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The electronic and vibrational spectra of benzonitrile cation, C6H5CN+ (BZN+), in the gas phase at low temperatures are reported. Measurements were carried out using a cryogenic ion trapping apparatus. The mid-infrared spectrum shows a strong CN stretch at 2130 ± 1 cm-1 (4.694 ± 0.002 µm). The electronic spectrum is reported in the range 5040-5750 Å. This covers the forbidden B2B2 â X2B1 and allowed C2B1 â X2B1 transitions. The spectrum is dominated by a broad absorption feature at wavelengths shorter than 5250 Å, with the strongest absorption located at 5140 Å. Experimental data are complemented with quantum chemical calculations carried out at the density functional theory and extended multi-configurational quasi-degenerate perturbation theory level. The spectroscopic results are discussed in the context of astronomical observations in the infrared and visible.
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PURPOSE: The autosomal dominant cancer predisposition disorders hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) are genetic conditions for which early identification and intervention have a positive effect on the individual and public health. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC and LS. METHODS: Participants were recruited from three geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; Jacksonville, FL). Participants underwent Exome+ sequencing (Helix Inc, San Mateo, CA) and return of results for specific genetic findings: HBOC (BRCA1 and BRCA1) and LS (MLH1, MSH2, MSH6, PMS2, and EPCAM). Chart review was performed to collect demographics and personal and family cancer history. RESULTS: To date, 44,306 participants have enrolled in Tapestry. Annotation and interpretation of all variants in genes for HBOC and LS resulted in the identification of 550 carriers (prevalence, 1.24%), which included 387 with HBOC (27.2% BRCA1, 42.8% BRCA2) and 163 with LS (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2, and 0.2% EPCAM). More than half of these participants (52.1%) were newly diagnosed carriers with HBOC and LS. In all, 39.2% of HBOC/LS carriers did not satisfy National Comprehensive Cancer Network (NCCN) criteria for genetic evaluation. NCCN criteria were less commonly met in underrepresented minority populations versus self-reported White race (51.5% v 37.5%, P = .028). CONCLUSION: Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have LS and HBOC cancer predisposition syndromes.
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Predisposição Genética para Doença , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Masculino , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Sequenciamento do Exoma , Guias de Prática Clínica como Assunto , Idoso , Testes Genéticos/métodos , Adulto Jovem , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , HeterozigotoRESUMO
INTRODUCTION: Metals and their metal ions have been shown to exhibit certain biological functions that make them attractive for use in biomaterials, for example in bone tissue engineering (BTE) applications. Recent data shows that Molybdenum (Mo) is a potent inducer of osteogenic differentiation in human bone marrow-derived mesenchymal stromal cells (BMSCs). On the other hand, while boron (B) has been shown to enhance vascularization in BTE applications, its impact on osteogenic differentiation is volatile: while improved osteogenic differentiation has been described, other data show that B might slow down osteogenic differentiation or reduce the calcification of the extracellular matrix (ECM) when applied in higher doses. Still, the combination of pro-osteogenic Mo and pro-angiogenic B is certainly attractive in the context of biomaterials intended for the use in BTE. METHODS: Therefore, the combined effect of molybdenum trioxide and boric acid at different ratios was investigated in this study to evaluate the effects on the viability, proliferation, osteogenic differentiation, ECM production and maturation of BMSCs. RESULTS: Mo ions proved to be stronger osteoinductive compared to B, in fact, while some osteogenic differentiation markers were downregulated in the presence of B, the presence of Mo provided compensation. The combined application of B and Mo indicated a combination of individual effects, partially even enhancing the expected combined performance of the single stimulations. CONCLUSIONS: The combination of B and Mo might be beneficial for BTE applications since the limited osteogenic properties of B can be compensated by Mo. Furthermore, since B is known to be pro-angiogenic, the combination of both substances may synergistically lead to improved vascularization and bone regeneration. Future studies should assess the angiogenic performance of this combination in greater detail.
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Ácidos Bóricos , Células-Tronco Mesenquimais , Osteogênese , Humanos , Molibdênio/farmacologia , Medula Óssea , Células Cultivadas , Diferenciação Celular , Óxidos/farmacologia , Materiais Biocompatíveis/farmacologiaRESUMO
Treating cancer patients with deep venous thrombosis/venous thromboembolism (DVT/VTE) can be challenging as patients are frequently unable to receive the standard therapy of anticoagulation due to the increased risk of bleeding complications seen in this population. Similarly, the hesitation of interventionalists to use thrombolytic agents due to bleeding risks limits percutaneous intervention options as well. Further, outcome data and guidelines do not exist for oncologic patients and often treatment is tailored to patient-specific factors after multidisciplinary discussion. This article reviews specific factors to consider when planning percutaneous treatment of cancer patients with DVT/VTE, focusing on the iliocaval system.
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Neoplasias , Tromboembolia Venosa , Trombose Venosa , Humanos , Terapia Trombolítica/efeitos adversos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Tromboembolia Venosa/terapia , Anticoagulantes/efeitos adversos , Trombectomia/efeitos adversos , Catéteres/efeitos adversos , Resultado do Tratamento , Neoplasias/complicações , Neoplasias/terapiaRESUMO
Although the concepts of pacing have been around for more than half a century, technological advances in cardiac implantable electronic devices (CIEDs) have changed the landscape for patients in need of pacing support or sudden death prevention. Nurses encounter patients with CIEDs in all aspects of the health care setting. Because exciting CIED therapies are on the horizon, nurses must stay up-to-date to promote optimal outcomes for CIED patients. This essential guide provides nurses with a comprehensive overview of the principles of pacing and implantable cardioverter defibrillators (ICDs), as well as innovative technologies such as leadless cardiac pacemakers and subcutaneous ICDs.
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Desfibriladores Implantáveis , Enfermeiras e Enfermeiros , Marca-Passo Artificial , HumanosRESUMO
Osteoarthritis of the knee is one of the most important degenerative joint diseases in the clinical routine. The treatment of knee osteoarthritis is not only based on the stage, symptoms and duration of the joint disease, but also depends on the existing arthrosis pattern. In the case of unicompartmental arthrosis, damage typical for osteoarthritis is limited to just one joint compartment. Both the conservative and the surgical treatment of unicompartmental osteoarthritis of the knee have to respect the individual characteristics of the respective forms of osteoarthritis. In the context of this manuscript, the genesis, the diagnostics and the guideline-based stage-adapted conservative and operative treatment of unicompartmental osteoarthritis of the knee are addressed.
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Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/diagnóstico , Artroplastia do Joelho/métodos , Osteotomia/métodos , Articulação do Joelho/cirurgia , Adaptação FisiológicaRESUMO
A highly adaptable and robust terahertz (THz) energy meter is designed and implemented to detect energetic THz pulses from high-intensity (>1018 W/cm2) laser-plasma interactions on the OMEGA EP. THz radiation from the laser driven target is detected by a shielded pyrometer. A second identical pyrometer is used for background subtraction. The detector can be configured to detect THz pulses in the 1 mm to 30 µm (0.3- to 10-THz) range and pulse energies from joules to microjoules via changes in filtration, aperture size, and position. Additional polarization selective filtration can also be used to determine the THz pulse polarization. The design incorporates significant radiation and electromagnetic pulse shielding to survive and operate within the OMEGA EP radiation environment. We describe the design, operational principle, calibration, and testing of the THz energy meter. The pyrometers were calibrated using a benchtop laser and show linear sensitivity to up to 1000 nJ of absorbed energy. The initial results from four OMEGA EP THz experiments detected up to â¼15µJ at the detector, which can correspond to hundreds of mJ depending on THz emission and reflection models.
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PURPOSE: To identify the variables associated with patient discharge disposition to optimize postprocedural care and discharge planning following lower extremity arterial interventions for peripheral artery disease (PAD). MATERIALS AND METHODS: The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program database was queried using current procedural terminology codes for endovascular infrainguinal interventions for PAD. The main outcome variable of interest was nonhome discharge. Covariates included patient sociodemographic variables, age quartile (upper quartile, ≥77 years), comorbidities (diabetes, renal disease, bleeding disorder, congestive heart failure [CHF], and chronic obstructive pulmonary disease), presence of an open wound before a procedure, type of procedure, operative time, symptom severity, American Society of Anesthesiologists class, and baseline functional status. Univariate analysis and multivariate logistic regression were performed on Stata/SE 15.1. RESULTS: A total of 3,190 patients met the inclusion criteria, of whom 664 (20.8%) had nonhome discharge. Multivariate regression revealed that age (odds ratio [OR], 1.9 for the upper age quartile [>77 years]; 95% confidence interval [CI], 1.46-2.50), operative time (OR, 1.2 per increase in quartile; 95% CI, 1.09-1.30), preoperative wound (OR, 1.5; 95% CI, 1.24-1.90), renal failure (OR, 1.7; 95% CI, 1.30-2.14), CHF (OR, 2.2; 95% CI, 1.51-3.24), symptom severity (OR, 1.7; 95% CI, 1.46-1.98), and independent functional status (OR, 0.74; 95% CI, 0.59-0.92; P = .007) were associated with nonhome discharge. All P values were ≤.001 unless otherwise stated. CONCLUSIONS: Prolonged procedural time, the presence of preprocedural wound and patient comorbidities, symptomatology, and baseline functional status may be used to identify patients who will require a nonhome discharge and early discharge planning.
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Alta do Paciente , Doença Arterial Periférica , Idoso , Humanos , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos VascularesRESUMO
OBJECTIVE: To understand practices of umbilical venous catheter (UVC) insertion in tertiary level neonatal intensive care units (NICU) and investigate the outcomes of subsequent attempts following a failed initial attempt. STUDY DESIGN: Prospective, multi-center observational study of UVC insertions at tertiary level NICUs between March 2019 and January 2020. RESULTS: Of the 101 UVCs inserted at 4 centers, seventy-two (71%) were central at the first attempt and 50% were central at subsequent attempts. Patients with at least 1 failed attempt at insertion were less likely to have a centrally placed UVC (p = .009). Manipulations were less likely to be required when UVC was centrally placed during the first attempt. Maneuvers such as posterior liver mobilization used during insertion were likely to be associated with successful central placement of UVC (p = .0243). The time to complete the procedure was significantly less when the UVC was central at the first attempt (34.2 ± 20.2 vs 46.9 ± 33.8) (p = .0292). Gestational age, birth weight, and age of the baby at the insertion of the UVC, experience of the provider, and type of catheter were comparable among groups. The Shukla formula was most commonly used by providers to measure the depth of UVC placement. CONCLUSION: Repetitive attempts and manipulations were less likely to be beneficial in the successful central placement of UVC in neonates. Additionally, repetitive attempts at insertion prolonged the overall duration of the procedure.
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Cateterismo Venoso Central , Cateterismo Periférico , Recém-Nascido , Humanos , Cateterismo Periférico/métodos , Estudos Prospectivos , Veias Umbilicais , Peso ao Nascer , CatéteresRESUMO
OBJECTIVE: In the United States, atrial fibrillation (AF) accounts for over 400,000 hospitalizations annually. Emergency Department (ED) physicians have few resources available to guide AF/AFL (atrial flutter) patient triage, and the majority of these patients are subsequently admitted. Our aim is to describe the characteristics and disposition of AF/AFL patients presenting to the University of North Carolina (UNC) ED with the goal of developing a protocol to prevent unnecessary hospitalizations. METHODS: We performed a retrospective electronic medical chart review of AF/AFL patients presenting to the UNC ED over a 15-month period from January 2015 to March 2016. Demographic and ED visit variables were collected. Additionally, patients were designated as either having primary or secondary AF/AFL where primary AF/AFL patients were those in whom AF/AFL was the primary reason for ED presentation. These primary AF/AFL patients were categorized by AF symptom severity score according to the Canadian Cardiovascular Society Severity of Atrial Fibrillation (CCS-SAF) Scale. RESULTS: A total of 935 patients presented to the ED during the study period with 202 (21.5%) having primary AF/AFL. Of the primary AF/AFL patients, 189 (93.6%) had mild-moderate symptom severity (CCS-SAF ≤ 3). The majority of primary AF/AFL patients were hemodynamically stable, with a mean (SD) SBP of 123.8 (21.3), DBP of 76.6 (14.1), and ventricular rate of 93 (21.9). Patients with secondary AF/AFL were older 76 (13.1), p < 0.001 with a longer mean length of stay 6.1 (7.7), p = 0.31. Despite their mild-moderate symptom severity and hemodynamic stability, nearly 2/3 of primary AF/AFL patients were admitted. CONCLUSION: Developing a protocol to triage and discharge hemodynamically stable AF/AFL patients without severe AF/AFL symptoms to a dedicated AF/AFL clinic may help to conserve healthcare resources and potentially deliver more effective care.
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Fibrilação Atrial , Flutter Atrial , Ablação por Cateter , Centros Médicos Acadêmicos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Flutter Atrial/diagnóstico , Flutter Atrial/epidemiologia , Flutter Atrial/terapia , Canadá , Serviço Hospitalar de Emergência , Humanos , Estudos Retrospectivos , Fatores de RiscoAssuntos
Cateterismo Periférico/normas , Melhoria de Qualidade/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Artéria Radial/diagnóstico por imagem , Radiografia Intervencionista/normas , Radiologia Intervencionista/normas , Cateterismo Periférico/efeitos adversos , Consenso , Humanos , Punções , Medição de Risco , Fatores de RiscoRESUMO
PURPOSE: Diabetic patients are at increased risk of developing lower extremity peripheral arterial disease (PAD) requiring revascularization. This study assessed the effect of insulin dependence in diabetics on post-procedural outcomes following infra-inguinal endovascular intervention. MATERIALS AND METHODS: The American College of Surgeon's National Surgical Quality Improvement Program database was used to identify 8022 patients undergoing infra-inguinal endovascular interventions between 2014 and 2017. Thirty-day post-procedural outcomes for patients without diabetes, with non-insulin-dependent diabetes mellitus (NIDDM), and with insulin-dependent diabetes mellitus (IDDM) were compared. RESULTS: At presentation, IDDM patients were more likely to present with critical limb ischemia compared to NIDDM and non-diabetic patients. In propensity score-weighted logistic regression analysis, IDDM status was an independent predictor for increased renal complication (odds ratio [OR] = 3.08, confidence interval [CI] = 1.44-6.65), sepsis (OR = 1.68, CI = 1.13-2.48), wound complication (OR = 1.57, CI = 1.09-2.25, p = 0.006), UTI (OR = 2.07, CI = 1.09-3.94, p = 0.03), and readmission (OR = 1.21, CI = 1.03-1.42). NIDDM status was an independent predictor for increased risk of renal complications (OR = 2.80, CI = 1.18-6.63). CONCLUSIONS: IDDM status is an independent predictor for increased risk of 30-day post-procedural complications and readmission compared to both NIDDM and non-diabetic status in patients undergoing lower extremity endovascular interventions for PAD.
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Diabetes Mellitus/sangue , Procedimentos Endovasculares/métodos , Insulina/sangue , Isquemia/etiologia , Doença Arterial Periférica/complicações , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Isquemia/sangue , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doença Arterial Periférica/sangue , Complicações Pós-Operatórias/sangue , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
STING is an endoplasmic reticulum (ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type I interferons; however, the role of STING in B cell receptor (BCR) signaling remains unclear. We generated STING V154M knock-in mice and showed that B cells carrying constitutively activated STING specifically degraded membrane-bound IgM, Igα, and Igß via SEL1L/HRD1-mediated ER-associated degradation (ERAD). B cells with activated STING were thus less capable of responding to BCR activation by phosphorylating Igα and Syk than those without activated STING. When immunized with T-independent antigens, STING V154M mice produced significantly fewer antigen-specific plasma cells and antibodies than immunized wild-type (WT) mice. We further generated B cell-specific STINGKO mice and showed that STINGKO B cells indeed responded to activation by transducing stronger BCR signals than their STING-proficient counterparts. When B cell-specific STINGKO mice were T-independently immunized, they produced significantly more antigen-specific plasma cells and antibodies than immunized STINGWT mice. Since both human and mouse IGHV-unmutated malignant chronic lymphocytic leukemia (CLL) cells downregulated the expression of STING, we explored whether STING downregulation could contribute to the well-established robust BCR signaling phenotype in malignant CLL cells. We generated a STING-deficient CLL mouse model and showed that STING-deficient CLL cells were indeed more responsive to BCR activation than their STING-proficient counterparts. These results revealed a novel B cell-intrinsic role of STING in negatively regulating BCR signaling in both normal and malignant B cells.
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Apoptose , Linfócitos B/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Proteínas de Membrana/fisiologia , Receptores de Antígenos de Linfócitos B/imunologia , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Masculino , Camundongos , Camundongos KnockoutRESUMO
In this work we demonstrate a high sensitivity atomic gradiometer capable of operation in earth-field level environments. We apply a light-pulse sequence at four times the Larmor frequency to achieve gradiometer sensitivity <20 fT/cm/Hz at the finite field strength of 22 µT. The experimental timing sequence can be tuned to the field magnitude of interest. Our all-optical scalar gradiometer performs a differential measurement between two regions of a single vapor cell on a 4 cm baseline. Our results pave the way for extensions to operation in higher dimensions, vector sensitivity, and more advanced gradiometers.