Bloqueio Atrioventricular Paroxístico como Causa de Síncope em Crianças sem Cardiopatia Congênita

Histórico: A síncope causada por bloqueio atrioventricular (AV) paroxístico, definido como bloqueio de segundo ou terceiro grau transitório, raramente é relatada em pacientes pediátricos sem cardiopatias congênitas. Métodos: Realizou-se uma revisao do banco de dados de arritmias da nossa instituiçao, de janeiro de 1988 a janeiro de 2007, para identificar todos os pacientes com menos de 18 anos de idade com anatomia cardíaca normal e episódios de síncope associados a bloqueio AV paroxístico. Informaçoes demográficas e clínicas foram coletadas. Resultados: Foram identificados seis pacientes, cinco do sexo feminino, com idade média de 9,3 ± 4,4 anos, que haviam sofrido episódios de síncope durante 5,6 ± 3,3 anos, em média, antes do diagnóstico (Tabela 1). Todos foram submetidos a exame físico, eletrocardiograma e ecocardiograma. Os resultados dos exames laboratoriais, inclusive para doença de Lyme, foram negativos. Nenhum deles recebia medicaçao capaz de interferir na conduçao AV nodal. Cinco dos seis episódios relatados foram atípicos para síncope vasovagal (com exceçao do paciente 6). Todos os pacientes tiveram bloqueio AV paroxístico documentado em monitor cardíaco ou gravador de Holter de 24 horas, registrado durante a síncope em pacientes internados. Houve manutençao ou aceleraçao do ritmo sinusal durante os episódios de síncope em todos os pacientes (ritmo atrial médio de 107 ± 37 bpm). Os seis pacientes receberam o implante de marcapasso transvenoso permanente, com a resoluçao dos sintomas durante um acompanhamento médio de 5,2 ± 6,3 anos. Conclusao: O bloqueio AV paroxístico é um achado raro em pacientes pediátricos, mas deve ser considerado uma etiologia possível naqueles que apresentam episódios atípicos de síncope vasovagal. A terapia utilizando marcapassos preveniu novas ocorrências em todos os seis pacientes

Bloqueio Atrioventricular Paroxístico como Causa de Síncope em Crianças sem Cardiopatia Congênita

Histórico: A síncope causada por bloqueio atrioventricular (AV) paroxístico, definido como bloqueio de segundo ou terceiro grau transitório, raramente é relatada em pacientes pediátricos sem cardiopatias congênitas. Métodos: Realizou-se uma revisao do banco de dados de arritmias da nossa instituiçao, de janeiro de 1988 a janeiro de 2007, para identificar todos os pacientes com menos de 18 anos de idade com anatomia cardíaca normal e episódios de síncope associados a bloqueio AV paroxístico. Informaçoes demográficas e clínicas foram coletadas. Resultados: Foram identificados seis pacientes, cinco do sexo feminino, com idade média de 9,3 ± 4,4 anos, que haviam sofrido episódios de síncope durante 5,6 ± 3,3 anos, em média, antes do diagnóstico (Tabela 1). Todos foram submetidos a exame físico, eletrocardiograma e ecocardiograma. Os resultados dos exames laboratoriais, inclusive para doença de Lyme, foram negativos. Nenhum deles recebia medicaçao capaz de interferir na conduçao AV nodal. Cinco dos seis episódios relatados foram atípicos para síncope vasovagal (com exceçao do paciente 6). Todos os pacientes tiveram bloqueio AV paroxístico documentado em monitor cardíaco ou gravador de Holter de 24 horas, registrado durante a síncope em pacientes internados. Houve manutençao ou aceleraçao do ritmo sinusal durante os episódios de síncope em todos os pacientes (ritmo atrial médio de 107 ± 37 bpm). Os seis pacientes receberam o implante de marcapasso transvenoso permanente, com a resoluçao dos sintomas durante um acompanhamento médio de 5,2 ± 6,3 anos. Conclusao: O bloqueio AV paroxístico é um achado raro em pacientes pediátricos, mas deve ser considerado uma etiologia possível naqueles que apresentam episódios atípicos de síncope vasovagal. A terapia utilizando marcapassos preveniu novas ocorrências em todos os seis pacientes

Analysis of broadband x-ray spectra of highly charged krypton from a microcalorimeter detector of an electron-beam ion trap

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Provider beliefs in effectiveness and recommendations for primary HPV testing in 3 health-care systems

In 2018, the US Preventive Services Task Force endorsed primary human papillomavirus testing (pHPV) for cervical cancer screening. We aimed to describe providers\u27 beliefs about pHPV testing effectiveness and which screening approach they regularly recommend. We invited providers who performed 10 or more cervical cancer screens in 2019 in 3 healthcare systems that had not adopted pHPV testing: Kaiser Permanente Washington, Mass General Brigham, and Parkland Health; 53.7% (501/933) completed the survey between October and December 2020. Response distributions varied across modalities (P \u3c .001), with cytology alone or cotesting being more often viewed as somewhat or very effective for 30- to 65-year-olds compared with pHPV (cytology alone 94.1%, cotesting 96.1%, pHPV 66.0%). In 21- to 29-year-olds, the pattern was similar (cytology alone 92.2%, 64.7% cotesting, 50.8% pHPV). Most providers were either incorrect or unsure of the guideline-recommended screening interval for pHPV. Educational efforts are needed about the relative effectiveness and recommended use of pHPV to promote guideline-concordant care

CK1ε Is Required for Breast Cancers Dependent on β-Catenin Activity

Background: Aberrant $\beta$-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate $\beta$-catenin activity for therapeutic purposes have proven elusive to date. Methodology: To uncover genetic dependencies in breast cancer cells that harbor active $\beta$-catenin signaling, we performed RNAi-based loss-of-function screens in breast cancer cell lines in which we had characterized $\beta$-catenin activity. Here we identify CSNK1E, the gene encoding casein kinase 1 epsilon (CK1$\varepsilon$) as required specifically for the proliferation of breast cancer cells with activated $\beta$-catenin and confirm its role as a positive regulator of $\beta$-catenin-driven transcription. Furthermore, we demonstrate that breast cancer cells that harbor activated $\beta$-catenin activity exhibit enhanced sensitivity to pharmacological blockade of Wnt/$\beta$-catenin signaling. We also find that expression of CK1$\varepsilon$ is able to promote oncogenic transformation of human cells in a $\beta$-catenin-dependent manner. Conclusions/Significance: These studies identify CK1$\varepsilon$ as a critical contributor to activated $\beta$-catenin signaling in cancer and suggest it may provide a potential therapeutic target for cancers that harbor active $\beta$-catenin. More generally, these observations delineate an approach that can be used to identify druggable synthetic lethal interactions with signaling pathways that are frequently activated in cancer but are difficult to target with the currently available small molecule inhibitors

Abundance of unknots in various models of polymer loops

A veritable zoo of different knots is seen in the ensemble of looped polymer chains, whether created computationally or observed in vitro. At short loop lengths, the spectrum of knots is dominated by the trivial knot (unknot). The fractional abundance of this topological state in the ensemble of all conformations of the loop of $N$ segments follows a decaying exponential form, $\sim \exp (-N/N_0)$, where $N_0$ marks the crossover from a mostly unknotted (ie topologically simple) to a mostly knotted (ie topologically complex) ensemble. In the present work we use computational simulation to look closer into the variation of $N_0$ for a variety of polymer models. Among models examined, $N_0$ is smallest (about 240) for the model with all segments of the same length, it is somewhat larger (305) for Gaussian distributed segments, and can be very large (up to many thousands) when the segment length distribution has a fat power law tail.Comment: 13 pages, 6 color figure

Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey)

Background Transthyretin amyloidosis (ATTR) is a heterogeneous disorder with multiorgan involvement and a genetic or nongenetic basis. Objectives The goal of this study was to describe ATTR in the United States by using data from the THAOS (Transthyretin Amyloidosis Outcomes Survey) registry. Methods Demographic, clinical, and genetic features of patients enrolled in the THAOS registry in the United States (n = 390) were compared with data from patients from other regions of the world (ROW) (n = 2,140). The focus was on the phenotypic expression and survival in the majority of U.S. subjects with valine-to-isoleucine substitution at position 122 (Val122Ile) (n = 91) and wild-type ATTR (n = 189). Results U.S. subjects are older (70 vs. 46 years), more often male (85.4% vs. 50.6%), and more often of African descent (25.4% vs. 0.5%) than the ROW. A significantly higher percentage of U.S. patients with ATTR amyloid seen at cardiology sites had wild-type disease than the ROW (50.5% vs. 26.2%). In the United States, 34 different mutations (n = 201) have been reported, with the most common being Val122Ile (n = 91; 45.3%) and Thr60Ala (n = 41; 20.4%). Overall, 91 (85%) of 107 patients with Val122Ile were from the United States, where Val122Ile subjects were younger and more often female and black than patients with wild-type disease, and had similar cardiac phenotype but a greater burden of neurologic symptoms (pain, numbness, tingling, and walking disability) and worse quality of life. Advancing age and lower mean arterial pressure, but not the presence of a transthyretin mutation, were independently associated with higher mortality from a multivariate analysis of survival. Conclusions In the THAOS registry, ATTR in the United States is overwhelmingly a disorder of older adult male subjects with a cardiac-predominant phenotype. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745

Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD