tbuckley/cabot-search huggingface dataset:
Abstract 17364: G-protein Signaling Regulation of the Hippo Pathway in Neonatal Heart Regeneration
Authors: Masahide Sakabe, Aishlin Hassan, Mei Xin
Journal: Circulation (2020)

Introduction: The regeneration potential in the adult mammalian heart is very limited due to the cessation of cardiomyocyte proliferation shortly after birth. Recent studies have revealed that changes after birth such as metabolic state, oxygen level, cardiomyocyte structure and maturity, immune system and polyploidy are among the factors contributing to the loss of the regenerative potential in the heart. The mechanisms that regulate the cardiac regenerative window are not well understood. Here we report that G-protein mediated signaling regulates Hippo-YAP in neonatal cardiomyocyte proliferation and heart regeneration through Rho activity. Hypothesis: Gas encoded by the Gnas gene, a downstream effector of beta-adrenergic receptor (βAR) inhibits cardiomyocyte proliferation via regulation of YAP activity. Methods: We pharmacologically inhibited the G protein coupled receptor mediated β adrenergic signaling with a β-blocker (metoprolol) at early postnatal stages, and genetically by deleting Gnas in the heart with αMHC-Cre. We accessed the cardiomyocyte proliferation, heart regeneration in these mice and elucidated molecular mechanisms. Results: We found that β-blocker enhanced cardiomyocyte proliferation and promoted cardiac regeneration post cardiac injury with improved cardiac function. Consistent with β-blocker treated mice, mice lacking Gnas in cardiomyocytes exhibited enlarged hearts with an increase in cardiomyocyte proliferation. RNA-seq analysis revealed that these cardiomyocytes maintained an immature status even at young-adult age. The genes associated with mitochondrial oxidative metabolism, the major energy source for mature cardiomyocytes, were downregulated. Moreover, YAP activity was upregulated in both cases. We also found that loss of Gαs function caused upregulation of RhoA activity, and inhibitor of Rho signaling pathway suppressed the YAP activity in cardiomyocytes. Conclusions: Our study reveals that Gαs negatively regulate cardiomyocyte proliferation and provides mechanistic insight for β-blocker treatment as a strategy for inducing cardiac dedifferentiation and proliferation in injured heart.
Racial and Socioeconomic Disparities in Pediatric Type 1 Diabetes: Time for a Paradigm Shift in Approach
Authors: Terri H. Lipman, Colin P. Hawkes
Journal: Diabetes Care (2020)

Advancements in diabetes technology have improved quality of life and glycemic control in children with type 1 diabetes. However, a subset of children is being left behind. Those from low-income families and non-Hispanic Black (NHB) children are not experiencing these benefits of technology (1,2) and continue to be at higher risk for complications and adverse outcomes through ongoing poor glycemic control (3). As Addala et al. have demonstrated in a study reported in this issue of Diabetes Care (4), this is a serious problem in the U.S., and there has been no sign of improvement in recent years. These data should be a trigger for all of us to reflect on the factors contributing to these disparities and consider our roles in driving meaningful change.

In this study, Addala et al. have compared technology use and socioeconomic status (SES) in children aged <18 years in the Type 1 Diabetes Exchange (T1DX) registry in the U.S. and the Diabetes Prospective Follow-up (Diabetes-Patienten-Verlaufsdokumentation [DPV]) registry in Germany (4). They sought to assess disparities in diabetes outcomes in technology use and glycemic control in both populations in 2010–2012 and 2016–2018 and have shone a light on a major problem. As expected, both registries demonstrated an overall increase in technology use over an 8-year period, but the differences between those in the highest and lowest SES categories across both populations highlight the magnitude of disparities in the U.S. In 2016–2018, there was a much larger gap between those of higher and lower SES in the U.S. in comparison with Germany for insulin pump use (39% vs. <6%), continuous glucose monitor use (37.3% vs. 8.6%), and hemoglobin A1c (HbA1c) (1.3% vs. 0.3%). Of particular concern …
Ramipril Decreases Lung and Kidney Angiotensin Converting Enzyme 2 (ACE2) in Diabetic Mice: Lessons for COVID-19 Infection
Authors: Ander Vergara, Conxita Jacobs Cachá, Pamela Domĭnguez Báez, Mireia Molina Van den Bosch, Anna Giralt-López, Clara Garcĭa-Carro, Daniel Serón, Maria Jose Soler
Journal: Journal of the American Society of Nephrology (2020)

Background: ACE2 is a component of the renin-angiotensin system(RAS) that mainly degrades angiotensin II to angiotensin(1-7)  It is expressed in renal tubular cells  Lung type 2 alveolar cells also express ACE2 where it acts as a receptor for SARS-CoV-2, which is responsible for the current coronavirus disease 2019(COVID-19) pandemic  A controversy raised regarding the use of RAS blockers in COVID-19 patients despite its demonstrated efficacy in cardiovascular disease  We studied the effect of ramipril on ACE2 expression in experimental diabetes  Methods: 12 weeks old diabetic db/db mice were given ramipril(8 mg/Kg/day) or vehicle during 8 weeks  db/m mice were used as controls  ACE2 expression and enzymatic activity were studied in kidney, heart and lung  Results: In non-treated db/db, ACE2 mRNA expression was increased in kidney(p<0 0001) and ramipril treatment reversed this effect  In heart, ACE2 expression decreased in db/db when compared to db/m(p=0 028) and ramipril had no effect  We found no differences in lung  ACE2 enzymatic activity was increased 23% in kidney and 22% in lung of db/db mice when compared to db/m  Ramipril treatment decreased ACE2 activity 25% in the lung and 13% in the kidney when compared to untreated db/db  In the heart, ACE2 activity tended to decrease in db/db mice when compared to db/m, and increased with ramipril, but did not exceed the cardiac ACE2 activity of the db/m  Conclusions: ACE2 is increased in the kidney and in the lung, and decreased in the heart of diabetic mice  Ramipril treatment restores ACE2  Our results suggest that diabetes and hypertension may per se be risk factors for COVID-19 and not the treatment with ACE inhibitors, which may exert a protective effect on COVID-19 infection
Gastroesophageal Reflux Disease
Authors: John Maret-Ouda, Sheraz R. Markar, Jesper Lagergren
Journal: JAMA (2020)

This JAMA Patient Page describes the causes, symptoms and signs, and treatments, including medication (eg, proton pump inhibitors) and surgery (eg, fundoplication), for gastroesophageal reflux disease (GERD).
The Tri-POCUS Approach for Assessment of Volume Status in Critically Ill Patients with COVID-19
Authors: Abhilash Koratala, Claudio Ronco, Olanrewaju A. Olaoye, Amir Kazory
Journal: Journal of the American Society of Nephrology (2020)

Background: The volume status of patients with coronavirus disease 2019 (COVID-19) is dynamic and can range from severe hypovolemia (on initial presentation) to overt hypervolemia (after fluid resuscitation) due to its distinct clinical features such as cytokine storm  While lung point-of-care ultrasound (POCUS) is established as an invaluable bedside tool in assessment of volume status of the critically-ill, its use in this setting is limited by expanding lung infiltrates and a tendency for acute respiratory distress syndrome (ARDS)  Methods: We developed a combinational bedside ultrasound program to overcome the limitations of the individual methods of POCUS and provide a more precise evaluation of the volume status in critically ill patients with COVID-19  The Tri-POCUS approach represents concurrent bedside assessment of the lungs, heart (focused cardiac ultrasound [FoCUS]), and the venous system (blood flow pattern in the hepatic, portal and intra-renal veins) (Figure-1)  Results: In patients with COVID-19, distinguishing ARDS from cardiogenic pulmonary edema by lung POCUS alone is challenging due to several overlapping features  FoCUS allows for both static measures of preload as well as dynamic assessment (e g  volume responsiveness to passive leg raise maneuver)  Evaluation of blood flow pattern in the hepatic, portal and intra-renal veins not only can gauge fluid status but it also allows for direct assessment of the congestive state in end organs hence monitoring response to therapy  Conclusions: The Tri-POCUS program is an extension of our previously published work on focused renal POCUS curriculum  The components of this combinational approach have been selected based on their ability to cover the limitations of each individual method and provide a synergistic effect, especially in clinical settings such as COVID-19 where there is a tendency for rapidly changing volume status confounded by distracting features (e g  expanding lung lesions)
Systematic review on estimated rates of nephrotoxicity and neurotoxicity in patients treated with polymyxins
Authors: Florian Wagenlehner, Ersilia Lucenteforte, Federico Pea, Alex Soriano, Lara Tavoschi, Victoria R. Steele, Anne Santerre Henriksen, Christopher Longshaw, Davide Manissero, Raymond Pecini, Jason M. Pogue
Journal: Clinical Microbiology and Infection (2021)

BackgroundNephrotoxicity and neurotoxicity are commonly associated with polymyxin treatment; however, the emergence of multidrug-resistant Gram-negative bacteria with limited therapeutic options has resulted in increased use of polymyxins.ObjectivesTo determine the rates of nephrotoxicity and neurotoxicity during polymyxin treatment and whether any factors influence these.Data sourcesMedline, Embase and Cochrane Library databases were searched on 2 January 2020.Study eligibility criteriaStudies reporting nephrotoxicity and/or neurotoxicity rates in patients with infections treated with polymyxins were included. Reviews, meta-analyses and reports not in English were excluded.ParticipantsPatients hospitalized with infections treated with systemic or inhaled polymyxins were included. For comparative analyses, patients treated with non–polymyxin-based regimens were also included.MethodsMeta-analyses were performed using a random-effects model; subgroup meta-analyses were conducted where data permitted using a mixed-effects model.ResultsIn total, 237 reports of randomized controlled trials, cohort and case–control studies were eligible for inclusion; most were single-arm observational studies. Nephrotoxic events in 35,569 patients receiving polymyxins were analysed. Overall nephrotoxicity rate was 0.282 (95% confidence interval (CI) 0.259–0.307). When excluding studies where >50% of patients received inhaled-only polymyxin treatment or nephrotoxicity assessment was by methods other than internationally recognized criteria (RIFLE, KDIGO or AKIN), the nephrotoxicity rate was 0.391 (95% CI 0.364–0.419). The odds of nephrotoxicity were greater with polymyxin therapies compared to non–polymyxin-based regimens (odds ratio 2.23 (95% CI 1.58–3.15); p < 0.001). Meta-analyses showed a significant effect of polymyxin type, dose, patient age, number of concomitant nephrotoxins and use of diuretics, glycopeptides or vasopressors on the rate of nephrotoxicity. Polymyxin therapies were not associated with a significantly different rate of neurotoxicity than non–polymyxin-based regimens (p 0.051). The overall rate of neurotoxicity during polymyxin therapy was 0.030 (95% CI 0.020–0.043).ConclusionsPolymyxins are associated with a higher risk of nephrotoxicity than non–polymyxin-based regimens.
Subsequent malignant neoplasms among children with Hodgkin lymphoma: a report from the Children’s Oncology Group
Authors: Lisa Giulino-Roth, Qinglin Pei, Allen Buxton, Rizvan Bush, Yue Wu, Suzanne L. Wolden, Louis S. Constine, Kara M. Kelly, Cindy L. Schwartz, Debra L. Friedman
Journal: Blood (2020)
Transgenerational transmission of genetic damage by depleted uranium and tungsten alloy
Authors: Alexandra Miller
Journal: Cancer Research (2007)

885  The radioactive heavy metal, depleted uranium (DU), an alpha-particle emitter, is used in U.S. military munitions. This use has resulted in a number of casualties among U.S. personnel injured by fragments from DU munitions. Additional soldiers may have been exposed via inhalation or ingestion of DU particles. Recently, an alloy of tungsten, nickel, and cobalt (WA) has also been used by the U.S. military. The Persian Gulf War and the Iraq War resulted in a number of casualties among U.S. and British personnel injured by fragments from DU munitions. It is unknown whether these embedded fragments will affect the long-term health of offspring conceived by these soldiers. Studies have demonstrated that paternal preconceptional exposure to radiation or heavy metals like cadmium can induce cancer in unexposed offspring. To address this question, we investigated the paternal transmission of genetic damage in offspring of male rodents carrying embedded DU or WA fragments using a transgenic mouse model. This system allows us to assess λlacIgene mutation frequency in multiple tissues obtained from progeny of exposed fathers by employing a λlacI shuttle vector carried by cells of a transgenic mouse (Big Blue: strain C57BL/6 hemizygous mice containing 40 copies of a λlacI shuttle vector per cell). Male rodents were internally exposed to DU or WA (high and low dose) and the mutation frequencies in testes and bone marrow were then measured. Offspring from exposed male parents were genotyped and those positive for the λlacI gene were assessed for transmission of genetic damage in bone marrow tissue. Data demonstrate that offspring from DU- and WA- exposed (high dose) male parents exhibited a significant increase in the mutation frequency of the λlacI gene in their bone marrow (9.4-fold elevation and 7.7-fold elevation, respectively. The λlacI mutation frequency in progeny from unimplanted fathers did not demonstrate an increase in bone marrow mutation frequency. The results from this study indicate the possibility of transmission of genomic instability from male parents carrying embedded DU and WA to the somatic cells of their offspring. Further studies are warranted to address these questions.  Supported by the Armed Forces Radiobiology Research Institute under work unit RAB5AA. Research was conducted according to the principles enumerated in the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources, National Research Council.  http://www.deploymentlink.osd.mil/du_library/du_ii/du_ii_tabp.htm  #
Aerosol generation and droplet spread during nasogastric intubation in the COVID-19 era
Authors: Wout Verbeure, Annelies Geeraerts, I-Hsuan Huang, Lien Timmermans, Joran Toth, Hannelore Geysen, Louise Cools, Florencia Carbone, Jolien Schol, Herman Devriese, Rico Haesaerts, Hideki Mori, Tim Vanuytsel, Jan Tack
Journal: Gut (2020)

Various signals during infection influence CD8 T cell memory generation, but these factors have yet to be fully defined. IL-12 is a proinflammatory cytokine that has been shown to enhance IFN-γ-producing T cell responses and has been widely tested as a vaccine adjuvant. In this study, we show that IL-12-deficient mice generate a weaker primary CD8 T cell response and are more susceptible to <i>Listeria monocytogenes</i> infection, but have substantially more memory CD8 T cells and greater protective immunity against reinfection. Kinetic analyses show that in the absence of IL-12 there is a reduced contraction of Ag-specific CD8 T cells and a gradual increase in memory CD8 T cells as a result of increased homeostatic renewal. By signaling directly through its receptor on CD8 T cells, IL-12 influences their differentiation to favor the generation of fully activated effectors, but hinders the formation of CD8 T cell memory precursors and differentiation of long-term CD8 T cell memory<sub>.</sub> These results have implications for understanding memory T cell development and enhancing vaccine efficacy, and offer new insight into the role of IL-12 in coordinating the innate and adaptive immune response.
Primary hip replacement prostheses and their evidence base: systematic review of literature
Authors: F. Kynaston-Pearson, A. M. Ashmore, T. T. Malak, I. Rombach, A. Taylor, D. Beard, N. K. Arden, A. Price, D. Prieto-Alhambra, A. Judge, A. J. Carr, S. Glyn-Jones
Journal: BMJ (2013)

<b>Objective</b> To determine the extent to which prostheses with no readily available evidence to support their use are being implanted in primary total hip arthroplasty. <b>Design</b> Systematic review of the literature. <b>Data sources</b> The 9th annual report of the National Joint Registry of England and Wales (NJR) was analysed to identify prostheses with an Orthopaedic Data Evaluation Panel rating of "unclassified" or "pre-entry" used in primary total hip arthroplasty in 2011. A systematic review of those prostheses was carried out using PubMed, Cochrane, Embase, OVID, and Google databases. <b>Study selection</b> Prostheses used in primary total hip arthroplasty as published in the NJR's 9th annual report were analysed. Only literature that included the name of the prosthesis was included. Literature yielded in the search results was excluded if it reported animal, non-orthopaedic, non-total hip arthroplasty, or non-device related studies. <b>Results</b> The systematic review found that 24% (57/235) of all hip replacement implants available to surgeons in the UK have no evidence for their clinical effectiveness. It also shows that 10 617 (7.8%) of the 136 593 components used in primary hip replacements in 2011 were implanted without readily identifiable evidence of clinical effectiveness. These comprised 157 cemented stems (0.5% of 34 655 implanted), 936 (2.8% of 33 367) uncemented stems, 1732 (7.1% of 24 349) cemented cups, and 7577 (17.1% of 44 222) uncemented cups. <b>Conclusions</b> This study shows that a considerable proportion of prostheses available to orthopaedic surgeons have no readily available evidence of clinical effectiveness to support their use. Concern exists about the current system of device regulation, and the need for a revised process for introducing new orthopaedic devices is highlighted.
The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium
Authors: Fabio Silvio Taccone, Nina Van Goethem, Robby De Pauw, Xavier Wittebole, Koen Blot, Herman Van Oyen, Tinne Lernout, Marion Montourcy, Geert Meyfroidt, Dominique Van Beckhoven
Journal: The Lancet Regional Health - Europe (2020)

Several studies have investigated the predictors of in-hospital mortality for COVID-19 patients who need to be admitted to the Intensive Care Unit (ICU). However, no data on the role of organizational issues on patients' outcome are available in this setting. The aim of this study was therefore to assess the role of surge capacity organisation on the outcome of critically ill COVID-19 patients admitted to ICUs in Belgium. We conducted a retrospective analysis of in-hospital mortality in Belgian ICU COVID-19 patients via the national surveillance database. Non-survivors at hospital discharge were compared to survivors using multivariable mixed effects logistic regression analysis. Specific analyses including only patients with invasive ventilation were performed. To assess surge capacity, data were merged with administrative information on the type of hospital, the baseline number of recognized ICU beds, the number of supplementary beds specifically created for COVID-19 ICU care and the "ICU overflow" (i.e. a time-varying ratio between the number of occupied ICU beds by confirmed and suspected COVID-19 patients divided by the number of recognized ICU beds reserved for COVID-19 patients; ICU overflow was present when this ratio is ≥ 1.0). Over a total of 13,612 hospitalised COVID-19 patients with admission and discharge forms registered in the surveillance period (March, 1 to August, 9 2020), 1903 (14.0%) required ICU admission, of whom 1747 had available outcome data. Non-survivors (n = 632, 36.1%) were older and had more frequently various comorbid diseases than survivors. In the multivariable analysis, ICU overflow, together with older age, presence of comorbidities, shorter delay between symptom onset and hospital admission, absence of hydroxychloroquine therapy and use of invasive mechanical ventilation and of ECMO, was independently associated with an increased in-hospital mortality. Similar results were found in in in the subgroup of invasively ventilated patients. In addition, the proportion of supplementary beds specifically created for COVID-19 ICU care to the previously existing total number of ICU beds was associated with increased in-hospital mortality among invasively ventilated patients. The model also indicated a significant between-hospital difference in in-hospital mortality, not explained by the available patients and hospital characteristics. Surge capacity organisation as reflected by ICU overflow or the creation of COVID-19 specific supplementary ICU beds were found to negatively impact ICU patient outcomes. No funding source was available for this study.
Undergoing pregnancy and childbirth as trans masculine in Sweden: experiencing and dealing with structural discrimination, gender norms and microaggressions in antenatal care, delivery and gender clinics
Authors: Felicitas Falck, Louise Frisén, Cecilia Dhejne, Gabriela Armuand
Journal: International Journal of Transgender Health (2020)

A sterilization requirement to change legal gender was removed from Swedish law in 2013, facilitating pregnancy in trans masculine individuals. The limited number of studies investigating pregnancy and childbirth among trans masculine individuals indicate increased gender dysphoria and negative experiences of pre- and post-natal healthcare, highlighting a need to improve care. Research focusing on Europe or contexts where sterilization to change legal gender was previously required by national law remains minimal.This study aimed to investigate how trans masculine individuals experience healthcare encounters in connection with pregnancy, delivery and nursing, in a setting where mandatory sterilization to change legal gender was recently removed.In-depth face-to-face interviews were conducted with 12 trans masculine individuals who attended Swedish prenatal care and delivered a child after the law on legal gender recognition was amended. Thematic content analysis was used.Providers in gender clinics, antenatal care and delivery were perceived to regard a masculine gender identity and pregnancy as incompatible. The main categories encompassed expectations and experiences of pregnancy related care and participant responses to it. Participants took charge of their care to ensure that their needs were fulfilled. The quality of care was inconsistent.A lack of knowledge, narrow gender norms and the legacy of the former legal sterility requirement limited access to diagnostic evaluation of gender dysphoria, information on reproduction and gender-affirming treatment. Medical safety during pregnancy, childbirth and nursing was impeded, gender dysphoria increased, and participants experienced minority stress. Attempts to avoid microaggressions guided healthcare encounters and birth wishes. Navigating healthcare required considerable attention, personal resources and energy, leaving particularly vulnerable individuals at risk of a lower quality of care. The paper concludes with clinical recommendations.
Evaluation of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata: A randomized observer-blinded, placebo-controlled, split-head pilot study
Authors: Vishal Gupta, Anita Singh Parihar, Vinod Kumar Sharma, Suman Jain, Vishwajeet Singh, Neena Khanna
Journal: Journal of the American Academy of Dermatology (2020)