bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptide-Based Fibrin-Targeting Fluorescent Probes for Murine Stasis Venous Thrombus Resolution
Authors: Ha Khanh , Vijay Aatira , Hagearty-Mattern Catherine , Jaffer Farouc , McCarthy Jason 
Published: May 2023

Background- The lack of a stasis venous thrombosis model (VT) in female mice has limited investigation of sex differences of anti-VT therapies, such as acetylsalicylic acid (ASA), which appears efficacious in preventing recurrent VT. Here we (i) develop a new extended stasis VT model; and (ii) examine the effects of ASA on stasis VT resolution in both female and male mice using serial intravital microscopy (IVM). Method- To extend stasis thrombus persistence beyond a single ligation (SL) model, the femoral vein was ligated, followed by a second ligation of saphenous vein near popliteal vein (Fig. A). Following FITC-dextran injection (10 mg/kg), FITC light irradiation (475/35nm, 20x) for three minutes across three illumination fields generated stasis VT. Subsequently, Dylight-649-GPIbβ agent was injected (100ug/kg, ex 630nm) to observe platelets. At T30’, fibrin targeting agent-FTP11-CyAm7 (150nmol/kg, ex 750 nm) was injected. ASA pre-treatment was done for 7 days (3mg/kg, n=5-6). Serial epifluorescence IVM images were acquired up to 24 hours (90i, NIS Elements software, Nikon). Thrombus area was quantified (NIH ImageJ). Results- DL thrombus was significantly larger and visualized through 24 hours (Fig B-G) and 48 hours (data not shown) versus SL thrombus (Fig. E). Corresponding sections of thrombus at T60’, T6h and T24h showed formation of a persistent thrombus core consisting platelets and fibrin (Fig. H-J). In the DL model, females developed reproducible stasis VT burden and resolution profiles as in males (Fig. K). ASA pre-treatment resulted in significant reduction in thrombus induction (T0’), and accelerated resolution in both sexes (Fig. L-P). ASA inhibited platelet recruitment to thrombi within T30’, consistent with its known anti-platelet effect via irreversible inhibition of Thromboxane A2. Furthermore, ASA inhibited fibrinogenesis, suggestive of an impaired platelet-fibrin interface. Conclusion- Here we establish a new extended stasis VT model applicable to both female and male mice that develops thrombus for up to 48 hours. Moreover, this model is amenable to study vein wall fibrosis-key aspect of post-thrombotic syndrome. Furthermore, ASA inhibits thrombus formation and accelerates thrombus resolution in a sex-independent manner, supporting its use in prevention of recurrent VT. AHA 953662; NIH 1R21AR081535-01; NIH R01GM126062 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.
Exercise augments small conductance Ca2+ -activated potassium channel (SK) function in the paraventricular nucleus (PVN) of Sprague Dawley rats to reduce sympathetic outflow
Authors: Miodonski Gregory , Bruning Jessica , Simet Derrick , Ruiter Haley , Johnson Christian , Gu Mingjun , Shan Zhiying , Chen Qinghui 
Published: May 2023

Elevated sympathetic outflow is a key feature of cardiovascular disease (CVD) that worsens disease progression. Our lab has shown that SK channels expressed in the PVN play a crucial role in regulating neuronal activity and sympathetic outflow, and that SK channels become dysfunctional in rats fed a high salt diet. Exercise has been shown to be an effective treatment for reducing sympathoexcitation in CVD including hypertension and heart failure, but the underlying mechanisms are not fully understood. We hypothesized that aerobic exercise would upregulate SK channel function in the PVN to reduce sympathetic nerve activity (SNA). To test this, 5–6 week old Sprague Dawley rats were randomly divided into sedentary (SED) and exercise (EXT) two groups and fed a 0.4% NaCl normal salt diet. Following acclimation, EXT groups ran on a motorized treadmill 5 days/week for 8-10 weeks. Conscious blood pressure was measured weekly via tail plethysmography. After 8-10 weeks, animals were anesthetized and underwent in vivo surgery to record the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) following PVN microinjection of the SK channel blocker, apamin (0.25mM, 60nL/side). The data showed that the RSNA response to PVN apamin was significantly enhanced in EXT rats compared with SED rats (320.8 ± 174.6 % baseline, n=9 vs 184.8 ± 143.1 % baseline, n=9; p = 0.02). The corresponding ABP response to apamin was not significantly different in EXT rats compared with SED rats (20.40 ± 9.98 mmHg, n=9 vs 25.27 ± 9.97 mmHg, n=8; p = 0.1658). Our data indicates exercise enhances PVN SK channel function to reduce sympathetic outflow. This improvement of SK channel function may be one mechanism by which exercise reduces SNA in CVD including hypertension and heart failure. Support: 1R15HL145655 (Chen); 1R15 HL150703 (Shan); MTU Health Research Institute. 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.
Brief Smell Identification Test-1, An odor impairment Test in Patients of Depression
Authors: BAJPAI MANISH 
Published: May 2023

It is often seen that the loss of olfaction is the first symptom in patients of depression. Cognitive functions are frequently altered in depression. Olfaction depends on the integration between olfactory tract and limbic system. Both olfactory bulb and limbic system are highly plastic structures that can change organization network based on environmental input. In patients of depression it is seen that there is significant alteration in olfactory bulb volume from normal healthy subjects. Brief smell identification-12 test, a 12-item version of the University of Pennsylvania Smell Identification Test. The test utilizes microencapsulated “scratch and sniff” odorants (Sensonics International, Haddon Heights, NJ). A BSIT score≤8 was considered abnormal. HYPOTHESIS Olfactory functioning is impaired in patients of depression. OBJECTIVES To study the association of olfactory function in patients of depression with clinical variable, if any. To study the olfactory function in patients of depression and compare it with healthy controls MATERIAL AND METHOD 35 Patients of depression as cases and 32 normal healthy controls attending “ Adult Psychiatry OPD Department, KGMU “ were included in this study (age and sex matched). Depression was classified as per ICD-10. BSIT-12 test for olfaction, MMSE and TMT were done for cognition and attention. RESULT The BSIT-12 test score was found lower in all patients of depression as compared with normal subjects. Statistical analysis t-test and chi-square test found value p <0.001. DISCUSSION AND CONCLUSION BSIT-12 as validated test for olfaction may be useful in diagnosing depression severity and prognosis with treatment. self funded 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.
Nimodipine exerts a protective effect against spreading depolarization and neuroinflammation
Authors: Frank Rita , Pesti István , Menyhárt Ákos , Szarvas Péter , Gulya Károly , Bari Ferenc , Farkas Eszter 
Published: May 2023

Hypothesis, objective: Voltage gated Ca2+ channels (VGCCs) are widely expressed in the central nervous system and implicated in neuronal injury and microglial activation. Nimodipine, a potent cerebrovascular dilator and VGCC antagonist is found to be effective against the vasoconstriction caused by spreading depolarization (SD) in preclinical studies of ischemia. However, it is still unclear whether the beneficial effect of nimodipine is achieved by the improvement of perfusion or a direct action on neuronal or glial cells. Our aim was to explore the direct action of nimodipine on the nervous tissue and microglia. Methods: Brain slices prepared from C57BL/6 mice (n=16) were perfused with artificial cerebrospinal fluid (aCSF). After 30 min nimodipine (nimo; 10 μM) incubation, low glucose aCSF (5 mM) and transient anoxia (1 min) were applied to mimic ischemia and to elicit SD. Intrinsic optical signal imaging was used to analyze SD features, TTC staining was applied to assess tissue injury. Primary mixed and pure microglia cultures prepared from the cortex of neonatal SPRD rats were treated with lipopolysaccharide (LPS;20 ng/ml) and nimodipine (5,10,20 μM), alone or in combination for 24 h. Microglial activation was evaluated by Iba1 immunolabeling (degree of arborization expressed by a transformation index (TI)), Western blot analysis and the visualization of phagocytosis with fluorescent microbeads. Results: In brain slices, nimodipine reduced the focal area of SD (2.37±0.94 vs 3.38±0.88%, nimo vs control), the total cortical area affected by SD (17.12±8.63 vs 39.88±22.42%, nimo vs control) and the propagation velocity of SD (0.19±0.79 vs 1.59±2.29mm/min, nimo vs control). Nimodipine decreased tissue injury, viability expressed as the number of TTC-stained particles (4.48±1.45 vs 3.52±1.52 particle/1000 μm2, nimo vs control). Nimodipine reduced microglial activation in LPS-treated cultures reflected by more ramified cell morphology (3.1±0.91 vs 1.89±0.41 TI, LPS+nimo vs LPS), decreased Iba1 intensity in Western blot analysis (108.3±20.1 and 77.2±8.49 vs 213.4±29.7 integrated optical density, LPS+nimo 10 and 20 μM vs LPS) and attenuated phagocytic activity (6±10 vs 22±20 bead/cell LPS+nimo vs LPS). Conclusion: Nimodipine was protective against SD and successfully reduced neuroinflammation by decreasing microglial activation. Neuroprotection was achieved independent of nimodipine’s vascular action. Our data suggest that nimodipine may be applicable against neuroinflammation and ischemia, in which neurodegeneration is believed to be linked to neurotoxic microglial activation. NKFIH K134377 and K134334, H2020 No. 739593, NAP3.0, TKP2021-EGA-28 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.
Incorporation of heart rate variability into police tactical group small unit tactics selection
Authors: Tomes Colin , Schram Ben , Canetti Elisa , Orr Robin 
Published: May 2023

Objective: Police tactical group (PTG) occupational requirements are known to expose officers to high levels of physical, mental, and emotional stressors. As such, selection courses must ensure candidates are not only physically, but mentally and emotionally competent. To assess personnel for suitability likewise requires a holistic approach; wearable technologies may provide organizational decision makers additional information. Heart Rate Variability (HRV), one metric obtainable from wearable technology, has been increasingly utilized as a stress biosignal, but the value of HRV data in the context of specialist police selection remains limited. Hypothesis: Therefore, the hypothesis of this study was: can HRV analysis effectively discriminate between high and low performing candidates attending PTG selection? Methods: This study was a prospective cross-sectional study of three male PTG candidates completing a highly demanding selection course. HR and HRV were measured from 1300 – 1800 on a single day of tactical maneuver training. HRV was analysed as follows: R to R interval (RRI) length, root-mean-square of successive RRI differences (RMSSD), percentage of adjacent RR intervals varying by at least 50ms (pRR50), nonlinear short-term variability (SD1), and nonlinear long-term variability (SD2).Data: Measures of central tendency were generated; the maximum, minimum, mean, and standard deviation were reported for each HRV measure and visualized with a box plot. Results: Data from one participant appeared to skew results; the maximum values for mean RRI (Max: 709ms, Min: 580ms, Mean: 632.67±67.68ms), RMSSD (Max value: 42.3ms, Min value: 18.8ms, Mean: 26.8±13.43ms), pRR50 (Max value: 12.47%, Min value: 1.98%, Mean: 5.76±5.82%), SD1 (Max value: 29.9ms, Min value: 13.3ms, Mean: 18.93±9.50ms), and SD2 (Max value: 61.1ms, Min value: 37.5ms, Mean: 49.87±11.84ms) all occurred in the same participant. That participant also held the lowest maximum HR (138bpm), lowest mean HR (85bpm) and was the highest performer as rated by unit leadership. Conclusions: Given the potential discriminatory capacity of HRV in this context, HRV may be a valuable objective metric to support PTG candidate selection by providing objective measurements of holistic stress response. This research was supported by a PhD scholarship awarded to the lead author by Bond University. No other funding or grant from any agency in the public, commercial or not-for-profit sectors was provided or otherwise obtained. 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.
Protectin DX as a therapeutic strategy against frailty in mice
Authors: Perazza Lais , Gower Adam , Brown-Borg Holly , Divieti Pajevic Paola , Thompson LaDora 
Published: May 2023

Frailty in aging is driven by the dysregulation of multiple biological pathways. Protectin DX (PDX) is a docosahexaenoic acid (DHA)-derived molecule that alleviates many chronic inflammatory disorders, but its potential effects on frailty remain unknown. Our goal is to identify age-related impairments in metabolic systems and to evaluate the therapeutic potential of PDX on frailty, physical performance, and health parameters. A set of 22-month-old C57BL/6 male and female mice were assigned to vehicle (Old) or PDX daily gavage treatment for 8 weeks, whereas 6-month-old (Adult) mice received only vehicle. Forelimb and hindlimb strength, endurance, voluntary wheel activity and walking speed determined physical performance and were combined with a frailty index score and body weight loss to determine frailty status. Our data shows that old vehicle-treated mice from both sexes had body weight loss paralleling visceromegaly, and old females also had impaired insulin clearance as compared to the Adult group. Aging was associated with physical performance decline together with higher odds of frailty development. There was also age-driven mesangial expansion and glomerular hypertrophy as well as bone mineral density loss. All of the in vivo and in vitro impairments observed with aging co-occurred with upregulation of inflammatory pathways and Myc signaling as well as downregulation of genes related to adipogenesis and oxidative phosphorylation in liver. PDX attenuated the age-driven physical performance (strength, exhaustion, walking speed) decline, promoted robustness, prevented bone losses and partially reversed changes in hepatic expression of Myc targets and metabolic genes. In conclusion, our data provides evidence of the beneficial therapeutic effect of PDX against features of frailty in mice. Further studies are warranted to investigate the mechanisms of action and the potential for human translation. The authors declare no conflict of interest. Funding: μCT analysis was performed by the Center for Skeletal Research Imaging and Biomechanical Testing Core at Massachusetts General Hospital (NIH P30 AR075042). We acknowledge the Boston University Microarray and Sequencing Resource Core Facility and the Clinical and Translational Science Institute (NIH UL1TR001430) for the RNA sequencing analysis. This work is supported, in part, by the Travis Roy Endowed Professorship (to L.V. Thompson) and the National Institute on Aging (R56 AG-067724 to L.V. Thompson and H. Brown-Borg, K07 AG-072124 to L.V. Thompson). 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.
Evaluating the diagnostic quality of exosomal versus free-circulating microRNAs as biomarkers of canine congestive heart failure
Authors: Belden Halle 
Published: May 2023

MicroRNAs (miRNA) show great potential as biomarkers, and eventually therapeutics in the form of mimics and inhibitors, in a diversity of diseases. MiRNA can be found freely-circulating in the bloodstream (FCmiRNA) or secreted from cells in exosomes as exosomal miRNA (exomiRNA). Exosomes are extracellular vesicles that carry cell-specific cargo to targeted cells elsewhere in the body, traveling through body fluids. ExomiRNA shows great potential to be more reliable than FCmiRNA as a biomarker of disease due to the added membrane, which preserves the miRNA cargo, and the theoretical increased likelihood of relevant miRNA to be present in exosomes. Multiple miRNAs have already been associated with the development of canine congestive heart failure (CHF) in dogs.In this study, we compared the expression of four miRNAs: miRNA 133, miRNA 1, miRNA29, and miRNA302 between healthy dogs and dogs with CHF, and compared the expression levels of these miRNAs as FCmiRNAs and exomiRNAs.Data from my previous study suggests that exomiRNA is better preserved in FCmiRNA from canine plasma samples. We predict that the results from this study will confirm association of the selected miRNAs and CHF status, meaning elevated levels of miRNA133 and miRNA1 correlate with presence of CHF, while decreased levels of miRNA29 and miRNA302 correlate with presence of CHF. We predict that exomiRNA expressions will be consistently higher than FCmiRNA expression among all four miRNAs, which suggests the exosomes protect the structural integrity of the miRNAs, and exomiRNA could be more reliable than FCmiRNA as a biomarker in diagnostic and prognostic clinical scenarios. 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.
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.