Efficient In Vivo Selection of a Novel Tumor-Associated Peptide from a Phage Display Library

We developed a screening procedure to identify ligands from a phage display random peptide library that are selective for circulating bone marrow derived cells homing to angiogenic tumors. Panning the library on blood outgrowth endothelial cell suspension in vitro followed by in vivo selection based on homing of bone marrow-bound phage to angiogenic tumors, yielded the peptide QFPPKLTNNSML. Upon intravenous injection phage displaying this peptide homed to Lewis lung carcinoma (LLC) tumors in vivo whereas control phage did not localize to tumor tissue. Phage carrying the QFPPKLTNNSML peptide labeled with 64Cu radionuclide when administered intravenously into a tumor bearing mouse was detected noninvasively with positron emission tomography (PET) around the tumor. These proof-of-principle experiments demonstrate the ability of the QFPPKLTNNSML peptide to deliver payload (radiolabeled phage conjugates) in vivo to sites of ongoing angiogenesis and point to its potential clinical utility in a variety of physiologic and pathologic processes where neovascular growth is a critical component

394 A convolutional neural networks model for the detection of cortical arousals from heart rate

Abstract Introduction Cortical arousals are transient events of disturbed sleep that occur frequently in sleep disordered breathing (SDB) and can be used as an indicator of sleep quality. While cortical arousals are typically scored from the electroencephalogram (EEG), arousals are associated with increased sympathetic activity and could therefore be detected from measures of sympathetic activity such as heart rate. Most home sleep test and consumer wearable devices enable continuous recording of heart rate via the electrocardiogram (ECG) or optical heart rate sensors without the inconvenience of EEG electrodes. In this preliminary study, we developed a deep learning-based convolutional neural networks (CNN) model to detect arousals from heart rate. Methods This study included 1,083 polysomnograms (PSGs) from five independent studies (Tucson Children’s Assessment of Sleep Apnea, Mechanisms of Pharyngeal Collapse in Sleep Apnea, Impact of the Arousal Threshold in Obstructive Sleep Apnea, Predicting Successful Sleep Apnea Treatment with Acetazolamide in Heart Failure Patients, Combination Therapy for the Treatment of Obstructive Sleep Apnea) that were scored for arousals according to American Academy of Sleep Medicine scoring rules. These studies included PSGs from both children and adults (ages 6 and above), with most data coming from participants with evidence or diagnosis of SDB. We used the Pan-Tomkins algorithm to detect R-peaks from the raw ECG signal, transformed the peaks into normalized instantaneous heart rate at 1 Hz frequency, and produced arousal probability in 1-second resolution using a simple CNN model. Due to slight asynchrony between the appearance of arousals in the EEG versus the heart rate, all overlaps between model-predicted arousals and manually scored arousals were considered true-positives. Results We evaluated the model on a validation set (n=216). The model achieved a gross area under precision-recall curve score of 0.67 and a gross area under receiver operating characteristics curve of 0.91 Correlation between the number of model-detected and manually scored arousal events was r=0.76. Conclusion This preliminary study demonstrates that a deep learning approach has the potential to accurately detect arousals in home sleep tests and consumer wearable devices that measure heart rate. Support (if any) The study was supported by grant #207-SR-19 from the American Academy of Sleep Medicine Foundation. </jats:sec

Out of Center Sleep Testing in Ostensibly Healthy Middle Aged to Older Adults

https://doi.org/10.13175/swjpcc016-19Background: Out of Center Sleep Testing (OCST) is used increasingly to diagnose obstructive sleep apnea (OSA). However, there are few data using OCST that quantify the amount of intrinsic apneic and hypopneic events among asymptomatic healthy persons, especially those who are elderly. This analysis reports the results of OCST in a small group of ostensibly healthy asymptomatic individuals. Methods: The study population was comprised of ostensibly healthy middle-aged to elderly volunteers for studies of circadian physiology. Before undergoing an OCST, they were found to be free of any chronic medical or psychiatry condition by history, physical and psychologic examination and by a variety of questionnaires and laboratory tests. Results: There were 24 subjects ranging in age from 55-70 years who had an OCST performed. Repeat studies were required in only 3 subjects. Over half the study population was over the age of 60 years (54.2% vs 45.8%); the majority were men (70.8%). The mean apnea hypopnea index (AHI) was 9.2 /hour with no difference between younger and older subjects. However, 11 had an AHI > 5 /hour. Five had an AHI >15 /hour and 2 had an AHI >40 /hour. Those with an AHI <15 /hour had a mean AHI of 4.4 /hour (95% CI:2.8-6.0 /hour). Conclusions: Although OCST has a low failure rate, there is a high prevalence of intrinsic obstructive apnea and hypopnea in ostensibly healthy asymptomatic persons.  Accepted Manuscrip

Out of Center Sleep Testing in Ostensibly Healthy Middle Aged to Older Adults

Background: Out of Center Sleep Testing (OCST) is used increasingly to diagnose obstructive sleep apnea (OSA). However, there are few data using OCST that quantify the amount of intrinsic apneic and hypopneic events among asymptomatic healthy persons, especially those who are elderly. This analysis reports the results of OCST in a small group of ostensibly healthy asymptomatic individuals. Methods: The study population was comprised of ostensibly healthy middle-aged to elderly volunteers for studies of circadian physiology. Before undergoing an OCST, they were found to be free of any chronic medical or psychiatry condition by history, physical and psychologic examination and by a variety of questionnaires and laboratory tests. Results: There were 24 subjects ranging in age from 55-70 years who had an OCST performed. Repeat studies were required in only 3 subjects. Over half the study population was over the age of 60 years (54.2% vs 45.8%); the majority were men (70.8%). The mean apnea hypopnea index (AHI) was 9.2 /hour with no difference between younger and older subjects. However, 11 had an AHI > 5 /hour. Five had an AHI >15 /hour and 2 had an AHI >40 /hour. Those with an AHI <15 /hour had a mean AHI of 4.4 /hour (95% CI:2.8-6.0 /hour). Conclusions: Although OCST has a low failure rate, there is a high prevalence of intrinsic obstructive apnea and hypopnea in ostensibly healthy asymptomatic persons.  National Institute of Aging AG009975Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Neuromuscular fatigue of the elbow flexors during repeated maximal arm cycling sprints: the effects of forearm position

Repeated sprint exercise (RSE) is often used to induce neuromuscular fatigue (NMF). It is currently not known whether NMF is influenced by different forearm positions during arm cycling RSE. The purpose of this study was to investigate the effects of a pronated versus supinated forearm position on elbow flexor NMF during arm cycling RSE. Participants (n = 12) completed ten 10-s maximal arm cycling sprints interspersed by 60 s of rest on 2 separate days using either a pronated or supinated forearm position. All sprints were performed on an arm cycle ergometer in a reverse direction. Prior to and following RSE, NMF measurements (i.e., maximal voluntary contraction (MVC), potentiated twitch (PT), electromyography median frequencies) were recorded. Sprint performance measures, ratings of perceived exertion (RPE) and pain were also recorded. Irrespective of forearm position, sprint performance decreased as sprint number increased. These decreases were accompanied by significant increases in RPE (p &lt; 0.001, ηp2 = 0.869) and pain (p &lt; 0.001, ηp2 = 0.745). Participants produced greater power output during pronated compared with supinated sprinting (p &lt; 0.001, ηp2 = 0.728). At post-sprinting, the percentage decrease in elbow flexor MVC and PT force from pre-sprinting was significantly greater following supinated than pronated sprinting (p &lt; 0.001), suggesting greater peripheral fatigue occurred in this position. The data suggest that supinated arm cycling RSE results in inferior performance and greater NMF compared with pronated arm cycling RSE. Novelty: NMF of the elbow flexors is influenced by forearm position during arm cycling RSE. Supinated arm cycling sprints resulted in worse repeated sprint performance and also greater NMF than pronated RSE. </jats:p

Neuromuscular fatigue of the elbow flexors during repeated maximal arm cycling sprints: The effects of forearm position

Repeated sprint exercise (RSE) is often used to induce neuromuscular fatigue (NMF). It is currently not known whether NMF is influenced by different forearm positions during arm cycling RSE. The purpose of this study was to investigate the effects of a pronated versus supinated forearm position on elbow flexor NMF during arm cycling RSE. Participants (n=12) completed ten, 10-s maximal arm cycling sprints interspersed by 60s of rest on two separate days using either a pronated or supinated forearm position. All sprints were performed on an arm cycle ergometer in a reverse direction. Prior to and following RSE, NMF measurements (i.e., maximal voluntary contraction (MVC), potentiated twitch (PT), electromyography median frequencies) were recorded. Sprint performance measures, ratings of perceived exertion (RPE) and pain were also recorded. Irrespective of forearm position, sprint performance decreased as sprint number increased. These decreases were accompanied by significant increases in RPE (pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Effect of the COVID-19 pandemic on emergency department utilization of computed tomography scans of appendicitis and diverticulitis

Abstract Purpose Investigating the effect of the COVID-19 lockdown on adult patient visits, computed tomography (CT) abdominal scans, and presentations of appendicitis and diverticulitis, to emergency departments (ED) in St. John’s NL. Methods A retrospective quantitative analysis was applied, using ED visits and Canadian Triage and Acuity Scale (CTAS) scores. mPower (Nuance Communications, UK) identified CT abdominal scan reports, which were categorized into (1) normal/other, (2) appendicitis, or (3) diverticulitis. Time intervals included pre-lockdown (January–February), lockdown (March–June), and post-lockdown (July–August). Data from 2018 to 2019 (January–August) were used to generate expected patient volumes for 2020, and pre- and post-lockdown were included to control for other variables outside the lockdown. Results Chi-squared goodness of fit tested for deviations from predicted means for 2018–2019. Compared to expectations, daily ED visits from January to August 2020 showed a significant (p &lt; 0.001) decrease in patient volumes independent of gender, age, and CTAS scores. During and post-lockdown, CT abdominal scans did not drop in proportion to patient volume. Appendicitis presentations remained indifferent to lockdown, while diverticulitis presentations appeared to wane, with no difference in combined complicated cases in comparison to what was expected. Conclusion During lockdown, significantly fewer patients presented to the ED. The proportion of ordered CT abdominal scans increased significantly per person seen, without change in CTAS scores. Considering combined pathology cases increased during the lockdown, ED physicians were warranted in increasing abdominal imaging as patients did not avoid the ED. This may have resulted from a change in clinical practice where the uncertainty of COVID-19 increased CT scan usage. </jats:sec

Spontaneous attentional failures reflect multiplicative interactions of chronic sleep loss with acute sleep loss and circadian misalignment

Objectives: acute and chronic sleep loss and circadian timing interact such that, depending on their combination, small or very large performance decrements are observed in tasks of attention. Here, we tested whether such nonlinear interactions extend to a physiological measure of spontaneous visual attentional failures, indicating a fundamental principle of sleep-wake regulation. Methods: nine healthy volunteers completed an in-laboratory 3-week forced desynchrony protocol consisting of 12 consecutive 42.85-hour cycles with a sleep-wake ratio of 1:3.3. The protocol induced increasing chronic sleep loss, while extended wake (32.85 hours) and sleep episodes (10 hours) occurred at multiple circadian phases. Attentional failure rate was quantified from continuous electrooculograms (number of 30-second epochs with slow eye movements/h of wakefulness) as a function of time since scheduled wake (acute sleep loss), week of study (chronic sleep loss), and circadian (melatonin) phase. Results: during the first ∼8 hours awake, attentional failure rate was low, irrespective of the week. During the following wake hours, attentional failure rate increased steadily but at a faster rate in weeks 2 and 3 compared to week 1. The effects of acute and chronic sleep loss on attentional failure rate were magnified during the biological night compared to the biological day. Conclusions: a single extended sleep episode can only temporarily reverse attentional impairment associated with chronic sleep loss. Multiplicative effects of acute and chronic sleep loss—further amplified during the biological night—substantiate the interaction of 2 homeostatic response mechanisms and caution against underestimating their disproportionate combined impact on performance, health, and safety.</p