bluuebunny/crossref_metadata_2025 huggingface dataset:
Probiotic strains isolated from natural products alleviate gut inflammation in a human epithelial HT-29 in vitro model
Authors: Park Bo Ram , Cheon Se Jin , Kim Sae Hun
Published: May 2023

Probiotics are living microorganisms known to benefit human health by maintaining gut microbiota balance and regulating the immune system and inflammation response. Gastrointestinal (GI) inflammation is associated with an unhealthy outcome such as inflammatory bowel disease, irritable bowel syndrome. And supplementation of probiotics can reduce GI inflammation by preventing the loss of tight junction proteins in intestinal epithelial cells, increasing intestinal integrity and reducing lipopolysaccharide (LPS) leakage. Therefore, this study aimed to isolate probiotics strains from natural products and investigate their anti-inflammatory properties. Stability and safety tests were conducted to select probiotic strains. The human colon epithelial HT-29 cell line were used to evaluate the effect of the probiotic strain on relieving intestinal inflammation. After lactic acid bacteria (LAB) treatment, changes in the expression of inflammatory and anti-inflammatory cytokines, tight junction proteins and apoptotic factors were analyzed. Compared to the LPS treatment, the expression of inflammatory and anti-inflammatory cytokines was regulated in the LAB treatment. In addition, the tight junction protein of HT-29 was regulated by LAB treatment and the expression of apoptosis factors increased by LPS was modulated by LAB treatment. As a result, the application of probiotic strains isolated from natural products may reduce intestinal apoptosis and alleviate intestinal inflammation by regulating the expression of cytokines and tight junction protein. Since GI inflammation and gut dysbiosis are related, and GI tract forms an 'axis' with various organs and can affect various aspects of human health, further research is needed to investigate the anti-inflammatory effect using cells from other organs.

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 exercise-mediated metabokine Beta-aminoisobutyric acid is an exercise mimetic driving skeletal muscle metabolic and functional adaptation
Authors: Daou Hélène N , Watt Nicole T , MacCannell Amanda DV , Scalabrin Mattia , Gad Shaimaa , Futers Simon , Beech David J , Bowen Scott T , Roberts Lee D
Published: May 2023

Skeletal muscle integrates many of the systemic signals, which contribute to the adaptive remodeling, and beneficial effects of exercise. One mechanism through which muscle mediates the systemic effects of exercise is through muscle-derived hormones known as myokines. We identified the metabolite β-aminoisobutyric acid (BAIBA) as an exercise-mediated small molecule myokine. BAIBA is secreted from muscle in response to increased expression of the transcriptional co-regulator PGC-1α, a master regulator of the muscle adaptive response to exercise. However, how BAIBA functions to regulate the adaptive responses of skeletal muscle to exercise remains poorly understood. We show that BAIBA improves muscle metabolism, exercise efficiency and performance in mice. Oxygen consumption (VO2) and energy expenditure are increased in BAIBA-treated mice. Furthermore, BAIBA increased soleus in situ muscle contractile force, fatigue resistance, mitochondrial number and function. We found that BAIBA drives muscle fiber-type switching to an oxidative phenotype in vivo. BAIBA regulates specific fiber-type gene expression in human myocytes through PPARΔ. Our findings demonstrate that BAIBA is a key paracrine myokine, which, in part, regulates the effects of exercise to improve muscle function with resultant effects on exercise performance.

H.N.D. acknowledges the support of the Biotechnology and Biological Sciences Research Council (BB/T004231/1).

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.
Angiotensin II induces endothelial dysfunction by downregulating TRPV4 channels
Authors: KONDAPALLI NARENDRA BABU , Katari Venkatesh , Dalal Kesha , Paruchuri Sailaja , Thodeti Charles
Published: May 2023

Angiotensin II (Ang II) is a potent vasoconstrictor of vascular smooth muscle cells and implicated in hypertension, but it’s role in the regulation of endothelial function is not well known. We and others have previously shown that mechanosensitive ion channel, TRPV4 mediates flow- and/or receptor-dependent vasodilation via nitric oxide (NO) production in endothelial cells. Ang II was demonstrated to crosstalk with TRPV4 via AT1R and beta-arresting signaling in epithelial and immortalized cells, however, the role of this crosstalk in endothelial cell function is unexplored. Here, we demonstrate that pre-treatment with Ang II (200 nM for 48 h) significantly abolished TRPV4 mediated calcium influx in human microvascular endothelial cells, HMEC-1 (human EC). Further, Ang II treatment significantly downregulated TRPV4 protein expression in human EC without altering TRPV4 mRNA levels. Furthermore, Ang II-treatment significantly inhibited TRPV4-induced eNOS phosphorylation in human EC. Taken together, these results suggest that Ang II, in addition to eliciting smooth muscle contraction, contributes to hypertension by reducing TRPV4 protein expression and dependent NO production in human EC.

This work is supported by NIH (1RO1HL119705, 1R15CA202847-01 and R01 HL148585), AHA Grant in Aid (14GRNT20380935, AHA- TPA-971237) and start-up funds from University of Toledo (CKT).

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.
Arterial and Intracranial Hypotension During and Following Exercise
Authors: Petersen Lonnie
Published: May 2023

Exercise induced arterial hypertension and post-exercise arterial hypotension (PEH) are well-described phenomena with direct impact on cerebral blood flow. Cerebral perfusion pressure is given by the difference between mean arterial pressure at brain-level (MAPbrain) and intracranial pressure (ICP), however, little is known about effects of moderate aerobic exercise on ICP. We hypothesize that moderate exercise does not increase ICP thereby facilitating the augmented cerebral blood flow and that a post-exercise decrease in ICP is a contributing mechanism to maintained cerebral blood flow during PEH.Non-invasive (N=14) and invasive (N=3) ICP recordings and cardiovascular parameters were measured upright and supine before, during, and after 30 minutes of seated moderate aerobic bicycle exercise. Exercise elevated MAPbrain from 68±4 to 82±7 mmHg (mean±SEM, P<0.05) without elevating ICP, thus increasing CPP (72±3 to 87±6 mmHg, P<0.05). Compared to before exercise, we found significant PEH with a decrease in MAPbrain of 5±3% (5 mmHg; P<0.05), predominantly driven by a 26±5% (P<0.0001) decrease in total peripheral resistance (TPR). Because post-exercise ICP decreased concomitantly by 58±20% (P<0.0001) CPP remained unchanged. Recovery of ICP towards baseline was similarly correlated to TPR-recovery (R2=0.92, P<0.001), all variables returned to baseline within one hour.Here, we show for the first time ICP during and following aerobic exercise and consequences for cerebral perfusion. Periodic PEH is cardio-vascular protective and has long-term benefits for hypertensive patients, here we suggest that post-exercise decreases in ICP could similarly be cerebo-protective and in part explain the long-term beneficial effects of exercise for cerebral health and cognition.

This work was supported by NASA grant no 80NSSC19K0020 and the Novo Nordic Foundation grant no NNF15OC0019196

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.
Leptin is a key regulator of glucose homeostasis in obesity
Authors: Simonds Stephanie , Pryor Jack , Cowley Michael
Published: May 2023

Approximately 9 out of 10 people with type-2 diabetes are overweight. Leptin is a hormone secreted from white fat cells that exerts control over both food intake and energy expenditure. We described the central mechanisms underlying the hypertensive effects of hyperleptinemia in obesity. Work presented here used continuous radiotelemetric glucose monitoring in mice in combination with multiple gold standard techniques in order to determine the effects of dorsomedial hypothalamic (DMH) leptin signalling on peripheral glucose control. A leptin receptor (LepR) antagonist administered directly into the brain impaired DIO mouse glucose tolerance demonstrating that leptin retains the ability to regulate blood glucose concentration in obesity. Knockdown of DMH LepR function using short hairpin adeno-associated virus (AAV) RNA significantly reduced brown adipose tissue (BAT) thermogenesis by -0.8 ± 0.1°C and increased basal blood glucose (14.3 ± 0.6mmol/l to 9.4 ± 0.5mmol/l) and impaired glucose tolerance. Conversely, chemogenic activation of LepR-expressing DMH neurons significantly elevated BAT thermogenesis (1.5 ± 0.2 °C increase). This increased BAT temperature was immediately followed by a decrease in plasma blood glucose concentration (7.6 ± 0.5 mmol/l to 5.8 ± 0.5 mmol/l). Work presented here demonstrates that increasing the activity of LepR expressing neurons in the DMH can improve glucose tolerance in obesity though an elevation of BAT metabolic activity.

This work was supported by the National Heart Foundation of Australia (SES), The National Health and Medical Research Council of Australia (SES and MAC).

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.
Sex Differences in Heart Rate Variability during Metaboreflex Activation
Authors: Pereira Tania , Edgell Heather
Published: May 2023

Women have been shown to experience blunted metaboreflex activation compared to men (Jarvis et al., 2011; Joshi & Edgell, 2019; Minahan et al., 2018; Samora et al., 2020), which may derive from altered autonomic balance. Since heart rate variability (HRV) estimates sympathetic and parasympathetic outflow, this study aims to determine if there are sex differences in HRV during metaboreflex activation. High frequency (HF) power and greater RR interval variability (SDRR) represent cardiac parasympathetic outflow, whereas the ratio between low frequency (LF) and HF power (LF/HF) represents cardiac sympathetic outflow. Thirty-two young, healthy men (n=16) and women (n=16) were recruited to perform 2mins of isometric handgrip at 40% of their maximal voluntary contraction followed by 3mins of post-exercise circulatory occlusion (PECO). ECG was continuously recorded, and HRV analysis was determined using 3mins of ECG at baseline or PECO. In response to PECO, heart rate (Women 71±12bpm vs. 73±13bpm; Men 68±12bpm vs. 72±13bpm; p=0.026) and mean arterial pressure (Women 84±8mmHg vs. 93±10mmHg; Men 85±9mmHg vs. 97±11mmHg; p<0.001) increased equally in both sexes. There were no significant differences in SDRR, root mean square standard deviation, and total power due to sex or PECO (all p>0.07). At all timepoints and compared to men, women had 1) significantly lower LF power (Women 19±10nu vs. 24±16nu; Men 42±21nu vs. 49±17nu; p<0.001), 2) higher HF power (Women 78±9nu vs. 74±16nu; Men 57±20nu vs. 50±17nu; p<0.001), 3) higher proportion of RR intervals differences greater than 50ms (Women 60±21% vs. 58±22%; Men 39±16% vs. 35±20%; p=0.003), regardless of time (p>0.2), and 4) lower LF/HF (Women 0.26±0.17 vs. 0.41±0.42; Men 1.01±0.90 vs. 1.34±1.30; p=0.002). Unlike previous findings, no sex differences were observed in the pressor response to metaboreflex activation. HRV did not differ in response to PECO in both sexes; however, women had greater cardiac parasympathetic dominance than men.

Funding provided by Natural Sciences and Engineering Research Council of Canada

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.
Corncob bedding alters fasting blood glucose and vascular function in mice
Authors: Sveeggen Timothy , Isakson Brant , Straub Adam , Bagher Pooneh
Published: May 2023

Rodent husbandry requires careful consideration of environmental factors that may impact colony performance and subsequent physiological studies. Of note, recent reports have suggested corncob bedding is potentially a confounding variable affecting a broad range of organ systems. As corncob bedding may contain digestible hemicelluloses, trace sugars, and fiber, we hypothesized that corncob bedding impacts murine vascular function and overnight fasting blood glucose. Here, we compared mice housed on corncob bedding, which were then fasted overnight on either corncob or ALPHA-dri bedding, a paper cellulose alternative. Male and female mice were used from two non-induced, endothelial-specific conditional knock-out strains (Cadherin 5-CreERT2, floxed hemoglobin alpha 1 [Hba1] or Cadherin 5-CreERT2, floxed cytochrome B5 reductase 3 [CyB5R3]) on a C57BL/6J genetic background. After fasting overnight, initial blood glucose was measured, and mice were anesthetized with isoflurane for measurement of blood perfusion via laser speckle contrast analysis using a PeriMed PeriCam PSI NR system. After a 15-minute equilibration, the mice were injected intraperitoneally with phenylephrine (5 mg/kg) or saline and monitored for changes in blood perfusion. After a 15-minute response period, blood glucose was remeasured post-procedure. Consistently, mice fasted on corncob bedding had higher blood glucose than the ALPHA-dri group. In the CyB5R3 strain, corncob bedding caused a reduction in phenylephrine-mediated vasoconstriction. In the Hba1 strain, phenylephrine-induced vasoconstriction was more variable in the corncob group. Altogether, this work suggests that corncob bedding could be a confounding variable for vascular measurements and fasting blood glucose in mice. To promote scientific rigor and improve reproducibility, bedding type should be included in published methods.

NIH R01HL155618

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.
Opioidergic Regulation of AgRP Neurons
Authors: Atasoy Deniz , Sayar Atasoy Nilufer , Yavuz Yavuz , Laule Connor , Dong Chunyang , Kim Hyojin , Aklan Iltan , Tian Lin
Published: May 2023

Opioids are generally known to promote hedonic consumption. Although much of the existing evidence is primarily based on studies in mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits; however, their role in homeostatic feeding remains unclear. The objective of this study is to understand the role of mediobasal hypothalamic opioid signaling in appetite regulation. We hypothesize that opioids may act as negative regulators of appetite through suppression of hunger neurons. Here we used a novel fluorescent opioid sensor, deltaLight for in vivo imaging of opioid dynamics along with ex vivo electrophysiology to study opioid's impact on appetite neurons. We report that mediobasal hypothalamic opioid levels rapidly increase by feeding, which, in turn, directly inhibit AgRP neurons through mu-opioid receptor (MOR). AgRP specific MOR expression increases by energy surfeit and contributes to opioid induced suppression of appetite. Conversely, its antagonists diminish suppression of AgRP neuron activity by food and satiety hormones. Mice with AgRP neuron specific ablation of MOR expression increased preference for palatable food consumption when given the choice. These results define AgRP neuron specific MOR signaling as a key mediator of diet choice thorough post-ingestive signals.

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.
Chronic hypoxia disrupts memory T regulatory cell phenotype which contributes to the pathogenesis of pulmonary hypertension
Authors: Lantz Benjamin , Moriwaki Mika , Oyebamiji Olufunmilola , Guo Yan , Garcia Selina , Gonzalez Bosc Laura
Published: May 2023

Pulmonary hypertension (PH) caused by chronic hypoxia (CH) is a multifaceted disease most often caused by sleep apnea, prolonged high-altitude exposure, or chronic obstructive pulmonary disease (COPD), with minimal treatment options, leading to right heart failure and death. One major contributor in the pathogenesis of PH that requires more characterization is the accompanying immune response.Our previous studies have demonstrated the importance of inflammation and self-immunity in CH-induced PH. We demonstrated pulmonary-perivascular localization of pro-inflammatory Th17 cells as well as an increase in total Th17 cells in the lung, while finding no overall changes in the number of anti-inflammatory T regulatory (Treg) cells present in the lung. Imbalance between Th17 and Treg cells has been shown to drive multiple inflammatory and metabolic diseases. One area of interest related to this balance has been the recent discovery and attempted characterization of exTregs, or cells that, at one point in time, were Tregs but lost their phenotype transitioning to pro-inflammatory Th17 cells, due to decreases in the expression of the transcription factor FoxP3. Therefore, we hypothesized that the increase in Th17 cells seen in CH is due to a decrease in Tregs and Treg suppressive capacity as well as a switching of Tregs to Th17 cells. Using a mouse model that allows the study of lineage stability and genetic mapping of Tregs, together with single-cell RNA sequencing (scRNA SEQ), we initially established that CH resulted in a gene expression profile consistent with exTregs or Tregs with less suppressive activity, such as downregulation of Il2ra gene and upregulation of Tnfrsf4 (adjusted p-value 0.03). To further establish a loss in Tregs as well as an increase in exTregs following CH exposure, we performed spectral flow cytometry of splenocytes on a Cytek Aurora to look for changes in protein expression and cell prevalence. Finally, we used a similar lineage mapping mouse model to look at Th17 cells. Following these experiments, we found supporting evidence of our scRNA SEQ data, finding a decrease in Tregs in both male and female mice following CH exposure, as well as an increase in exTregs in both groups exposed to CH. We also further supported this data finding Th17 cells tracked through our model to be increased following CH. These results support the importance of immune cell balance and inflammation in the pathogenesis of CH-induced PH.

R56 HL153065-01 NIH, AHA 18TPA34170037, AHA967925 & T32 HL07736 NIH

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.
Cardiomyocyte-specific overexpression of Larp6 protects against angiotensin II-induced cardiac dysfunction
Authors: Russell Jacob , Yoshida Tadashi , Ma Lixin , Davis Daniel , Grisanti Laurel , Russell Adam , Ruff Margot , Bailey Chastidy , Bender Shawn , Chandrasekar Bysani
Published: May 2023

Introduction: La ribonucleoprotein 6 (Larp6) is a multifunctional mRNA binding protein that interacts with type I collagen mRNA to increase its half-life, translation, and deposition. However, its role in the heart is not known. To investigate the role of Larp6 in cardiac function and remodeling, we generated a cardiomyocyte-specific Larp6 overexpressing (OE) transgenic mouse model (Larp6-Tg), and investigated its role at (i) baseline and (ii) following hypertensive challenge with angiotensin II (Ang II). We hypothesized that Larp6 OE exacerbates Ang II-induced cardiac remodeling and dysfunction. Methods: Cross-sectional studies were performed from 2-8 months of age in male and female Larp6-Tg and wild-type (WT) littermates. Baseline cardiac function was assessed by 7-T MRI and echocardiography. In another set of mice, hypertension was induced by infusion of Ang II by osmotic minipump (1000 ng/kg/min) and compared to vehicle infusion. Blood pressure (BP) was assessed 14-17 days post-surgery via tail-cuff, cardiac function by echocardiography after 21 days, and a mid-section of heart was fixed for histochemistry. Results: Baseline cross-sectional studies revealed that Larp6 OE had no significant effect on cardiac function (7-T MRI), BP, or gross morphology regardless of sex. At 10 months of age, histochemistry revealed increased cardiomyocyte Larp6 protein expression and fibrosis in Larp6 OE mice. In 10-month-old mice, Ang II infusion increased BP and induced cardiac hypertrophy in both male and female Larp6-Tg and WT mice. Ang II induced systolic dysfunction in WT mice, however Larp6 OE significantly protected against Ang II-induced decreases in ejection fraction, fractional shortening, and cardiac output independent of sex. These data provide insight into novel roles of Larp6 in the heart worth further examination. Conclusions: Transgenic overexpression of Larp6 in cardiomyocytes doesn’t affect basal cardiac function. However, under hypertensive conditions, its overexpression protects against systolic dysfunction independent of sex. These unanticipated protective effects of Larp6 will be further evaluated through histology and transcriptomics to understand the underlying molecular mechanisms of protection. Together, our data show for the first time that induction of Larp6 has potential to blunt the progression of hypertensive heart disease.

Funding: NHLBI R01 HL088105, R01 HL136386, R01 HL142770, NIDDK DK130243, SRCS (IK6BX004016), and merit BX005845.

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.
Evaluation and Implementation of Lifestyle Habits and Life's Simple 7 in Northwest Indiana
Authors: Thivierge Grant , Ladwig Matthew , Mutai Ezra , Bishop Reagan , Durocher John
Published: May 2023

The CDC’s Social Vulnerability Index (SVI) provides insight into many factors that contribute to the lack of health equity, such as poverty, lack of transportation, and crowded housing. Purdue University Northwest (PNW) has campuses located in Hammond, IN (Lake County) and in Westville, IN (LaPorte County). Because of the high SVI near the Hammond (i.e., 0.9615) and Westville (i.e., 0.8816) campuses, PNW is uniquely positioned to help address the health issues and challenges associated with high SVI. The purpose of this ongoing project is to evaluate and implement lifestyle changes suggested by the American Heart Association’s Life’s Simple 7™ in at least 60 local residents. To accomplish this goal, the PNW Integrative Physiology and Health Sciences (IPHS) Center offers free seminars on each of the Life’s Simple 7™ topics as well as free health screenings to reduce barriers to preventive care among students and community members. To-date, 48 (21 male; 27 female) unique individuals have attended a seminar and / or utilized the free health screening services. The seminar topics include, 1) How to Manage Blood Pressure, 2) How to Control Cholesterol, 3) How to Eat Better, 4) How to Stop Smoking, 5) How to Manage Weight, 6) How to Be More Active, and 7) How to Reduce Blood Sugar. Students and community members that attend lectures in person or virtually also receive take-home educational materials related to improving and maintaining cardiovascular health as well as giveaways including blood pressure monitors, pulse oximeters, pedometers, resistance band kits, and at-home A1C testing kits. The health screenings include blood pressure, body composition, cholesterol, blood sugar, triglycerides, and hemoglobin A1C, as well as healthy eating information, dietary surveys, and physical activity surveys. This project will continue through June 30, 2023.

The Indiana Department of Health (Health Issues and Challenges Grant)

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 Effects of Mindfulness-Based Stress Reduction and Stress Management Education on Arterial Stiffness, Trait Anxiety, and Sympathetic Regulation
Authors: Thivierge Grant , Vyas Aditi , Morin Brigitte , Larson Robert , Durocher John
Published: May 2023

Mindfulness-based stress reduction (MBSR) has been shown to reduce blood pressure and anxiety in several studies, but the effects of MBSR on arterial stiffness and muscle sympathetic nerve activity (MSNA) have not been studied. We hypothesized that MBSR would lower arterial stiffness and MSNA. The present study randomized 22 adults (17 male; 5 female; age 25±1 years; BMI 26±1 kg/m2) with elevated blood pressure (i.e., ≥120/80 mmHg) into 8 weeks of MBSR or stress management education (SME). We examined resting blood pressure, heart rate, trait anxiety, arterial stiffness, and MSNA within 10 days before and after each of the 8-week interventions. Ten participants were randomized into the MBSR group, and 12 into the SME group. Resting blood pressure and heart rate were recorded as the average of three readings from an automated cuff in the seated position. Arterial stiffness was estimated as the average of two carotid-femoral pulse wave velocity (cfPWV) recordings in the supine position, and MSNA was recorded as burst frequency via direct post-ganglionic recordings from the peroneal nerve in a subset of participants. Mean arterial blood pressure was unchanged from pre- to post in either group, but heart rate was reduced from pre- to post in the MBSR participants (77±4 vs. 69±3 beats/min; p=0.01). There was a significant time-effect for trait anxiety, with raw scores reduced from pre- to post (38±3 vs. 34±2 a.u.; p=0.02). cfPWV was unchanged from pre to post (5.6±0.2 vs. 5.4±0.2 m/s; p=0.25), and MSNA was also unchanged (time-effect p=0.51) by MBSR (14±2 vs. 12±3 bursts/min; n=5) or SME (16±1 vs. 15±2 bursts/min; n=5). Results of the present study confirm that MBSR can have beneficial effects such as reducing HR and trait anxiety. Our results suggest that MBSR and SME do not change arterial stiffness or resting MSNA, but this may deserve further investigation in other at-risk populations.

NIH (1R15HL140596-01)

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.
Malignant hyperthermia and Alzheimer's disease causative mutations modulate calcium signaling in T lymphocytes.
Authors: Fomina Alla , Fuller-Wilmarth Eva , Williamson Casey
Published: May 2023

Intracellular Ca2+ channels play a pivotal role in lymphocyte Ca2+ signaling and functions, but how the mutations in these channels that cause diseases of the brain and muscle affect the T cell Ca2+ signaling are poorly understood. Gain-of-function RyR1-p.R163C mutation in ryanodine receptor 1 (RyR1) deregulates Ca2+ signaling in skeletal muscle and causes malignant hyperthermia syndrome in humans under triggering conditions. Mutations in the presenilin 1 gene have been associated with an early onset of familial Alzheimer's dementia (AD). We explored whether mutations in ryanodine receptor 1 ( RyR1-p.R163C) and presenilin 1 (PS1-dE9) genes encoding intracellular Ca2+ release channels affect Ca2+ responses in T lymphocytes.We found that T lymphocytes from heterozygous RyR1-p.R163C knock-in mutant mice (HET T cells) display measurable aberrations in resting cytosolic Ca2+ concentration ([Ca2+]i), Ca2+ release from the intracellular store, and store-operated Ca2+ entry (SOCE), compared with the WT T cells. Pretreatment of HET T cells with ryanodine receptor inhibitors ryanodine or dantrolene reduced disparities between HET and WT T cells in the resting [Ca2+]i, and the ability of thapsigargin, an inhibitor of the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA), to mobilize Ca2+ from the store. Furthermore, T cells from TgF344-AD rats (TgF344-AD T cells) expressing mutant PS1-dE9 gene display enhanced SOCE elicited in the presence of SERCA activity compared with the WT T cells. Pretreatment of TgF344-AD T cells with dantrolene reduced differences in SOCE between TgF344-AD T cells and WT T cells. These findings indicate that intracellular Ca2+ release channel channelopathies associated with neurological and skeletal muscle dysfunctions may affect T cell-mediated immune responses. Whether the altered immune cell responses contribute to the pathogenesis of malignant hyperthermia and AD diseases remains to be determined.

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.
Baby-Friendly Hospital Initiative and exclusive breastfeeding during hospital stay
Authors: Von Seehausen Mariana Pujól , Oliveira Maria Inês Couto de , Leal Maria do Carmo , Domingues Rosa Maria Soares Madeira , Boccolini Cristiano Siqueira
Published: May 2023

OBJECTIVE: To estimate the prevalence of exclusive breastfeeding during maternity hospital stay (outcome) and to analyze the association between delivery in a Baby-Friendly Hospital (BFH) and the outcome. The hypothesis is that accreditation to this program improves exclusive breastfeeding during maternity hospital stay. Exclusive breastfeeding is essential in reducing neonatal morbidity and mortality. METHODS: This study is based on secondary data collected by the “Birth in Brazil: National Survey into Labour and Birth”, a population-based study, conducted with 21,086 postpartum women, from February 1, 2011, to October 31, 2012, in 266 hospitals from all five Brazilian regions. Face-to-face interviews were conducted mostly within the first 24 hours after birth, regarding individual and gestational characteristics, prenatal care, delivery, newborn’s characteristics, and breastfeeding at birth. A theoretical model was created, allocating the exposure variables in three levels based on their proximity to the outcome. This hierarchical conceptual model was applied to perform a multiple logistic regression (with 95%CI and p < 0.05). RESULTS: In this study, 76.0% of the babies were exclusively breastfed from birth until the interview. Babies born in public (AOR = 1.73; 95%CI: 1.10–2.87), mixed (AOR = 2.48; 95%CI: 1.35–4.53) and private (AOR = 5.54; 95%CI: 2.38–12.45) BFHs were more likely to be exclusively breastfed during maternity hospital stay than those born in non–BFHs, as well as those born by vaginal birth (AOR = 2.16; 95%CI: 1.79–2.61), with adolescent mothers (AOR = 1.83; 95%CI: 1.47–2.26) or adults up to 34 years old (AOR =1 .31; 95%CI: 1.13–1.52), primiparous women (AOR = 1.51; 95%CI: 1.34–1.70), and mothers living in the Northern region of Brazil (AOR = 1.99; 95%CI: 1.14–3.49). CONCLUSIONS: The Baby-Friendly Hospital Initiative promotes exclusive breastfeeding during hospital stay regarding individual and hospital differences.
Covid-19 hospital mortality using spatial hierarchical models: cohort design with 74,994 registers
Authors: Chiaravalloti Neto Francisco , Bermudi Patricia Marques Moralejo , Aguiar Breno Souza de , Failla Marcelo Antunes , Barrozo Ligia Vizeu , Toporcov Tatiana Natasha
Published: May 2023

OBJECTIVE: To investigate the relationship between covid-19 hospital mortality and risk factors, innovating by considering contextual and individual factors and spatial dependency and using data from the city of São Paulo, Brazil. METHODS: The study was performed with a spatial hierarchical retrospective cohort design using secondary data (individuals and contextual data) from hospitalized patients and their geographic unit residences. The study period corresponded to the first year of the pandemic, from February 25, 2020 to February 24, 2021. Mortality was modeled with the Bayesian context, Bernoulli probability distribution, and the integrated nested Laplace approximations. The demographic, distal, medial, and proximal covariates were considered. RESULTS: We found that per capita income, a contextual covariate, was a protective factor (odds ratio: 0.76 [95% credible interval: 0.74–0.78]). After adjusting for income, the other adjustments revealed no differences in spatial dependence. Without income inequality in São Paulo, the spatial risk of death would be close to one in the city. Other factors associated with high covid-19 hospital mortality were male sex, advanced age, comorbidities, ventilation, treatment in public healthcare settings, and experiencing the first covid-19 symptoms between January 24 and February 24, 2021. CONCLUSIONS: Other than sex and age differences, geographic income inequality was the main factor responsible for the spatial differences in the risk of covid-19 hospital mortality. Investing in public policies to reduce socioeconomic inequities, infection prevention, and other intersectoral measures should focus on lower per capita income, to control covid-19 hospital mortality
“A gente quer abraçar o amigo”: a pandemia de covid-19 entre adolescentes de baixa renda
Authors: Cabral Cristiane da Silva , Guimarães Jamile Silva , Teixeira Amanda , Generoso Nicolas Kimura , França Junior Ivan , Borges Ana Luiza Vilela
Published: May 2023

OBJETIVO: Examinar as percepções de adolescentes estudantes de uma escola pública, de ambos os sexos, moradores de uma região periférica da cidade de São Paulo, Brasil, em relação à pandemia de covid-19, com especial enfoque em suas experiências quanto à educação e sociabilidade. MÉTODOS: Este estudo faz parte do Global Early Adolescent Study. Foram conduzidos sete grupos focais presenciais com adolescentes entre 13 e 16 anos (19 meninas e 15 meninos), em 2021. RESULTADOS: A experiência do ensino remoto foi frustrante para as/os adolescentes, sem o acompanhamento cotidiano e personalizado de professoras(es). Ao acesso difícil ou impossível aos dispositivos e à ausência de suporte das escolas é acrescido o ambiente doméstico, que dificultou o processo de escolarização, em especial para as meninas, obrigadas a assumir mais tarefas de cuidado da casa e da família. A escola fechada bloqueou espaço importante de socialização e forçou o convívio familiar, gerando conflitos e estresse. A abrupta ruptura trouxe sentimentos de medo, incerteza, angústia e solidão. A evocação iterativa das palavras “presa/o”, “sozinha/o” e “solidão” e da frase “não teve ninguém pra conversar” mostra como grande parte das/os adolescentes experienciou o período de distanciamento. A pandemia agravou as condições objetivas e subjetivas de sentimentos preexistentes, como “não saber o futuro” e as perspectivas de projeto de vida. CONCLUSÃO: Foi documentado como medidas de controle da pandemia implementadas de forma fragmentada e sem suporte às famílias mais empobrecidas têm efeitos negativos em outras esferas da vida, em particular para jovens pobres. A escola é um território privilegiado para se propor/construir ações que auxiliem as/os adolescentes a lidar com problemas agravados na/pela pandemia.
Is chemical exposure present in informal work associated with Sars-CoV-2 infection?
Authors: Salles Fernanda Junqueira , Leroux Isabelle Nogueira , Araujo Alda Neis Miranda de , Assunção Nilson Antonio , Luz Maciel Santos , Veiga Glaucia Raquel Luciano da , Fonseca Fernando Luiz Affonso , Diaz-Quijano Fredi Alexander , Olympio Kelly Polido Kaneshiro
Published: May 2023

OBJECTIVE: To compare the incidence of Covid-19 symptoms between informal home-based workers and a control group and to assess the association of these cases with blood elements concentrations and other relevant risk factors for Sars-Cov-2 infection. METHODS: Welders chemically exposed to potentially toxic elements (PTEs) (n = 26) and control participants (n = 25) answered questionnaires on adherence to social distancing and signs and symptoms of the disease for five months during the Covid-19 pandemic. After follow-up, Covid-19 serology tests were performed on a subsample of 12 chemically exposed workers and 20 control participants. Before the pandemic, PTE concentrations in blood (As, Mn, Ni, Cd, Hg, Sb, Sn, Cu, Zn, and Pb) were measured by ICP-MS. RESULTS: The chemically exposed group had higher lead and cadmium levels in blood (p < 0.01). The control group presented lower adherence to social distancing (p = 0.016). Although not significant, welders had a 74% greater chance of having at least one Covid-19 symptom compared with control participants, but their adherence to social distancing decreased this chance by 20%. The use of taxis for transportation was a risk factor significantly associated with Covid-19 symptoms. CONCLUSION: The lower adherence to social distancing among the control group greatly influences the development of Covid-19. The literature lacks data linking exposure to PTEs and Sars-Cov-2 infection and/or severity. In this study, despite chemical exposure, working from home may have protected welders against Covid-19, considering that they maintained greater social distancing than control participants.
The genus Sympetrum Newman, 1833 in Thailand, with description of S. thailandensis sp. nov. (Odonata: Libellulidae)
Authors: MAKBUN NOPPADON
Published: May 2023

The records of genus Sympetrum Newman, 1833 from Thailand were analysed. The unidentified Sympetrum sp. reported from Chiang Mai and Loei provinces in the past is confirmed as S. hypomelas (Selys, 1884) and additional provincial records of this species are also provided. Sympetrum thailandensis sp. nov. is described and figured based on the adult specimens of both sexes from Hin Tung, Muang, Nakhon Nayok province, Central Thailand. The new species belongs to infuscatum-group and is most similar to S. darwinianum (Selys, 1883). However, it is different from the congener by a combination of morphological and colouration characters. The key to species of Sympetrum known from Thailand is also presented.
Exploring the Value of a High-Precision Targeted Observation Strategy for Mobile Radiosonde Deployment
Authors: Arseneau Isaac , Ancell Brian
Published: May 2023

Ensemble sensitivity analysis (ESA) is a numerical method by which the potential value of a single additional observation can be estimated using an ensemble numerical weather forecast. By performing ESA observation targeting on runs of the Texas Tech University WRF Ensemble from the spring of 2016, a dataset of predicted variance reductions (hereinafter referred to as target values) was obtained over approximately 6 weeks of convective forecasts for the central United States. It was then ascertained from these cases that the geographic variation in target values is large for any one case, with local maxima often several standard deviations higher than the mean and surrounded by sharp gradients. Radiosondes launched from the surface, then, would need to take this variation into account to properly sample a specific target by launching upstream of where the target is located rather than directly underneath. In many cases, the difference between the maximum target value in the vertical and the actual target value observed along the balloon path was multiple standard deviations. This may help to explain the lower-than-expected forecast improvements observed in previous ESA targeting experiments, especially the Mesoscale Predictability Experiment (MPEX). If target values are a good predictor of observation value, then it is possible that taking the balloon path into account in targeting systems for radiosonde deployment may substantially improve on the value added to the forecast by individual observations.
Societal Attention to Heat Waves Can Indicate Public Health Impacts
Authors: Bogdanovich Ekaterina , Guenther Lars , Reichstein Markus , Frank Dorothea , Ruhrmann Georg , Brenning Alexander , Denissen Jasper M. C. , Orth René
Published: May 2023

Both the frequency and intensity of hot temperature extremes are expected to increase in the coming decades, challenging various socioeconomic sectors including public health. Therefore, societal attention data available in real time, such as Google search attention, could help monitor heat-wave impacts in domains with lagged data availability. Here, we jointly analyze societal attention and health impacts of heat waves in Germany at weekly time scales. We find that Google search attention responds similarly to hot temperatures as indicators of public health impacts, represented by excess mortality and hospitalizations. This emerges from piecewise linear relationships of Google search attention to and health impacts of temperature. We can then determine temperature thresholds above which both attention and public health are affected by heat. More generally, given the clear and similar response of societal indicators to heat, we conclude that heat waves can and should be defined from a joint societal and meteorological perspective, whereby temperatures are compared with thresholds established using societal data. A better joint understanding of societal attention and health impacts offers the potential to better manage future heat waves.
Examining the Impact of Cholecystectomy on Tumor Recurrence in Breast Cancer Patients
Authors: Seger Meghan Eileen , Cook Katherine Loree , Hsu Fang-Chi , Chiba Akiko
Published: May 2023

Previous studies have found that bile acids influence the growth of breast cancer cells in vitro, suggesting that naturally occurring bile acids may also influence the growth of human breast cancer cells. Cholecystectomy alters modulation of bile acid metabolites, and therefore postcholecystectomy women could be at an increased risk of cancer development and recurrence. This study examined the breast cancer outcome in women who underwent cholecystectomy as compared to those with intact gallbladder. Ninety-three patients diagnosed with Stage I-III invasive mammary carcinoma in 2014 were retrospectively identified and patient demographics, treatment, and outcomes were collected and statistically analyzed. Results revealed 36% of patients who underwent cholecystectomy had recurrence compared to 25% recurrence in patients with intact gallbladders ( p = .30). Forty-six percent of cholecystectomy patients were deceased, and 23% of those with intact gallbladder were deceased ( p = .024). The effect of cholecystectomy on bile acid modulation and breast cancer recurrence requires further investigation.
Impact of Nasal Cavity CT Opacification Upon Sinonasal Quality of Life
Authors: Shih Michael C. , Edwards Thomas S. , Snyder Jacob , Germroth Matthew , Nguyen Shaun A. , Schlosser Rodney J.
Published: May 2023

Background:

Current methods of quantifying inflammation in chronic rhinosinusitis (CRS) on computed tomography (CT) imaging focus on opacification of the paranasal sinuses and show limited correlation with patient-reported outcome measures.

Objective:

This study aimed to determine if quantifying CT opacification of the nasal cavity correlated with Sino-Nasal Outcomes Test scores (SNOT-22).

Methods:

Thirty patients with CRS were enrolled. Lund-Mackay and SNOT-22 scores were measured. Nasal cavity regions of interest (ROIs) were measured by 2 independent raters using ImageJ at 3 points on coronal CT scans: anteriorly at the lacrimal duct, at the approximate midpoint demarcated by the posterior aspect of the globe, and posteriorly at the transition from the hard to soft palate. Superior and inferior regions were defined based upon the root of the inferior turbinate. Percent opacification was calculated for each ROI. Analyses were conducted bilaterally and for the side with greater opacification (worse side).

Results:

Interrater reliability was strong for all ROIs. Lund-Mackay scores correlated with nasal blockage only ( r = .495, P = .01) and did not correlate with nasal cavity ROI opacification. Inferior nasal cavity opacification for worse-sided anterior ROI and middle ROI correlated with SNOT-22 scores for nasal blockage (anterior r = .41, P = .03) (middle r = .42, P = .023) and runny nose (anterior r = .44, P = .02) (middle r = .38, P = .04). Posterior ROIs did not correlate with SNOT-22.

Conclusions:

Traditional CT scoring of sinus opacification does not correlate well with nasal cavity opacification or SNOT-22. Inferior nasal cavity inflammation provides unique correlations with SNOT-22 nasal questions and may guide targeted interventions in these regions.
Meningitis Risk and Role of Prophylactic Antibiotics in Spontaneous Lateral Skull Base CSF Leaks
Authors: Quimby Alexandra E. , De Ravin Emma , Eliades Steven J. , Brant Jason A. , Bigelow Douglas , Ruckenstein Michael J.
Published: May 2023

Objective:

To review the literature and our institutional experience regarding the risk of meningitis in patients with spontaneous lateral skull base cerebrospinal fluid (sCSF) leaks awaiting surgical repair, and the roles of antibiotic prophylaxis and pneumococcal vaccination, if known.

Methods:

A retrospective chart review and systematic review of the literature was undertaken to identify the incidence of meningitis in patients with sCSF leaks awaiting surgical repair. Adults managed surgically for sCSF leaks at an academic tertiary care center over a 10-year period were included. Data was collected on receipt of prophylactic antibiotics and/or pneumococcal vaccines during the timeframe between diagnosis and surgical repair.

Results:

Institutional review identified 87 patients who underwent surgical repair of spontaneous leaks, with a 0% incidence of meningitis over a median duration of 2 months while awaiting surgery (mean 5.5 months, range 0.5-118 months). Eighty-eight percent of patients did not receive prophylactic antibiotics. No studies in the published literature demonstrated the impact of prophylactic antibiotics or pneumococcal vaccine on meningitis risk.

Conclusions:

There appears to be a low risk of meningitis among patients with lateral skull base sCSF leaks awaiting surgery for short durations (≤2 months), even in the absence of prophylactic antibiotics. There is a substantial gap in the published literature assessing the risk of meningitis and roles of antibiotics and vaccination in this patient population, indicating the need for large-scale study to conclusively elucidate the nature of this risk.