bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-activation of diaphragm and bicep in response to trans-spinal magnetic stimulation in healthy males
Authors: Ren Ming-Yue , Lee Kun-Ze 
Published: May 2023

Magnetic stimulation is a non-invasive approach to activate the neural tissue and induce the motor evoked potential. Diaphragm and bicep are innervating by motoneurons located within the mid-cervical spine cord; thus, the present study was designed to evaluate whether trans-spinal magnetic stimulation can co-activate the diaphragm and bicep in healthy male subjects (n=12) (KMUHIRB-F(I)-20210039). The two wings of the figure-of-eight magnetic coil (MCF-B65, inner diameter: 35 mm; out diameter: 75 mm) were placed on the dorsal vertebrae from the fifth cervical to the second thoracic vertebral column and its handle was vertical to the spine. The surface electromyogram of the bilateral diaphragm and bicep was recorded in response to trans-spinal magnetic stimulation with 20-100% maximum output of the stimulatory device. The results showed that trans-spinal magnetic stimulation can co-activate both muscles when the stimulatory intensity reached 60%. Notably, the intensity-response curve of motor evoked potential was significantly different between diaphragm and bicep. Specifically, the normalized response curve of the bicep was generally greater than that of the diaphragm, suggesting the excitability and responsiveness of bicep were greater than that of the diaphragm during trans-spinal magnetic stimulation. In addition, the motor evoked potential of the right diaphragm and bicep was greater than the left side during low stimulatory intensity, indicating there are anatomical and/or physiological differences between left and right muscles. In conclusion, trans-spinal magnetic stimulation with two coil wings along the vertebrae can co-activate the diaphragm and bicep. This trans-spinal magnetic stimulatory configuration can be considered as a feasible and efficient neuro-rehabilitative strategy to activate muscles innervating by the cervical spinal cord in subjects with impaired respiratory and forelimb motor function. The Ministry of Science and Technology (MOST 110-2636-B-110-001 & 111-2636-B-110-001). 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.
Applying patient personalized organoid model system to understand complex GI manifestations in cystic fibrosis disease
Authors: Arora Kavisha , Sundaram Nambirajan , Ramananda Yashaswini , Helmrath Michael , Naren Anjaparavanda P 
Published: May 2023

Background: Stem cell-derived organotypic culture has become a revolutionary tool in transforming care for patients with multiple GI-disorders. Cystic fibrosis is a deadly genetic disorder with multiple GI complications, such as Distal intestinal obstruction syndrome (DIOS), chronic constipation, Gastroesophageal reflux disease (GERD), and in some cases pancreatitis, caused by loss of function mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) chloride/bicarbonate ion channel. Due to genetic and environmental influences, CF patients exhibit large phenotypic variation. These factors make clinical trials difficult and largely impractical due to limited and heterogenous patient pools, and additionally, the benefit of approved small-molecule CF therapy in a large number of rare mutation patients is not known. Moreover, critical questions of whether CFTR contributes to the development of intestine and how it contributes to GI-related issues remain unanswered. Results: In this study, we performed a comprehensive bench-side study using in vitro patient enteroids and in vivo mice implanted Human Intestinal Organoids (HIOs) to test highly effective CFTR modulators -Ivacaftor response for a rare CF mutation patient. Based on the positive Ivacaftor response in the enteroids, the patient was enrolled in N=1 clinical trial and showed improved GI outcomes upon Ivacaftor treatment. HIO implantation model allowed in vivo modulator dosing and provided an elegant human organ-based demonstration of bench-to-bedside testing of modulator effects. Additionally, using the CF HIO model the role of CFTR function in the maturation of human intestine was reported for the first time. In HIOs derived from a stop mutation CF patient and CFTR-corrected HIOs as control, we performed single cell RNAseq analysis to generate a molecular map of GI-cell type specific transcriptomic alterations and identify key targetable pathways relevant to stop mutations in CFTR for which currently there is no small molecule therapy. Conclusion: In all, we demonstrate that these models effectively serve to translate data from the lab to the clinic and back so that patient specific therapies could be validated, or new therapies be devised. Additionally, single-cell RNA sequencing in patient HIOs will provide useful insights into cell population specific and transcriptomic level alterations that are associated with abnormalities in GI function in CF. Nothing to disclose 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.
Distinct roles of kindlin-3 and talin-1 in neutrophil beta2 integrin clustering
Authors: Wu Yuanyuan , Wen Lai , Ley Klaus , Fan Zhichao 
Published: May 2023

Neutrophils are the most abundant leukocytes in human blood. Neutrophil malfunction may cause various immunological diseases. Beta2 integrins are critical for neutrophil recruitment. Kindlin-3 and talin-1 are important regulators for beta2 integrin activation. We have confirmed this using conformation-specific antibodies KIM127 and mAb24 that recognize activation epitopes in beta2 integrin. Besides activation, clustering is also critical for beta2 integrin avidity and adhesion of neutrophils. Whether kindlin-3 and talin-1 are involved in beta2 integrin clustering remains unclear. Here we used super-resolution stochastic optical reconstruction microscopy (STORM) to study their roles in beta2 integrin clustering on human neutrophil-like HL60 cells. We find that lymphocyte function-associated antigen 1 (LFA-1) and macrophage-1 antigen (Mac-1) are significantly clustered in wild-type cells after IL-8 or fMLP stimulation. Using CRISPR-Cas9-mediated kindlin-3 and talin-1 knockout HL60 cells, we found that kindlin-3 but not talin-1 are responsible for beta2 integrin clustering. Our study provides new insights into the regulation of beta2 integrin clustering and leukocyte recruitment. Supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute, USA (R01HL145454), and a startup fund from UConn Health. 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.
Comparing psychological and physiological factors involved in perceived threats in behaviorally inhibited individuals
Authors: Wiseman Connor , Ehlert Luke , Apostoli Giana , Wolf Olivia , Harshberger Mary , Miller Justin , Martino Paul , Miller Daniel , Terrill Sarah , Allen Michael 
Published: May 2023

Behavioral inhibition (BI) is a temperament characteristic which is associated with increased vulnerability to stress compared to non-behaviorally inhibited (NBI) counterparts. The physiologic and psychologic substrate which underlies the difference between BI and NBI individuals is unknown. Our previously published study demonstrated that BI individuals have decreased heart rate variability (HRV) relative to NBI individuals suggesting that BI individuals have less parasympathetic nervous system (PNS) output; however, it is unknown how BI affects perceived stress. Our current study tested the hypothesis that BI individuals would have higher perceived stress and physiologic stress during transdermal electrical stimulation (TES). Participants were administered TES beginning at 5mV and increased by 5mV increments until 100mV was reached. We used the Adult Measure of Behavioral Inhibition (AMBI) and the Perceived Stress Scale (PSS) to measure perceived stress, State-Trait Anxiety Inventory (STAI) scores to measure current stress, and a series of self-reported questionnaires to measure BI. Additionally, we used a BIOPAC data acquisition system to measure heart rate (HR), HRV, and blood pressure (BP) to measure physiological stress. Our pilot data suggests there was a non-significant trend of higher perceived stress after TES in BI individuals; however, there was a significant relationship between perceived stress and STAI scores. There was no significant difference in HR, HRV and BP between BI and NBI individuals. In conclusion, our pilot data suggests that a person’s BI or NBI status affects their perceived stress after a stressor is induced. BI individuals will have higher perceived stress after a stressor is presented as opposed to NBI individuals. We will conduct further studies using TES to further study this finding. Identification of these physiological factors could provide an additional mechanism for identifying individuals who are at a higher risk for developing stress and anxiety disorders. 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 behavioral inhibition on avoidance behavior during transdermal electrical stimulation
Authors: Apostoli Giana , Ehlert Luke , Wiseman Connor , Wolf Olivia , Harshberger Mary , Martino Paul , Miller Daniel , Miller Justin , Terrill Sarah , Allen Michael 
Published: May 2023

Behavioral inhibition (BI) is a temperament characteristic that is associated with increased vulnerability to stress compared to their non-behaviorally inhibited (NBI) counterparts. Our previous study demonstrated that BI individuals have lower heart rate variability (HRV) than NBI individuals. This suggests that BI individuals have significantly less parasympathetic nervous system (PNS) output at rest. However, it is unknown how BI affects avoidance acquisition using a mildly stressful stimulus. Previous studies have shown that there are differences in the behavior found in Wistar-Kyoto rats, which exhibit BI behavior, compared to Sprague-Dawley control rats. Our current study will test the hypothesis that BI individuals learn to make escape and avoidance responses using subdermal ulnar nerve transdermal electrical stimulation (TES) more rapidly than NBI individuals, and also experience a greater increase in heart rate (HR) and blood pressure (BP). BI individuals were identified through a series of self-reported questionnaires. Three levels (30 mV, 50 mV, and 70 mV) of subdermal ulnar nerve TES were delivered to participants while receiving warning signals that predict the delivery of the TES. Participants had access to a button that when pressed during the light the warning signal prevented the delivery of the TES. This was scored as an avoidance response. If the button was pressed during the TES, it terminated the stimulation and was scored as an escape. HR and BP were also measured during TES using a BIOPAC data acquisition system. Our preliminary results do not suggest a difference between BI and NBI individual differences in HR or BP during TES (n=13); however, our future studies will investigate the differences in HRV and the acquisition of avoidance behavior during TES. 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.
Glucagon-like peptide-1 receptor agonists and cardiometabolic risk factors in Polycystic Ovary Syndrome: role of race/ethnicity
Authors: Pruett Jacob , Romero Damian , Yanes Cardozo Licy 
Published: May 2023

Background: Polycystic Ovary Syndrome (PCOS), the most common endocrine disorder in reproductive-age women, is characterized by androgen excess, polycystic appearance of the ovaries, and ovulatory dysfunction. PCOS women have an increased prevalence of cardiovascular risk factors, such as increased blood pressure, insulin resistance (IR), and obesity. We have previously demonstrated that glucagon-like peptide-1 receptor agonists (GLP1RA) improve IR and obesity in a rat model of PCOS. Recent evidence suggests that Black Women (BW) with PCOS have an increased incidence of cardiometabolic risk factors compared to their White Women (WW) counterparts. We tested the hypothesis that GLP1RA has a differential effect on cardiometabolic risk factors in BW with PCOS versus WW with PCOS. Methods: The University of Mississippi Medical Center de-identified patient data from January 2013 – September 2022 were obtained from electronic medical records (EMR) using UMMC's Research Data Warehouse. Patients with 1) PCOS, 2) type 2 diabetes mellitus (T2DM), 3) documented hemoglobin A1c (HbA1c), and 4) GLP1RA prescription were identified. Cardiometabolic risk factors such as HbA1c, body mass index (BMI), and systolic and diastolic blood pressure (SBP and DBP respectively) were analyzed and compared between BW and WW with PCOS/T2DM. ICD-10 code of PCOS and T2DM: E28.2 and E11.9 respectively. Data are presented as mean ± standard deviation. Results: EMRs of 3756 PCOS patients were obtained. 13.8% of PCOS patients also had a diagnosis of T2DM with documented HbA1c, and 10.4% of them (54 patients) were on a GLP1RA. Of the 54 patients, 35 were BW. In our cohort, BW with PCOS/T2DM had a similar age (38 ± 12 vs 34 ± 11 years of age, p=NS), perimenopausal status, and smoking status as WW with PCOS/T2DM. Compared to WW with PCOS/T2DM on GLP1RA, BW women with PCOS/T2DM had significantly higher HbA1c (8.0 ± 1.0 vs 7.0 ± 0.7 %, p<0.05). There was no difference in BMI, SBP, or DBP between groups. Furthermore, on GLP1RA, there was no difference in the magnitude of change of HbA1c, BMI, SBP, or DBP in BW compared in WW on GLP1RA. Conclusions: BW with PCOS/T2DM had higher HbA1c on GLP1RA compared to WW counterparts. However, there was similar BMI, SBP, and DBP between the two groups. Furthermore, there was no difference in the magnitude of change in cardiometabolic parameters on GLP1RA between the two groups. Race/ethnicity may significantly effect HbA1c, but it does not appear to affect the efficaciousness of GLP1RA on the cardiometabolic profile in women with PCOS. NIGMS P20GM121334 and P20GM104357, NIDDK R21DK11350 and F30DK127527, NHLBI P01HL51971 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.
Neuro-glial underpinning mechanisms in myelin plasticity for memory enhancement
Authors: Wahid Reham , Hassan Nancy , Samy Walaa , Talaat Aliaa , Elsayed Heba 
Published: May 2023

Background and aim: Learning continually shapes our neuronal circuits to form new memories. Neural plasticity was considered as the principal mechanism for learning many decades ago. Although myelin was considered for a long time as static inert insulator, recent studies showed that myelination is dynamically changed to enhance neuronal activity under neural plasticity umbrella in terms of myelin plasticity, so our study aims to figure out the underlying mechanisms of myelin plasticity associated with learning and memory. Hypothesis: We hypothesized that many mechanisms promote memory consolidation by enhancing myelination and that glial cells have a crucial role in this myelin plasticity effect. Methods: The study was conducted on 24 rats, divided into 3 groups, with 8 rats in each; Group I (control); rats remained in their home cage, Group II (control untrained); rats were allowed to move and explore the maze for equal time but there was no active platform location learning, and Group III (trained); rats were trained using Barnez maze behavior test including three days of acquisition trials (AT), followed by two probe trials (PT). The gene expression analysis for SOX10, MYRF, NRG, EDGF, SERPINE2 and MBP was evaluated by qRT-PCR in hippocampus tissues, in addition, histopathological assessment was done with immunohistochemistry for Myelin Basic Protein (MBP), Glial Fibrillary Acidic Protein (GFAP), and Gallyas-Braak Silver staining. Furthermore, Pearson correlation was done comparing all genes with MBP expression. Results and data: The present study showed improved spatial memory with increased myelination in the trained group compared to all other groups (P<0.001), in addition to increase of SOX10, and MYRF expression in the trained group indicating more OPC differentiation into mature oligodendrocytes (P<0.001). NRG and EDGF were highly expressed in the trained group compared to other groups, in addition to the marked increase of number of the neuronal cells with more dendrites formation. SERPINE 2 and GFAP as markers of astrocytes showed high expression in the trained group in comparison with other groups (P<0.001) with strong positive correlation between SEPRINE 2 and MBP (r= 0.76, P=0.02). Conclusion: Myelin plasticity as one of the crucial learning mechanisms, was influenced by different neural and environmental signals. Although role of glial cells was almost apparent in oligodendrocytes differentiation and proliferation, there was a significant role of astrocytes in promoting such myelination effect. There were no external funding sources for this study, it is self-funding 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.
Surfactant dysfunction due to e-cigarette aerosol exposure with and without additional insults
Authors: Graham Emma , McCaig Lynda , Tejura Akash , Shui-Kei Lau Gloria , Cao Anne , Veldhuizen Ruud 
Published: May 2023

Introduction: The use of e-cigarettes (ECs) remains a popular habit for young populations, in part due to the variety of appealing flavours available. However, EC use has been associated with acute lung injury via unknown mechanisms. During a deep inhalation, one of the first compounds the EC aerosol comes into contact within the lungs is pulmonary surfactant. This complex mixture of lipids and surfactant associated proteins lines the alveolar surface and reduces surface tension to near zero values upon exhalation. Surfactant dysfunction, associated with serum protein leak and oxidative stress, contributes to lung injury. We hypothesized that exposure to EC aerosol impairs pulmonary surfactant function, and thereby increases its susceptibility to protein inhibition or oxidative stress. Methods: Bovine lipid extract surfactant (BLES) was used as a model exogenous surfactant. 2ml of BLES (2mg/ml) was placed in a syringe (30ml) attached to an EC, drawing in and expelling the aerosol 30 times. Vehicle e-liquid (VG:PG 50:50) as well as e-liquid containing flavouring additives and nicotine were utilized. Two models of injury were used, the first being addition of serum containing plasma proteins and the second oxidization by hypochlorous acid following aerosol exposure. Surface tension reduction of all samples after exposure was performed using a constrained drop surfactometer (CDS), where samples underwent 20 dynamic compression and expansion cycles. Results: Minimum surfaces tensions were significantly higher after exposure to EC aerosol across 20 compression/expansion cycles. Menthol and red wedding flavoured aerosol exposure resulted in significantly increased minimum surface tensions compared to unflavoured vehicle e-liquid, although nicotine had no additional effects beyond that of the vehicle e-liquid. The addition of plasma containing serum proteins significantly increased minimum surface tensions in aerosol exposed samples compared to those unexposed to serum and air controls. Oxidized surfactant had higher minimum surface tensions compared to control, however EC aerosol exposure had no additional effect on the inhibition of the surfactant’s function. Conclusion: EC aerosols alter surfactant function through increases in minimum surface tension. Variability in the severity of inhibition exists between flavouring additives, however the base common across all e-liquids is able to effectively inhibit surfactant. This inhibition is amplified in the presence of serum proteins. From these results we conclude that vaping impairs the pulmonary surfactant system and increases susceptibility to damage by secondary insults. Lawson Health Research Institute, NSERC 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.
Diet-Induced weight loss improves vascular insulin sensitivity in patients with type 2 diabetes
Authors: Smith James , Soares Rogerio , Burr Katherine , Ramirez-Perez Francisco , Martinez-Lemus Luis , Padilla Jaume , Manrique-Acevedo Camila 
Published: May 2023

Background: Insulin-stimulated blood flow plays a key role in glucose and insulin delivery to target tissues, such as skeletal muscle. With the development of obesity and type 2 diabetes (T2D), there are impairments in vascular insulin signaling and, consequently, blunting of insulin-induced vasodilation. However, it remains unknown if diet-induced weight loss attenuates vascular insulin resistance in both men and women with T2D. Methods: Nine women (aged 61.9±2.8 yrs; BMI 36.1±1.8) and seven men (aged 54.9±6.0 yrs; BMI 37.6±2.6) with T2D were recruited to undergo a six-month diet to induce weight loss by reducing sugar intake to <5% of energy and total daily energy intake by 500 kilocalories. Anthropometrics, superficial femoral artery blood flow and skeletal muscle perfusion responses to systemic insulin infusion, brachial artery flow-mediated dilation (FMD), carotid-to-femoral pulse wave velocity (PWV), and biochemical parameters were assessed at baseline and at the end of the six-month dietary intervention. Dietary records were analyzed using Nutrition Data System for Research software. Results: The low-energy diet was effective at reducing body weight, as well as other metabolic outcomes including markers of liver function and inflammation. These improvements were accompanied with an increase in FMD, but not a reduction in PWV. Lastly, leg blood flow and skeletal muscle perfusion responses to insulin infusion were enhanced following the dietary intervention, an effect primarily driven by women. Conclusions: Our results indicate that diet-induced weight loss enhances vascular insulin sensitivity in patients with T2D and that these effects are primarily observed in women. 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.