bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex‐specific Effects of Nuclear and Membrane Progesterone Receptors on Breathing Stability in Newborn Rats
Authors: Boukari Ryma , Bairam Aida , Joseph Vincent 
Published: November 2023

We tested the hypothesis that the nuclear (nPR) and membrane progesterone receptors α (mPRα) and β (mPRβ) have sex‐specific effects on respiratory control and breathing stability in newborn rats. The expression of nPR, mPRα or mPRβ in the brainstem region was attenuated by intracisternal injection of specific small interfering RNA (siRNA) to 10 days‐old male and female rats. An artificial cerebrospinal fluid was injected to the control animals. Twenty‐four hours after the injection, ventilation was recorded using whole body plethysmography during normoxia (21% O2, 50 min), hypoxia (12% O2, 5 min) and hypercapnia (5% CO2, 5 mim). The frequency of sighs and apneas was determined in normoxia and reported as events/hour. Treatments with siRNA against nPR, mPRα, or mPRβ had no effect on ventilation in normoxia, hypoxia, and hypercapnia. In male rats, the treatment with the siRNA against nPR had no effect on the frequency of sighs and apneas, while the treatment with the siRNA against mPRα increased the frequency of sighs (from 24±2 to 44±8, p=0.003) and the treatment with the siRNA against mPRβ increased the frequency of apneas (51±10 to 83±16, p=0.04). In female rats, the treatment with the siRNA against nPR increased the frequency of apneas (from 47±5 to 101±15, p=0.0003), but the treatment with the siRNAs against mPRα or mPRβ had no effect. We conclude that in newborn male rats mPRα and mPRβ, while in newborn female rats nPR contributes to breathing stability. These data could be useful to develop innovative approaches for pharmacological treatments of apnea of prematurity.Support or Funding InformationFunded by CIHR (operating grants ‐ VJ, AB) and FRQ‐S (PhD fellowship ‐ RB).
Arousal defects and apnea in rat pups deficient in central 5‐HT: interactions with sleep state
Authors: Young Jacob O , Hodges Matthew , Cummings Kevin 
Published: November 2023

Sudden Infant Death Syndrome (SIDS) occurs during sleep periods and is preceded by apnea and abnormal arousal from sleep. Histological abnormalities within serotonin (5‐HT) neurons, including reduced 5‐HT, are consistently identified in SIDS cases, but we have an incomplete understanding of how these abnormalities increase the risk of sudden death during sleep. Given that the activity of 5‐HT neurons varies with state of vigilance, so too may their influence on respiratory function and arousal. We previously showed that rat pups deficient in tryptophan hydroxylase 2 (TPH2−/−) had delayed arousal responses to increasing CO2 mainly in quiet sleep (QS). We hypothesized that the apnea displayed by TPH2−/− pups would also be most obvious in QS, and that the delayed arousal was not a generalized defect but rather was specific for increasing CO2. To address these hypotheses we used TPH2−/− and wild‐type (WT) rat pups between postnatal days (P)14–16. Two groups of pups were used: Group 1 (normoxia): 10 WT, 8 TPH2−/−; Group 2 (hypoxia): n= 8 WT, 8 TPH2−/−. Group 1 pups were allowed to sleep normally in room air over two hours. Group 2 pups were exposed to episodes mild hypoxia (~17% O2, balance N2) at the start of AS and QS until arousal. For group 1 pups we measured the number and duration of apneas occurring in each state, as well as the duration of AS and QS episodes. For Group 2 pups we measured the latencies to arousal in response to hypoxia. TPH2−/− pups displayed significantly more apneas than WT in both sleep states, but especially in AS: TPH2−/− pups experienced ~13 more apneas/hr than WT in QS, and this rose to ~75 more apneas/hr in AS (effect of genotype within AS: p<0.001). The overall % time spent in each sleep state was not influenced by central 5‐HT deficiency. However, TPH2−/− pups exhibited longer periods of QS and AS, with AS being particularly prolonged (genotype × state: p=0.003). In contrast to CO2, the arousal latencies of TPH2−/− pups in response to hypoxia were not significantly different than WT. These findings suggest that 5‐HT‐deficient infants are especially vulnerable during AS because they experience profound apnea and a severely compromised ability to arouse.Support or Funding InformationFunding for this research was provided by the American Physiological Society Undergraduate Research Excellence Fellowship (to J.Y.) and by an American Heart Association Scientist Development Grant (14SDG18560022; PI: KJC).
Cervical C2 hemisection acutely induces swallow hyperreflexia
Authors: Huff Alyssa , Greene Clint , Cheffer Kimberly A , O'Steen Wilbur A , Howland Dena R , Pitts Teresa 
Published: November 2023

The effects of cervical hemisection on swallow have not been determined. We hypothesized that cervical hemisection would increase swallow excitability and shift the pattern of swallow breathing coordination to maintain pharyngeal clearance. Electromyograms of the mylohyoid, geniohyoid, thyrohyoid, thyroarytenoid, thyropharyngeus, cricopharyngeus and diaphragm (costal and crural) muscles were recorded in anesthetized, spontaneously breathing anesthetized cats prior to and after a C2 hemisection. Swallow was elicited by infusion of 3ccs of water into the oropharynx. Acute C2 cervical hemisection significantly increased EMG amplitudes across all upper airway muscles during swallow, and swallow frequency increased from 3.3 ± 1.2 to 8 ± 1.4 per infusion. Significant changes in swallow‐breathing coordination were noted with all swallows occurring in E1 (as opposed to late E2), significantly increasing the risk for potential aspiration. These results support a theory of spinal cord inhibition/modulation of the swallow pattern generator and upper airway muscle excitability, as well as the importance of its role in swallow/breathing integration.Support or Funding InformationSupported by R00‐HL 111215, The Kentucky Spinal Cord and Head injury Trust, The Commonwealth of Kentucky Challenge for Excellence, the Rebecca F Hammond Trust and RCS‐VA RR&D B9249S. The contents of this abstract do not represent the views of the DVA or US government.
Activation of esophageal mechanoreceptors alters the pharyngeal phase of swallow
Authors: Brown Alyssa , King Suzanne N , Poliacek Ivan , Pitts Teresa 
Published: November 2023

The effects of esophageal mechanoreceptors on the pharyngeal phase of swallow have not been determined. We hypothesized that rapid activation of esophageal mechanoreceptors would increase swallow excitability to ensure successful movement of the bolus from the pharynx into the esophagus. Electromyograms of the mylohyoid, geniohyoid, thyrohyoid, thyroarytenoid, thyropharyngeus, cricopharyngeus and costal diaphragm were recorded in 8 spontaneously breathing cats. Swallow was elicited by infusion of water into the oropharynx and mechanoreceptor activation was produced by distension of a balloon in the upper third of the esophagus. Esophageal distension alone produced swallows in all animals in at least 1 trial. Trials in which the esophagus was distended while water was infused in the mouth had increased swallow‐related EMG recruitment of all recorded muscles compared to swallows produced by distension alone (p<.05). Water alone increased swallow‐related EMG recruitment on supra‐hyoid muscles (mylohyoid and geniohyoid) compared to esophageal distension alone (p<.05). Swallow duration was unchanged across all conditions. These results support a theory of esophageal afferent feedback modifying the excitability of the pharyngeal phase of swallow, and could be a novel therapeutic target in patients with dysphagia.Support or Funding InformationSupported by R00‐HL111215, the Kentucky Spinal Cord and Head injury Trust, and The Commonwealth of Kentucky Challenge for Excellence.
Ovalbumin – Induced Airway Inflammation Enhances Hypoxic Ventilatory Response In Rats
Authors: Broytman Oleg , Brinkman Jacqueline , Pegelow David , Morgan Barbara , Teodorescu Mihaela 
Published: November 2023

RationalePatients with asthma have an increased risk of developing obstructive sleep apnea (OSA). However, the underlying mechanisms are unknown. Allergen‐induced airway inflammation may affect control of breathing through cytokine signaling in the chemoreceptors or through mechanoreceptor feedback from lungs. We tested the effects of allergen induced lower airway inflammation on the hypoxic ventilatory response.MethodsBrown‐Norway rats (n=4–6/group) were sensitized to ovalbumin (OVA) or saline (SAL) via subcutaneous injection. All animals were challenged with nebulized 1% OVA solution. Ventilation under room air, moderate hypoxia (12% FiO2) and severe hypoxia (9% FiO2) was measured by awake/behaving plethysmography 24 hours after OVA challenge. Ventilatory oxygen (V̇E/V̇O2) and carbon dioxide (V̇E/V̇CO2) equivalents were calculated. Measurements were repeated after 20 minutes exposure to nebulized formoterol. Negative Pressure Forced Expiration (NPFE) maneuvers, before and after formoterol, were performed on anesthetized animals, 48 hours after OVA challenge. Serum OVA‐specific IgE levels were measured using sandwich ELISA. Two‐way (± Repeated Measures) ANOVA was used to compare the groups.ResultsOVA‐sensitized animals had 1) elevated V̇E/V̇O2 during moderate hypoxia (p=0.003); 2) significantly higher slope of V̇E/V̇O2 response to moderate hypoxia (p=0.039), compared to SAL‐sensitized animals. These effects were augmented by formoterol. 3) After formoterol administration, OVA‐sensitized rats also mounted steeper V̇E/V̇CO2 responses to both moderate and severe hypoxia (p=0.012 and p=0.016, respectively), compared to SAL‐sensitized controls. 4) Formoterol significantly increased forced expiratory volume (FEV0.1/FVC) during NPFE measurements (p=0.04). 5) OVA‐specific IgE levels were significantly elevated in sera of OVA‐sensitized animals (p=0.036).ConclusionsOur results suggest increased chemoreceptor loop gain in animals with OVA‐induced lung inflammation, which may involve the carotid body. Data suggest asthma patients may be prone to hyperventilation in response to hypoxia, which could lead to hyperventilation‐induced apneas during sleep. These effects appear mediated in part via pathways independent of alterations in lung mechanics. Further studies will be needed to understand these pathways and how to intervene to attenuate them.Support or Funding InformationSupported by University of Wisconsin Department of Medicine Pilot Funding.
Isolated bullfrog rostral brainstems exhibit a DAMGO‐insensitive lung‐like episodic rhythm in the presence of bicuculline
Authors: Reed Mitchell , Iceman Kimberly , Harris Michael , Taylor Barbara 
Published: November 2023

Respiratory behavior in terrestrial animals is primarily controlled via neural circuits in the medulla. A site in the amphibian rostral medulla at the level of the abducens nerve (CN VI) is believed to be homologous to the pre‐Bötzinger complex in mammals. The μ‐opioid agonist DAMGO has a suppressive effect, and the GABAA receptor antagonist bicuculline has an excitatory effect on lung activity in mammals and amphibians. However, the locations of action in amphibians are unknown. Therefore, we examined the effect of DAMGO and bicuculline on isolated rostral brainstem tissue.We isolated brainstems from bullfrog tadpoles, placed them in a recording chamber, and allowed them to recover for 1 hour perfused with artificial cerebral spinal fluid (aCSF) equilibrated with 98.5% O2 and 1.5% CO2 (pH 7.8). During this time, neural activity from the facial (CN VII) and hypoglossal (CN XII) cranial nerves was recorded. Following recovery, brainstems were transected just rostral to the trigeminal (CN V) nerve, and at the level of the glossopharyngeal nerve (CN IX), removing the caudal medulla. Then activity from the trigeminal (CN V) and facial (CN VII) nerves was recorded. A cocktail containing either DAMGO (120 nM) and bicuculline methochloride (5 μM) or bicuculline alone was subsequently bath applied for 30 minutes.The transection alone resulted in a loss of discernable respiratory rhythm. However, bicuculline application caused a lung‐like episodic rhythm to reappear. Contrary to the suppressive effect DAMGO has on lung activity in other preparations (including intact isolated amphibian brainstems), this rhythm was not affected by the addition of DAMGO in our transected preparation. This work informs the comparison of amphibian and mammalian respiratory oscillators and the consideration of their homology and differences.Support or Funding InformationNIH under Award Numbers UL1GM118991, TL4GM118992, or RL5GM118990.
The Effect of Equilibriative Nucleoside Transporter 1 on Pseudomonas Aeruginosa‐Induced Acute Lung Injury
Authors: Chambers Eboni Delorse , Healy Abigail , Morrison Alan , Rounds Sharon , Lu Qing 
Published: November 2023

Acute lung injury (ALI) is hallmarked by lung edema, excessive inflammation, and respiratory failure resulting in 40% mortality. Multidrug resistant Pseudomonas aeruginosa (P. aeruginosa) infections often cause ALI in patients with compromised immunity. It is well established that Adenosine, a signaling nucleoside increased upon tissue injury, has been shown to protect against ALI through activation of adenosine receptors (ARs). Extracellular and intracellular adenosine concentrations are regulated by equilibriative nucleoside transporters (ENTs). Whether altering adenosine signaling and uptake can prevent or treat bacterial P. aeruginosa‐induced ALI is unknown. We hypothesize that ENT1 inhibition will increase extracellular adenosine and protect against P. aeruginosa‐induced ALI via activation of ARs. ENT1 pharmacological inhibitors and null mice were used to determine the effects of ENT1 inhibition on P. aeruginosa‐induced ALI. We found that P. aeruginosa infections induced ALI in C57BL/6 mice in a dose dependent manner. Pharmacological inhibition of ENT1 via NBTI significantly attenuated P. aeruginosa‐induced ALI, as assessed by wet‐to‐dry lung weight, bronchoalveolar lavage (BAL) protein levels, BAL inflammatory cells, and pulmonary function determined by static lung compliance, tissue damping, and tissue elastance. NBTI also increased bacterial clearance in mice infected with P. aeruginosa. Additionally, NBTI attenuated P. aeruginosa‐induced IL‐1β levels in the BAL of mice. Consistent with ENT1 pharmacological inhibitor data, ENT1 null mice attenuated P. aeruginosa‐induced ALI as assessed by BAL protein and BAL cell counts. Finally, agonists of A2AR and A2BR mimicked NBTI blunting of P. aeruginosa‐induced ALI, whereas, antagonists against A2AR or A2BR diminished the protective effect of NBTI inhibition on P. aeruginosa‐induced ALI. These results suggest that inhibition of ENT1 protects against P. aeruginosa‐induced ALI via adenosine‐mediated activation of A2AR and A2BR. Inhibition of ENT1 may be a novel approach to prevent and treat P. aeruginosa‐ induced ALI.Support or Funding InformationThis work was in part supported by NIGMS P20GM103652 to S. Rounds and Q. Lu, RO1 HL130230 to Q. Lu, PULM‐019‐14F to S. Rounds, and NIEHS T32 ES007272 to E. Chambers.
Bioactive Fibrin Scaffolds for Use in Regenerative Medicine
Authors: Braga Sarah Felicio , Aquino Renata , Carvalho Antonio , Trovatti Eliane , Iemma Mônica , Amaral André Capaldo 
Published: November 2023

Regenerative medicine has been shown to be a promising approach for treatment of musculoskeletal injuries, using as biological strategies scaffolds, cell therapy and biomolecules. The autologous fibrin matrix, derived from leukocyte (LEU) and platelet (PLA)‐rich plasma (L‐PRP) and LEU and PLA‐rich fibrin (L‐PRF) techniques, presents a great potential to act as a bioactive support in regenerative medicine, being able to contribute with the intrinsic maintenance of the cellular viability, stimulation of proliferation and the repopulation potential in the injury site. The aim of this research was to characterize the intrinsic cell viability maintenance potential of different bioactive fibrin scaffolds containing PLA and LEU. For such, blood samples from 3 male volunteers were collected and processed to obtain fibrin clots from the L‐PRP and L‐PRF techniques, using a fibrin matrix devoid of PLA and LEU as a control. In order, to characterize the in vitro viability potential, the human fibroblast cell line (MG07492) was used. After the sowing procedure (104cells), the scaffolds were maintained for 5 days in standard culture conditions in serum‐free Dulbecco's Modified Eagle Medium and subsequently submitted to analysis by scanning electron and fluorescence microscopy. The results demonstrated a distinct potential to promote intrinsic viability between L‐PRP and L‐PRF scaffolds, with L‐PRP responsible for the highest levels of viability. No cells were identified in the fibrin matrix used as control. These results allow the conclusion that fibrin scaffolds from the L‐PRP and L‐PRF techniques present intrinsic cell viability potential and represent promising alternatives for use as bioactive scaffold in musculoskeletal regenerative medicine.Support or Funding InformationCNPq‐ Conselho Nacional de Desenvolvimento Científico e Tecnológico.
Student Performance in and Perception of Gross Anatomy in Varied Curricular Material Organization in Multiple Cohorts
Authors: Thompson Kristjan L 
Published: November 2023

PURPOSEThe first and second year curriculum at Mercer University School of Medicine provides students an opportunity to learn the subject material in a Problem Based Learning case format. The Musculoskeletal Phase provides students with their first Gross Anatomy Laboratory dissection experience. This study looks at student performance when one group of students followed a case order that paralleled the laboratory dissection sequence (Dissection) compared to that of one which did not (Traditional). This study also evaluated student perception of their learning experiences in the Anatomy Laboratory.RESULTSStudy participants were found in two different cohorts (2017 and 2018 graduating classes). Students in the Dissection group (n=132) scored a Gross Anatomy average of 78.15 and an overall phase average of 79.39. Students in the Traditional group (n= 81) had a Gross Anatomy average of 79.98 and an overall Phase average of 79.88. The results indicate that the case order presentation does not significantly alter the overall student performance within the discipline (p= 0.178) or the Phase (p= 0.566). One hundred thirty out of the 213 students participated in the survey assessing their perception of the learning experience within the Phase. Students felt laboratory was helpful in learning the phase material and that they would prefer to dissect in the same order as the PBL cases were presented. Those students within the Dissection group felt more prepared for laboratory experiences compared to their Traditional order counterparts.CONCLUSIONSOrder of case presentation does not have an effect on student performance in the discipline or examination as a whole.
Correlation of Brief COPE and Academic Performance in First Year PA and Dental Students During Human Structure Course
Authors: Thiessen Amy S , Halliday Nancy 
Published: November 2023

PurposeThe purpose of this study is to examine the relationship between items of the Brief COPE and exam grades. This correlation data can be used to help identify students that may lack key strategies needed for academic performance.MethodsStudents were administered the Brief COPE survey after exams. Participation was voluntary. The survey was administered online for convenience and anonymity. Data analysis included two‐tailed t test of individual survey items and exam score. Correlations between Brief COPE items was also done.ResultsReports of high rates of self‐criticism had decreased exam scores. Reporting self‐criticism also has a correlation to disengagement and denial. Substance use as a coping strategy was correlated to disengagement.DiscussionStudents using poor coping and help strategies had reduced academic performance. Identification of these students can improve academic and social intervention and early identification of at risk students.Support or Funding InformationUniversity of Oklahoma Health Sciences CenterCollege of MedicineOklahoma City, OklahomaUniversity of Oklahoma NormanCollege of Education
Introductory Anatomy Laboratory Teaching, Correlations Between Contact Hours and Student Success
Authors: Oh Alice Joowon , Georger Lesley , Rokitka Elizabeth M , Holz Jonathan , Olivieri Nina R , Stephen Frank , Olivieri Marion P 
Published: November 2023

Anatomy is a critical subject for medical and health care education. Many colleges require minimum grades, only some schools allow repeating courses without penalty. The high stakes cause borderline students, often underclassmen, to withdraw to avoid low grades. Those that master the subject have better opportunity to earn admission into desired programs, while others have to face reassessment of career and life goals while potentially dealing with academic, scholarship and financial aid probations or dismissal from programs and/or college sometimes indefinitely. Repeating courses may impact student indebtedness, financial aid access, full‐time status, scholarships, and graduation conferral dates.Effective teaching methods continue to be debated among educators. At D'Youville College, introductory anatomy laboratory classes have traditionally employed full‐time faculty utilizing models, slides, digital images and student cat dissection. During the fall semester of 2014, without adding material, an additional hour was added to the laboratory sessions. In 2015 peer‐tutor availability was increased during open laboratory sessions. In 2016, with addition of a new anatomy masters program, the masters candidates were employed as assistants in the teaching laboratories and to proctor open laboratory sessions often on the weekends. The objectives are to prepare better anatomy teachers as well as improve the success rate of our students. Each laboratory section includes a masters degree candidate to work alongside the faculty to assist students. In order to indicate relationships between the feline dissections and human anatomy, during class, the graduate students present a pro‐section of a human cadaver for comparison.With the added contact time, z‐tests indicated a statistically significant difference (p< 0.0001) in the withdrawal rate that was reduced from 36% to 21%. Comparing the combined fall 2013 and 2014 withdrawal rate to the combined fall 2015 and 2016 it is shown that increasing the contact hours of the faculty and graduate students inside and outside the classroom is associated with an increase in student course completion.Support or Funding InformationWork supported by the Department of Biology and Mathematics, D'Youville College.