Instrumentos de avaliação multidimensional de fragilidade para uso no cuidado de idosos com doença cardiovascular / Multidimensional frailty assessment tools for use in the care of older adults with cardiovascular disease / Instrumentos de evaluación multidimensional de la fragilidad en la atención de adultos mayores con enfermedad cardiovascular

Objetivo: identificar quais os instrumentos disponíveis para avaliação multidimensional da fragilidade em idosos com doença cardiovascular, potencialmente aplicáveis durante a realização do Processo de Enfermagem. Método: revisão sistemática conduzida em oito bases de dados/portais, para identificação de estudos que apresentassem instrumentos multidimensionais de avaliação de fragilidade em idosos com doença cardiovascular e que fossem aplicáveis ao processo de enfermagem. Resultados: foram incluídos 19 instrumentos multidimensionais. O Brief Frailty Index for Coronary Artery Disease foi desenvolvido para uso no cuidado cardiovascular de idosos. O Frailty Index for Adults e o Maastricht Frailty Screening Tool for Hospitalized Patients foram desenvolvidos para uso no Processo de Enfermagem. Conclusão: apesar de apenas um instrumento ter sido desenvolvido para o idosos com doença cardiovascular e apenas dois serem aplicáveis ao processo de enfermagem, a maioria deles tem potencial de adaptação e validação para uso nesta população durante a avaliação de enfermagem.

Objective: to identify which tools are available for multidimensional frailty assessment of older adult with cardiovascular disease and which are potentially applicable during the Nursing Process. Method: a systematic review conducted in eight databases/portals to identify studies that presented multidimensional frailty assessment tools for older adult with cardiovascular disease and that were applicable to the nursing process. Results: a total of 19 multidimensional tools were included. The Brief Frailty Index for Coronary Artery Disease was developed for use in the cardiovascular care of older adult. The Frailty Index for Adults and the Maastricht Frailty Screening Tool for Hospitalized Patients were developed for use in the Nursing Process. Conclusion: although only one tool was developed for older adults with cardiovascular disease and only two are applicable to the nursing process, most of them have the potential to be adapted and validated for use in this population during nursing assessment.

Objetivo: identificar qué instrumentos están disponibles para la evaluación multidimensional de la fragilidad en personas mayores con enfermedad cardiovascular, que se puedan aplicar en el Proceso de Enfermería. Método: revisión sistemática realizada en ocho bases de datos/portales, para identificar estudios que presentaran instrumentos multidimensionales para la evaluación de la fragilidad en adultos mayores con enfermedad cardiovascular y que fueran aplicables al proceso de enfermería. Resultados: se incluyeron 19 instrumentos multidimensionales. El Brief Frailty Index for Coronary Artery Disease se desarrolló para usarlo en el cuidado cardiovascular de las personas mayores. El Frailty Index for Adults y la Maastricht Frailty Screening Tool for Hospitalized Patients se elaboraron para ser usados en el Proceso de Enfermería. Conclusión: aunque sólo se elaboró un instrumento para adultos mayores con enfermedad cardiovascular y sólo dos son aplicables al proceso de enfermería, la mayoría de ellos tienen el potencial para ser adaptados y validados para ser usados en esa población en la evaluación de enfermería.

Diagnostic Accuracy of Artificial Intelligence in Endoscopy: Umbrella Review.

Background: Some research has already reported the diagnostic value of artificial intelligence (AI) in different endoscopy outcomes. However, the evidence is confusing and of varying quality. Objective: This review aimed to comprehensively evaluate the credibility of the evidence of AI's diagnostic accuracy in endoscopy. Methods: Before the study began, the protocol was registered on PROSPERO (CRD42023483073). First, 2 researchers searched PubMed, Web of Science, Embase, and Cochrane Library using comprehensive search terms. Then, researchers screened the articles and extracted information. We used A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR2) to evaluate the quality of the articles. When there were multiple studies aiming at the same result, we chose the study with higher-quality evaluations for further analysis. To ensure the reliability of the conclusions, we recalculated each outcome. Finally, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to evaluate the credibility of the outcomes. Results: A total of 21 studies were included for analysis. Through AMSTAR2, it was found that 8 research methodologies were of moderate quality, while other studies were regarded as having low or critically low quality. The sensitivity and specificity of 17 different outcomes were analyzed. There were 4 studies on esophagus, 4 studies on stomach, and 4 studies on colorectal regions. Two studies were associated with capsule endoscopy, two were related to laryngoscopy, and one was related to ultrasonic endoscopy. In terms of sensitivity, gastroesophageal reflux disease had the highest accuracy rate, reaching 97%, while the invasion depth of colon neoplasia, with 71%, had the lowest accuracy rate. On the other hand, the specificity of colorectal cancer was the highest, reaching 98%, while the gastrointestinal stromal tumor, with only 80%, had the lowest specificity. The GRADE evaluation suggested that the reliability of most outcomes was low or very low. Conclusions: AI proved valuabe in endoscopic diagnoses, especially in esophageal and colorectal diseases. These findings provide a theoretical basis for developing and evaluating AI-assisted systems, which are aimed at assisting endoscopists in carrying out examinations, leading to improved patient health outcomes. However, further high-quality research is needed in the future to fully validate AI's effectiveness.

Addressing Worker Safety and Health Through the Lens of Strategic Enforcement-Part One.

Ensuring the safety and health of workers in this country, who are employed at millions of workplaces that present a dizzying array of hazards, is daunting. Every day, workers are maimed or die from workplace injuries or occupational illnesses. Hence, government agencies must use all available means to ensure the laws intended to keep workers safe and healthy in their workplaces are maximally effective in accomplishing that purpose. This paper addresses this challenge through the lens of strategic enforcement. It examines how federal and state authority are designed to interact to ensure worker protection in this space, and focuses on what tools for deterring violations - many unrecognized or underutilized by worker safety agencies - are available to leverage the limited resources that inevitably constrain the agencies' reach. The forthcoming Part II will, among other things, showcase a number of noteworthy state and local initiatives that exceed the federal standard.

Perceived usefulness of digital self-tracking among people with multiple sclerosis.

Background and aim: Self-care technologies may support patients with multiple sclerosis (MS) in their everyday disease management by enabling self-monitoring of various health indicators, such as symptom levels and physical activity levels. The aim of this study was to assess the usefulness of tracking self-selected MS- and health-related measures via a digital self-tracking tool for people with MS (PwMS) over a period of six weeks. Methods: An initial development phase was followed by a six-week testing phase with 58 test participants. The evaluation phase followed a sequential, exploratory mixed-methods design, consisting of 14 interviews with test participants during the testing phase, followed by a survey of all participants after the testing phase to confirm and elaborate on the interview findings. The interview data were analyzed through a five-step thematic analysis, and the survey data were analyzed descriptively. Results: The results of the mixed-methods study can be summarized in the following findings: (1) Use of the self-tracking tool assisted users in clarifying patterns regarding their symptoms, physical activity, sleep quality and emotional well-being. (2) Tracking physical activity and, to some extent, sleep had a motivational effect on participants in relation to increasing activity and/or changing habits. (3) Data quality/accuracy constitutes an important criterion for considering the self-tracking tool relevant. (4) The self-tracking tool may support dialogue between patients and healthcare professionals, and/or it may potentially play a role in peer-to-peer support. Conclusion: The results of the present study indicate that the self-tracking of symptoms, sleep, physical activity and other measures may contribute positively to everyday self-management among PwMS. Professional support in interpreting and acting upon the data should be considered.

Performance of a Tic Screening Tool (MOVeIT) in Comparison to Expert Clinician Assessment in a Developmental-Behavioral Pediatrics Clinic Sample.

Youth with intellectual and developmental disabilities typically have higher rates of tics and stereotypies compared to children with otherwise typical development. Differentiating between these two pediatric movement disorders can be challenging due to overlapping clinical features, but is relevant due to distinct treatment modalities. The current study evaluated sensitivity and specificity of a tic screening measure, the Motor or Vocal Inventory of Tics (MOVeIT) in a pediatric sample enriched for stereotypy and tics. Children (n=199, age 2-15 years old) receiving care in a developmental-behavioral pediatrics clinic underwent a gold-standard diagnostic assessment by a tic expert; these evaluations were compared to the MOVeIT. The MOVeIT demonstrated good sensitivity (89.8%) and relatively lower specificity (57.1%) compared to tic expert for detecting tics in the overall sample. Specificity of the MOVeIT to identify tics improved to 75% when excluding children with co-occurring stereotypy. For children with tics and co-occurring stereotypy, sensitivity remained high (91.9%) but specificity was low (39.1%). The area under the curve (AUC) value to detect tics on the MOVeIT compared to the tic expert gold standard was significantly higher for children without stereotypy (AUC=85.7%) than those with stereotypy (AUC=64.3%, p <0.01). Overall, the ability to detect tics was better in those without co-occurring stereotypy symptoms. Further work is needed to establish the utility of the MOVeIT in populations where there is a high likelihood of co-occurring tics and stereotypy and in general population settings. Accurate distinction between tics and stereotypy will guide choices for intervention and anticipatory guidance for families.

Building sustainability assessment: A comparison between ITACA, DGNB, HQE and SBTool alignment with the European Green Deal.

The environmental impact of the construction industry is very heavy. Therefore, the global community is further developing green building assessment tools in order to enhance their efficiency in matching sustainability goals and being more environmentally friendly. An analysis approach by means of Multi-Criteria Decision Making (MCDM) was carried out to examine the degree of response of different green building tools utilized in Europe, namely (Innovazione e Trasparenza degli Appalti e la Compatibilità Ambientale ITACA, Deutsches Guetsiegel Nachhaltiges Bauen (DGNB), Haute Qualité Environnementale (HQE) and Sustainable Building Tool (SBTool), to the eight criteria of the European Green Deal (EGD), a roadmap elaborated by the European Commission to enhance sustainability deployment in the region. The first phase of the analysis consisted of a Boolean MCDM aiming to define to which criterion of the EGD each indicator in the tools checklists is linked. These data obtained were later examined by means of Fuzzy Logic to obtain comparable results showing how much each tool helps more following the European roadmap towards sustainability. This work intends to compare the efficiency of the most used tools in Europe for building sustainability evaluation while being based on a particular specified reference and not only the sustainable goals in general. This work also shows the efficiency of combining two MCDCM techniques to obtain better analyzing output. The result of this study shows that the DGNB is the most effective method for connecting all EGD criteria in a balanced manner. The HQE tool demonstrated a strong ability to effectively integrate the objectives of the EGD, except for the energy evaluation aspect. For the ITACA tool, it closely aligned DGNB in its response to the EGD, although it had an absent focus on the smart and sustainable shift of mobility. SBTool demonstrated average performance when compared to other protocols. This was expected since SBTool was the basis on which ITACA, DGNB, and HQE were constructed.

Understanding the molecular mechanisms of human diseases: the benefits of fission yeasts.

The role of model organisms such as yeasts in life science research is crucial. Although the baker's yeast (Saccharomyces cerevisiae) is the most popular model among yeasts, the contribution of the fission yeasts (Schizosaccharomyces) to life science is also indisputable. Since both types of yeasts share several thousands of common orthologous genes with humans, they provide a simple research platform to investigate many fundamental molecular mechanisms and functions, thereby contributing to the understanding of the background of human diseases. In this review, we would like to highlight the many advantages of fission yeasts over budding yeasts. The usefulness of fission yeasts in virus research is shown as an example, presenting the most important research results related to the Human Immunodeficiency Virus Type 1 (HIV-1) Vpr protein. Besides, the potential role of fission yeasts in the study of prion biology is also discussed. Furthermore, we are keen to promote the uprising model yeast Schizosaccharomyces japonicus, which is a dimorphic species in the fission yeast genus. We propose the hyphal growth of S. japonicus as an unusual opportunity as a model to study the invadopodia of human cancer cells since the two seemingly different cell types can be compared along fundamental features. Here we also collect the latest laboratory protocols and bioinformatics tools for the fission yeasts to highlight the many possibilities available to the research community. In addition, we present several limiting factors that everyone should be aware of when working with yeast models.

The sample locator: A federated search tool for biosamples and associated data in Europe using HL7 FHIR.

BACKGROUND: This study outlines the development of a highly interoperable federated IT infrastructure for academic biobanks located at the major university hospital sites across Germany. High-quality biosamples linked to clinical data, stored in biobanks are essential for biomedical research. We aimed to facilitate the findability of these biosamples and their associated data. Networks of biobanks provide access to even larger pools of samples and data even from rare diseases and small disease subgroups. The German Biobank Alliance (GBA) established in 2017 under the umbrella of the German Biobank Node (GBN), has taken on the mission of a federated data discovery service to make biosamples and associated data available to researchers across Germany and Europe. METHODS: In this context, we identified the requirements of researchers seeking human biosamples from biobanks and the needs of biobanks for data sovereignty over their samples and data in conjunction with the sample donor's consent. Based on this, we developed a highly interoperable federated IT infrastructure using standards such as Fast Healthcare Interoperability Resources (HL7 FHIR) and Clinical Quality Language (CQL). RESULTS: The infrastructure comprises two major components enabling federated real-time access to biosample metadata, allowing privacy-compliant queries and subsequent project requests. It has been in use since 2019, connecting 16 German academic biobanks, with additional European biobanks joining. In production since 2019 it has run 4941 queries over the span of one year on more than 900,000 biosamples collected from more than 170,000 donors. CONCLUSION: This infrastructure enhances the visibility and accessibility of biosamples for research, addressing the growing demand for human biosamples and associated data in research. It also underscores the need for improvements in processes beyond IT infrastructure, aiming to advance biomedical research and similar infrastructure development in other fields.

A novel ionic model for matured and paced atrial-like human iPSC-CMs integrating IKur and IKCa currents.

This work introduces the first atrial-specific in-silico human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) model, based on a set of phenotype-specific IKur,IKCa and IK1 membrane currents. This model is built on novel in-vitro experimental data recently published by some of the co-authors to simulate the paced action potential of matured atrial-like hiPSC-CMs. The model consists of a system of stiff ordinary differential equations depending on several parameters, which have been tuned by automatic optimization techniques to closely match selected experimental biomarkers. The new model effectively simulates the electronic in-vitro hiPSC-CMs maturation process, transitioning from an unstable depolarized membrane diastolic potential to a stable hyperpolarized resting potential, and exhibits spontaneous firing activity in unpaced conditions. Moreover, our model accurately reflects the experimental rate dependence data at different cycle length and demonstrates the expected response to a specific current blocker. This atrial-specific in-silico model provides a novel computational tool for electrophysiological studies of cardiac stem cells and their applications to drug evaluation and atrial fibrillation treatment.

Enhancing informed consent through multimedia tools in pediatric spinal surgery: a comprehensive review.

Pediatric spine surgery is a high complexity procedure that can carry risks ranging from pain to neurological damage, and even death. This comprehensive mini review explores current best practice obtaining valid and meaningful informed consent (IC) prior to pediatric spinal surgery, including modalities that support effective comprehension and understanding. An evaluation of the literature was performed to explore understanding of surgical IC by patients or their guardians and the role of multimedia tools as a possible facilitator. The evidence discussed throughout this review, based on legal and ethical perspectives, reveals challenges faced by patients and guardians in achieving comprehension and understanding, especially when facing stressful medical situations. In this context, the introduction of multimedia tools emerges as a patient-centered strategy to help improve comprehension and decrease pre-operative uncertainty. This review highlights the need for a tailored approach in obtaining IC for pediatric patients and suggests a potential role of shared decision-making (SDM) in the surgical discussion process.

Can the AI tools ChatGPT and Bard generate energy, macro- and micro-nutrient sufficient meal plans for different dietary patterns?

Artificial intelligence chatbots based on large language models have recently emerged as an alternative to traditional online searches and are also entering the nutrition space. In this study, we wanted to investigate whether the artificial intelligence chatbots ChatGPT and Bard (now Gemini) can create meal plans that meet the dietary reference intake (DRI) for different dietary patterns. We further hypothesized that nutritional adequacy could be improved by modifying the prompts used. Meal plans were generated by 3 accounts for different dietary patterns (omnivorous, vegetarian, and vegan) using 2 distinct prompts resulting in 108 meal plans total. The nutrient content of the plans was subsequently analyzed and compared to the DRIs. On average, the meal plans contained less energy and carbohydrates but mostly exceeded the DRI for protein. Vitamin D and fluoride fell below the DRI for all plans, whereas only the vegan plans contained insufficient vitamin B12. ChatGPT suggested using vitamin B12 supplements in 5 of 18 instances, whereas Bard never recommended supplements. There were no significant differences between the prompts or the tools. Although the meal plans generated by ChatGPT and Bard met most DRIs, there were some exceptions, particularly for vegan diets. These tools maybe useful for individuals looking for general dietary inspiration, but they should not be relied on to create nutritionally adequate meal plans, especially for individuals with restrictive dietary needs.

Multi-omics Integration Analysis: Tools and Applications in Environmental Toxicology.

Nowadays, traditional single-omics study is not enough to explain the causality between molecular alterations and toxicity endpoints for environmental pollutants. With the development of high-throughput sequencing technology and high-resolution mass spectrometry technology, the integrative analysis of multi-omics has become an efficient strategy to understand holistic biological mechanisms and to uncover the regulation network in specific biological processes. This review summarized sample preparation methods, integration analysis tools and the application of multi-omics integration analyses in environmental toxicology field. Currently, omics methods have been widely applied being as the sensitivity of early biological response, especially for low-dose and long-term exposure to environmental pollutants. Integrative omics can reveal the overall changes of genes, proteins, and/or metabolites in the cells, tissues or organisms, which provide new insights into revealing the overall toxicity effects, screening the toxic targets, and exploring the underlying molecular mechanism of pollutants.

Young Adults' Daily Participation Scale: A measure of objective and subjective participation.

INTRODUCTION: Participation in occupations is considered essential for individuals' health and wellbeing. Participation is a multidimensional construct that encompasses objective and subjective dimensions that transform over the course of life. Nonetheless, there is a lack of comprehensive measures that examine young adults' participation in age-appropriate activities. Therefore, we developed the Young Adults' Daily Participation Scale (YADAPS) and aimed to explore its psychometric properties. METHODS: In Study 1, the content validity of the YADAPS was established based on nine experts. Its internal consistency, criterion, convergent, and construct validity were explored among 115 typical young adults (21-35 years). Using a different sample, Study 2 examined YADAPS discriminant validity among 33 young adults with developmental coordination disorder (DCD) and 52 typical peers. CONSUMER AND COMMUNITY INVOLVEMENT: No consumer and community involvement was included in these studies. RESULTS: The relevance of YADAPS items was sufficient. Internal consistency was acceptable to excellent in most scales (.74 ≤ α ≤ .89). Criterion validity was supported by correlations between the subjective participation scales and a wellbeing measure. Convergent validity was found for all scales. No gender effect was observed (p ≥ .05). However, significant differences (p ≤ .05) were found between individuals with and without DCD. CONCLUSIONS: The YADAPS appears to be a promising measure of objective and subjective dimensions of participation in young adults. The results support the importance of examining various participation dimensions, including occupational experience. Thus, it may be used for clinical purposes among young adults as well as for occupational science research, to broaden our understanding on the interplay between participation dimensions in various life situations in young adulthood. However, further research is needed on psychometric properties, the most suited scoring method, and to consolidate their robustness among diverse populations of young adults. PLAIN LANGUAGE SUMMARY: Participation, or how one engages in daily life activities, greatly affects wellbeing. The activities in one's routine change over the lifespan, in accordance with one's developmental phase. Existing assessments of participation have limitations, like not considering young adults' concerns or only focussing on certain aspects of participation. By focussing on both the objective-observable and subjective-experiential aspects of participation, the Young Adults' Daily Participation Scale (YADAPS) strives to be a comprehensive assessment tool designed specifically for reflecting activities relevant in young adulthood. This manuscript provides preliminary validity and reliability for the YADAPS, a new questionnaire that assesses objective and subjective aspects of participation in activities relevant for individuals in young adulthood. Furthermore, the questionnaire is able to distinguish between young adults with and without participation difficulties; therefore, it is suitable for research and clinical use.

The most frequent HLA alleles around the world: A fundamental synopsis.

A comprehensive knowledge of human leukocyte antigen (HLA) molecular variation worldwide is essential in human population genetics research and disease association studies and is also indispensable for clinical applications such as allogeneic hematopoietic cell transplantation, where ensuring HLA compatibility between donors and recipients is paramount. Enormous progress has been made in this field thanks to several decades of HLA population studies allowing the development of helpful databases and bioinformatics tools. However, it is still difficult to appraise the global HLA population diversity in a synthetic way. We thus introduce here a novel approach, based on approximately 2000 data sets, to assess this complexity by providing a fundamental synopsis of the most frequent HLA alleles observed in different regions of the world. This new knowledge will be useful not only as a fundamental reference for basic research, but also as an efficient guide for clinicians working in the field of transplantation.

Coupling tensile test with LC-OCT and ultrasound imaging: investigation of the skin sublayers mechanical behaviour.

The skin is an envelope that covers the entire body. Nowadays, understanding and studying the mechanical, biological and sensory properties of the skin is essential, especially in dermatology and cosmetology. The in-depth study of the skin's mechanical behaviour is a highly intriguing challenge, enabling the differentiation of the behaviour of each layer. An extension device was developed to perform relaxation and extension tests to characterize the skin. The device has also been coupled with imaging tools (LC-OCT and ultrasound), allowing us to observe layer-by-layer deformations during the tests. Relaxation tests revealed significant skin anisotropy, as well as an influence of age and gender on skin viscoelastic parameters calculated from relaxation curves and a skin viscoelastic model. These tests also unveiled their ability to distinguish certain characteristic pathologies that alter the mechanical properties of the skin, such as scleroderma or heliodermatitis. Furthermore, the optical-mechanical coupling and deformation calculation through image analysis demonstrated that the skin layers exhibit distinct mechanical behaviours owing to their different structures. Finally, Poisson's ratio of the skin was obtained by calculating the deformation in two directions for each layer.

Molecular tools to capture active neural circuits.

To understand how neurons and neural circuits function during behaviors, it is essential to record neuronal activity in the brain in vivo. Among the various technologies developed for recording neuronal activity, molecular tools that induce gene expression in an activity-dependent manner have attracted particular attention for their ability to clarify the causal relationships between neuronal activity and behavior. In this review, we summarize recently developed activity-dependent gene expression tools and their potential contributions to the study of neural circuits.

Geospatial insights into Alphonso mango cultivation: a comprehensive land suitability study in the coastal belt of Maharashtra, India.

Land suitability assessment is integral to the advancement of precision agriculture. This inquiry is focused on identifying optimal regions for cultivating Alphonso mango in the coastal belt of Maharashtra, spanning across Palghar, Raigad, Thane, Ratnagiri, and Sindhudurg districts. Employing a GIS-based Analytic Hierarchy Process (AHP) methodology, 10 crucial parameters have been considered, encompassing climatic, physical, and chemical soil characteristics: cation exchange capacity, organic carbon, slope, rainfall, soil pH, soil texture, mean annual soil temperature, base saturation, soil drainage, and soil depth. Weights are assigned to these parameters based on expert opinions and existing literature to determine their significance in developing a soil suitability map. The study reveals distinct land suitability zones for Alphonso mango cultivation. The land suitability map designates 25.78% of the study area as highly suitable, while 9.18% is considered unsuitable for Alphonso mango cultivation. To validate the study, the Receiver Operating Characteristic (ROC) curve has been employed, indicating an 83% approval rate for the reliability and performance of the soil suitability. The results categorise soil suitability classes, providing valuable insights for farmers and agricultural planners to make informed decisions regarding Alphonso mango cultivation in similar geoenvironmental regions.

Modulating metabolism through synthetic biology: Opportunities for two-stage fermentation.

Bio-based production of fuels, chemicals and materials is needed to replace current fossil fuel based production. However, bio-based production processes are very costly, so the process needs to be as efficient as possible. Developments in synthetic biology tools has made it possible to dynamically modulate cellular metabolism during a fermentation. This can be used towards two-stage fermentations, where the process is separated into a growth and a production phase, leading to more efficient feedstock utilization and thus potentially lower costs. This article reviews the current status and some recent results in application of synthetic biology tools towards two-stage fermentations, and compares this approach to pre-existing ones, such as nutrient limitation and addition of toxins/inhibitors.

Assessment of the utilization of real-time prescription benefits for patient cost savings within an outpatient setting.

Background: This study evaluates the impact of Real-Time Prescription Benefits (RTPB), a tool integrated into electronic health records (EHRs), on patient out-of-pocket costs in an academic institution. RTPB provides prescribers with alternative, less expensive medications based on insurance plans. The primary measure was cost-savings, defined as the difference between the out-of-pocket cost of the prescribed medication and its alternative. Methods: A retrospective analysis of prescriptions from outpatient clinics in a university-based health system was conducted between May 2020 and July 2021. Prescriptions were analyzed at the 2nd level of the Anatomical Therapeutic Chemical (ATC) classification system. Costs were standardized to a 30-day supply. Standardized cost and total cost per prescription, and overall savings for the top 20 medication classes at the 2nd ATC level were calculated. The overall impact of RTPB was estimated based on selecting the least expensive alternative suggested by RTPB. Results: The study found that RTPB information was provided for 22% of prescriptions, with suggested alternatives for 1.26%. Among prescriptions with an alternative selected, the standardized average cost saving was $38.83. The study realized $15,416 in patient total cost savings. If the least expensive RTPB-suggested alternative were chosen for all prescriptions, an estimated $276,386 could have been saved. Psychoanaleptic and psycholeptic medications were the most prescribed with an alternative, with most savings in specialty drugs like anthelmintic and immunostimulant medications. Conclusion: The study highlights the importance of RTPB in reducing patient costs. It reports patient cost-savings with RTPB in prescribing decisions. Future research could explore the impact of RTPB on medication adherence using pharmacy claims data.

Computer-aided design and implementation of efficient biosynthetic pathways to produce high added-value products derived from tyrosine in Escherichia coli.

Developing efficient bioprocesses requires selecting the best biosynthetic pathways, which can be challenging and time-consuming due to the vast amount of data available in databases and literature. The extension of the shikimate pathway for the biosynthesis of commercially attractive molecules often involves promiscuous enzymes or lacks well-established routes. To address these challenges, we developed a computational workflow integrating enumeration/retrosynthesis algorithms, a toolbox for pathway analysis, enzyme selection tools, and a gene discovery pipeline, supported by manual curation and literature review. Our focus has been on implementing biosynthetic pathways for tyrosine-derived compounds, specifically L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine, with significant applications in health and nutrition. We selected one pathway to produce L-DOPA and two different pathways for dopamine-one already described in the literature and a novel pathway. Our goal was either to identify the most suitable gene candidates for expression in Escherichia coli for the known pathways or to discover innovative pathways. Although not all implemented pathways resulted in the accumulation of target compounds, in our shake-flask experiments we achieved a maximum L-DOPA titer of 0.71 g/L and dopamine titers of 0.29 and 0.21 g/L for known and novel pathways, respectively. In the case of L-DOPA, we utilized, for the first time, a mutant version of tyrosinase from Ralstonia solanacearum. Production of dopamine via the known biosynthesis route was accomplished by coupling the L-DOPA pathway with the expression of DOPA decarboxylase from Pseudomonas putida, resulting in a unique biosynthetic pathway never reported in literature before. In the context of the novel pathway, dopamine was produced using tyramine as the intermediate compound. To achieve this, tyrosine was initially converted into tyramine by expressing TDC from Levilactobacillus brevis, which, in turn, was converted into dopamine through the action of the enzyme encoded by ppoMP from Mucuna pruriens. This marks the first time that an alternative biosynthetic pathway for dopamine has been validated in microbes. These findings underscore the effectiveness of our computational workflow in facilitating pathway enumeration and selection, offering the potential to uncover novel biosynthetic routes, thus paving the way for other target compounds of biotechnological interest.