Nandi, Kenichi Katsurada, Michael J. Moulton, Hong Zheng, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous clinical syndrome characterized by diastolic dysfunction, concentric cardiac left ventricular (LV) hypertrophy, and myocardial fibrosis with preserved systolic function. However, the underlying mechanisms of HFpEF are not clear. We hypothesize that an enhanced central sympathetic drive is sufficient to induce LV dysfunction and HFpEF in rats. Male Sprague-Dawley rats were subjected to central infusion of either saline controls (saline) or angiotensin II (Ang II, 20 ng/min, i.c.v) via osmotic mini-pumps for 14 days to elicit enhanced sympathetic drive. Echocardiography and invasive cardiac catheterization were used to measure systolic and diastolic …

A Critical Role For Staphylococcal Nitric Oxide Synthase In Controlling Flavohemoglobin Toxicity, Ryan M. Singh, Sujata S. Chaudhari, Sasmita Panda, Elizabeth H. Hutfless, Cortney E. Heim, Dhananjay Shinde, Abdulelah A. Alqarzaee, Margaret F. Sladek, Vineet Kumar, Matthew C. Zimmerman, Paul D. Fey, Tammy Kielian, Vinai Chittezham Thomas

Journal Articles: Cellular & Integrative Physiology

Most coagulase-negative staphylococcal species, including the opportunistic pathogen Staphylococcus epidermidis, struggle to maintain redox homeostasis and grow under nitrosative stress. Under these conditions, growth can only resume once nitric oxide (NO) is detoxified by the flavohemoglobin Hmp. Paradoxically, S. epidermidis produces endogenous NO through its genetically encoded nitric oxide synthase (seNOS) and heavily relies on its activity for growth. In this study, we investigate the basis of the growth advantage attributed to seNOS activity. Our findings reveal that seNOS supports growth by countering Hmp toxicity. S. epidermidis relies on Hmp activity for its survival in the host under NO stress. …

Elevated Crp And Tnf-Α Levels Are Associated With Blunted Neural Oscillations Serving Fluid Intelligence, Sarah M. Dietz, Mikki Schantell, Rachel K. Spooner, Megan E. Sandal, Amirsalar Mansouri, Yasra Arif, Hannah J. Okelberry, Jason A. John, Ryan Glesinger, Pamela E. May, Elizabeth Heinrichs-Graham, Adam J. Case, Matthew C. Zimmerman, Tony W. Wilson

Journal Articles: Cellular & Integrative Physiology

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf.

METHODS: Seventy adults between the ages of 20-66 years …

Restoration Of Normal Blood Flow In Atherosclerotic Arteries Promotes Plaque Stabilization, Morgan A. Schake, Ian S. Mccue, Evan T. Curtis, Thomas J. Ripperda, Samuel Harvey, Bryan T. Hackfort, Anna Fitzwater, Yiannis S. Chatzizisis, Forrest M. Kievit, Ryan M. Pedrigi

Journal Articles: Cellular & Integrative Physiology

Blood flow is a key regulator of atherosclerosis. Disturbed blood flow promotes atherosclerotic plaque development, whereas normal blood flow protects against plaque development. We hypothesized that normal blood flow is also therapeutic, if it were able to be restored within atherosclerotic arteries. Apolipoprotein E-deficient (ApoE^−/−) mice were initially instrumented with a blood flow-modifying cuff to induce plaque development and then five weeks later the cuff was removed to allow restoration of normal blood flow. Plaques in decuffed mice exhibited compositional changes that indicated increased stability compared to plaques in mice with the cuff maintained. The therapeutic benefit of …

Commonalities And Differences In Carotid Body Dysfunction In Hypertension And Heart Failure, Igor S. A. Felippe, Rodrigo Del Río, Harold D. Schultz, Benedito H. Machado, Julian F R Paton

Journal Articles: Cellular & Integrative Physiology

Carotid body pathophysiology is associated with many cardiovascular-respiratory-metabolic diseases. This pathophysiology reflects both hyper-sensitivity and hyper-tonicity. From both animal models and human patients, evidence indicates that amelioration of this pathophysiological signalling improves disease states such as a lowering of blood pressure in hypertension, a reduction of breathing disturbances with improved cardiac function in heart failure (HF) and a re-balancing of autonomic activity with lowered sympathetic discharge. Given this, we have reviewed the mechanisms of carotid body hyper-sensitivity and hyper-tonicity across disease models asking whether there is uniqueness related to specific disease states. Our analysis indicates some commonalities and some potential …

Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. …

Sight Deprivation And Metabolic Effects During The Ymca Bench Press Test, Kyle Cruz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Several studies have investigated the effect of sensory deprivation, particularly sight. However, very few have demonstrated the impact of sight deprivation while exercising to cadence blindfolded. This study aimed to determine exercise performance during a common muscular endurance evaluation, the YMCA Bench Press Test (YBPT), while blindfolded compared to a sighted condition. Twenty-five healthy participants (11 male, 14 female, 168 ± 7.7cm, 68 ± 11.7kg, 23 ± 7.5% fat mass) were recruited from the University of Nevada, Las Vegas student populations and communities. After a YBPT familiarization session, participants completed testing in a counterbalanced order, following the same procedures. A …

Diurnal Regulation Of Exercise-Induced Myocardial Signaling And Transcription, Charli Aguilar

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: Exercise is well known for its many benefits on the body and most notably the heart. Recent emphasis, and significant resources, have been dedicated to elucidating the molecular mechanisms through which exercise exerts its pluripotent beneficial effects on health and the prevention of disease. A continuous evolution in this field has sought to modulate and optimize exercise in various ways to maximize the benefits. In recent years, a growing appreciation for the impact of circadian rhythms has gained traction and their influence on many essential biological functions have been integrated into exercise physiology (i.e. - chrono-exercise), as well as …

Gut Microbiome And Metabolome Variations In Self-Identified Muscle Builders Who Report Using Protein Supplements, Lauri O. Byerley, Karyn M. Gallivan, Courtney J. Christopher, Christopher M. Taylor, Meng Luo, Scot E. Dowd, Gregory M. Davis, Hector F. Castro, Shawn R. Campagna, Kristin S. Ondrak

School of Graduate Studies Faculty Publications

Muscle builders frequently consume protein supplements, but little is known about their effect on the gut microbiota. This study compared the gut microbiome and metabolome of selfidentified muscle builders who did or did not report consuming a protein supplement. Twenty-two participants (14 males and 8 females) consumed a protein supplement (PS), and seventeen participants (12 males and 5 females) did not (No PS). Participants provided a fecal sample and completed a 24-h food recall (ASA24). The PS group consumed significantly more protein (118 ± 12 g No PS vs. 169 ± 18 g PS, p = 0.02). Fecal metabolome and …

Comparative Genomics, Evolutionary Epidemiology, And Rbd-Hace2 Receptor Binding Pattern In B.1.1.7 (Alpha) And B.1.617.2 (Delta) Related To Their Pandemic Response In Uk And India, Chiranjib Chakraborty, Ashish Ranjan Sharma, Manojit Bhattacharya, Bidyut Mallik, Shyam Sundar Nandi, Sang-Soo Lee

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: The massive increase in COVID-19 infection had generated a second wave in India during May-June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant.

METHODS: This study was performed in three directions to understand the pandemic response of the two emerging variants. First, …

T-Lymphocyte Tyrosine Hydroxylase Regulates T H 17 T-Lymphocytes During Repeated Social Defeat Stress, Safwan K. Elkhatib, Cassandra M. Moshfegh, Gabrielle F. Watson, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which results in deleterious changes to psychological and physical health. Patients with PTSD are especially susceptible to life-threatening co-morbid inflammation-driven pathologies, such as autoimmunity, while also demonstrating increased T-helper 17 (T_H17) lymphocyte-driven inflammation. While the exact mechanism of this increased inflammation is unknown, overactivity of the sympathetic nervous system is a hallmark of PTSD. Neurotransmitters of the sympathetic nervous system (i.e., catecholamines) can alter T-lymphocyte function, which we have previously demonstrated to be partially mitochondrial redox-mediated. Furthermore, we have previously elucidated that T-lymphocytes generate their own catecholamines, and strong …

Time-Dependent Alteration In The Chemoreflex Post-Acute Lung Injury, Kajal Kamra, Nikolay Karpuk, Ryan Adam, Irving H. Zucker, Harold D. Schultz, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

Acute lung injury (ALI) induces inflammation that disrupts the normal alveolar-capillary endothelial barrier which impairs gas exchange to induce hypoxemia that reflexively increases respiration. The neural mechanisms underlying the respiratory dysfunction during ALI are not fully understood. The purpose of this study was to investigate the role of the chemoreflex in mediating abnormal ventilation during acute (early) and recovery (late) stages of ALI. We hypothesized that the increase in respiratory rate (fR) during post-ALI is mediated by a sensitized chemoreflex. ALI was induced in male Sprague-Dawley rats using a single intra-tracheal injection of bleomycin (Bleo: low-dose = 1.25 mg/Kg or …