bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated plasma aldosterone impairs functional hyperemia and cognitive function
Authors: Stine Nathan , Sancho Maria , Wellman George , Koide Masayo 
Published: May 2024

Aldosterone, a steroid hormone, plays an important role in blood pressure homeostasis and the maintenance of plasma electrolyte levels by activating the mineralocorticoid receptor (MR) in renal distal tubule and collecting duct epithelial cells. Recent studies revealed that MRs are also expressed in other tissues, including cardiac myocytes, vascular smooth muscle cells, and vascular endothelial cells (EC), and that elevated plasma aldosterone, termed hyperaldosteronemia (HA), has deleterious effects on the cardiovascular system. HA is present in 10-30% of hypertensive patients and unrecognized and asymptomatic HA is estimated to occur in > 10% of individuals with normal blood pressure. Despite the high prevalence of HA, little is known about its impact on cerebral blood flow (CBF) regulation and brain health. This study focused on the physiological processes that support the on-demand delivery of blood to regions of heightened neuronal activity (functional hyperemia). Specifically, we examined the impact of HA on the recently discovered novel mechanism, termed capillary-to-arteriole signaling, through which capillaries and their strong inward rectifier K+ (Kir 2.1) channels play a significant role in functional hyperemia. Importantly, early deficits in functional hyperemia are a hallmark of small vessel diseases of the brain, which are significant contributors to cognitive impairment and dementia. Employing HA model mice, we examined the impact of HA on functional hyperemia, capillary-to-arteriole signaling, Kir2.1 channel activity in freshly isolated capillary ECs (cECs), and cognitive function. Functional hyperemia, measured as whisker stimulation-induced CBF increases using laser Doppler flowmetry, was impaired in HA animals compared to vehicle-treated animals. Retrograde capillary-to-arteriole signaling, evaluated as upstream arteriolar dilation in response to capillary stimulation with 10 mM K+ in Capillary-Parenchymal Arteriole (CaPA), preparations was significantly attenuated in HA mice. Furthermore, cEC Kir2.1 channel currents, recorded using the conventional whole-cell configuration of the patch-clamp technique, were significantly smaller in HA mice compared to vehicle-treated mice. Further, HA model animals obtained lower scores in the Novel Object Recognition test, indicating that cognitive function in the form of memory retention may be impacted by elevated plasma aldosterone. These data suggest that HA impairs functional hyperemia and cognitive function, and that HA may be a novel risk factor for vascular cognitive impairment. This work was supported by The National Institute of Health (P20-GM-135007 to MK and R01-HL-142888 to GCW). This is the full abstract presented at the American Physiology Summit 2024 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.
Incorporating Concept Maps into Physiology Laboratory Protocols to Support Content Mastery
Authors: Steele Keeler , Wonderlin Bill , Wehrwein Erica 
Published: May 2024

The journey of an undergraduate physiology student weaves a tapestry of knowledge. Despite even the best pedagogical practices, misconceptions or missed key concepts are inevitable - in some respects, these (hopefully small) gaps may even be preferable for continued learning. Many degree programs have a capstone course or project that is the culmination of this journey. At Michigan State University (MSU), the Capstone Laboratory Course in Physiology has taken these knowledge gaps in stride and applied the use of concept maps to stitch the final pieces together. Concept maps are diagrams of physiologic phenomena and mechanisms broken down into simplistic parts, usually an effector and resultant change or process. Resembling circuit diagrams, these concept maps take an engineering approach to physiology, demonstrating how each component plays a role in the system in parallel or in series with each other. We used a collection of maps curated by Dr. William Wonderlin of MSU College of Human Medicine on a browser-based application of his own creation called PhysNav.org. In the pre-lab preparatory materials, students are shown a concept map showing the primary mechanism associated with a given week’s lab procedures. Each week students are asked to hypothesize the outcome of the in class experiment (e.g., “Will ECG lead I, II, or III show the largest QRS deflection”) and explain mechanistically using a concept map why they made that prediction. Before doing the weekly in-class human physiology lab protocol, students are asked to draw the map on a white board and annotate the changes that are expected to occur during an experiment based on their written hypothesis. Each team of students must verbally explain the mechanism and annotations to the teaching staff to be checked off before proceeding with the experiment. This checkpoint is essential to discover any misconceptions. Once approved, teams take a photo of the map to use for studying and post-lab homework. Students rate concept maps 4.23/5 for usefulness in review of content (n=53). The course also has independent projects where students develop their own concept map. Student rate concept maps 4.1/5 as being helpful for explaining project mechanisms (n=53). Student feedback about these concept maps has been positive, with some developmental critiques that have been well-received. Many students note that without these maps, they would not be prompted to diagram a concept or develop this type of approach to a mechanism. In conclusion, we have successfully incorporated concept mapping to ensure that lab protocols focus on physiology mechanisms and not just cookbook procedures. Michigan State University Department of Physiology. This is the full abstract presented at the American Physiology Summit 2024 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.
Increasing Confidence in the HPV Vaccine
Authors: Bordenave Madison 
Published: May 2024

HPV causes approximately 26,600 new cancer cases every year in the United States. HPV vaccination initiatives have helped lower HPV infection rates. However, vaccination rates still remain incredibly low. Less than 40% of adolescents that qualify for vaccination have completed a full series. Community engagement through focus groups, interviews, pre and post online surveys of parents have been shown to improve attitudes toward vaccinations. This is a qualitative cross-sectional survey using both quantitative and non-numerical data collected through interviews in order to further understand the reasoning of HPV vaccine hesitant parents who decide to either opt out of vaccination or fail to complete the vaccine series. The study seeks to implement educational strategies such as the testing of a website that works to close the information gap, the amount of available knowledge regarding HPV vaccination compared to the level of knowledge parents actually have. These strategies are implemented with the goal of addressing the concerns of vaccine hesitant parents and assessing their level of hesitancy before and after providing the requisite information regarding HPV vaccination through the interview process. The goal of this study is to both educate and aid in parents decision making when deciding to vaccinate their children for HPV. There is limited community based research available on HPV vaccination hesitancy amongst parents. The approach of using educational materials along with a webpage is new in addressing vaccine hesitancy with regards to HPV. This research could help increase HPV vaccination rates in order to lower HPV related cancers in the future. We found that knowledge played a critical role in improving attitudes toward the HPV vaccine and that improving the knowledge quality of vaccine participants may improve vaccination rates. This work was supported by the American Cancer Society. This is the full abstract presented at the American Physiology Summit 2024 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.
Role of cholinergic agonists & hyperthermia on regional skin barriers: exposure science implications
Authors: Bullens Kelsey , Empey Natalie , McGrath Ashley , Wilson Thad 
Published: May 2024

Regional differences in skin barrier properties are common in mammals, as some exterior surfaces are fairly impermeable and others are leakier. Neural-induced changes in skin physiology and temperature have the potential to alter skin barrier properties, but the circumstances and mechanisms are unclear. We hypothesized that increasing methylcholine (MCh) or acetylcholine (ACh) concentration would decrease the transepithelial resistance (an index of the skin barrier) measured across mouse paw pad skin jacketed at neutral skin (32°C) or internal (37°C) temperature. Additionally, we hypothesized that paw pads would have lower transepithelial resistance compared to mouse tail skin, and subjecting samples to 40°C (local cutaneous heat stress) would lower transepithelial resistance compared to paw pad skin tested at 32°C. 30 C57BL/6 mouse rear paw pads (containing sweat glands) and 7 mouse tail skins (no sweat glands) were dissected and mounted into a vertical Ussing chamber filled with Kreb’s bicarbonate buffer, gassed with 95% O₂ & 5% CO₂, and encased in a temperature jacket. Transepithelial resistance utilized a current clamp and was measured with Ag-AgCl2 electrodes placed in both epidermal and hypodermal baths during hypodermal-side-only cholinergic dosing (5 min/dose). ACh (0, 0.0833, 0.1666, 0.2499, 0.4166, 0.58323, and 0.74989 M) significantly decreased transepithelial resistance in paw pads clamped at 37°C in a dose-dependent manner. Tail skin had significantly higher transepithelial resistance than paw pad skin. However, transepithelial resistance decreased significantly with MCh (same dosing as ACh) at both skin sites. Increasing jacket temperature to 40°C did not alter the magnitude of decrease in transepithelial resistance to MCh in paw pads compared to 32°C. Transepithelial resistance observations were similar when data were expressed as absolute or relative changes to baseline. Increased ion movement in murine skin (signifying a leakier epithelium) occurred with cholinergic stimulation but not with local hyperthermia, suggesting that neural influences can suffciently affect skin function to directly alter regional skin barriers. P30ES026529 with additional support from TL1TR001997 and R25ES027684. This is the full abstract presented at the American Physiology Summit 2024 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 Management of Spinal and Epidural Anesthesia-related Hypotension in the United States during C-section Childbirth
Authors: Nadella Harshita 
Published: May 2024

Currently, neuraxial analgesia is the most effective method of analgesia during childbirth. However, the leading side effect, hypotension, makes it crucial to understand the existing treatments for spinal anesthesia-induced hypotension. This study attempts to elucidate anesthesia-induced hypotension and existing therapies. Researchers performed a scoping review using PubMed and Rayyan to select articles. Inclusion criteria were peer-reviewed articles written in English within the last five years, and nulligravida/primigravida women under 35 years old who reside in the USA. Researchers revealed the different means of treatment to reduce the incidence of spinal anesthesia-induced hypotension in mothers during C-sections. Norepinephrine and epinephrine showed to be more effcacious in maintaining blood pressure while avoiding unfavorable sequelae for the mother following delivery. The study outcome of participants receiving fixed-rate infusions of either norepinephrine or phenylephrine favored the use of norepinephrine. These patients exhibit lower rates of bradycardia ( p=0.004), contributing to a lesser need for bolus rescue of atropine ( p=0.01). Using colloid solutions during C-section compared to crystalloid solutions also revealed a lower incidence of hypotension with a p-value of < 0.00001. Modalities such as wrapping and subsequent elevation of the lower extremities also displayed a significantly higher systolic and diastolic blood pressure and ephedrine dose than the control group. Pharmacological treatment modalities are more effective than non-pharmacological treatments at preventing maternal hypotension. Epinephrine was the most effective treatment for maintaining maternal blood pressure, heart rate, and cardiac output. Further studies should be done to determine the optimal epinephrine dosage. There was no funding provided for this research. This is the full abstract presented at the American Physiology Summit 2024 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 spatial distribution of CFTR-rich Ionocytes cells in the postnatal mouse airway development
Authors: Villanueva Sandra , Apablaza Tabata , Hernández Sebastián , Flores Carlos A. 
Published: May 2024

Ionocytes are a new type of rare airway epithelial cells expressing Ascl3 and Foxi1 transcription factors, as well as 50% of Cftr-transcripts in mouse airways. However, their role and precise location remain mostly unexplored. This research aimed to shed light on ionocyte ontogeny and distribution within the mouse airway epithelium. Mice were bred in the C57Bl6/J background and maintained in the Specific Pathogen Free mouse facility of Centro de Estudios Científicos (CECs) with access to food and water ad libitum. We used 1,7, 10, 14,21 and 28-days-old wild-type mice, 6 and 8-week-old, and 1 year wild-type and 14-days-old 6 and 8-week-old CftrΔF508/ΔF508 animals. The tracheas were sliced in frontal sections, and the ionocytes were identified by immunofluorescence against the FOXI1 transcription factor. All values were expressed as mean ± S.E.M. All animal procedures were approved by the institutional IACUC (CECS-2022-03). We found that FOXI1+cells had a triangular shape with a basolateral process. Unexpectedly, we observed that FOXI1+cells appear postnatally close to the submucosal glands (SMG), and its number increases drastically between 6 and 8-week-old wild type mice. The quantity of FOXI1+cells cells in the adult trachea decreased towards the distal part (proximal=11.2±1.2 vs distal=4.0±0.9 FOXI1+cells/mm basal lamina, n=7, P=<0,001, t-test), and we did not find significative differences between WT and CftrΔF508/ΔF508 adult mouse. FOXI1+cells were often observed in the epithelia around the collecting duct exit and in the collecting duct epithelium of the SMG. In conclusion, our study provides new insights into the localization and distribution of ionocytes in the mouse airway epithelium. Our results indicate that ionocytes may play a role in regulating mucus composition in upper airways. We suggest that age-dependent changes in cell quantity might reflect the need of increased CFTR function in adult stages. Further research is needed to fully understand the function of ionocytes in the airway and their potential role in respiratory diseases such as cystic fibrosis. Proyecto Postdoctoral 3220672 Proyecto FONDECYT 1221257. This is the full abstract presented at the American Physiology Summit 2024 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.
Neutrophils orchestrate early cardiac remodeling after cardiac pressure overload
Authors: Chalise Upendra , Souza-Neto Fernando , van Berlo Jop 
Published: May 2024

Cardiac pressure overload is a chronic condition where the left ventricle undergoes pathological hypertrophy and fibrosis ultimately causing heart failure. Increased myocardial stretch in left ventricular pressure overload initiates activation of an inflammatory and fibrotic response within resident cells leading to infiltration of immune cells. Neutrophils and monocytes are among the first responders during cardiac injury. While the role of monocytes and macrophages in pressure overload has been somewhat elucidated by multiple groups, including our lab, the role of neutrophils in chronic cardiac injury such as pressure overload is still unclear. We hypothesized that, like acute ischemic injury, neutrophils infiltrate to the heart early in pressure overload and initiate an inflammatory cascade which worsens cardiac dysfunction after TAC and that depletion of neutrophils in the first week of TAC would improve cardiac function. Our published single cell RNAseq dataset of immune cells (CD45+) cells from sham and TAC heart at day (D) 7 shows a distinct clustering of neutrophils with S100a9 (34-fold) , S100a8 (31-fold) , Retnlg (9-fold) , Il1b (5-fold) , and Slpi (5-fold) as top 5 differentially expressed genes (DEGs). Geneset enrichment analysis of top 58 DEGs (≥1.5-folds), shows significant association with pathways such as innate immune system, neutrophil degranulation, and signaling by interleukins by Reactome 2022 pathway. Using a murine model of transaortic constriction (TAC) to induce left ventricular pressure overload, we evaluated cardiac neutrophil counts by flow cytometry over the first week of TAC at D 2, 4 and 7. We observed that neutrophils (CD45+Ly6G+CD11b+) numbers consistently increase until D4, with a 7-fold increase at D2 to a 17-fold increase at D4 before returning to sham levels by D7. Using antibody (Anti Gr-1, 4 ug/g) mediated depletion of neutrophils, we observed that neutrophil depletion showed a protective effect in females compared to isotype controls with decreased cardiac hypertrophy and improved ejection fraction; while in male mice no change was observed between isotype and antibody treated groups. In conclusion, our data show that neutrophils peak early in pressure overload and orchestrate early cardiac remodeling with a potential for a sexually dimorphic role. We acknowledge funding from National Institute of Health under the awards numbers HL155993 and HL160665. This is the full abstract presented at the American Physiology Summit 2024 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.
Establishment of Anoxia/cytokine-induced Injury and Regeneration in Colonoids
Authors: Miko Corina , Kim Jain , Jin Younggeon 
Published: May 2024

Intestinal epithelial cells (IECs) play key roles in nutrient absorption and fluid secretion, providing a barrier to protect cells. IECs, derived from intestinal stem cells (ISCs), are crucial in maintaining intestinal homeostasis and regeneration, which is crucial in gastrointestinal diseases such as inflammatory bowel disease (IBD). To study epithelial injury/regeneration, primary cultured colonoids were utilized as a model system to mimic injury. They retain the composition and differentiation of the tissue, making it a suitable model for studying homeostasis and regeneration of ISCs in vitro. Anoxia and proinflammatory cytokines frequently coexist and exacerbate one another during intestinal injury. However, anoxic conditions have been mainly ignored in previous research. Thus, we developed a regeneration model using cytokines/anoxia injury to better recapitulate intestinal inflammation. Colonoids were treated with cytokines TNF-α and IFN-γ (5 ng/μL) in anoxic conditions for 24 hours to provoke an injury. After 24 hours of injury, the colonoids were exposed to normal oxygen and media conditions for regeneration. Regeneration was observed for 24, 48, and 72 hours and documented using photomicrographs. Morphological analysis detailed that injury was most severe 24 hours post-injury with the combined induction of cytokines and anoxia resulting in decreased colonoid area and number of buds compared to control groups. RT-PCR analysis detailed mRNA expression of stem cell markers ( Lgr5, Bmi1, and Hopx), Wnt ( Axin2, Myc2, and Ascl2), and YAP target genes ( Sca1 and Ctgf) were increased at peak injury and returned to pre-injury levels at 72 hours of recovery. Regeneration of the colonoids is consistent with in vivo observations, thus confirming the validity of the model. This versatile model can be used to study responses to injury and regeneration of intestinal epithelium and the function of ISCs with applications in intestinal disease therapeutics. University of Maryland College of Agriculture and Natural Resources and the Maryland Agricultural Experiment Station Undergraduate Research Grant Grant #4307572 from the Maryland Stem Cell Research Fund. This is the full abstract presented at the American Physiology Summit 2024 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.