Chemoreflex Mediated Arrhythmia during Apnea at 5050m in Low but not High Altitude Natives

Peripheral chemoreflex mediated increases in both parasympathetic and sympathetic drive under chronic hypoxia may evoke bradyarrhythmias during apneic periods. We determined whether 1) voluntary apnea unmasks arrhythmia at low (344 m) and high (5,050 m) altitude, 2) high-altitude natives (Nepalese Sherpa) exhibit similar cardiovagal responses at altitude, and 3) bradyarrhythmias at altitude are partially chemoreflex mediated. Participants were grouped as Lowlanders ( n = 14; age = 27 ± 6 yr) and Nepalese Sherpa ( n = 8; age = 32 ± 11 yr). Lowlanders were assessed at 344 and 5,050 m, whereas Sherpa were assessed at 5,050 m. Heart rate (HR) and rhythm (lead II ECG) were recorded during rest and voluntary end-expiratory apnea. Peripheral chemoreflex contributions were assessed in Lowlanders ( n = 7) at altitude after 100% oxygen. Lowlanders had higher resting HR at altitude (70 ± 15 vs. 61 ± 15 beats/min; P &lt; 0.01) that was similar to Sherpa (71 ± 5 beats/min; P = 0.94). High-altitude apnea caused arrhythmias in 11 of 14 Lowlanders [junctional rhythm ( n = 4), 3° atrioventricular block ( n = 3), sinus pause ( n = 4)] not present at low altitude and larger marked bradycardia (nadir −39 ± 18 beats/min; P &lt; 0.001). Sherpa exhibited a reduced bradycardia response during apnea compared with Lowlanders ( P &lt; 0.001) and did not develop arrhythmias. Hyperoxia blunted bradycardia (nadir −10 ± 14 beats/min; P &lt; 0.001 compared with hypoxic state) and reduced arrhythmia incidence (3 of 7 Lowlanders). Degree of bradycardia was significantly related to hypoxic ventilatory response (HVR) at altitude and predictive of arrhythmias ( P &lt; 0.05). Our data demonstrate apnea-induced bradyarrhythmias in Lowlanders at altitude but not in Sherpa (potentially through cardioprotective phenotypes). The chemoreflex is an important mechanism in genesis of bradyarrhythmias, and the HVR may be predictive for identifying individual susceptibility to events at altitude. NEW &amp; NOTEWORTHY The peripheral chemoreflex increases both parasympathetic and sympathetic drive under chronic hypoxia. We found that this evoked bradyarrhythmias when combined with apneic periods in Lowlanders at altitude, which become relieved through supplemental oxygen. In contrast, high-altitude residents (Nepalese Sherpa) do not exhibit bradyarrhythmias during apnea at altitude through potential cardioprotective adaptations. The degree of bradycardia and bradyarrhythmias was related to the hypoxic ventilatory response, demonstrating that the chemoreflex plays an important role in these findings. </jats:p

Muscle sympathetic reactivity to apneic and exercise stress in high-altitude Sherpa

Lowland-dwelling populations exhibit persistent sympathetic hyperactivity at altitude that may alter vascular function. High altitude populations, such as Sherpa, exhibit greater peripheral blood flow in response to acute stress, suggesting Sherpas may exhibit lower sympathetic activity and reactivity to stress than Lowlanders. Muscle sympathetic activity (MSNA; microneurography) including frequency (bursts/min), incidence (bursts/100HB), amplitude (% of max burst), was measured at rest in Lowlanders (n=14; age=27±6yrs) at 344m and following a 8- 9 days of graded ascent to 5050m. Sherpa (age=32±11yrs) were tested at 5050m (n=8). Neurovascular reactivity (i.e., change in MSNA patterns) was measured during maximal end expiratory apnea, isometric hand-grip (IHG; 30% maximal voluntary contraction for 2 minutes) and post exercise circulatory occlusion (PECO; 3 minutes). Total normalized SNA (au/min) was calculated over 10 cardiac cycles during baseline and pre-volitional apnea breakpoint. Lowlander burst frequency (11±5 bursts/min to 30±7 bursts/min; Mean±SD; p<0.001) and burst incidence (25±13 bursts/100HB to 53±15 bursts/100HB; p<0.001) increased at 5050m. In contrast, Sherpas had lower burst frequency (23±11 bursts/min; p<0.05) and incidence (30±13 bursts/100HB; p<0.05) at 5050m. MSNA increases in Lowlanders and Sherpa during apnea at 5050m were significantly lower than Lowlanders at 344m (both P<0.05), with a possible sympathetic ceiling reached in Lowlanders at 5050m. MSNA increased similarly during the IHG/PECO in Lowlanders at 334m and 5050m altitude and Sherpa at 5050m. Sherpa demonstrate overall lower sympathetic activity and reactivity during severe stress. This may be a result of improved systemic hemodynamic function associated with evolutionary adaptations to permanent residency at altitude

The Victorian Newsletter (Fall 1970)

The Victorian Newsletter is edited for the English X Group of the Modern Language Association by William E. Buckler, New York University, New York, N.Y. 10003.Dickens' Portrait of the Artist / Edward Hurley -- Black and White Characters in Hard Times / Mary Rose Sullivan -- "All Her Perfections Tarnished": The Thematic Function of Esther Summerson / Mary Daehler Smith -- Another Look at Hardy's "Afterwards" / David S. Thatcher -- Meredith's Experiments with Ideas / J. Raban Bilder -- Huxley, Holmes, and the Scientist as Aesthete / Phyllis Rose -- Tory Noodles in Sydney Smith and Charles Dickens: An Unnoticed Parallel / Robert Simpson McLean -- Stanza Form in Meredith's Modern Love / Willie D. Reader -- Recent Publications: A Selected List / Arthur F. Minerof -- English X New

The Lantern Vol. 61, No. 2, Summer 1994

• She Was a Woman of Dignity • Retake, Scene 16 • Las Vegas Sweatshirt • Pitcher Hill • In Preparation for Wisdom (Teeth) • Moist Slacks • My Mother\u27s Purse • It Comes and Goes Everyday • The Simplicity of Marriage • The First Performance • Hunger • Pushkin\u27s Dream • Tuesday, October 19 • Poetry of Baseball • Some Things are More Important Than Others • Musician • Of What Befell Our Good Knight • Piranha • Oceans Apart • Brooklyn Cantos • Snowshower • Thankfully in Australia • Toothpaste and Tuna Fish • Living Space • Blue Monday • Afterglow • A Path to Consider • Endless Summer • Scaredy-Cathttps://digitalcommons.ursinus.edu/lantern/1144/thumbnail.jp

Highs and Lows of Sympathetic Neuro-cardiovascular Transduction: Influence of Altitude Acclimatization and Adaptation

High-altitude (>2500m) exposure results in increased muscle sympathetic nervous activity (MSNA) in acclimatizing lowlanders. However, little is known about how altitude affects MSNA in 66 indigenous high-altitude populations. Additionally, the relationship between MSNA and blood 67 pressure regulation (i.e., neurovascular transduction) at high-altitude is unclear. We sought to 68 determine 1) how high-altitude effects neuro-cardiovascular transduction and 2) whether 69 differences exist in neuro-cardiovascular transduction between low and high-altitude 70 populations. Measurements of MSNA (microneurography), mean arterial blood pressure (MAP; 71 finger photoplethysmography), and heart rate (electrocardiogram) were collected in: I) 72 lowlanders (n=14) at low (344m) and high-altitude (5050m), II) Sherpa highlanders (n=8; 73 5050m), and III) Andean (with and without excessive erythrocytosis) highlanders (n=15; 74 4300m). Cardiovascular responses to MSNA burst sequences (i.e. singlet, couplet, triplet, and 75 quadruplets) were quantified using custom software (coded in MATLAB, v2015b). Slopes were 76 generated for each individual based on peak responses and normalized total MSNA. High 77 altitude reduced neuro-cardiovascular transduction in lowlanders (MAP slope: high-altitude, 78 0.0075±0.0060 vs low-altitude, 0.0134±0.080; p=0.03). Transduction was elevated in Sherpa 79 (MAP slope, 0.012±0.007) compared to Andeans (0.003±0.002; p=0.001). MAP transduction 80 was not statistically different between acclimatizing lowlanders and Sherpa (MAP slope, p=0.08) 81 or Andeans (MAP slope, p=0.07). When accounting for resting MSNA (ANCOVA), transduction 82 was inversely related to basal MSNA (bursts/min) independent of population (RRI, r= 0.578 83 p<0.001; MAP, r= -0.627 p<0.0001). Our results demonstrate transduction is blunted in 84 individuals with higher basal MSNA, suggesting blunted neuro-cardiovascular transduction is a 85 physiological adaptation to elevated MSNA rather than an effect or adaptation specific to 86 chronic hypoxic exposure

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Veritas & Vanitas: A Journal of Creative Nonfiction

A journal of creative nonfiction produced by students at the Marion campus of The Ohio State University with contributions from the students and faculty at the Marion campus of The Ohio State University and Marion Technical College