bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSEN1 as an Adjunct for Diagnosis of Human Myocarditis
Authors: Hanson Paul J , Jang Erika L , Rai Harpreet , Chang Angela Y , Mo Angela Y , McManus Bruce M , Seidman Michael A 
Published: November 2023

BackgroundMyocarditis, defined as inflammation of the heart muscle, is a spectrum of conditions causing considerable morbidity and mortality, resulting from various etiologies, including infection, autoimmunity, or chemical exposure. As such, diagnosing myocarditis can be quite difficult and determining etiology even more so. The gold standard of diagnosis is endomyocardial biopsy showing inflammation with or without myocyte damage in the absence of an ischemic event. However, due to the spatial and structural heterogeneity of myocarditis, diagnostic sensitivity is estimated as low as 30%. To improve upon this, we examined several markers implicated in the pathogenesis of viral myocarditis in animal models as possible diagnostic adjuncts. PSEN1 (the gene encoding presenilin 1) emerged as a promising candidate. This study aims to formally evaluate PSEN1 as a diagnostic adjunct.DesignFifty (50) cases were examined for PSEN1 staining (20 lymphocytic active or healing myocarditis, 4 eosinophilic myocarditis, 4 idiopathic dilated cardiomyopathy, 4 hypertrophic cardiomyopathy, 4 sarcoidosis, 4 coronary artery disease, 3 transplant rejection, 1 Lyme disease, 1 toxoplasmosis, and 5 normal controls). All cases were obtained from the Cardiovascular Tissue Registry in the Centre for Heart Lung Innovation, under approved human ethics protocols. Levels of PSEN1 were evaluated using colour segmentation and scoring conducted by three individual subspecialty cardiac pathologists blinded to diagnosis. Statistical analysis was performed using Mann Whitney U test and receiver operating characteristics (ROC) curves.ResultsColour segmentation and pathologist scoring correlated with each other well (Spearman's rho correlation coefficient 0.71 or better in all comparisons). PSEN1 is expressed at significantly higher levels in lymphocytic myocarditis cases as compared to normals and to all other pathologies (all pvalues less than 0.005). The ROC curves for diagnosing myocarditis as compared to other pathologies using PSEN1 staining have areas under the curve (AUCs, or cstatistics) ranging from 0.78 to 0.88. Of note, several “false positive” cases were those with idiopathic dilated cardiomyopathy, such cardiomyopathy reflects the end stage of a prior lymphocytic myocarditis. Case subset analyses and validation on biopsy specimens are under way.ConclusionPSEN1 immunohistochemistry appears to be a helpful diagnostic adjunct for identifying myocarditis, even in minimally inflamed specimens and in tissue obtained long after the initial insult.Support or Funding InformationFunding and support from St. Paul's Foundation
Aliskiren Does Not Protect the Heart from the Acute Histopathological Effects of Fat Embolism when it Protects the Lungs
Authors: Ponnapureddy Rakesh , Poisner Alan , Fletcher Amanda , Patel Chirag , Tappeta Kathyayini , Fotouhi Ariana , Molteni Agostino 
Published: November 2023

IntroductionFat embolism (FE) can lead to both acute and chronic lung injury. In an animal model of FE induced by Triolein, the histopathological damage was not limited to the lungs but also involved the heart and kidneys. We have previously demonstrated that losartan, an angiotensin receptor blocker, prevented the damage induced by FE in both the lungs and the heart at 10 weeks. We also identified significant pulmonary damage as early as 48 hours and it was prevented by the direct renin inhibitor, Aliskiren suggesting the role of Renin‐Angiotensin System (RAS) in the pathogenesis of fibrosis. In the current study we examined the acute effects of FE (48 hours) on the heart, the influence of Aliskiren on this organ and compared it to the effects on the lungs.MethodsTwenty‐two rats were divided into controls (n=4, Group A) and three FE groups (n=6, Groups B, C & D). FE induction was done with Triolein 0.2 mL i.v. at 0 hours, and an hour later the animals received 0.2 ml i.p. saline (Groups A&B), Aliskiren at 50 mg/kg (Group C) or at 100 mg/kg (Group D). Rats were euthanized at 48 hours and hearts were fixed and stained with H&E for lumen patency measurements, Masson's Trichrome (MT) for collagen, and alpha‐smooth muscle actin (SMA) for myofibroblasts.ResultsRats in FE only group (group B) had higher percentage of SMA staining around the branches of the coronary arteries compared to the control group (A) (P<0.05). There were no significant differences in lumen patency, media‐adventitia ratios and MT staining among the four groups. Aliskiren at both doses (C & D) did not show a significant effect on SMA staining compared to FE only (B). In contrast, Aliskiren at both doses showed reduction in SMA and MT staining in the Lungs.ConclusionAnimals subjected to FE sustained acute injury (48 hours) of both the heart and the lungs, with less prominent changes in the heart. While Aliskiren significantly reduced the fibrotic damage in the lungs, such effect was not seen in the hearts of the same animals. This is in contrast to the delayed effects of FE at 10 weeks when there was similar extent of damage to both organs and protection by AT1 blocker losartan. These varying results suggest different pathophysiological processes in the evolution of the fibrosis in the two organs.Support or Funding InformationMary Katherine Geldmacher Research Foundation, St. Louis, MO
Three‐dimensional Histochemistry and Imaging of Extracellular Matrix‐rich Human Tissues
Authors: Van Noorden Cornelis J.F. 
Published: November 2023

For 3‐dimensional (3D) imaging of tissues, 3 methodological steps are essential and their successful application depends on specific characteristics of the type of tissue. The steps are 1. clearing of the opaque tissue to render it transparent for microscopy, 2. fluorescence labeling of the tissues and 3. 3D imaging. In the past decades, new methodologies were introduced for the clearing steps with their specific advantages and disadvantages. Most of these clearing techniques are based on dissolving membranes and have been applied to the central nervous system and other tissues that contain relatively low amounts of extracellular matrix (ECM). Tissues containing large amounts of ECM such as dermis in skin and gingiva are difficult to clear in this way. We report here that the BABB method using a mixture of benzyl alcohol and benzyl benzoate and iDISCO using dibenzylether (DBE) are the most successful methods for clearing ECM‐rich tissues. The principle of this type of clearing is that the entire tissue has one refractive index, that of BABB or DBE. We applied the BABB method in combination with immunofluorescence staining of CD31, an endothelial marker, and YOYO‐3, a fluorescent DNA dye, light‐sheet microscopy and Imaris‐based image analysis and processing to investigate the vasculature network in 3D in 12 human gingiva samples without signs of inflammation. 3D images showed the vascular network in 3D in the lamina propria of gingiva with loops into the papillae. The vascular network showed a high degree of tortuosity and irregularities in structure which are not apparent in images of sections of gingiva. This 3D histochemistry and imaging methodology is an excellent tool to study structural aspects of human gingiva that are involved in diseased periodontium.Support or Funding InformationNo funding.
Scientometric Analysis of Publications on Three‐dimensional Bioprinting
Authors: Sohn Eunsoo , Sohn Eun‐Hwa 
Published: November 2023

Three‐dimensional (3D) printing has emerged as a disruptive technology for rapid prototyping and additive manufacturing. Bioprinting, the process of creating spatially controlled cell patterns with the use of 3D printers, has been developing personalized living tissues or artificial organs specific to each patient. Recent advances in bioprinting of tissues and organs has been driving new innovations in a variety of areas including tissue engineering and regenerative medicine, manufacturing, and biosciences such as biomedical research, transplantation and clinics, drug discovery and delivery. The aim of this study is to analyze the global scientific research output indexed in Web of Science database and estimate its R&D trend in the field of bioprinting through scientometric methods. Total 1,644 articles were retrieved and further analyzed. KnowledgeMatrix Plus, Gephi and VOSviewer software have been also used for analysis. Results showed that the R&D activivities on bioprinting have increased dramatically in recent years and major topics of this bioprinting field were identified. Recent advances in each nation's research activities and the international collaboration network in bioprinting have also been discussed.Support or Funding InformationThis research was supported by Korea Institute of Science and Technology Information under the program “Development of Technology Intelligence System for Exploring Future Technologies” from the Ministry of Science, ICT and Future Planning in Korea.
Biosafety Assessment of Petroleum Ether Oil of Ricinus communis C in Wistar Rats
Authors: Adenike Adeyemo Christy , Adeniyi Adedayo Francis , Adeniyi Adedotun Anthony 
Published: November 2023

ObjectivesThe study was aimed at evaluating the biosafety of reported insecticidal potency of Ricinus communis petroleum extract (RCPE) used on stored products using wistar rats as a model.MethodologyRicinus communis seeds were extracted using soxhlet extractor and the filtrate later concentrated using the rotary evaporator to obtain R. communis petroleum ether extract (RCPE). Twenty four rats were divided into four groups labeled I, II, III and IV (six rats per group). Group I served as the control group and were administered orally with Dimethyl Sulphoxide (DMSO) and normal saline, Group II were administered orally with 500mg/kg of RCPE, Group III were administered orally with1000mg/kg of RCPE while Group IV were administered orally with 2000mg/kg of RCPE all dissolved in DMSO and Normal saline. Animals were weighed, anesthetized and blood samples were collected at the end 5 days of oral administration. Blood samples were collected by cardiac puncture for some biochemical parameters such as Total proteins, bilirubin, cholesterol, uric acid, creatinine, Urea and Uric acid activities as well as serum, AST and ALT were determined.ResultsAt the end of this research work, it was discovered that at doses higher than 500mg/kg there were enzymatic leakages from the organs (kidney and liver) into the serum, compared to the control group.ConclusionThe study revealed that it is advisable to use minimal dosages for the management of insect pest on products meant to be consumed by human, to prevent damage to vital organs as observed in the results at higher doses while higher doses should be for seeds meant for propagation.Support or Funding InformationNone
The Impact of Early Detection of Mental Illness in Jails and Prisons
Authors: Ekwe Benneth I , Einstein George P , Tulp Orien L 
Published: November 2023

The research was concerned with discovering the impact of early detection of mental illness in prisons, using selected prisons across the five regions of the United States as case studies. Therefore, the research project set out with the following research questions: (a) What is psychological trauma, and how vulnerable are individuals who are experiencing an unwanted change of scene (from their homes to prisons) to becoming traumatic?, (b) Is the prison system equipped to detect mental illness among incoming inmates?, (c) What are the effects of the inability to detect mental illness among new prisoners on the prison?, (d) To what extent has the justice system contributed to mental illness of imprisoned individuals?, (e) To what extent can the actions of concerned reformed groups prevent the exacerbation of mental illness among incoming prison inmates?, and (f) What recommendations can be made to engender reformation of the prison system in order to bring about salutary benefits to the society, prison inmates, and prison administrators?. Consequently, relevant literatures were reviewed with respect to as the concept of mental illness, early signals of mental illness, symptoms and signs of mental illness and mental illness in prisons. A survey was carried out via the questionnaire method among ninety‐eight informed stakeholders in the prison system with the aim of providing solutions to the above broad research questions. Findings from the survey revealed that: (i) the American prison system is apparently not well equipped to detect mental illness among incoming inmates, (ii) the justice system contributed to mental illness among convicts, and (iii) advocacy and pressure groups have played a significant role in preventing the exacerbation of mental illness among incoming prison inmates. Thus, this study showed that the prison system must engender researches that will provide prison officers with needed technical, medical, and psychological tools for the early detecting of mental illness among incoming inmates at an early stage of their incarceration.Support or Funding InformationSupported by Institutional Resources of USAT and Einstein Medical Institute
Autonomic nervous tone during histopathological diagnosis of oral squamous cell carcinoma in virtual images
Authors: Mondragon Edward Acero 
Published: November 2023

INTRODUCTIONBy morphophysiological connections between autonomic nervous system or ANS with heart sinus node pacemarker cells, is documented activity of ANS by analysis of variability of heart frequence or HFV and cognitive events. The histopathologic diagnosis is a cognitive challenge by enormous integration of basic and clinical in a little time and that has his effect on ANSOBJECTIVEDuring cognitive task to build a diagnosis of oral squamous cell carcinoma or OSCC in virtual histological images exist an autonomic tone and this is different when diagnosis fail?MATERIALS Y METHODSTen residents of surgery maxillo facial in his first year during postgraduate histology course were recruited to use a device and measure his HVF to extract off line his power spectral and to find sympathetic activitiy in band LF (0,04 –0,15Hz) and parasympathetic activity in HF (0,4–0,15Hz) during free interactions with OSCC virtual image until to make a diagnosis. The autonomic tone was calculated with the time predominant in any band during visual interaction.RESULTSEight residents achieving diagnosis of OSCC in different times ×= 1,45s, SD=0,50s) of interaction with virtual images but with sympathetic autonomic tone in Gaussian distribution; while two residents with more time of virtual interaction (×= 2,23s, SD=0,31s) also with sympathetic tone his profile was incremental tone sympathetic with Gaussian distribution and who failed using more time and also had an autonomic tone sympathetic but incrementalCONCLUSIONEight residents facial maxillofacial surgery in their first year achieving a cognitive task to diagnosis of oral squamous cell carcinoma or OSCC in virtual images, they have an autonomic nervous tone sympathetic with Gaussian distribution, and those who fail have used more time and also have a nervous tone sympathetic but of incremental distributionSupport or Funding InformationDoctorado en Educación. Universidad de Baja California. Tepic, Nayarit‐México
Role of Opioid‐Sensitive Descending Pain Modulatory Pathways in Affective and Sensory Components of Chronic Pain in Rats
Authors: Robles Dagoberto , Gomtsian Lusine , Navratilova Edita , Porreca Frank 
Published: November 2023

Pain is a complex, multidimensional experience that is composed of sensory, affective and cognitive features. For unknown reasons, in some individuals, pain may become chronic. Unfortunately, there are no cures for chronic pain. Opioids remain one of the most important classes of drugs to treat pain but whether they are useful in chronic pain remains uncertain. Additionally, these drugs have significant side effects including tolerance, dependence and addiction. As a result, there is an urgent medical need to elucidate the underlining mechanisms by which relief of pain occurs. Opioids produce their effects primarily by alleviating the aversive qualities of pain. How this occurs is not known but pain aversiveness is thought to be integrated, in part, in the anterior cingulate cortex (ACC). Cortical regions in the brain likely contribute to context dependent modulation of the pain experience through projections that ultimately converge on the rostral ventromedial medulla (RVM). Here, we determined the effects of microinjection of morphine in several regions of the rat ACC in rats with chronic experimental neuropathic pain induced by ligation of the spinal nerve (SNL model). The possible effect of ACC or RVM morphine on mechanical hypersensitivity was evaluated using von Frey filaments. Microinjection of morphine into different sites of the ACC failed to reverse mechanical hypersensitivity in nerve‐injured animals. In contrast, morphine injection in the RVM reversed evoked thresholds in SNL animals. These findings suggest that morphine may differentially modulate affective dimensions of pain within the ACC without altering sensory components. The primary goal of this research is to understand the nature of the neuroanatomical contributions of the ACC and its role in descending pain modulatory pathways. Further studies exploring other sites within the ACC with measures of affective qualities of pain may ultimately lead to a better understanding of opioid‐sensitive circuitry.Support or Funding InformationSupported by DA034975 from the NIH.
In vivo characterization of the novel delta opioid receptor positive allosteric modulator BMS‐986187
Authors: Dripps Isaac J , Boyer Brett , Traynor John , Jutkiewicz Emily 
Published: November 2023

The delta opioid receptor (DOPr) is a member of the opioid receptor family of G protein‐coupled receptors (GPCR). Activation of DOPr induces antinociception, antihyperalgesia, and antidepressant‐like effects in animal models. However, some DOPr agonists cause convulsions, hindering their development as therapeutics in humans. Positive allosteric modulators (PAMs) bind to a receptor site distinct from the orthosteric binding site of a GPCR and may have several advantages over orthosteric agonists including greater selectivity, a larger safety margin and preservation of the spatiotemporal integrity of the endogenous system. Therefore, a PAM could be an effective strategy for eliciting DOPr‐mediated therapeutic effects without convulsions. To evaluate this hypothesis, we investigated the ability of the DOPr PAM BMS‐986187 to elicit DOPr‐mediated behaviors in mice alone or in combination with the DOPr orthosteric agonist SNC80. DOPr‐mediated antinociception was assessed in the acetic acid‐induced stretch assay. Antihyperalgesia was evaluated using a nitroglycerin‐induced thermal hyperalgesia assay. Antidepressant‐like effects were measured using the forced swim test. BMS‐986187 enhanced the potency of SNC80 to induce antinociception and antihyperalgesia without altering SNC80‐induced convulsions. BMS‐986187 alone produced antidepressant‐like effects without convulsions. These antidepressant‐like effects were blocked by the DOPr antagonist naltrindole and absent in DOPr knockout mice, indicating a DOPr‐mediated effect. Pretreatment with the enkephalinase inhibitor RB101 produced a synergistic effect in the forced swim test with BMS‐986187 but not SNC80 suggesting that BMS‐986187 exerts it antidepressant‐like effects by enhancing the actions of endogenous enkephalins. Overall, these findings suggest that BMS‐986187 functionally increases the therapeutic index of SNC80 and that a DOPr PAM could be a safer alternative to an orthosteric agonist as a novel treatment for depression.Support or Funding InformationThis project was partially funded by a PhRMA Foundation Starter Grant to EMJ and by NIH Grant DA035316 to JRT.
Novel synthetic opioids produce potent morphine‐like discriminative stimulus effects in rats
Authors: Korber Matthew Gerard , Chambers Christina , Walker Ellen 
Published: November 2023

An increasing number of novel psychoactive substances have emerged over the past decade, several of which act on the opioid neurotransmission system. Recently, a series of compounds with fentanyl‐like structures appeared on the illicit drug market and have been responsible for fatalities. The purpose of the present study was to examine four novel synthetic opioids for their relative potency to the reference opioids morphine and fentanyl, and to characterize the relative susceptibility to naltrexone antagonism using drug discrimination. In animal models of substance abuse, drug discrimination techniques are useful due to the pharmacological selectivity and sensitivity to underlying mechanisms. Male, Sprague Dawley rats (n=11) were trained to discriminate between 3.2 mg/kg morphine, s.c. and saline in a two‐choice, drug discrimination procedure under a fixed ratio‐5 schedule to receive a sucrose pellet reward. Single trial training and testing were used to evaluate doses of saline, morphine, fentanyl, acetyl fentanyl, butyryl fentanyl, AH‐7921, and MT‐45. Rats learned the morphine vs. saline discrimination in 34 days (range 12–110 days). Fentanyl and all four synthetic opioids fully‐substituted for morphine in a dose dependent manner in all rats with the following rank order of potency: fentanyl>butyryl fentanyl>acetyl fentanyl>AH‐7921>MT45>morphine. Although all opioids were blocked by naltrexone, MT‐45 and AH‐7921 appeared especially sensitive to naltrexone antagonism. Butyryl fentanyl was the least sensitive to naltrexone antagonism. In conclusion, the synthetic opioids were significantly more potent than morphine but nevertheless less potent than fentanyl and sensitive to naltrexone antagonism suggesting that these compounds have a similar abuse liability as either fentanyl or morphine.Support or Funding Information(Support by Department of Justice, DJD‐15‐ HQ‐P‐ 0740)
Exploring the pharmacologic and discriminative effects of abused psychostimulants and the bath salt component mephedrone in rats
Authors: Milewski Andrew J , Rawls Scott , Walker Ellen A , Saber Iman 
Published: November 2023

The underlying mechanisms of both commonly abused and novel psychostimulants such as mephedrone are still a critical area of study. Comparing mephedrone to other more well‐known drugs in an established drug discrimination protocol allows for increased understanding of their pharmacological profiles and potential abuse liabilities. We hypothesize that mephedrone exhibits mixed pharmacology with low doses having a primarily serotonergic mechanism, and higher doses having a primarily dopaminergic mechanism. Male Sprague‐Dawley rats were trained using two‐choice drug discrimination assays to examine the stimulus properties of either a low dose of 0.5 mg/kg mephedrone (n=12) vs saline or a high dose of 3.2 mg/kg mephedrone vs saline (n=11). Rats learned the low and high dose discriminations in 74 and 175 sessions, respectively. Current results show that mephedrone substitutes in a dose‐dependent fashion in both groups, although with different potencies. In the low dose cohort, dopamine (DA) agonists (cocaine and D‐amphetamine) partially substitute for mephedrone whereas methamphetamine fully substitutes. However, we did not see full substitution of the aforementioned DA agonists in the high mephedrone training dose group. The serotonergic agonist (2,5‐Dimethoxy‐4‐iodoamphetamine or DOI) in moderate to high doses (0.5 to 1.0 mg/kg) partially substituted for both high and low doses of mephedrone. In conclusion, mephedrone appears to mimic pharmacological properties similar to other psychostimulants that possess dual DA and 5‐HT mechanisms and the high dose mephedrone training dose cohort may be less sensitive to DA activation than the low dose cohort. Further analysis will focus more on the susceptibility of mephedrone to DA and 5‐HT antagonism.Support or Funding InformationSupported by R21DA032718