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Early stages of life likely employed catalytic RNAs (ribozymes) in many functions that are today filled by proteins. However, the earliest life forms must have emerged from heterogenous chemical mixtures, which included amino acids, short peptides, and many other compounds. Here we explored whether the presence of short peptides can help the emergence of catalytic RNAs. To do this, we conducted an in vitro selection for catalytic RNAs from randomized sequence in the presence of ten different peptides with a prebiotically plausible length of eight amino acids. This in vitro selection generated dozens of ribozymes, one of them with ∼900-fold higher activity in the presence of one specific peptide. Unexpectedly, the beneficial peptide had retained its N-terminal Fmoc protection group, and this group was required to benefit ribozyme activity. The same, or higher benefit resulted from peptide conjugates with prebiotically plausible polyaromatic hydrocarbons (PAHs) such as fluorene and naphthalene. This shows that PAH-peptide conjugates can act as potent cofactors to enhance ribozyme activity. The results are discussed in the context of the origin of life.

To explore how an early, RNA-based life form could have functioned, in vitro selection experiments have been used to develop catalytic RNAs (ribozymes) with relevant functions. We previously identified ribozymes that use the prebiotically plausible energy source cyclic trimetaphosphate (cTmp) to convert their 5'-hydroxyl group to a 5'-triphosphate. While these ribozymes were developed in the presence of Mg2+, we tested here whether lanthanides could also serve as catalytic cofactors because lanthanides are ideal catalytic cations for this reaction. After an in vitro selection in the presence of Yb3+, several active sequences were isolated, and the most active RNA was analyzed in more detail. This ribozyme required lanthanides for activity, with highest activity at a 10:1 molar ratio of cTmp : Yb3+. Only the four heaviest lanthanides gave detectable signals, indicating a high sensitivity of ribozyme catalysis to the lanthanide ion radius. Potassium and Magnesium did not facilitate catalysis alone but they increased the lanthanide-mediated kOBS by at least 100-fold, with both K+ and Mg2+ modulating the ribozyme's secondary structure. Together, these findings show that RNA is able to use the unique properties of lanthanides as catalytic cofactor. The results are discussed in the context of early life forms.

This mixed-methods research was conducted to understand the impact of learning and player growth in a League of Legends summer camp. Eighteen adolescents engaged in a three-day sleep-over summer camp with various team building activities. Data collected included API metadata from pre- and post-camp as well as semi-structured interview data with youth who attended the camp. Exposing the participants to teamwork methods had a significant impact on changing how players approached competitive game play and engagement in digital environments. In particular, we find that participation in the summer camp led to significant changes in vision score, the most team-focused aspect of the game for which statistics were available. Furthermore, as demonstrated by the qualitative data, evidence suggests youth have an understanding for how teamwork can positively influence peer interactions within digital environments. These findings are important as they demonstrate that teaching team-focused activities can have a significant impact on the players of competitive esports games, and it also implies that the role of teamwork within various digital platforms needs deeper study. Findings indicate that a transfer of learning occurs between physical and digital spaces and that youth recognize the importance of teamwork and team-building activities in digital learning spaces.

This study investigates the relationships among factor correlations, inter-item correlations, and the reliability estimates of subscores, providing a guideline with respect to psychometric properties of useful subscores. In addition, it compares subscore estimation methods with respect to reliability and distinctness. The subscore estimation methods explored in the current study include augmentation based on classical test theory and multidimensional item response theory (MIRT). The study shows that there is no estimation method that is optimal according to both criteria. Augmented subscores show the most improvement in reliability compared to observed subscores but are the least distinct.

A three-dimensional appreciation of the human body is the cornerstone of clinical anatomy. Spatial ability has previously been found to be associated with students' ability to learn anatomy and their examination performance. The teaching of anatomy has been the subject of major change over the last two decades with the reduction in time spent on dissection and greater use of web-based and computer-based resources. In this study, we examine whether the relationship between spatial ability and performance in anatomy examinations is sustained in a contemporary curriculum. A comparison of students' performance in a series of tests of spatial ability to their anatomy examination scores in biomedical sciences course exhibited only weak association (r?=?0.145 and P?=?0.106). This has implications for the use of spatial ability as a predictor of success in introductory subjects in the teaching of anatomy.

This paper reports the findings of one case study from a larger project, which aims to quantify the claimed efficiencies of reusing learning objects to develop e-learning resources. The case study describes how an online inquiry project "Diabetes: A waste of energy" was developed by searching for, evaluating, modifying and then integrating as many pre-existing learning objects as possible into a learning design. Development times for the reuse approach were recorded and compared to estimates for the "de novo" development of an equivalent project. Outcomes suggest that considerable savings can be made using the reuse approach; we estimate a threefold increase in time to develop the "Diabetes" project using new objects in comparison to reuse. In this case study, gaining permission from owners to reuse objects was not a barrier to reuse. However, in some circumstances, being unable to source pre-existing objects to meet specific requirements, or having to modify objects for reuse, could be problematic. (Contains 4 tables.)

The view from Pikes Peak is breathtaking. In the summer of 1893, Katherine Lee Bates sat on the summit of Pikes Peak, inspired by the panorama to pen the words to "America the Beautiful." Her poem was set to the tune "Materna" by Samuel Augustus Ward two years later to become one of our nation's most beloved anthems. Many educated Americans in the first half of the eighteenth century held an opinion that differed greatly from Bates's description of America's plains, considering the vast steppe between the Mississippi River and the Rocky Mountains a Great American Desert that posed a barrier to westward expansion. The Stephen Long Expedition of 1820 did more to promulgate this idea than any other source. Thomas Say, the mission's zoologist, reported that the group dreaded the journey across "the trackless desert." Dr. Edwin James, the official chronicler of the expedition, stated that the explorers passed through "a barren and desolate region."

Post-COVID, it was evident that there were severe signs of burnout and a mass exodus from nursing. It is imperative that nurse leaders focus on strategies to engage and recognize the values and opinions of the staff. From multiple appreciative inquiries (AIs), leadership was able to solicit meaningful projects that would directly affect the staff. Historically, it is known that the relationship between perianesthesia and the medical surgical (med-surg) floors can be tense and at times collaboration is low. The AIs produced an innovative idea that came from the perianesthesia staff nurses who had recently transitioned from the floor. Their overarching goal was to bridge the gap between both specialties and forge a professional relationship that consisted of mutual understanding, bidirectional communication, and increased patient/staff satisfaction. Goals of this project were to enhance the relationship between units, to create an environment of mutual understanding, respect, trust, and to improve nurse/patient satisfaction. In theory, if staff and patients are satisfied, increased patient experience and outcomes would subsequently increase. Three mutual goals were identified between the two departments: a better understanding of daily operations, clarification of assumptions surrounding workflow, and assistance with patient progression. Following the National Database of Nursing Quality Indicators results, leadership conducted multiple AIs or listening sessions, to formulate meaningful action plans. There was a reoccurring theme of teamwork, communication and respect. The idea of forming a workgroup between perianesthesia and med-surg was introduced. Staff and leadership outlined the framework of what this workgroup would accomplish. Quarterly meetings were established, structured shadowing sessions were carried out, and pre/post surveys were collected to provide feedback from the shadowing experience. Through the quarterly meetings both perianesthesia and med-surg staff were able to bring forward pain points, top of minds, and actively participate in the resolution of quality improvement initiatives. Ideas such as daily huddles, continuous text communication, and real time feedback were initiatives introduced by the staff. Pre/post surveys, quarterly meetings, and bidirectional communication allowed leadership to obtain real time feedback from the staff nurses. The ago old acceptance of perianesthesia against the inpatient team can no longer be accepted. Leadership should strive to forge a psychologically safe environment that elevates and engages the staff. Holding frequent AIs allowed the team to gauge what was important to these staff members. Bridging this gap empowered the nurses with knowledge, collaboration opportunities, and allowed for innovative strategies to improve patient and staff experience. [ABSTRACT FROM AUTHOR]

Abstract Background Patient encounters are the core learning activity of Australian general practice (family practice) training. Exposure to patient demographics and presentations may vary from one general practice registrar (vocational trainee) to another. This can affect comprehensiveness of training. Currently, there is no mechanism to systematically capture the content of GP registrar consultations. The aim of the Registrar Clinical Encounters in Training (ReCEnT) study is to document longitudinally the nature and associations of consultation-based clinical and educational experiences of general practice registrars. Methods/design This is an ongoing prospective multi-site cohort study of general practice registrars’ consultations, entailing paper-based recording of consultation data. The study setting is general practices affiliated with three geographically-based Australian general practice regional training providers. Registrars record details of 60 consecutive consultations. Data collected includes registrar demographics, details of the consultation, patient demographics, reasons for encounter and problems managed. Problems managed are coded with the International Classification of Primary Care (second edition) classification system. Additionally, registrars record educational factors related to the encounter. The study will follow the clinical exposure of each registrar six-monthly over the 18 months to two years (full-time equivalent) of their general practice training program. Conclusions The study will provide data on a range of factors (patient, registrar and consultation factors). This data will be used to inform a range of educational decisions as well as being used to answer educational research questions. We plan to use ReCEnT as a formative assessment tool for registrars and help identify and address educational needs. The study will facilitate program evaluation by the participating training providers and thus improve articulation of educational programs with practice experience. From the research point of view it will address an evidence gap – the in-practice clinical and educational experience of general practice trainees, determinants of these experiences, and the determinants of registrars’ patterns of practice (for example, prescribing practice) over the course of their training.

Abstract International public health workers are challenged by a burden of arthropod-borne disease that remains elevated despite best efforts in control programmes. With this challenge comes the opportunity to develop novel vector control paradigms to guide product development and programme implementation. The role of vector behaviour modification in disease control was first highlighted several decades ago but has received limited attention within the public health community. This paper presents current evidence highlighting the value of sub-lethal agents, specifically spatial repellents, and their use in global health, and identifies the primary challenges towards establishing a clearly defined and recommended role for spatial repellent products in disease control.

Abstract Background Accumulating evidence supports the role of the mineralocorticoid receptor (MR) in the pathogenesis of diabetic nephropathy. These findings have generated renewed interest in novel MR antagonists with improved selectivity against other nuclear hormone receptors and a potentially reduced risk of hyperkalemia. Characterization of novel MR antagonists warrants establishing translatable biomarkers of activity at the MR receptor. We assessed the translatability of urinary sodium to potassium ratio (Na+/K+) and plasma aldosterone as biomarkers of MR antagonism using eplerenone (Inspra®), a commercially available MR antagonist. Further we utilized these biomarkers to demonstrate antagonism of MR by PF-03882845, a novel compound. Methods The effect of eplerenone and PF-03882845 on urinary Na+/K+ and plasma aldosterone were characterized in Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Additionally, the effect of eplerenone on these biomarkers was determined in healthy volunteers. Drug exposure-response data were modeled to evaluate the translatability of these biomarkers from rats to humans. Results In Sprague-Dawley rats, eplerenone elicited a rapid effect on urinary Na+/K+ yielding an EC50 that was within 5-fold of the functional in vitro IC50. More importantly, the effect of eplerenone on urinary Na+/K+ in healthy volunteers yielded an EC50 that was within 2-fold of the EC50 generated in Sprague-Dawley rats. Similarly, the potency of PF-03882845 in elevating urinary Na+/K+ in Sprague-Dawley rats was within 3-fold of its in vitro functional potency. The effect of MR antagonism on urinary Na+/K+ was not sustained chronically; thus we studied the effect of the compounds on plasma aldosterone following chronic dosing in SHR. Modeling of drug exposure-response data for both eplerenone and PF-03882845 yielded EC50 values that were within 2-fold of that estimated from modeling of drug exposure with changes in urinary sodium and potassium excretion. Importantly, similar unbound concentrations of eplerenone in humans and SHR rats yielded the same magnitude of elevations in aldosterone, indicating a good translatability from rat to human. Conclusions Urinary Na+/K+ and plasma aldosterone appear to be translatable biomarkers of MR antagonism following administration of single or multiple doses of compound, respectively. Trial Registration For clinical study reference EE3-96-02-004, this study was completed in 1996 and falls out scope for disclosure requirements. Clinical study reference A6141115: http://clinicaltrials.gov, http://NIHclinicaltrails.gov; NCTID: NCT00990223

Purpose: Prosthetic joint infection (PJI) is a rare complication of temporomandibular joint replacement (TJR). This study evaluated TJR PJIs at the authors' institution over a 20-year period, including micro-organisms cultured, antibiotic resistance patterns, and intraoperative protocols of TJR.Patients and Methods: Patients were identified using Current Procedural Terminology and International Classification of Diseases, Ninth Revision codes and surgical logs from January 1995 through 2015. Inclusion criteria were adults older than 18 years with previous alloplastic TJR and the presence of infection of the prosthesis at explantation. Exclusion criteria were patients younger than 18 years and who received hemiarthroplasty. Primary outcomes included culture data and antibiotic selection for PJI. Secondary outcomes included intraoperative duration and in vivo duration.Results: Eleven patients were identified and 15 joints were explanted. Average length in vivo was 232 months (standard deviation, 478.9 months). Six percent (n = 1) were identified as early PJI (0 to 3 months), 46% (n = 7) were intermediate PJI (3 months to 2 yr), and 33% (n = 5) were late PJI (>2 yr). One patient could not be classified as early, intermediate, or late. Staphylococcus aureus was present in 53% of patients and was the predominant organism isolated. Propionibacterium acnes was isolated in 33% of patients. Penicillin was the antibiotic with the greatest organism resistance (46%).Conclusion: In the present study, the most commonly cultured organism was S aureus (53%), a finding consistent with current literature. The prevalence of P acnes colonization was noted in 33% of cases. Although the relevance of P acnes and its contribution to PJI requires further investigation, it is associated with PJI and biofilm formation. Based on this study, consideration could be given to the use of vancomycin and first-generation cephalosporins as perioperative antibiotic coverage. [ABSTRACT FROM AUTHOR]

The article discusses droughts in Northwest Texas which lasted from 1854 to 1865. The author talks about how society is no longer dependent on good weather to sustain itself. The author explains how droughts caused many to leave their homes and move back to more settled regions of Texas. How paleoclimatologists use tree-rings to study the presence of major droughts is discussed. Subjects of the article also include a gunfight over the use of a watering hole during a drought, the effect of the U.S. Civil War on Texas society, and immigrants who arrived during the Civil War.

This article discusses the dilemma faced by the Choctaw Indian tribe in Mississippi during the Civil War. The dilemma is in the form having to choose to ally with the Confederacy and the pressure of drought that threaten their livelihood and lives. The Choctaw tribe wanted to avoid making a commitment with the Confederacy but their dependence on agriculture made them dependent on the Confederate's agriculture. Fortunately the Choctaw tribe was able to secure help from the U.S.

The article analyzes the horrific nature of George Sluizer's film "The Vanishing," by emphasizing the shifts in narration from one major section of the film to the next. The author argues that the shifts thematically connect two major characters and contribute to the horrific nature of the film's narrative. These shifts are presented in four narrative sections which depicted the characters of Rex, Saskia and Raymond, played by actors Gene Bervoets, Johanna ter Steege and Bernard-Pierre Donnadieu, respectively.