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The elastic scattering of the radioactive proton-rich carbon isotope 10C has been investigated. A full differential angular distribution for the elastic scattering of 10C on a 58Ni target has been measured at ELab=35.3 MeV, which is just above the Coulomb barrier for this system (VB=27 MeV). The obtained angular distribution was analyzed in terms of coupled-channels, coupled-reaction-channels, and continuum-discretized coupled-channels calculations. In the coupled-channels calculation, several inelastic transitions of the target and the first (2+) excited state of the 10C projectile were considered. The coupling to the first (2+) excited state of 10C was shown to be very important to describe the rising of the cross section at backward angles. We also performed an analysis with the continuum-discretized coupled channels, considering the 9B+p and 6Be+α channels, which indicated a strong cluster configuration for the 10C projectile. [ABSTRACT FROM AUTHOR]

The (d,n) reaction has been studied with targets of 9Be, 11B, 13C, 14,15N, and 19F at Ed = 16 MeV using a deuterated liquid-scintillator array. Advanced spectral unfolding techniques with accurately measured scintillator response functions were employed to extract neutron energy spectra without the need for long-path neutron time-of-flight. An analysis of the proton-transfer data at forward angles to the ground states of the final nuclei, using finite-range distorted-wave Born approximation analysis with common bound-state, global, and local optical-model parameter sets, yields a set of self-consistent spectroscopic factors. These are compared with the results of several previous time-of-flight measurements, most done many years ago for individual nuclei at lower energy and often analyzed using zero-range transfer codes. In contrast to some of the earlier published data, our data generally compare well with simple shell-model predictions, with little evidence for uniform quenching (reduction from shell-model values) that has previously been reported from analysis of nucleon knock-out reactions. Data for low-lying excited states in 14N from 13C(d,n) also is analyzed and spectroscopic information relevant to nuclear astrophysics obtained. A preliminary study of the radioactive ion beam induced reaction 7Be(d,n), E(7Be) = 30 MeV was carried out and indicates further improvements are needed for such measurements, which require detection of neutrons with En < 2 MeV. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) therapies have recently gained tremendous traction with the approval of mRNA vaccines for the prevention of SARS-CoV-2 infection. However, manufacturing challenges have complicated large scale mRNA production, which is necessary for the clinical viability of these therapies. Not only can the incorporation of the required 5' 7-methylguanosine cap analog be inefficient and costly, in vitro transcription (IVT) using wild-type T7 RNA polymerase generates undesirable double-stranded RNA (dsRNA) byproducts that elicit adverse host immune responses and are difficult to remove at large scale. To overcome these challenges, we have engineered a novel RNA polymerase, T7-68, that co-transcriptionally incorporates both di- and tri-nucleotide cap analogs with high efficiency, even at reduced cap analog concentrations. We also demonstrate that IVT products generated with T7-68 have reduced dsRNA content.

Objective: The Pharma Collaboration for Transparent Medical Information (phactMI™) benchmarking survey of 32 pharmaceutical companies describes the use of technology by Medical Information Departments., Methods: A survey was distributed to phactMI™ member companies in June 2022 and included 79 closed and open-ended questions. The survey's six sections included demographics, chatbot, social media, instant messaging applications, websites, and technology., Results: Most Medical Information Departments have implemented innovative technology since 2019 with the main driver of remaining up-to-date. A total of 94% have a Medical Information website. Of those with a Medical Information website for healthcare professionals (HCPs), 97% allow for self-authentication. Most HCP-based websites have webforms for inquiries and 1-800 numbers, while only few offer video chat, chatbot, and the ability to identify local representatives. These websites also link to clinicaltrials.gov, publications, posters, and congress materials. Only 30% have a website for patients/caregivers. Most websites are discoverable by Google™. Awareness of Medical Information Websites occurs in a variety of ways, with most using multiple strategies to reach HCPs. There is wide variation in the technology platform used for the core functions of Medical Information., Conclusion: As technology continues to advance and omnichannel content remains a key objective, Medical Information needs to remain agile and transformative in their strategic and tactical planning and execution. Based on this benchmarking survey, the authors recommend that Medical Information Departments focus on expanding services for patients/caregivers, leverage digital innovations, expanding awareness, building efficiencies in workflow through technology, and continually improving website functionalities with innovative technologies., (© 2023. The Author(s).)

Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid metabolism affecting several thousand individuals worldwide. MSUD patients have elevated levels of plasma leucine and its metabolic product α-ketoisocaproate (KIC), which can lead to severe neurotoxicity, coma, and death. Patients must maintain a strict diet of protein restriction and medical formula, and periods of noncompliance or illness can lead to acute metabolic decompensation or cumulative neurological impairment. Given the lack of therapeutic options for MSUD patients, we sought to develop an oral enzyme therapy that can degrade leucine within the gastrointestinal tract prior to its systemic absorption and thus enable patients to maintain acceptable plasma leucine levels while broadening their access to natural protein. We identified a highly active leucine decarboxylase enzyme from Planctomycetaceae bacterium and used directed evolution to engineer the enzyme for stability to gastric and intestinal conditions. Following high-throughput screening of over 12 000 enzyme variants over 9 iterative rounds of evolution, we identified a lead variant, LDCv10, which retains activity following simulated gastric or intestinal conditions in vitro. In intermediate MSUD mice or healthy nonhuman primates given a whey protein meal, oral treatment with LDCv10 suppressed the spike in plasma leucine and KIC and reduced the leucine area under the curve in a dose-dependent manner. Reduction in plasma leucine correlated with decreased brain leucine levels following oral LDCv10 treatment. Collectively, these data support further development of LDCv10 as a potential new therapy for MSUD patients., (© 2023 Codexis Inc. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

The workup and diagnosis of cardiovascular emergencies represent the present and future risk to emergency physicians. Eliciting and documenting key details of a cardiovascular complaint, as well as following established standards for accurate and timely diagnosis of emergencies, is central to the medico-legal aspects of cardiovascular emergencies. Key elements of documentation include history, physical exam, diagnostic workup, and medical decision making. Key elements of medical malpractice include the existence of a legal duty, breach of the legal duty, causation, and presence of damages. All 4 legal elements must be present for medical malpractice to be proven in a court of law., Competing Interests: Disclosures The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Growth is often impaired in infants with congenital heart disease. Poor growth has been associated with worse neurodevelopment, abnormal behavioral state, and longer time to hospital discharge. Nutritional interventions, drug therapy, and surgical palliation have varying degrees of success enhancing growth. Passive range of motion (PROM) improves somatic growth in preterm infants and is safe and feasible in infants with hypoplastic left heart syndrome (HLHS), after their first palliative surgery (Norwood procedure)., Methods: This multicenter, Phase III randomized control trial of a 21-day PROM exercise or standard of care evaluates growth in infants with HLHS after the Norwood procedure. Growth (weight-, height- and head circumference-for-age z-scores) will be compared at 4 months of age or at the pre-superior cavopulmonary connection evaluation visit, whichever comes first. Secondary outcomes include neonatal neurobehavioral patterns, neurodevelopmental assessment, and bone mineral density. Eligibility include diagnosis of HLHS or other single right ventricle anomaly, birth at ≥37 weeks gestation and Norwood procedure at <30 days of age, and family consent. Infants with known chromosomal or recognizable phenotypic syndromes associated with growth failure, listed for transplant, or expected to be discharged within 14 days of screening are excluded., Conclusions: The TEAM 4 Growth trial will make an important contribution to understanding the role of PROM on growth, neurobehavior, neurodevelopment, and BMD in infants with complex cardiac anomalies, who are at high risk for growth failure and developmental concerns., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This project was implemented to determine if the combination of video recording and reflection could enhance student learning of specific nursing skills. Students' answers to open-ended questions validated the importance of iPad videos for their skill improvement. The findings confirmed that iPad videos provided an effective tool for students to evaluate their performance and reflect on methods for improvement.

Toll-like receptor (TLR) 2 dependent pathways have an important role in the antimicrobial defense of human keratinocytes, and various factors and compounds have been shown to affect those pathways. Investigating Toll-like receptor function in canine keratinocytes and the potential for their modulation is of similar relevance in dogs due to the frequency of staphylococcal skin infections in this species, particularly in the context of canine atopic dermatitis. This pilot study hypothesized that ciclosporin would have a modulatory effect on the cytokine and TLR mRNA expression of canine progenitor epidermal keratinocytes in response to TLR2 agonists. No detectable up-regulation of TLR2, TLR4, IL-8 and TNF-α mRNA was detected following exposure to FSL-1, Pam3CSK4 and staphylococcal peptidoglycan (PGN). Ciclosporin alone did not alter the expression levels of these transcripts but in the presence of ciclosporin, TNF-α mRNA expression was upregulated in response to all three agonists and both TNF-α and IL-8 transcript abundance was increased in response to Pam3CSK4. The enhanced responsiveness of canine keratinocytes to TLR2 agonists in response to ciclosporin may imply that administration of this drug might enhance the innate immune barrier of skin., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To define current use patterns of Facebook and Twitter among pharmacy preceptors and assess perceptions regarding use of social media within professional practice., Methods: An electronic survey instrument was sent to 315 pharmacists registered as advanced pharmacy practice experience (APPE) preceptors for Purdue University College of Pharmacy., Results: Approximately 60% of the 155 respondents used a Facebook account and 9% used a Twitter account. Respondents were willing to complete continuing education (CE) credit (46%) using social media, and were interested in following professional organizations (39%) on social media; however, the majority were not interested in obtaining drug or disease-state information, identifying employment opportunities, or participating in clinical discussion forums via social media., Conclusion: Despite the growing popularity of social media across multiple disciplines, the majority of pharmacy preceptors surveyed were not willing to use these venues in professional practice.

Objectives: To test the hypothesis that high-dose dexmedetomidine can be successfully used for pediatric magnetic resonance imaging (MRI) sedation without significant hemodynamic compromise., Background: The dexmedetomidine dose required to achieve optimal sedation is often higher than its recommended dose. High doses of dexmedetomidine can lead to significant hemodynamic side effects., Methods: Dexmedetomidine use for pediatric MRI over a 1-year period was retrospectively reviewed. A dexmedetomidine bolus of 2 μg·kg(-1) intravenous followed by 1 μg·kg(-1)·h(-1) infusion was used. Dexmedetomidine efficacy, side effects, timing of side effects, and additional use of medications were analyzed. Data were compared by t-test, Mann-Whitney rank-sum test, Fisher's exact test, and anova., Results: High-dose dexmedetomidine was used in 77 patients, and MRI was completed in 76 (99%) patients. A second bolus of dexmedetomidine was required in 28 (36%) patients, and 22 (29%) patients required additional medications (midazolam, fentanyl, or ketamine) for adequate sedation. A 25% decrease in blood pressure (BP) was observed in 10.5%, a transient increase in BP in 3.9%, and a heart rate <60 min(-1) in 7.9% of cases. These side effects resolved spontaneously. There were no apneas or respiratory depression. Vital sign changes, recovery time, and discharge time were not significantly different in subgroups of patients receiving one or two boluses of dexmedetomidine with or without additional medications. Transient hypertension was more common in patients receiving two boluses of dexmedetomidine (P = 0.048)., Conclusions: High-dose dexmedetomidine can be successfully used for pediatric MRI sedation, but a significant number of children require additional medications for optimal control. Hemodynamic side effects resolved spontaneously. High-dose dexmedetomidine did not result in respiratory depression., (© 2011 Blackwell Publishing Ltd.)

Introduction: We studied the impact of an 11-bed inpatient palliative care unit (PCU) on site of death and observed mortality in the health system, oncology, and palliative care units. Observers were concerned that an active PCU would attract dying patients and worsen comparative mortality rates for Medicare and U.S. News & World Report comparisons., Methods: We reviewed 10 years of experience with all patients who died in the hospital before and after we opened our PCU in 2000., Results: The PCU concentrated dying patients on the PCU but total deaths did not change over 10 years and remained approximately 3% of admissions. Within 2 years, one quarter of all health system decedents died on the PCU. The proportion who died on the oncology floor and general units declined, but the number of intensive care unit deaths did not change., Conclusions: An inpatient PCU did not increase the hospital-wide death rate. The PCU did change the site of death to a more appropriate venue for one quarter of patients.

Malondialdehyde (MDA), a byproduct of non-enzymatic lipid peroxidation and prostaglandin biosynthesis, has been shown to be a weak frameshift mutagen in Salmonella mutagenicity assays. Because it is a dialdehyde, MDA can undergo self condensation to form polymeric products. It is possible that these condensation products are highly mutagenic and have contributed to previously reported estimates of MDA mutagenicity. We synthesized two major MDA polymerization products, (1) 2-(3'-oxo-1'-propenyl)-malondialdehyde [(MDA)2] and (2) 2,4-dihydroxymethylene-3-(2,2-dimethoxyethyl)glutaraldehyde [(MDA)3Me2] and tested their mutagenicity in the Salmonella frameshift tester strains hisD3052 and TA94 (hisD3052/pKM101). Analysis of the reversion rates revealed both (MDA)2 and (MDA)3Me2 to be weak mutagens, approximately equipotent to MDA. Although both (MDA)2 and (MDA)3Me2 are mutagenic, the fact that their formation is thermodynamically unfavorable under physiological conditions suggests they do not contribute significantly to the mutagenicity of MDA solutions.

Otostrongylus circumlitus (Railliet, 1899) from Pacific harbor seals (Phoca vitulina richardsi) and northern elephant seals (Mirounga angustirostris) were examined using morphological and molecular methods to determine whether northern elephant seals along the central California coast are infected by the same species of Otostrongylus as are Pacific harbor seals in the same area. Fixed nematodes were examined and measured using light microscopy. The polymerase chain reaction (PCR) was used to amplify and sequence the second internal transcribed spacer (ITS-2) and D3 expansion (26S) regions of ribosomal DNA of O. circumlitus from Pacific harbor and northern elephant seals. The ITS-2 region was also amplified from Parafilaroides sp. from the Pacific harbor seal, northern elephant seal, and California sea lion (Zalophus californianus) and used for restriction fragment length polymorphism (RFLP) analysis. Morphologically, it was not possible to distinguish O. circumlitus from Pacific harbor and northern elephant seals, and over a consensus length of 443 base pairs (bp) for ITS-2 and 321 bp for D3 the sequences of O. circumlitus from both hosts were identical. With the PCR-RFLP assay, it was possible to distinguish O. circumlitus from Parafilaroides sp. The results suggest that O. circumlitus is the same species in Pacific harbor and northern elephant seals, and molecular methods make it possible to distinguish this nematode from related nematodes.