bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skeletal muscle derived pro-brain derived neurotropic factor promotes ischemia-reperfusion induced inflammation
Authors: Aby Katherine , Antony Ryan , Li Yifan 
Published: May 2023

Skeletal muscle ischemia-reperfusion (IR) injury is prevalent in trauma, peripheral vascular diseases, and following surgical procedures, however, effective prevention and treatment for skeletal muscle IR injury are lacking. Brain-derived neurotrophic factor (BDNF), originally discovered in the brain, is expressed and released from skeletal muscle as a myokine. However, the transcription splice variants, posttranslational modifications, and functions of BDNF in skeletal muscle are poorly defined. In this study, we first showed that skeletal muscle expressed unique splice variants of BDNF compared to the brain. At the protein level, Western blot comparing BDNF in brain and skeletal muscle revealed that skeletal muscle expresses significantly more proBDNF than mature BDNF under basal conditions, opposite to brain tissue. Consistent with this, the levels of the major protein convertases in skeletal muscle were significantly lower compared to the brain, suggesting that the high level of proBDNF is at least partially due to the low cleavage activity in skeletal muscle. The potential function of the proBDNF in disease conditions was then examined in mice with skeletal muscle IR injury. IR injury was induced in 3-month-old male and female C57BL/6 mice by placing a tourniquet on one hind limb for 1 hour, then removing it, allowing reperfusion for 1-14 days, with the contralateral hind limb serving as a control. We hypothesize that proBDNF may be necessary for facilitating the inflammatory response, while mature BDNF may be necessary for promoting inflammation resolution and myogenesis following IR injury. Remarkably, the level of proBDNF, but not mature BDNF, was increased significantly in IR muscle compared to the contralateral control (p=0.013). This was accompanied by increased proinflammatory cytokines and macrophage infiltration in the injured muscle. Mice with skeletal muscle-specific knockout of BDNF showed a significant reduction in proinflammatory cytokine production and macrophage infiltration following IR injury compared to wild-type animals. To confirm the role of proBDNF in this finding, the receptor for proBDNF, p75NTR, was blocked using the small molecule LM11A-31. In IR injured muscle, LM11A-31 treatment significantly reduced the proinflammatory response and macrophage infiltration compared to control animals, similar to what is seen in BDNF knockout animals. Collectively, these results indicate that myokine proBDNF promotes inflammation and macrophage recruitment in the IR-injured muscle, and therefore is a potential target for the treatment of skeletal muscle injury. This work was funded by NIH grant R01HL147105 and NIH Training Grant T32-GM136503. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Use of Simplex Learning Index to Identify a Course Deficit
Authors: Bao Sujin 
Published: May 2023

Difficulty index and its derivative performance index (PFI) have been commonly used to measure student learning outcomes. However, these indices have a high volatility and low sensitivity. This work has established simplex learning index (SLI) that has a low volatility and high sensitivity. To construct SLI, students were divided into two groups based on their scores on the whole quiz. The item SLI and lecture SLI were derived from the results of students in the high-scoring group. Exam results from 9 cohorts of medical students in two phases of learning were analyzed. The volatility, measured by the ratio between the standard deviation and the mean, was >65% lower in SLI than in PFI. Using the lecture SLI as a metric, one lecture B22 (Metabolism of Amino Acids) was identified that had an average SLI of 0.66 in earlier four student cohorts in Phase 1 learning. Two major changes were made on the lecture – lecture organization and the delivery method – in Phase 2. Students from recent five cohorts in Phase 2 had an average SLI of 0.84, which was 26.6% higher than that in Phase 1 ( P<0.02). In contrast, when using PFI, the change was only 13.46% and insignificant ( P=0.29). In the same period, implementation of the same delivery method did not yield significant changes in learning outcomes in lecture B24 (Metabolism of Nucleotides). Taken together, this work shows that SLI is a better indicator for learning outcomes and suggests that lecture reorganization is the key to improved student learning. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Identification of a panel of plasma protein biomarkers for determining Chronic Traumatic Encephalopathy in adults
Authors: Zafar Umema , Habib Syed Hamid , Bashir Shahid 
Published: May 2023

Importance: Chronic Traumatic Encephalopathy (CTE) which results from trauma to the head can be a debilitating condition. If the patient luckily has no complications immediately, the long-term effects like gradually progressing tauopathy can seriously affect the individual's quality of life. This review aims to identify a panel of plasma neurobiomarkers that can be used to screen CTE in adults. Observations: This is a scoping review based on the methodological framework presented by Arksey & O'Malley, in 2005. Keywords were used to search the literature and articles were screened to identify the plasma biomarkers involved in chronic brain injury. A total of 38 plasma protein biomarkers were identified. A rubric was designed keeping in view the characteristics highlighted in the literature. The biomarkers were then scored on the basis of the rubric devised. The biomarkers which obtained the highest scores were Neurofilament Light chain (NfL), Phosphorylated forms of tau (P-Tau), and Neuron specific enolase (NSE) with 12, 12, and 11 scores respectively. Both NfL and p-Tau are present in serum and Cerebrospinal fluid (CSF) with equal sensitivity. Both originate mainly from the brain, are present at the pico level of quantification, and represent chronic brain injury. NSE on the other hand is detected with higher sensitivity in CSF than in blood. The rest of its qualities equate with those of NfL and p-Tau. Conclusion and relevance: In conclusion, NfL, p-Tau, and NSE have the optimum characteristics that are the best fit for diagnosing CTE as compared to other biomarkers. The specificity in terms of origin from the brain, representation of chronic brain trauma, and detecting the smallest amount present in plasma with almost the same detection sensitivity as CSF, are the qualities that make these biomarkers the most suitable ones. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The prevalence and predictors of tidal expiratory flow limitation during peak exercise do not differ between genders in healthy adolescents and young adults.
Authors: Welch Ryan , Kolbe John , Kevin Ellyett 
Published: May 2023

Introduction: Tidal expiratory flow limitation (EFLT) occurs when the tidal breath reaches its maximal capacity to generate flow despite increased expiratory effort. It has been suggested there are gender differences; females tend to develop EFLT due to lower markers of ventilatory capacity, and the primary determinants of EFLT in males relate to higher oxygen demand. Aim/hypothesis: This study aimed to determine the prevalence and predictors of EFLT during peak exercise in healthy subjects aged 10-24 years. We hypothesised that the prevalence and predictors of EFLT would not differ between males and females. Method: Healthy, physically active subjects (n=122, 69M:53F) with normal spirometry and gas exchange completed a maximal cardiopulmonary exercise test. The presence and degree of EFLT during peak exercise was determined by the vector-based analysis technique described by Welch et al (2021). Student’s T-test compared continuous variables and predictors of EFLT were determined by two-way ANOVA for sex and the presence of EFLT. Results: EFLT was present in 70% of subjects, with no difference in the prevalence between males and females (74 vs. 66%). The degree of EFLT was significantly greater in the males compared to females (40 vs. 30% of tidal volume, p<0.05). Subjects demonstrating EFLT had relatively lower forced expired volume in the first second (FEV1), FEV1/forced vital capacity ratio, and mid expiratory flows. During peak exercise, male and female subjects demonstrating EFLT had higher relative peak oxygen consumption, ventilatory equivalents, breathing frequency, and minute ventilation relative to body weight. Conclusion: This study showed no gender difference in the prevalence of EFLT in healthy, physically active subjects. For both genders, lower markers of ventilatory capacity and higher markers of oxygen demand were predictors of EFLT. This research was supported by an award from The Green Lane Research and Education Fund Board. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effect of Rebreathing-Induced Intermittent Hypoxia on Glucose Tolerance in Adults with Type 2 Diabetes
Authors: Zhao Jiahui , Guei Jamie , Lalande Sophie 
Published: May 2023

Hypoxia stimulates glucose uptake through an insulin-independent pathway. The aim of this study was to examine the acute effect of rebreathing-induced hypoxia on plasma glucose and insulin levels in adults with type 2 diabetes. We hypothesized that rebreathing-induced hypoxia would attenuate the increase in glucose and insulin levels during an oral glucose tolerance test. Nine individuals with type 2 diabetes (5 men, age: 53±10 years, body mass index: 35±7 kg/m2, HbA1c: 7.1±0.5%) visited the laboratory on two occasions. On both visits, a 2-hour, 75 g oral glucose tolerance test was conducted while simultaneously performing a rebreathing-induced hypoxia protocol (RIH) or breathing room air (Norm). Venous blood samples were collected 0, 30, 60, 90, and 120 min following ingestion of the high-glucose drink to measure plasma glucose and insulin levels. The rebreathing-induced hypoxia protocol consisted of two series of five 2-min rebreathing bouts in a low-volume, closed circuit system interspersed with two minutes of breathing room air. The first and second series of rebreathing bouts were performed within the first 30 min and 30-60 min after ingestion of the high-glucose drink, respectively. Rebreathing-induced hypoxia resulted in a nadir oxygen saturation of 88±4 % and a nadir fraction of inspired oxygen of 12±5%. Plasma glucose responses to the oral glucose tolerance test were not different between conditions, however, insulin levels were lower during rebreathing-induced hypoxia than normoxia (RIH vs. Norm: 0: 17±13 vs. 21 ±14; 30: 37 ±28 vs. 42±26; 60: 57±32 vs. 77±52; 90: 88±67 vs. 116±81; and 120: 114±96 vs. 136 ±111 ulU/ml, p=0.03), suggesting an acutely improved insulin sensitivity. Accordingly, the insulin area under the curve was lower during rebreathing-induced hypoxia than normoxia (124±84 vs. 157±102, p=0.02). In conclusion, exposure to short and intermittent rebreathing-induced hypoxia following the ingestion of a high-glucose drink acutely improves insulin sensitivity in adults with type 2 diabetes. Rebreathing-induced hypoxia could therefore represent a novel and simple strategy to improve glycemic control in individuals living with type 2 diabetes. College of Education Small Grants Program This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Melanocortin 4 receptor signaling in Sim-1 neurons permits sexual receptivity in female mice
Authors: Hill JH , Harberson Mitchell , Semple Erin 
Published: May 2023

Female sexual dysfunction affects approximately 40% of women in the United States, yet few therapeutic options exist for these patients. The melanocortin system is a new treatment target for Hypoactive Sexual Desire Disorder (HSDD), but the neuronal pathways involved are unclear. In this study, female MC4R knockout mice lacking melanocortin 4 receptors (MC4Rs) paired with males were found to approach males less and have reduced receptivity to copulation, as indicated by a low lordosis quotient. The mice were then bred to express MC4Rs exclusively on Sim1 neurons (tbMC4RSim1 mice) or on oxytocin neurons (tbMC4ROxt mice). Lordosis behavior was normalized in tbMC4RSim1 mice and improved in tbMC4ROxt mice. In contrast, approach behavior was unchanged in tbMC4RSim1 mice but greatly increased in tbMC4ROxt animals. The changes were independent of melanocortin-driven metabolic effects. These results implicate MC4R signaling in Oxt neurons in appetitive behaviors and MC4R signaling in Sim1 neurons in female sexual receptivity, while suggesting melanocortin-driven sexual function does not rely on metabolic neural circuits. R01HD081792 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Potential role of brown adipose tissue-derived extracellular vesicles in mediating the cardioprotective effect of CNS leptin infusion after ischemia/reperfusion injury
Authors: Omoto Ana Carolina Mieko , Vechetti Ivan , Rule Blake , do Carmo Jussara , da Silva Alexandre , Aitken Nikaela , Dai Xuemei , Nelson Benjamin , Wang Zhen , Li Xuan , Mouton Alan , Hall John 
Published: May 2023

Ischemic heart disease is the leading cause of death in the U.S. and worldwide. We recently demonstrated that infusion of leptin into the central nervous system (CNS) dramatically improves cardiac metabolism and function following ischemia/reperfusion (IR) injury. How the brain communicates with the heart during central leptin infusion to improve cardiac function after IR injury is still unknown. One potential mechanism may be via activation of brown adipose tissue (BAT), as central leptin administration has been shown to induce BAT-mediated thermogenesis. Furthermore, BAT has been proposed as an important source of extracellular vesicles (EVs) carrying bioactive molecules with cardioprotective effects. Thus, we investigated whether BAT contributes to the cardioprotective effect of central leptin infusion and the potential role of EVs in this protection. Male Sprague-Dawley rats (~8 weeks of age) were submitted to interscapular BAT ablation (iBATx) and instrumented with an intracerebroventricular (ICV) cannula in the brain lateral ventricle. After recovery and baseline assessment of cardiac function by echocardiography (ECHO), myocardial IR was induced by temporary (60 min) ligation of the left anterior descending coronary artery. Vehicle (saline, 0.5 μL/hr) or leptin (0.62 μg/hr) was infused chronically for 28 days starting 30 min after reperfusion using osmotic pumps implanted subcutaneously in the scapular region and connected to the ICV cannula. Cardiac function was assessed weekly by ECHO. Another set of animals with intact iBAT was treated with ICV leptin or vehicle for 2 weeks and had their iBAT collected for EVs isolation and quantification by differential ultracentrifugation and nanoparticle tracking analysis, respectively. Compared to vehicle-treated animals, ICV leptin infusion increases iBAT-derived EVs (5.6x109 vs 1.6 x109 particles/mg of tissue), and removal of iBAT prevent leptin’s CNS-mediated cardioprotective effects after IR injury as indicated by a lack of improvement in ejection fraction (26.9±2.5 vs 40.9±1.2%), stroke volume (154.6±15 vs 275.3±8μL) and global longitudinal strain (-7.4±1.1 vs -13.9±0.5%) at week 4 post-IR. These results suggest that the BAT plays an important role in mediating the cardioprotective effect of CNS leptin administration after I/R injury and that iBAT-derived EVs may be involved in delivering protective molecules to the heart during central leptin infusion. AHA 835218, NIGMS P20GM104357, NIDDK R00DK113280, R01DK121411 and P20GM104320 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Impaired Erythropoietin Response to Intermittent Hypoxia in Patients with Type 2 Diabetes
Authors: Wojan Frank , Stray-Gundersen Sten , Zhao Jiahui , Lalande Sophie 
Published: May 2023

Patients with type 2 diabetes (T2D) exhibit, on average, a 20% decline in maximal oxygen consumption when compared to healthy adults. Hemoglobin mass strongly correlates to maximal oxygen consumption. A reduced total blood volume has been observed in patients with T2D, suggesting that a reduced hemoglobin mass contributes to the decreased maximal oxygen consumption in this population. Hypoxia stimulates the release of erythropoietin (EPO), the hormone regulating red blood cell production. We previously showed that intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, increases EPO levels. Thus, the objective of this study was to determine the effect of a single session of intermittent hypoxia on serum EPO levels and hemoglobin mass in patients with T2D. We hypothesized that a single session of intermittent hypoxia would raise serum EPO levels and lead to an increase in hemoglobin mass in patients with T2D. Ten patients with T2D (4 women, age: 53 ± 10 years, body mass index: 36.2 ± 8.5 kg/m2, HbA1c: 7.2 ± 1.2%) were exposed to an intermittent hypoxia protocol consisting of eight 4-min cycles at a targeted oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Air was made hypoxic by titrating nitrogen into a breathing circuit. Pulmonary gas exchange, oxygen saturation, and hemodynamics were continuously measured throughout the protocol. EPO levels were measured before and 4.5 hours after the beginning of the protocol. Hemoglobin mass was assessed via carbon monoxide rebreathing before and seven days following intermittent hypoxia. Intermittent hypoxia lowered oxygen saturation (&shy;&shy;97 ±&shy; 2 to 81 ± 2%, p<0.01), which resulted in a lower fraction of inspired oxygen (20.8 ±&shy; 0.1 to 11.1 ± 1.0%, p<0.01). There was no significant change in EPO levels following exposure to intermittent hypoxia (11.9 ± 5.3&shy; to 12.1 ± 4.3 mU/ml, p=0.83). There was also no change in hemoglobin mass in response to intermittent hypoxia (864 ± 152&shy; to 850 ± 150 g, p=0.64). Intermittent hypoxia did not affect mean arterial pressure (94 ± 5 to 97 ± 7 mmHg, p=0.18) but increased cardiac output (9.1 ± 2.7 to 9.8 ± 2.8 L/min, p=0.03) due to an increase in heart rate (78 ± 9 to 84 ± 10 bpm, p<0.01). In conclusion, a single session of intermittent hypoxia did not increase serum EPO levels or hemoglobin mass in patients with T2D. These findings suggest an impaired EPO response to decreased oxygen levels in patients with T2D, which may contribute to the reduced hemoglobin mass and total blood volume observed in this population. College of Education Small Grants Program This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effect of cyclooxygenase inhibition on thermal hyperemia in skeletal muscle of humans
Authors: Richey Rauchelle , Cope Heidi , Ruiz Ysabella , Moore Amy , Walsh Mackenzie , Olivencia-Yurvati Albert , Romero Steven 
Published: May 2023

Acute heat exposure increases skeletal muscle blood flow in humans. However, the vasodilator mechanisms mediating this hyperemic response remain unknown. The cyclooxygenase pathway is active in skeletal muscle, is heat sensitive, and contributes to cutaneous vasodilation during heat exposure in young healthy humans. Therefore, the purpose of this investigation was to test the hypothesis that inhibition of cyclooxygenase via high dose ingestion of ibuprofen would attenuate blood flow in the vastus lateralis muscle during localized heating. Four participants (26 ± 2 yrs) were studied on two separate occasions: 1) time control; 2) ingestion of 800 mg ibuprofen, a non-selective cyclooxygenase inhibitor. Experiments were randomized, counter-balanced, and separated by at least 10 days. Microdialysis was utilized to bypass the cutaneous circulation and directly measure local blood flow in the vastus lateralis muscle of each leg via the ethanol washout technique. Pulsed short-wave diathermy was used to induce deep heating of the vastus lateralis for 90 min, whereas the contralateral leg served as a thermoneutral control. Local muscle temperature was measured within ~1-2 cm of each microdialysis probe via a thermocouple. Temperature of the vastus lateralis measured through 90 min of heating did not differ between conditions (control, 39.2 ± 1.0 °C; ibuprofen, 39.7 ± 1.0 °C; P = 0.6 for interaction). Interestingly, local blood flow increased during heat exposure, but did not differ between control (baseline, 15 ± 11 mL· min-1 · 100g-1; 30 min, 23 ± 12 mL· min-1 · 100g-1; 60 min, 25 ± 12 mL· min-1 · 100g-1; 90 min, 38 ± 12 mL· min-1 · 100g-1) and ibuprofen (baseline, 14 ± 11 mL· min-1 · 100g-1; 30 min, 29 ± 12 mL· min-1 · 100g-1; 60 min, 32 ± 12 mL· min-1 · 100g-1; 90 min, 53 ± 12 mL· min-1 · 100g-1; P = 0.2 for interaction) conditions. Muscle temperature and local blood flow did not differ between conditions or across time for the thermoneutral leg (both P > 0.3). Taken together, cyclooxygenase-derived vasodilator prostanoids do not appear to contribute to thermal hyperemia in skeletal muscle of young healthy humans. This work was supported by grants from the National Institutes of Health (T32 AG020494; R01AG059314) and the American Heart Association (TPA958179). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.