In this study, we use a hybrid sentiment analysis approach to identify and assess service quality dimensions (i.e., technical and functional quality) in unstructured textual reviews and employ econometric methods to theorize and test the impact of these service quality signals on online physician selection. By analyzing a data set with 246,294 reviews based on 5,452 physicians in 8 disease markets from an online health consultation platform, this study reports that technical and functional quality cues are important market signals used by patients to select online physicians. More importantly, this study provides strong evidence that the effects of these signals on online physician selection are substantially contingent on disease market competition intensity. Furthermore, this market competition effect is moderated by the level of disease risk. This study contributes insight into patients' physician choice behavior by introducing the role of market-level characteristics. It also guides online health consultation platforms in developing operational strategies to increase patient engagement.
The first generation of this Microsoft (MS) Excel (Redmond, WA, USA) tool for method validation, EZSTATSG1, was designed for methods utilizing only linear calibration curves requiring seven calibration levels, and quadratic calibration models were not supported. This significantly improved version, EZSTATSG2, includes all of the features of the original template such as weighted linear calibration models, bias and precision data, dilution integrity and ion suppression. New features in this version include flexible five-, six- or seven-point calibration curves, six weighted quadratic calibration models, standardized residuals by use of frequency plots overlaid with the normal distribution function along with five-number summary data and processed sample stability. The implementation of Visual Basic for Applications in Excel UserForms prevents accidental alteration of existing formulas and also ensures that pertinent cells are relocked every time a file is reopened. The quadratic models feature the 95% confidence intervals for checking the significance of the second order term and are fully-characterized by providing the equations for the axis of symmetry, directrix, and coordinates for vertex and focus. Example data of α-hydroxymidazolam demonstrates that the quadratic calibration curves fit the data more adequately than the linear models for this method. This second-generation tool summarizes all of the validation parameters of a method for both linear and quadratic calibration models. Models with the lower average sum of relative errors and higher R2 values are color coded green, indicating the likelihood of a better fitting model. Like the EZSTATSG1, the redesigned EZSTATSG2.xltm MS Excel self-actuating validation tool and a completed PDF example are available to the scientific community for download as Supplementary data. Updates to the template can be found at https://www.EZSTATS4validation.com.
The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit.
One area of cancer research is cancer prevention, specifically the use of polyphenols as anti-cancer compounds. The proposed anti-cancer effects of polyphenols include epigenetic changes in the genome that alter expression levels of a variety of genes. Cinnamon extract has high polyphenolic content that has been shown to regulate signaling proteins as well as key transcription factors. Observations suggest that a significant morphological change occurs with cinnamon treatment of MCF-7 breast cancer cells, suggesting the epigenetic modifications may be occurring which alter the standard cell morphology. This study was aimed at determining if in addition to the morphological changes there were also expression changes in Akt1, FoxO1, and SIRT1, all genes which have been associated with epigenetic changes. Cells were grown to 70-80% confluence and treated with either cinnamon extract or vehicle for 48-96 hours, collected by trypsin release for RNA isolation in preparation of the real-time PCR reactions used to measure relative gene expression levels of Akt1. Initial data suggests cinnamon extract pretreatment has only minor effects of SIRT1 expression but cinnamon extract may alter the activity of SIRT1. Future studies will evaluate the expression levels of FoxO1 and SIRT1 in order to determine if any correlation exists.
Hypertension and depression are major health problems in the US. Overactivity of the renin angiotensin system (RAS) plays an important role in the pathophysiology of hypertension and depression. The actions of the main effector peptide of the RAS, angiotensin II (Ang II), are mediated by the Ang II type 1 receptor whose activity is modulated by regulator of G-protein signaling (RGS) proteins, including RGS2. In this study, we assessed the effects of genetic deletion of RGS2 on Ang II-induced increases in blood pressure (using tail cuff plethysmography) and depression-like behavior (using the tail suspension test) in adult male and female mice. Adult male and female RGS2 wild-type (RGS2+/+ ) and RGS2-deficient (RGS2-/- ) mice were treated with osmotic minipumps containing either vehicle (saline) or Ang II (1 mg/kg/d) for 21 days. In males, baseline SBP was lower in RGS2-/- (SBP = 103±5 mmHg, n=14) vs RGS2+/+ (SBP = 120±6 mmHg, n=13, P<0.05 vs RGS2-/- ) mice. By contrast, in females there was no difference in baseline SBP between RGS2+/+ and RGS2-/- mice, suggesting that deletion of RGS2 results in lower baseline SBP in females only. Chronic treatment with Ang II increased SBP in both RGS2+/+ and RGS2-/- mice compared to saline controls, irrespective of sex. There was no difference in Ang II-induced increases in SBP in RGS2+/+ and RGS2-/- male mice, suggesting that RGS2 does not protect against Ang II-induced increases in SBP in male mice. By contrast, in female mice, Ang II-induced increases in SBP were greater in RGS2-/- compared to RGS2+/+ mice (for example, after 21 days of Ang II treatment, change in SBP from baseline in RGS2+/+ mice was 47±11 mmHg, n=5, and in RGS2-/- mice it was 73±15 mmHg n=4, P<0.05) suggesting that RGS2 protects against Ang II-induced increases in SBP in female, but not male mice. Chronic Ang II treatment also resulted in decreased immobilization time in RGS2+/+ female mice, but not RGS2-/- mice compared to respective saline controls (immobilization time in vehicle-treated RGS2+/+ = 187±14 sec, n=5; Ang II-treated RGS2+/+ = 124±27 sec, n=5, P<0.05 vs vehicle-treated RGS2+/+ ; vehicle-treated RGS2-/- = 196±16 sec, n=5; Ang II-treated RGS2-/- = 192±13 sec, n=4, P<0.05 vs Ang II-treated RGS2+/+ ). These data suggest that RGS2 protects against depression-like behavior in the presence of elevated Ang II levels in female mice. In contrast to female mice, Ang II treatment and RGS2 deficiency had no effect on depression-like behavior in adult male mice. Overall, these data suggest that RGS2 protects against blood pressure increases and depression-like behavior after exposure to elevated Ang II levels in female mice, suggesting that RGS2 activation is a promising therapeutic target to treat elevated blood pressure and depression during conditions of elevated Ang II levels in females.
Regulators of G-protein signaling (RGS) is a family of approximately 30 proteins that bind to the alpha subunits of G-proteins (Galpha ) and accelerate their GTP hydrolysis rates. This deactivates the G-protein and terminates G-Protein Coupled Receptors (GPCRs) signaling. RGS proteins, therefore, play important roles in regulating GPCR signaling and most members are implicated in human diseases such as hypertension, depression, and others. Regulator of G-protein Signaling 2 (RGS2) is a regulator of angiotensin-II receptor signaling and a modulator of oxytocin receptor signaling as well. More importantly, RGS2 was reported to be over expressed in the majority of solid breast cancers and in metastatic prostate cancer. For this reason, we sought to develop RGS2 inhibitors as potential chemotherapeutic agents. We utilized structure-based drug design approaches to develop inhibitors of RGS2-Galpha-q interactions. Available structures of the RGS2-Galpha complex were used to extract a pharmacophore model for searching of commercially available chemical databases. The identified hits were docked to different RGS structures to screen for compounds with the highest binding potential and most selectivity towards RGS2. We report the first group of inhibitors of RGS2-Galpha-q interactions developed through rational drug design that interfered with RGS2 signaling in cell-based assays. In addition, inhibitor AJ-3 inhibited the growth of MCF-7 breast cancer cells in cell culture assays, which suggests that RGS2 inhibitors may have a potential to be a new class of chemotherapeutic agents.
Sirtuins (SIRTs) are a family of enzymes that are involved in several metabolic and inflammatory pathways in diseases. Sirtuins are histone-deacetylase enzymes which remove an acetyl group from lysine residues in histone proteins. Acetylation of histones plays a role in epigenetic regulation of gene expression. Recent studies demonstrate that SIRT enzymes can regulate fasting glucose, concentration of circulating insulin, insulin resistance, pancreatic activity, and inflammation. Metabolic parameters, like glucose homeostasis and chronic inflammation, contribute to the development of diseases like type 2 diabetes mellitus (T2DM). Increasing expression of SIRT can aid in the regulation of these metabolic parameters and may be involved in diseases like T2DM. Our research aims to analyze the activity of HDACs and SIRT in 3T3L-1 cells. 3T3L-1 cells were grown in bovine calf serum and nuclear extracts were collected using a nuclear extraction kit. Nuclear extracts were then analyzed for protein concentration and added to the Epigenase™ Universal SIRT Activity/Inhibition Assay Kit. The data collected suggests that cinnamon does alter the activity of SIRT and further research will be explored to determine the extent to which this effect proves useful in the treatment of T2DM.
Peroxisome-proliferator activated receptor (PPARγ) plays a role in tumor growth inhibition and metabolic activity. Cinnamon extract components have been proposed as a possible PPARγ ligand and we sought to investigate if cinnamon treatment of cells affected the PPARγ and adiponectin expression. 3T3-L1 cells were cinnamon treated for 72 and 120 hours. Media was collected for ELISA quantification of Adiponectin levels. Copy DNA was produced from the total RNA and expression levels of PPARγ and Adiponectin were examined by TaqMan real-time PCR assays. Expression of PPARγ increases significantly in both post-differentiated cells at 72 hours and in non-differentiated cells at 120 hours. Expression of AdipoQ is increased in post-differentiated cells significantly when compared to non-differentiated cells. AdipoQ expression increases at 72 hours post differentiation. Post differentiation cells demonstrated high levels of adiponectin in the media. No significant difference was observed between the cinnamon treated cells and the vehicle control cells. Higher levels of PPARγ in the post-differentiated cells correlate with the increase in adiponectin expression and adiponectin secreted in the post-differentiation cells. A lag between the adipoQ expression increases at 72 hours post-differentiation and adiponectin in the media was detected at high levels at 120 hours. Although there is no significant difference in the adiponectin in the media between vehicle samples and cinnamon treated samples, the expression data compares the control to the cinnamon treated cells, therefore the expression changes observed result from cinnamon treatment. This data suggests that perhaps a mechanism exists that stops adiponectin at the translation level.
Introduction: Good preconception and interconception health are fundamental to optimizing women's health and reducing risk factors for adverse maternal-infant outcomes. Although rural women in the United States tend to experience health disparities, no published qualitative studies have focused on their preconception/interconception health. The purpose of this study was to determine what rural, Midwestern women perceive to be their most pressing health needs and effective ways to provide outreach and education regarding preconception/interconception health and care. Methods: Non-pregnant, reproductive-age women in Hardin County, Ohio, regardless of parity, were recruited through convenience sampling. Semi-structured interviews with four domains (beliefs and behaviors; perceived needs; knowledge and information sources; barriers to care) were conducted in May-June 2021 until saturation was reached. Qualitative methods were used to analyze data and determine themes. Binomial tests were used to compare selected demographic characteristics of participants to the county's reproductive-age residential female population. Results: Nineteen women aged 20-44 years were individually interviewed. Comparing race/ethnicity, education, and insurance status, participants appeared to be representative of the county population. Four themes were identified: (1) needs regarding healthcare and other resources; (2) lack of preconception/interconception care and perceived unimportance due to intergenerational knowledge transfer and paucity of healthcare providers; (3) difference in understanding of the term "women's health" and low health literacy; and (4) suggested interventions including education and outreach. Conclusion: Interviews with rural Midwestern women revealed needs regarding preconception/interconception health and care and potential ways to raise awareness. These findings can inform strategies to improve rural women's health and birth outcomes.
Aging and elevated activity of the renin-angiotensin-system (RAS) are associated with hypertension, vascular and emotional behavioral abnormalities, like anxiety and depression. Many actions of the main effector hormone of the RAS, angiotensin II (Ang II), are mediated by Ang II type 1 receptor whose activity is modulated by the regulator of G-protein signaling 5 (RGS5) protein. We assessed the role of RGS5 on blood pressure, vascular and emotional behavioral outcomes in aged male mice in the presence and absence of chronically elevated Ang II levels. We used aged (∼21 month old) male RGS5-deficient (RGS5-/-) and wild-type (RGS5+/+) mice treated with vehicle (saline) or Ang II (1 mg/kg/d for 21 days). RGS5 deficiency increased baseline systolic blood pressure (SBP), and cerebral vascular superoxide levels in the presence of chronically elevated Ang II levels, suggesting that RGS5 deficiency leads to elevated blood pressure and deleterious cerebral vascular outcomes in aged mice. RGS5 deletion had no effect on Ang II-induced increases in SBP. Chronically elevated Ang II levels increased spontaneous locomotor activity in RGS5+/+, but not RGS5-/- mice. RGS5 deficiency and Ang II treatment had no effect on anxiety- and depression-like behavior. This is the first study to assess the effects of deficiency of an RGS protein in the vasculature or on emotional behavioral outcomes in aged mice. We report that RGS5 has protective effects on blood pressure and the cerebral vasculature in aged mice. Clinically, these data suggest that RAS blockers may significantly reduce cerebrovascular disease risk in aged males lacking RGS5.
BKCa channels are large-conductance calcium and voltage-activated potassium channels that are heterogeneously expressed in a wide array of cells. Activation of BKCa channels present in mitochondria of adult ventricular cardiomyocytes is implicated in cardioprotection against ischemia-reperfusion (IR) injury. However, the BKCa channel’s activity has never been detected in the plasma membrane of adult ventricular cardiomyocytes. In this study, we report the presence of the BKCa channel in the plasma membrane and mitochondria of neonatal murine and rodent cardiomyocytes, which protects the heart on inhibition but not activation. Furthermore, K+ currents measured in neonatal cardiomyocyte (NCM) was sensitive to iberiotoxin (IbTx), suggesting the presence of BKCa channels in the plasma membrane. Neonatal hearts subjected to IR when post-conditioned with NS1619 during reoxygenation increased the myocardial infarction whereas IbTx reduced the infarct size. In agreement, isolated NCM also presented increased apoptosis on treatment with NS1619 during hypoxia and reoxygenation, whereas IbTx reduced TUNEL-positive cells. In NCMs, activation of BKCa channels increased the intracellular reactive oxygen species post HR injury. Electrophysiological characterization of NCMs indicated that NS1619 increased the beat period, field, and action potential duration, and decreased the conduction velocity and spike amplitude. In contrast, IbTx had no impact on the electrophysiological properties of NCMs. Taken together, our data established that inhibition of plasma membrane BKCa channels in the NCM protects neonatal heart/cardiomyocytes from IR injury. Furthermore, the functional disparity observed towards the cardioprotective activity of BKCa channels in adults compared to neonatal heart could be attributed to their differential localization.
Current pharmacotherapy for post-traumatic stress disorder (PTSD), a debilitating psychiatric condition that develops in a subset of traumatized individuals, is inadequate. Over the past two decades, numerous studies have shown that ketamine, a non-competitive NMDA receptor antagonist, exerts rapid antidepressant effects in both humans and rodents, but the anxiolytic profile of ketamine, as well as its ability to treat PTSD-related symptoms, is still unclear. Thus, we examined the ability of a single administration of ketamine to prevent the onset of PTSD-like sequelae in a chronic psychosocial stress model of PTSD. Adult male and female Sprague-Dawley rats were exposed to a cat on two occasions, in combination with chronic social instability. Immediately following the cat exposure on Day 1, rats were given intraperitoneal injections of 10 mg/kg or 15 mg/kg ketamine or vehicle; control rats were injected with vehicle. Three weeks after the second cat exposure, we assessed symptoms of hyperarousal and anxiety-like behavior in the rats. In males, chronic stress led to greater anxiety on the elevated plus maze and in the open field; in females, chronic stress resulted in an exaggerated startle response and greater anxiety in the open field. These effects were most effectively prevented by the administration of 10 mg/kg ketamine. These findings demonstrate that ketamine can prophylactically prevent the onset of PTSD-like behaviors in males and females. Their sex-dependent nature is consistent with previous preclinical research and highlights the need for future research to examine their neurobiological basis.
Conversations of educational equity in mathematics necessitate a more deliberate, nuanced look at the mathematical processes of learning for students of color from historically marginalized communities. This paper describes the theoretical work of a research collaborative that seeks to develop understanding of the experiences around mathematical identity of Latinas labeled with Learning Disabilities in mathematics classrooms. Expanding the theory of Complex Embodiment from Disability Studies, we explore new interdisciplinary theoretical and methodological tools to analyze the emotional, embodied experience of learning mathematics in the social worlds of mathematics classrooms, using emotional discourse. We take up theoretical and methodological practices around intersectionality through analysis of how power and positioning operate in mathematics identity development. We find that the young woman whose narratives we explore in this paper is positioned through deficit discourses around disability and multilingual learners, yet she understands herself through a positive mathematical affinity she shares with her mother. Over time, we see her narratives shift emotionally away from mathematics, as well as away from this connection with her mother. Her narratives help us develop a theoretical perspective that understands emotion in mathematics learning as both embodied and socially constructed.
Calcium ions are the major signaling ions in the cells. They regulate muscle contraction, neurotransmitter secretion, cell growth and migration, and the activity of several proteins including enzymes and ion channels and transporters. They participate in various signal transduction pathways, thereby regulating major physiological functions. Calcium ion entry into the cells is regulated by specific calcium channels and transporters. There are mainly six types of calcium channels, of which only two are prominent in the heart. In cardiac tissues, the two types of calcium channels are the L type and the T type. L-type channels are found in all cardiac cells and T-type are expressed in Purkinje cells, pacemaker and atrial cells. Both these types of channels contribute to atrioventricular conduction as well as pacemaker activity. Given the crucial role of calcium channels in the cardiac conduction system, mutations and dysfunctions of these channels are known to cause several diseases and disorders. Drugs targeting calcium channels hence are used in a wide variety of cardiac disorders including but not limited to hypertension, angina, and arrhythmias. This review summarizes the type of cardiac calcium channels, their function, and disorders caused by their mutations and dysfunctions. Finally, this review also focuses on the types of calcium channel blockers and their use in a variety of cardiac disorders.
Aversive effects of nicotine play an important role in the development of nicotine dependence. However, neural substrates and/or brain regions that play a role in the aversive effects of nicotine have not been fully identified. Previous work done in our laboratory showed that systemic administration of kappa opioid receptors (KORs) agonist ±U50488 increased the aversive effects of nicotine. In this study, we assessed the effects of KOR activation in specific brain regions, namely, the nucleus accumbens (NAcc) core and ventral tegmental area (VTA) on the aversive effects of nicotine using the conditioned taste aversion model. Separate groups of Wistar rats were implanted with cannulae above either the NAcc core or the VTA. KOR agonist (±U50488) was bilaterally infused in the NAcc core (0, 0.3, and 3 ug/0.5 ul/side) or VTA (0, 0.3, 1.5, and 3 ug/0.5 ul/side) prior to receiving nicotine (0.4 mg/kg, base; s.c.) during conditioning. Bilateral infusion of the KOR agonist (3 ug/0.5 ul/side) in the NAcc core or the VTA increased the aversive effects of nicotine compared with respective saline controls. Together, these results suggest that pharmacological activation of the KORs in the NAcc core and VTA dose dependently modulate the aversive effects of nicotine. Because aversive effects of nicotine determine susceptibility to development of nicotine dependence, we can conclude that KOR activity in the NAcc and VTA after administration of nicotine may determine susceptibility to the development of nicotine dependence.
Melanoma continues to be the most aggressive and devastating form of skin cancer for which the development of novel therapies is required. The present study aimed to determine the effects of antagonism of the transient receptor potential melastatin‑2 (TRPM2) ion channel in primary human malignant melanoma cells. TRPM2 antagonism via use of the antifungal agent, clotrimazole, led to decreases in cell proliferation, as well as dose‑dependent increases in cell death in all melanoma cell lines investigated. The targeting of TRPM2 channels was verified using TRPM2 knockdown, where treatment with TRPM2 small‑interfering RNA led to similar levels of cell death in all melanoma cell lines when compared with clotrimazole treatment. Minimal effects on proliferation and cell death were observed following antagonism or knockdown of TRPM2 in non‑cancerous human keratinocytes. Moreover, characteristics of TRPM2 were explored in these melanoma cells and the results demonstrated that TRPM2, localized to the plasma membrane as a non‑specific ion channel in non‑cancerous cells, displayed a nuclear localization in all human melanoma cell lines analyzed. Additional characterization of these melanoma cell lines confirmed that each expressed one or more established multidrug resistance genes. Results of the present study therefore indicated that antagonism of the TRPM2 channel led to antitumor effects in human melanoma cells, including those that are potentially unresponsive to current treatments due to the expression of drug resistance genes. The unique cellular localization of TRPM2 and the specificity of the antitumor effects elicited by TRPM2 antagonism suggested that TRPM2 possesses a unique role in melanoma cells. Collectively, the targeting of TRPM2 represents a potentially novel, efficacious and readily accessible treatment option for patients with melanoma.
Three benzofluorenone derivatives, benzo[a]fluorenone (BFA), benzo[b]fluorenone (BFB), and benzo[c]fluorenone (BFC), were studied spectroscopically in comparison to 9‐fluorenone (9‐FL) in solvents of various polarities to better understand the solvatochromism and excited‐state deactivation processes in these molecules. Time‐resolved transient absorption, steady‐state absorption, emission, and fluorescence lifetimes were utilized in this endeavor. Differences in the excited‐state deactivation processes are observed which can be attributed to the varied characters of the singlet and triplet excited states in these molecules which arise from structural differences and solvatochromism. The main deactivation pathway in all of the studied molecules was internal conversion (IC). Ignoring IC, the competition between intersystem crossing (ISC) and fluorescence is highly dependent on the molecule‐solvent system. BFA was found to decay mainly via a triplet state in cyclohexane but via fluorescence in ethyl acetate and acetonitrile. BFB was found to decay via both ISC to a triplet state and emission from the singlet state in cyclohexane but only via ISC in ethyl acetate and acetonitrile. Only emission from the singlet state was observed in BFC in all solvents.
Institution pages aggregate content on ResearchGate related to an institution. The members listed on this page have self-identified as being affiliated with this institution. Publications listed on this page were identified by our algorithms as relating to this institution. This page was not created or approved by the institution. If you represent an institution and have questions about these pages or wish to report inaccurate content, you can contact us here.