Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic ...reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes.
Summary Background A lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research. Objective ...This initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures. Methods The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round. Results Five key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery. Conclusion An agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions.
Abstract
Nurses are at a high risk for short sleep duration and poor sleep quality due to irregular work schedules and high occupational stress. Considering the effect of nurses' sleep on the safety ...and health of themselves and their patients, it is important to promote healthy sleep for nurses. We sought to synthesize the published experimental and quasi‐experimental studies that address interventions to improve sleep in nurses. A systematic search was conducted for studies published in English up until May 15, 2023, using the databases PubMed, CINAHL, Academic Search Ultimate, and PsycINFO. In total, 38 articles were included, covering 22 experimental and 16 quasi‐experimental studies with sample sizes ranging from 9 to 207. Studies were assessed using the Cochrane Risk of Bias tool and considered as low to medium quality. Thirty‐six of the 38 studies reported positive findings for at least one sleep outcome. Intervention types included aroma therapy, dietary supplements, cognitive behavioral therapy, light therapy, mind‐body therapy, sleep education, exercise, napping, shift schedule modification, and multicomponent intervention, all of which showed moderate effectiveness in promoting sleep outcomes of nurses. Comparing and contrasting studies on specific interventions for improving sleep in nurses is sparse and often equivocal. With the variations of research methodology and outcome measures, it is difficult to make a conclusion about each intervention's effectiveness on specific sleep outcomes. Additional high‐quality research, including randomized controlled trials, is needed to evaluate strategies for improving sleep in this unique, safety‐sensitive occupational group.
In light of replication and translational failures, biomedical research practices have recently come under scrutiny. Experts have pointed out that the current incentive structures at research ...institutions do not sufficiently incentivise researchers to invest in robustness and transparency and instead incentivise them to optimize their fitness in the struggle for publications and grants. This cross-sectional study aimed to describe whether and how relevant policies of university medical centres in Germany support the robust and transparent conduct of research and how prevalent traditional metrics are.
For 38 German university medical centres, we searched for institutional policies for academic degrees and academic appointments as well as websites for their core facilities and research in general between December 2020 and February 2021. We screened the documents for mentions of indicators of robust and transparent research (study registration; reporting of results; sharing of research data, code and protocols; open access; and measures to increase robustness) and for mentions of more traditional metrics of career progression (number of publications; number and value of awarded grants; impact factors; and authorship order).
While open access was mentioned in 16% of PhD regulations, other indicators of robust and transparent research were mentioned in less than 10% of institutional policies for academic degrees and academic appointments. These indicators were more frequently mentioned on the core facility and general research websites. Institutional policies for academic degrees and academic appointments had frequent mentions of traditional metrics.
References to robust and transparent research practices are, with a few exceptions, generally uncommon in institutional policies at German university medical centres, while traditional criteria for academic promotion and tenure still prevail.
Aim
Creation of a diverting stoma in patients with Crohn's disease (CD) can counteract luminal inflammation. The clinical utility of a diverting stoma with the prospect of restoration of ...gastrointestinal continuity warrants further investigation. The aim of this work was to evaluate the long‐term effects of creation of a diverting stoma on the disease course in patients with luminal colonic CD.
Method
In this retrospective, multicentre cohort study we investigated the disease course of patients who received a diverting stoma in the biological era. Clinical characteristics, medication use and surgical course were assessed at the time of creation of the diverting stoma and during follow‐up. The primary outcome was the rate of successful and lasting reestablishment of gastrointestinal continuity.
Results
Thirty six patients with refractory luminal CD from four institutions underwent creation of a diverting stoma. Of the overall cohort, 20 (56%) patients had their gastrointestinal continuity reestablished after initial stoma creation and 14 (39%) who had their stoma reversed remained stoma‐free during a median of 3.3 years follow‐up (interquartile range 2.1–6.1 years). Absence of stoma reversal was associated with the presence of proctitis (p = 0.02). Colorectal resection after creation of a diverting stoma was performed in 28 (78%) patients, with 7 (19%) having a less extensive resection and 6 (17%) having a more extensive resection compared with the surgical plan before stoma creation.
Conclusion
A diverting stoma could potentially be an alternative to immediate definitive stoma placement in specific populations consisting of patients with luminal colonic CD, especially in the absence of proctitis.
In multilayer white organic light-emitting diodes the electronic processes in the various layers--injection and motion of charges as well as generation, diffusion and radiative decay of ...excitons--should be concerted such that efficient, stable and colour-balanced electroluminescence can occur. Here we show that it is feasible to carry out Monte Carlo simulations including all of these molecular-scale processes for a hybrid multilayer organic light-emitting diode combining red and green phosphorescent layers with a blue fluorescent layer. The simulated current density and emission profile are shown to agree well with experiment. The experimental emission profile was obtained with nanometre resolution from the measured angle- and polarization-dependent emission spectra. The simulations elucidate the crucial role of exciton transfer from green to red and the efficiency loss due to excitons generated in the interlayer between the green and blue layers. The perpendicular and lateral confinement of the exciton generation to regions of molecular-scale dimensions revealed by this study demonstrate the necessity of molecular-scale instead of conventional continuum simulation.
The study of certain differential operators between Sobolev spaces of sections of vector bundles on compact manifolds equipped with rough metric is closely related to the study of locally Sobolev ...functions on domains in the Euclidean space. In this paper, we present a coherent rigorous study of some of the properties of locally Sobolev-Slobodeckij functions that are especially useful in the study of differential operators between sections of vector bundles on compact manifolds with rough metric. The results of this type in published literature generally can be found only for integer order Sobolev spaces Wm,p or Bessel potential spaces Hs. Here, we have presented the relevant results and their detailed proofs for Sobolev-Slobodeckij spaces Ws,p where s does not need to be an integer. We also develop a number of results needed in the study of differential operators on manifolds that do not appear to be in the literature.
Evidence for the importance of focusing on participation to promote health and wellbeing in childhood-onset disability exists, but practice is slow to change. This paper provides a knowledge ...translation roadmap to accelerate uptake of participation evidence into day-to-day practice.
A structured roadmap to guide knowledge translation initiatives for implementing participation-based practices in co-creation with service users was developed based on elements from: the Five-factorframework for predicting implementation outcomes, the Cultural Cone framework, and the Knowledge-to-Action model.
Guiding principles paired with examples of multi-component knowledge implementation strategies to facilitate readiness for change by stakeholders at the micro (e.g., client/family, service providers), meso (e.g., administrators within organisations such as rehabilitation centres, hospitals, schools) and macro (e.g., local and governmental policy, regulatory bodies) levels are introduced. Solution-based strategies are provided to facilitate "readiness to change" for each stakeholder group. The strategies are examples for successful implementation of evidence-based interventions/approaches that can be contextualized across settings.
The knowledge translation roadmap can assist children and families, service providers, administrators, and policymakers to bridge existing knowledge-to-practice gaps surrounding participation. Partnering and collaborating through a "family-clinician-manager-community leader-policymaker" synergy is key for achieving strategic practice change focussed on participation.
Implications for Rehabilitation
Sound evidence surrounding the topic of participation, including effective assessments and interventions, is available and ready for use.
Shifting towards participation-focused practices for children and youth with disabilities requires a systemic multi-level KT approach.
Our Participation-KT roadmap, comprised of a framework and a list of principles and strategies for implementation, can be used to guide all stakeholders to foster a shift in practice.
Forming partnerships and working collaboratively with all stakeholders is key for successful implementation.
Summary
This protocol describes an innovative study to investigate the relationship between sleep, shift work and the immune response to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2; ...coronavirus disease 2019 COVID‐19) vaccination. As the COVID‐19 pandemic is a global crisis with devastating health, social and economic impacts, there is a pressing need for effective vaccination programmes. Previous influenza and hepatitis vaccination studies suggest that lack of sleep can negatively alter immune responsiveness, while circadian misalignment most likely may also play an important role in the immune response to vaccination. Our present study will be the first to address this question in actual shift workers and in relation to COVID‐19 vaccination. We hypothesise that the occurrence of recent night shifts and diminished sleep will negatively alter the immune response to vaccination in shift workers compared to dayworkers. We aim to recruit 50 shift workers and 50 dayworkers. Participants will receive an mRNA‐based vaccination, through the Dutch vaccination programme. To assess immune responsiveness, blood will be drawn at baseline (before first vaccination), 10 days after first vaccination, the day prior to the second vaccination; and 28 days, 6 and 12 months after the second vaccination. Actigraphy and daily sleep e‐diaries will be implemented for 7 days around each vaccination to assess sleep. The Pittsburgh Sleep Quality Index will be used to monitor sleep in the long term. Optimising the efficacy of the COVID‐19 vaccines is of outmost importance and results of this study could provide insights to develop sleep and circadian‐based interventions to enhance vaccination immunity, and thereby improve global health.
•Universal GC-FID method for analysis of volatile amines.•Separation of over 30 amines and other basic polar species in a single 16min run.•Method was fully validated for over 25 of the amines and ...other basic polar species and implemented for pharmaceutical analysis.•Useful method for analysis of other basic polar species beyond the validated list described in this study.
Volatile amines are among the most frequently used chemicals in organic and pharmaceutical chemistry. Synthetic route optimization often involves the evaluation of several different amines requiring the development and validation of analytical methods for quantitation of residual amine levels. Herein, a simple and fast generic GC-FID method on an Agilent J&W CP-Volamine capillary column (using either He or H2 as the carrier gas) capable of separating over 25 volatile amines and other basic polar species commonly used in pharmaceutical chemistry workflows is described. This 16min method is successfully applied to the analysis and quantitation of volatile amines in a variety of pharmaceutically-related drugs and synthetic intermediates. Method validation experiments showed excellent analytical performance in linearity, recovery, repeatability, and limit of quantitation and detection. In addition, diverse examples for the application of this method to the simultaneous determination of other amine-related chemicals in reaction mixtures are illustrated, thereby indicating that these GC-FID method conditions can be effectively used as starting point during method development for the analysis of other basic polar species beyond the validated list of amines described in this study.
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