Transient Ischemic Attacks—Populations and Prognosis

Patent Foramen Ovale Closure for Remote Stroke: Better Late Than Never?

Adverse Cardiovascular, Cerebrovascular, and Peripheral Vascular Effects of Marijuana Inhalation: What Cardiologists Need to Know

BackgroundIn-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is higher in those with COVID-19 than in those without COVID-19. The factors that predispose to this mortality rate and their relative contribution are poorly understood. This study developed a risk score inclusive of clinical variables to predict in-hospital mortality in patients with COVID-19 and STEMI.MethodsBaseline demographic, clinical, and procedural data from patients in the North American COVID-19 Myocardial Infarction registry were extracted. Univariable logistic regression was performed using candidate predictor variables, and multivariable logistic regression was performed using backward stepwise selection to identify independent predictors of in-hospital mortality. Independent predictors were assigned a weighted integer, with the sum of the integers yielding the total risk score for each patient.ResultsIn-hospital mortality occurred in 118 of 425 (28%) patients. Eight variables present at the time of STEMI diagnosis (respiratory rate of >35 breaths/min, cardiogenic shock, oxygen saturation of <93%, age of >55 ​years, infiltrates on chest x-ray, kidney disease, diabetes, and dyspnea) were assigned a weighted integer. In-hospital mortality increased exponentially with increasing integer risk score (Cochran-Armitage χ2, P ​< ​.001), and the model demonstrated good discriminative power (c-statistic ​= ​0.81) and calibration (Hosmer-Lemeshow, P ​= ​.40). The increasing risk score was strongly associated with in-hospital mortality (3.6%-60% mortality for low-risk and very high–risk score categories, respectively).ConclusionsThe risk of in-hospital mortality in patients with COVID-19 and STEMI can be accurately predicted and discriminated using readily available clinical information.

Cardiac Papillary Fibroelastoma: A Treatable Cause of Transient Ischemic Attack and Ischemic Stroke Detected by Transesophageal Echocardiography

Coronary evaluation in patients with stroke: Recognizing the risk

Is rivaroxaban safer and more effective than warfarin in patients with atrial fibrillation and stroke or TIA?

Outcomes associated with hypogonadism in women with chronic kidney disease

Elderly and forgetful with transient neurological spells: A story of two amyloids?

Benefit of Long-Term Dual Anti-Platelet Therapy in Patients Treated With Drug-Eluting Stents: From the NHLBI Dynamic Registry

Transforming growth factor beta (TGF-beta) and related growth factors are essential regulators of embryogenesis and tissue homeostasis. The signaling pathways mediated by their receptors and Smad proteins are precisely modulated by various means. Xenopus BAMBI (bone morphogenic protein (BMP) and activin membrane-bound inhibitor) has been shown to function as a general negative regulator of TGF-beta/BMP/activin signaling. Here, we provide evidence that human BAMBI (hBAMBI), like its Xenopus homolog, inhibits TGF-beta- and BMP-mediated transcriptional responses as well as TGF-beta-induced R-Smad phosphorylation and cell growth arrest, whereas knockdown of endogenous BAMBI enhances the TGF-beta-induced reporter expression. Mechanistically, in addition to interfering with the complex formation between the type I and type II receptors, hBAMBI cooperates with Smad7 to inhibit TGF-beta signaling. hBAMBI forms a ternary complex with Smad7 and the TGF-beta type I receptor ALK5/TbetaRI and inhibits the interaction between ALK5/TbetaRI and Smad3, thus impairing Smad3 activation. These findings provide a novel insight to understand the molecular mechanism underlying the inhibitory effect of BAMBI on TGF-beta signaling.

IL-13 in asthma and allergic disease: Asthma phenotypes and targeted therapies

The multipotentiality and self-renewal ability of stem cells are controlled by intrinsic genetic pathways that are subject to regulation by extrinsic signals emanating from the stem cell niche. The stem cell niche provides a microenvironment composed of cellular structures or extracellular matrix in which stem cells are maintained as undifferentiated (1Li L. Xie T. Annu. Rev. Cell Dev. Biol. 2005; 21: 605-631Crossref PubMed Scopus (942) Google Scholar, 2Lin H. Nat. Rev. Genet. 2002; 3: 931-940Crossref PubMed Scopus (305) Google Scholar, 3Scadden D.T. Nature. 2006; 441: 1075-1079Crossref PubMed Scopus (1508) Google Scholar, 4Spradling A. Drummond-Barbosa D. Kai T. Nature. 2001; 414: 98-104Crossref PubMed Scopus (1215) Google Scholar, 5Watt F.M. Hogan B.L. Science. 2000; 287: 1427-1430Crossref PubMed Scopus (1474) Google Scholar, 6Fuchs E. Tumbar T. Guasch G. Cell. 2004; 116: 769-778Abstract Full Text Full Text PDF PubMed Scopus (1481) Google Scholar). 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Two HSC niches have been proposed in murine BM, an osteoblastic niche and a vascular niche, in which osteoblasts and vascular endothelial cells have been demonstrated as major components, respectively (34Zhang J. Niu C. Ye L. Huang H. He X. Tong W.G. Ross J. Haug J. Johnson T. Feng J.Q. Harris S. Wiedemann L.M. Mishina Y. Li L. Nature. 2003; 425: 836-841Crossref PubMed Scopus (2385) Google Scholar, 35Calvi L.M. Adams G.B. Weibrecht K.W. Weber J.M. Olson D.P. Knight M.C. Martin R.P. Schipani E. Divieti P. Bringhurst F.R. Milner L.A. Kronenberg H.M. Scadden D.T. Nature. 2003; 425: 841-846Crossref PubMed Scopus (2799) Google Scholar, 36Arai F. Hirao A. Ohmura M. Sato H. Matsuoka S. Takubo K. Ito K. Koh G.Y. Suda T. Cell. 2004; 118: 149-161Abstract Full Text Full Text PDF PubMed Scopus (1540) Google Scholar, 37Nilsson S.K. Johnston H.M. Whitty G.A. Williams B. Webb R.J. Denhardt D.T. Bertoncello I. Bendall L.J. Simmons P.J. Haylock D.N. 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Xie T. Annu. Rev. Cell Dev. Biol. 2005; 21: 605-631Crossref PubMed Scopus (942) Google Scholar, 4Spradling A. Drummond-Barbosa D. Kai T. Nature. 2001; 414: 98-104Crossref PubMed Scopus (1215) Google Scholar). CBs undergo four incomplete cell divisions to form an interconnected 2–16-cell germ line cyst. In addition to the GSC, another type of cell called the ESC also attaches to cap cells interspersed between the GSCs. Together with cap cells, ESCs encapsulate GSCs to separate GSCs from their differentiated daughter cells. When the GSCs divide and detach from the niche to produce CBs and cyst cells, the ESCs also proliferate and differentiate to produce more escort cells. The escort cells expand and continue to encapsulate CBs and cysts during the process of cyst formation and are finally replaced by follicle cells after the 16-cell germ line cyst stage (Fig. 1a). Interestingly, the newly formed cysts (prior to the eight-cell cyst stage, while still encapsulated by the escort cell) can revert to the stem cell state under certain circumstances, suggesting that they may still retain (albeit limited) stem cell properties (47Kai T. Spradling A. Nature. 2004; 428: 564-569Crossref PubMed Scopus (267) Google Scholar). A similar niche is also found in Drosophila testis and is composed of hub cells located at the end of the testis (48Le Bras S. Van Doren M. Dev. Biol. 2006; 294: 92-103Crossref PubMed Scopus (96) Google Scholar). Male GSCs surrounding the hub cells are interspersed with CPs (which are counterparts of ESCs in the ovary). Both GSCs and CPs are attached to the hub cells through an adhesion junction. Similar to ESCs in the ovary, proliferation and differentiation of CPs always accompany proliferation and differentiation of GSCs. CPs in the testis produce cyst cells, which encapsulate the gonialblasts (the immediate daughters of male GSCs) during spermatogonium formation (Fig. 1b). The newly formed gonialblasts can also revert to stem cells under certain circumstances, resembling their counterpart cells (CBs and cysts) in the ovary (49Brawley C. Matunis E. Science. 2004; 304: 1331-1334Crossref PubMed Scopus (326) Google Scholar). The role of cap and hub cells in GSC regulation has been well studied, but the contribution of ESCs and their offspring in the ovary and CPs and their progeny in the testis to GSC self-renewal, proliferation, and differentiation is largely unknown. However, it is known that a dialogue between the two types of cells is required for the coordination during organogenesis (30King F.J. Szakmary A. Cox D.N. Lin H. Mol. Cell. 2001; 7: 497-508Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). Cap and hub cells provide an attachment point for anchoring GSCs to the niche; they also produce signals that inhibit differentiation but promote self-renewal of stem cells (17Tulina N. Matunis E. Science. 2001; 294: 2546-2549Crossref PubMed Scopus (506) Google Scholar). The stem cell niches in mammals are very complicated because of the complexity of cellular components of mammalian tissues, even though the mechanism for niche regulation is conserved from invertebrate to vertebrate. In mammals, BM tissue is composed of more than eight different hematopoietic cell lineages supported by a network of mesenchymal stromal cells and vascular endothelial cells. The two HSC niches, osteoblastic (34Zhang J. Niu C. Ye L. Huang H. He X. Tong W.G. Ross J. Haug J. Johnson T. Feng J.Q. Harris S. Wiedemann L.M. Mishina Y. Li L. Nature. 2003; 425: 836-841Crossref PubMed Scopus (2385) Google Scholar, 35Calvi L.M. Adams G.B. Weibrecht K.W. Weber J.M. Olson D.P. Knight M.C. Martin R.P. Schipani E. 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The concurrence of hematopoiesis and osteogenesis in BM suggests a close relationship between bone-forming cells and hematopoietic cells (57Patt H.M. Maloney M.A. Proc. Soc. Exp. Biol. Med. 1972; 140: 205-207Crossref PubMed Scopus (35) Google Scholar, 58Maloney M.A. Patt H.M. Proc. Soc. Exp. Biol. Med. 1975; 149: 94-97Crossref PubMed Scopus (12) Google Scholar). Early studies demonstrated that endosteal BM is more highly enriched with HSCs/progenitors compared with central BM (59Lord B.I. Testa N.G. Hendry J.H. Blood. 1975; 46: 65-72Crossref PubMed Google Scholar, 60Gong J.K. Science. 1978; 199: 1443-1445Crossref PubMed Scopus (195) Google Scholar). The facts that hematopoiesis recovery after myeloablative injury occurs on the endosteal bone surface (45Heissig B. Hattori K. Dias S. Friedrich M. Ferris B. Hackett N.R. Crystal R.G. Besmer P. Lyden D. Moore M.A. Werb Z. Rafii S. 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Compelling evidence shows a strong correlation between accumulation of neurotoxic β-amyloid (Aβ) peptides and oxidative stress in the brains of patients afflicted with Alzheimer disease (AD). One hypothesis for this correlation involves the direct and harmful interaction of aggregated Aβ peptides with enzymes responsible for maintaining normal, cellular levels of reactive oxygen species (ROS). Identification of specific, destructive interactions of Aβ peptides with cellular anti-oxidant enzymes would represent an important step toward understanding the pathogenicity of Aβ peptides in AD. This report demonstrates that exposure of human neuroblastoma cells to cytotoxic preparations of aggregated Aβ peptides results in significant intracellular co-localization of Aβ with catalase, an anti-oxidant enzyme responsible for catalyzing the degradation of the ROS intermediate hydrogen peroxide (H(2)O(2)). These catalase-Aβ interactions deactivate catalase, resulting in increased cellular levels of H(2)O(2). Furthermore, small molecule inhibitors of catalase-amyloid interactions protect the hydrogen peroxide-degrading activity of catalase in Aβ-rich environments, leading to reduction of the co-localization of catalase and Aβ in cells, inhibition of Aβ-induced increases in cellular levels of H(2)O(2), and reduction of the toxicity of Aβ peptides. These studies, thus, provide evidence for the important role of intracellular catalase-amyloid interactions in Aβ-induced oxidative stress and propose a novel molecular strategy to inhibit such harmful interactions in AD.

Kingdom-Agnostic Metagenomics and the Importance of Complete Characterization of Enteric Microbial Communities

Many eukaryotic transcription factors are bimodal in their regulatory properties and can both repress and activate expression of their target genes. These divergent transcriptional properties are conferred through recruitment of auxiliary proteins, denoted coactivators and corepressors. Repression plays a particularly critical role in the functions of the nuclear receptors, a large family of ligand-regulated transcription factors involved in metazoan development, differentiation, reproduction, and homeostasis. The SMRT corepressor interacts directly with nuclear receptors and serves, in turn, as a platform for the assembly of a larger corepressor complex. We report here that SMRT is expressed in cells by alternative mRNA splicing to yield two distinct variants or isoforms. We designate these isoforms SMRTalpha and SMRTtau and demonstrate that these isoforms have significantly different affinities for different nuclear receptors. These isoforms are evolutionarily conserved and are expressed in a tissue-specific manner. Our results suggest that differential mRNA splicing serves to customize corepressor function in different cells, allowing the transcriptional properties of nuclear receptors to be adapted to different contexts.