bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isometric Handgrip Echocardiography is a More Powerful Diastolic Discriminator than Conventional Cycle Echocardiography
Authors: Samuel T. Jake , Beaudry Rhys , Haykowsky Mark , Sarma Satyam , Nelson Michael Douglas 
Published: June 2021

Cycle echocardiography is currently recommended for assessing cardiac involvement (i.e. left ventricular diastolic dysfunction) in patients with unexplained dyspnea on exertion. However, cycle echocardiography is often limited by movement and respiratory artifact, particularly in obese patients with dyspnea. Our group has recently shown that isometric handgrip echocardiography is a powerful diastolic discriminator, capable of unmasking subclinical stress induced diastolic dysfunction. How isometric handgrip echocardiography compares to conventional cycle echocardiography however, remains unclear and was the focus of the present investigation. We hypothesized that isometric handgrip echocardiography would unmask more diastolic dysfunction, given its markedly different hemodynamic load compared to cycle echocardiography. To test this hypothesis, we recruited 24 individuals from the community (9 male, 15 female, age range: 18 – 80), who all performed 3 minutes of isometric handgrip echocardiography followed by 3 minutes of dynamic cycle exercise (20 W). At rest and during the final minute of each exercise protocol heart rate (HR), mean arterial pressure (MAP) and Doppler derived E/e′ were recorded. Consistent with our previous work, and that of others, responders were defined as ΔE/e′ > 1.5 while non‐responders were defined as ΔE/e′ < 1.5. Both isometric handgrip and low‐intensity cycle exercise resulted in a similar rise in HR (ΔHR: 22 ± 13 vs. 25 ± 7, handgrip vs. cycle exercise, P > 0.05), while isometric handgrip resulted in a larger increase in MAP (ΔMAP: 28 ± 14 vs. 16 ± 12, handgrip vs. cycle exercise, P = 0.0003). Remarkably, the isolated increase in afterload experienced by the myocardium during isometric handgrip exercise was more sensitive at unmasking sub‐clinical diastolic dysfunction in community dwelling individuals compared to cycle exercise (handgrip: n = 14 vs. n = 10; and cycle: n = 10 vs. n = 14, responders vs. non‐responders, respectively). Taken together, these data highlight the usefulness of isometric handgrip echocardiography at isolating myocardial diastolic relaxation abnormalities in community dwelling individuals, beyond that of dynamic cycle exercise. Future work should focus on confirming the sensitivity of this method in individuals at risk for or with diagnosed heart failure.Support or Funding InformationAHA 16SDG27260115 and the Harry S. Moss Heart Trust.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Respiratory Muscle Training Positively Affects Vasomotor Response in Young Healthy Women
Authors: Esposito Fabio , Bisconti Angela Valentina , Devoto Michela , Venturelli Massimo , Bryner Randall , Olfert Mark Ivan , Chantler Paul 
Published: June 2021

Vasomotor response is related to the capacity of the vessel to maintain the homeostasis of the vascular tone. Two main control mechanisms are involved: the autonomic control of the sympathetic neural drive (global control) and the endothelial smooth cells capacity to respond to mechanical stress by releasing vasoactive factors (local control). The aim of the study was to evaluate the effects of respiratory muscle training (RMT) on vasomotor response, assessed by flow‐mediated dilation and heart rate variability, in young healthy females. The hypothesis was that RMT may enhance the balance between sympathetic and parasympathetic neural drive and reduce vessels shear stress. To this purpose, twenty‐four women were assigned randomly to RMT or SHAM group. Maximal inspiratory mouth pressure and maximum voluntary ventilation were utilized to assess the effectiveness of the RMT program, which consisted of three sessions of isocapnic hyperventilation per week, eight weeks, for a total of twenty‐four training sessions. Heart rate variability was utilized to evaluate the autonomic balance, a global factor regulating vasomotor response. Endothelial function was determined by measuring brachial artery vasodilation normalized by the shear rate (%FMD/SR). After RMT, maximal inspiratory mouth pressure and maximum voluntary ventilation increased significantly (+31% and +16%, respectively) only in RMT. Changes in heart rate variability were negligible in both groups. Only RMT exhibited a significant increase in endothelial function (%FMD/SR +45%; p<0.05). These data indicate a positive effect of RMT on vasomotor response likely via a reduction in shear stress in the vessels, and not through a modulation of sympatho‐vagal balance.Support or Funding InformationGrant from the Department of Biomedical Sciences for Health, Università degli Studi di Milano.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of High‐intensity Interval Training and Moderate‐intensity Continuous Training on Circulating MicroRNAs in Sedentary Males
Authors: Chen Kuan Ming , Huang Ching‐Hui , Wang Jong‐Shyan 
Published: June 2021

Circulating microRNAs (c‐miRs) serve as the reliable biomarkers for exercise adaption. The present study aimed to clarify the relationships between changes of c‐miRs expressions and aerobic capacity/hemodynamic functions caused by various exercise regimens in men. Twenty‐four healthy sedentary males were randomized to engage in either high‐intensity interval training (HIIT, 3‐minute intervals at 40% and 80% of VO2max, n=12) or moderate‐intensity continuous training (MICT, sustained 60% of VO2max, n=12) for 30 minutes/day, 5 days/week for 6 weeks. Various c‐miRs involved in angiogenesis (miR‐126), cardiac hypertrophy (miR‐222, miR‐221), and hypoxia/ischemia adaptation (miR‐21, miR‐146a) were measured by qRT‐PCR, respectively. The analyzed results showed that 6‐week HIIT and MICT significantly enhanced VO2max, which were accompanied by increased stroke volume and cardiac output during exercise. Moreover, both HIIT and MICT increased expressions of miR‐126 (1.49±0.03 and 1.27±0.09 folds) and miR‐222 (1.32±0.10 and 1.25±0.15 folds), respectively. Additionally, HIIT elevated miR‐146a expression (1.33±0.09 folds), whereas MICT upregulated miR‐21 (1.32±0.08 folds). However, no significant change in plasma miR‐221 level was occurred after both HIIT and MCT. Therefore, we conclude that the exercise‐induced cardiovascular adaptions are associated with the changes of angiogenesis/hypertrophy‐related c‐miRs following either HIIT or MCT.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
SPECC1L: A Novel Cytoskeletal Regulator of Epithelial Organization in Craniofacial Morphogenesis
Authors: Saadi Irfan 
Published: June 2021

Craniofacial anomalies are extremely common among birth defects, with clefts of the lip and palate affecting approximately 1/700 live‐births. While many contributory genes have been identified, a large proportion of the genetic component of this complex disease is unknown. Thus, there is a continued need to identify additional genes and to understand underlying pathogenetic mechanisms. We first identified heterozygous SPECC1L mutations in two patients with atypical facial clefts and cleft palate. New heterozygous missense SPECC1L mutations have been identified in two autosomal dominant Opitz G/BBB syndrome families with hypertelorism and cleft palate, and in two patients with Teebi hypertelorism syndrome, underscoring the importance of SPECC1L in craniofacial development. To understand the role of SPECC1L, we have generated several mouse models with null and hypomorphic (truncation, in‐frame deletion, missense) mutations. Mutants for these alleles manifest a range of structural malformations, including exencephaly, cleft palate and ventral body wall defects. The homozygous null mutants die by embryonic day 9.5 (E9.5) with an open neural tube and failure of cranial neural crest cells to delaminate from the neuroectoderm. We have shown that the latter is due to increased expression of adherens junction markers in the neuroectoderm and reduced PI3K‐AKT signaling. Homozygous mutants for a hypomorphic allele that results in SPECC1L truncation die perinatally and show midline subepidermal blebbing with no cleft palate. Specc1lnull/hypo compound mutants with moderate SPECC1L deficiency show palate elevation defects at E14.5, which resolve within one embryonic day such that only a few mutants are born with cleft palate. However, these compound mutants show abnormal organization of the oral periderm of palatal shelves and occasional oral adhesions at E13.5. Consistent with these periderm anomalies, SPECC1L expression in the palate requires IRF6, thus making it a novel member of the IRF6/GRHL3 pathway in periderm development. Lastly, homozygous mouse mutants carrying human Opitz G/BBB patient mutation (T397P) show highly penetrant cleft palate, indicating a gain‐of‐function that specifically affects palatogenesis. Given the broad phenotypic spectrum of Specc1l allelic series mutants, our studies indicate that SPECC1L regulates epithelial organization at various stages and in multiple tissues throughout embryonic development.Support or Funding InformationThis research is supported by NIH/NIDCR R01DE026172.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective Effects of Human Milk Oligosaccharides on Intestinal Epithelial Function Assessed in Enteroid‐Derived Monolayers
Authors: Drobny Alice , Ibeawuchi Stella Rita , Das Soumita , Bode Lars , Barrett Kim Elaine 
Published: June 2021

Human milk oligosaccharides (HMOs) are structurally diverse carbohydrates that are unique to human milk and have beneficial effects on the growth and development of the intestine and immune system in breastfed infants. Infectious diarrheal diseases account for significant morbidity and mortality in young children and breastfeeding is protective against non‐typhoidal Salmonella infections and associated diarrhea in infants. Several studies suggest that HMOs may prevent enteric infections in breastfed infants and/or improve barrier function in transformed cell lines. Some of the beneficial effects of HMOs may be attributable to changes in the microbiota, but they likely have direct effects on the epithelium as well. The purpose of this study was therefore to evaluate mechanisms whereby HMOs may improve intestinal integrity and any protective effects of HMOs on Salmonella infection in a more clinically‐relevant model. We previously showed that Salmonella infection decreases epithelial barrier function in murine colon and in murine enteroid‐derived monolayers (EDM). In the present study, EDM were developed on permeable supports and, after differentiation, were exposed to pooled HMOs and then subsequently infected with Salmonella typhimurium at a multiplicity of infection of 10:1. Barrier integrity was determined by measuring transepithelial electrical resistance (TEER). We also measured bacterial internalization using a gentamicin protection assay followed by colony counts. Exposure of EDM to 10 mg/mL pooled HMOs for 2–8 h progressively increased TEER. Prior exposure to pooled HMOs prevented the decrease in TEER that was otherwise produced by Salmonella infection at 1 h after infection, but this effect was lost at later time‐points. Pooled HMOs had no effect on numbers of intracellular bacteria and did not alter bacterial growth when added to bacteria directly. Our results suggest that HMOs act directly on intestinal epithelial cells to strengthen intestinal barrier function both at baseline and when compromised by a pathogen. These effects may contribute to protection against the adverse outcomes of neonatal enteric infections.Support or Funding InformationLarsson Rosenquist Foundation Mother Milk Infant Center of Research ExcellenceThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
OVARIECTOMIZED RATS EXHIBIT ANXIETY‐LIKE BEHAVIOR AND INCREASED NEURONAL ACTIVATION IN THE PERIVENTRICULAR NUCLEUS
Authors: Campos Glenda Siqueira Viggiano , Noronha Sylvana , De Souza Aline Viggiano , Lima Paulo , Chianca‐Jr Deoclecio , De Menezes Rodrigo 
Published: June 2021

IntroductionOvarian follicle failure and subsequent estradiol deficiency as a result of menopause leads to impairments in the cardiovascular system and brain. Reduction of estradiol levels is associated with the development of hypertension and anxiety, suggesting estradiol exerts cardioprotective and neuroprotective effects. Furthermore, studies have shown that estradiol deficiency increases circulating and tissues levels of the vasoconstrictor angiotensin II, which itself can increase anxiety responses. The paraventricular nucleus (PVN) is a brain area that has a high density of angiotensin type 1 receptors (AT1R) and beta‐estrogen receptors (ERβ). These observations suggest estradiol modulates anxiety responses in part through regulation of the renin angiotensin system (RAS). The aim of this study was to evaluate the impact of estradiol on anxiety‐like behavior and the neuronal activation on the PVN.MethodsThree month old (mo) female Fischer rats were divided into Intact (INT), ovariectomized (OVX) and Sham‐operated (SHAM) animal groups. Three weeks after surgery, the animals were submitted to a battery of anxiety tests including the elevated T‐maze (ETM), open field (OF) and light/dark box (LDB). Ninety minutes later, the animals were euthanized and the brains were collected to assess c‐Fos activity. Anxiety tests in INT animals were conducted during proestrus or diestrus phase while Sham animals were tested in the diestrus phase. A handling group (H), which was not exposed to behavioral tests, was added as a control for the c‐Fos protocol.ResultsOur results found that the different phases of the estrus cycle did not influence the behavior of the INT group on the ETM, OF and LDB behavioral tests (p>0.05, Mann‐Whitney test). In contrast, the OVX group showed increased inhibitory avoidance and reduced escape latencies in the ETM (p<0,05, Mann‐Whitney test) and also reduced numbers of entries on the dark side of the LDB test (p<0.05, Mann‐Whitney test) in comparison to the Sham control, indicating anxiety‐like behavior. Moreover, the OVX group showed higher neuronal activation in the PVN compared to the other animal groups including OVX‐H (p < 0.001), INT (p < 0.001), and Sham (p < 0.01) by one‐way ANOVA.ConclusionEstradiol deprivation caused by ovariectomy induces anxiety‐like behavior in a myriad of behavioral tests under conditions in which neuronal activation of the PVN occurs.Support or Funding InformationCAPES, CNPq, FAPEMIG, UFOPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neurobiological Correlates of Pain Avoidance Behavior in Opioid vs. Alcohol Dependence
Authors: Pahng Amanda R. , Paulsen Rod I. , McGinn M. Adrienne , Schindler Mackenzie E. , Edwards Kim N. , Edwards Scott 
Published: June 2021

In contrast to their analgesic properties, excessive use of either alcohol or opioids produces a paradoxical emergence of heightened pain sensitivity to noxious stimuli, termed hyperalgesia, which may promote further drinking or use of opioids to manage worsening pain symptoms. Hyperalgesia has traditionally been measured in rodents via reflex‐based assays, including the von Frey method. To better model the cognitive/motivational dimension of pain in a state of alcohol/opioid dependence and withdrawal, we employed a recently developed non‐reflex‐based method for measuring pain avoidance‐like behavior in animals (Mechanical Conflict Avoidance test). Adult male Wistar rats were administered an escalating dose regimen of morphine (opioid‐dependent group) or repeated saline (control group). Morphine‐dependent rats exhibited significantly greater avoidance of noxious stimuli during withdrawal. Such pain avoidance‐like behavior exhibited a modest correlation with mechanical paw withdrawal thresholds as measured via the von Frey method (r=−0.4413, p=0.0452), indicating that the two behavioral assays measure overlapping but not entirely similar pain‐like conditions. We next investigated individual relationships between pain avoidance‐like behavior and alterations in protein phosphorylation in central motivation‐related brain areas. We discovered that pain avoidance‐like behavior was significantly correlated with alterations in phosphorylation status of protein kinases (ERK, CaMKII), transcription factors (CREB), presynaptic markers of neurotransmitter release (Synapsin), and the rate‐limiting enzyme for dopamine synthesis (TH) across specific brain regions. Separate groups of male Wistar rats were made dependent on alcohol via exposure to chronic, intermittent ethanol vapor and compared to air‐exposed (non‐dependent) controls. Here, alcohol‐dependent animals exhibited enhanced pain avoidance‐like behavior of shorter probe heights that were innocuous (i.e., not avoided) in non‐dependent animals, indicative of a state of allodynia. We are currently examining the neural correlates of pain avoidance in these groups to compare to our results in opioid‐dependent animals. Our findings suggest that alterations in phosphorylation events in specific brain centers may support cognitive/motivational responses to avoid pain, and that qualitatively distinct dimensions of pain avoidance‐like behavior (hyperalgesia vs. allodynia) may exist in opioid‐ vs. alcohol‐dependent animals.Support or Funding InformationNational Institute on Alcohol Abuse and Alcoholism (T32AA007577, ARP; R00AA020839, SE), LSUHSC School of Medicine start‐up funds.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparison of effects of serine racemase knockout on nociceptive behavior among different models of neuropathic and inflammatory pain
Authors: Kato Eiko , Saotome Toshiya , Fukushima Teruyuki , Takasusuki Toshifumi , Yamaguchi Shigeki , Hori Yuuichi 
Published: June 2021

Peripheral nerve injury and tissue inflammation often induce abnormal pain. The activation of N‐methyl‐D‐aspartate (NMDA) receptors mediates the development and maintenance of such abnormal pain. D‐serine co‐localizes with NMDA receptors and acts as an endogenous co‐agonist of the NMDA receptor at the glycine binding site. D‐serine is synthesized from L‐serine by serine racemase (SR), which is an enzyme that is abundant in the central nervous system. It remains unclear how alterations in SR activity are involved in modulation of neuropathic and inflammatory pain behavior. In the present investigation, we compared pain behaviors in SR knockout (KO) mice and wild‐type (WT) mice after subjection to a chronic constriction injury (CCI model of Bennett), partial sciatic nerve ligation (PSL model of Seltzer), spinal nerve ligation (SNL model of Chung), and an inflammatory pain model that was induced by subcutaneous formalin.Seven‐ to nine‐week‐old male WT and SR‐KO mice were used for the experiments. Under halothane anesthesia, the mice were subjected to neuropathic surgery. Three types of nerve ligation were performed, as previously described by Bennett et al. (1988), Kim and Chung (1992), and Seltzer et al. (1990). The left sciatic nerve was tied loosely with four ligatures of chromic gut at the mid‐thigh level (Bennett model), the left L5 and L6 spinal nerves were isolated and ligated tightly with a 4‐0 silk thread (Chung model), and the dorsal one‐third to one‐half of the left sciatic nerve was tightly ligated (Seltzer model). Mechanical allodynia was assessed by measuring the frequency of withdrawal responses using von Frey filaments both before and after ligation. To induce inflammatory pain, paraformaldehyde (50 μL, 25% in distilled water) was injected subcutaneously in the dorsal surface of the left hind paw. The mice were continuously observed for 60 min after the formalin injection, and the number of flinches of the injected paw was measured during the observation period.Behavioral observations showed the following results: 1) The second phase of the formalin‐induced licking response was augmented in SR‐KO mice, while the first phase was not; 2) mechanical allodynia in the Seltzer model was quite similar between SR‐KO mice and WT mice; 3) mechanical allodynia in both the Chung and Bennett models was significantly augmented in SR‐KO mice compared with WT mice.The mechanisms of the presently observed different effects of SR knockout on different pain models are unclear. We are currently investigating how differently synaptic circuit activity in the spinal dorsal horn is affected by SR knockout in different pain models.Support or Funding InformationDokkyo Med Univ Mutual FundThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
An Examination of Virtual Reality Interventions as a Resource for the Treatment of Phantom Limb Pain
Authors: Johnson Ashley , Todd Tyler , Block Helen , Preston Ashton , Raynes Edilberto 
Published: June 2021

Virtual reality is a new and developing technique entering the medical community that may be effective in relieving pain. A specific type of pain termed phantom limb pain (PLP), is the occurrence of pain in an area that has been amputated and is reported to affect more than 50% of patients with amputations. Currently, the treatment of phantom limb pain is highly variable in the strategies used and their effectiveness. Based on the theory of maladaptive cortical reorganization causing PLP, we hypothesized that the use of a virtual reality intervention would elicit a reduction in PLP. Using the Oxford Centre of Evidence‐based Medicine (OCEBM) classification, a systematic review of the literature, was conducted to determine the pathophysiological mechanisms contributing to PLP and how virtual reality techniques could beneficially impact cortical reorganization. Based on OCEBM, the majority of the articles reviewed were level 2 evidence and supported virtual reality as a resource for alleviating PLP. We concluded that the available evidence supports that the use of virtual reality could be an alternative treatment for PLP and could decrease PLP.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.