Spectroscopic and Computational Comparisons of Thiolate-Ligated Ferric Nonheme Complexes to Cysteine Dioxygenase: Second-Sphere Effects on Substrate (Analogue) Positioning

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    Parallel spectroscopic and computational studies of iron(III) cysteine dioxygenase (CDO) and synthetic models are presented. The synthetic complexes utilize the ligand tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (Ph2TIP), which mimics the facial three-histidine triad of CDO and other thiol dioxygenases. In addition to the previously reported [FeII(CysOEt)(Ph2TIP)]BPh4 (1; CysOEt is the ethyl ester of anionic l-cysteine), the formation and crystallographic characterization of [FeII(2-MTS)(Ph2TIP)]BPh4 (2) is reported, where the methyl 2-thiosalicylate anion (2-MTS) resembles the substrate of 3-mercaptopropionate dioxygenase (MDO). One-electron chemical oxidation of 1 and 2 yields ferric species that bind cyanide and azide anions, which have been used as spectroscopic probes of O2 binding in prior studies of FeIII-CDO. The six-coordinate FeIII-CN and FeIII-N3 adducts are examined with UV–vis absorption, electron paramagnetic resonance (EPR), and resonance Raman (rRaman) spectroscopies. In addition, UV–vis and rRaman studies of cysteine- and cyanide-bound FeIII-CDO are reported for both the wild-type (WT) enzyme and C93G variant, which lacks the Cys-Tyr cross-link that is present in the second coordination sphere of the WT active site. Density functional theory (DFT) and ab initio calculations are employed to provide geometric and electronic structure descriptions of the synthetic and enzymatic FeIII adducts. In particular, it is shown that the complete active space self-consistent field (CASSCF) method, in tandem with n-electron valence state second-order perturbation theory (NEVPT2), is capable of elucidating the structural basis of subtle shifts in EPR g values for low-spin FeIII species. Synopsis The geometric and electronic structures of thiolate-ligated FeIII complexes of relevance to the active sites of thiol dioxygenases have been elucidated with spectroscopic and computational methods. Data collected for the synthetic models are compared to those previously obtained for the analogous enzymatic species, and newly collected resonance Raman spectra of Cys- and CN-bound FeIII-CDO are presented. The combined enzymatic/synthetic approach reveals that second-sphere residues perturb the positions of substrate (analogues) coordinated to the nonheme iron site of CDO

    Creation and Implementation of a Pediatric Advanced Practice Nurse Critical Care Fellowship Program

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    Advanced practice registered nurses (APRNs) who begin their careers in the pediatric intensive care unit (PICU) may be challenged in this practice environment. Inadequate prior experience as a staff nurse, limited opportunities for clinical placements in the PICU during graduate education, and being in a fast-paced, high-acuity practice environment without prior exposure to critically ill children are practice challenges in the PICU setting. The goal of postgraduate education training programs (fellowship programs) for the acute care pediatric nurse practitioner (ACPNP) is to prepare students to become beginner practitioners who can function effectively in the acute care setting within a few months of being hired, much like that of their physician counterparts who complete a fellowship. The health care environment continues to be influenced by trends in national health care reform, shifts in the models for physician training, and the Accreditation Council for Graduate Medical Education resident duty hour restrictions. These emerging trends have given health care organizations the opportunity to evaluate their current care delivery and training models. It is expected that the demand for APRNs with specialty training will increase. The aim of this article is to describe our experience in the creation and implementation of a critical care pediatric nurse practitioner (CCPNP) fellowship training program at a large midwestern U.S. tertiary care center. It is expected that the demand for APRNs with specialty training will increase. When this fellowship was created, there were no known fellowships available for pediatric nurse practitioners (PNPs) interested in pediatric critical care. To meet the needs of these providers, a focused training program is required to provide specific preparation and competencies to practice to the full extent of the provider\u27s license. A recent recommendation is for health care administrators to consider implementing fellowship training programs to assist nurse practitioners transitioning into specialty roles (Kells, Dunn, Melchiono, & Burke, 2015). We used several online search engines to identify pediatric health care institutions with active advanced practice provider postgraduate fellowships. Our search in June 2017 identified fellowship programs in primary care, pediatric hematology/oncology, palliative care, neuro-critical care, and urgent care/emergency department. To our knowledge, this fellowship program was the first of its kind and seeks to provide postgraduate specialty training and education focused on the unique requirements of critically ill children and their families to help fill a knowledge gap when entering practice in this highly specialized practice environment

    Exercise-Induced Alterations in Sympathetic-Somatomotor Coupling in Incomplete Spinal Cord Injury

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    The aim of this study was to understand how high- and low-intensity locomotor training (LT) affects sympathetic-somatomotor (SS) coupling in people with incomplete spinal cord injury (SCI). Proper coupling between sympathetic and somatomotor systems allows controlled regulation of cardiovascular responses to exercise. In people with SCI, altered connectivity between descending pathways and spinal segments impairs sympathetic and somatomotor coordination, which may have deleterious effects during exercise and limit rehabilitation outcomes. We postulated that high-intensity LT, which repeatedly engages SS systems, would alter SS coupling. Thirteen individuals (50 ± 7.2 years) with motor incomplete spinal cord injuries (American Spinal Injury Association Impairment Scale C or D; injury level \u3eT6) participated in a locomotor treadmill training program. Patients were randomized into either a high-intensity (high-LT; 70–85% of maximum predicted heart rate; n = 6) group or a low-intensity (low-LT; 50–65% of maximum predicted heart rate; n = 7) group and completed up to 20 LT training sessions over 4–6 weeks, 3–5 days/week. Before and after taining, we tested SS coupling by eliciting reflexive sympathetic activity through a cold stimulation, noxious stimulation, and a mental math task while we measured tendon reflexes, blood pressure, and heart rate. Participants who completed high- versus low-LT exhibited significant decreases in reflex torques during triggered sympathetic activity (cold: −83 vs. 13%, p \u3c 0.01; pain: −65 vs. 54%, p \u3c 0.05; mental math: −43 vs. 41%; p \u3c 0.05). Mean arterial pressure responses to sympathetic stimuli were slightly higher following high- versus low-LT (cold: 30 vs. −1.5%; pain: 6 vs. −12%; mental math: 5 vs. 7%), although differences were not statistically significant. These results suggest that high-LT may be advantageous to low-LT to improve SS coupling in people with incomplete SCI

    Effect of Finish Line Design and Metal Alloy on The Marginal and Internal Gaps of Selective Laser Melting Printed Copings

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    Statement of problem Selective laser melting (SLM) technology has been introduced for printing metal dental restorations from Co-Cr base alloys or Au-Pt high noble alloys. However, information regarding the fit of restorations fabricated by using this technique is limited. Purpose The purpose of this in vitro study was to determine the effect of 3 different finish line designs on the marginal and internal gaps of metal copings made from a base (Co-Cr), high noble (Au-Pd-Ag), and noble alloy (Co-Pd) by using the SLM technology. Material and methods Three Ivorine right maxillary central incisors were prepared with a chamfer, deep chamfer, or shoulder finish line. The preparations were scanned by using a TRIOS scanner, and a total of 90 dies were printed using DPR 10 Resin (30×3 finish line designs). Ten SLM copings were fabricated for each margin design and metal alloy combination for a total of 90 copings (10×3 finish line designs×3 alloys). Copings were cemented onto dies using an autopolymerizing composite-resin luting material. All coping-die assemblies were sectioned buccolingually by using a low-speed diamond saw, and images were obtained by using an inverted bright field metallurgical microscope at ×100 magnification. Marginal and internal gaps were measured at 5 locations: buccal margin, midfacial, incisal, midlingual, and lingual margin. After gap measurements, representative specimens were embedded in autopolymerizing resin and prepared for metallographic examination. A 2-way multivariate analysis of variance (MANOVA) was conducted to determine the overall significance, followed by ANOVA for each dependent variable (α=.05). Results The results indicated that alloy type and finish line had a significant influence on marginal gap of copings (PPP=.337). No statistically significant interactions occurred. Base alloys were printed with almost no observable porosity, whereas noble and high noble alloys exhibited hot tears and porosity. Conclusions The finish line type did not influence the internal gap between copings and dies, whereas the alloy type influenced the marginal gap between copings and dies. SLM-fabricated Co-Cr copings on teeth prepared with a deep chamfer finish line demonstrated the lowest marginal gap

    Zuckerberg Facebook video live with Governor Newsom and Priscilla Chan

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    Who Owns the Air?

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    The Influence of Religiosity and Contraception on the Likelihood of Abortion among Reproductive Age Women

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    The purpose of this paper is to discuss the influence of the three most frequently used methods of contraception (i.e., the hormonal pill, the male condom, and sterilization – male and female) on the likelihood of having an abortion among United States (US) reproductive age women (15-44). A second purpose is to determine the influence of Church attendance and importance of religion on the likelihood of having an abortion among US reproductive age women. Findings show the ever use of contraceptive methods increased the likelihood of abortion from 56% to more than 11 times and that frequent church attendance and those women who hold religion to be very important in their lives decreased the likelihood of abortion compared to women who were not religious and not on the three methods of contraception. Recommendations included supporting traditional religiosity that supports chastity, marriage, and family planning methods that integrate human sexuality

    Passiflora vitifolia flower

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