Teaching critical thinking in nutritional sciences: a model course and assignments.

Critical thinking is a common and important learning outcome in college curricula. Case-based and problem-based learning can be used to assess and foster critical thinking skills. HNF 250-Contemporary Issues in Human Nutrition is a critical thinking course developed during the redesign of a nutritional sciences major program. Course assignments were designed to assess the course and nutritional sciences major learning outcomes. The nutrition and health claim assignment is scaffolded across the academic semester as three assignments: 1) bibliography assignment; 2) poster presentation; and 3) paper. Course lectures and materials have been designed to prepare students for completion of each assignment. The assignments have been modified over time based on classroom observations and student performance. In 2021, the course learning outcomes were examined by assessing several assignments including the nutrition and health claim poster and paper. Course learning outcome benchmarks using these assessments generally included 80% of students achieving an 80% for each criterion. Results revealed that students were not meeting most of these assessment benchmarks during the 2021 iteration, although benchmark data from other course assessments were more satisfactory. It is possible that the transition from a virtual to an in-person format negatively influenced student performance on these course learning outcomes. This course and the nutrition and health claim assignment example can provide a course design and learning outcome assessment framework for other higher education critical thinking courses.NEW & NOTEWORTHY This paper describes how a scaffolded nutrition and health claim assignment is used to teach critical thinking skills among nutritional sciences students and examine the program's learning outcomes. Further, this course example is to serve as an model for STEM majors on how to incorporate case-based and problem-based learning strategies into an undergraduate course.

Suboptimal Clinical and Quality of Life Outcomes in Patients with Psoriasis Undertreated with Oral Therapies: International Physician and Patient Survey.

INTRODUCTION: Psoriasis is a chronic, inflammatory, immune-mediated disease. This study assessed the time at which patients switched from a conventional oral systemic treatment to a biologic therapy; patient clinical and quality of life (QoL) outcomes associated with oral systemic treatments; and the proportion of patients who persisted on oral therapy (nonswitchers), despite reported suboptimal clinical and QoL outcomes. METHODS: This data analysis used the Adelphi Real World Psoriasis Disease Specific Programme, a non-interventional, retrospective, cross-sectional survey conducted in the USA, France, Germany, and United Kingdom (August 2018-April 2019). Kaplan-Meier (KM) analysis assessed switching from oral to biologic therapy in patients treated ≥ 3 years at survey completion (n = 597). The severity of psoriasis was reported by physicians as the percentage of body surface area (BSA) affected by psoriasis. Dermatology Life Quality Index (DLQI) scores were calculated for three groups: nonswitchers who met treatment failure criteria, nonswitchers who did not meet failure criteria, and switchers to a biologic therapy. RESULTS: In KM analysis, approximately 50% of the patient population switched by 24 months. A substantial portion of nonswitchers continued to have moderate-to-severe psoriasis. Among nonswitchers, 57-77% had BSA ≥ 3% and 16-24% had BSA ≥ 10% at the time of the survey compared with 37% of switchers who had BSA of ≥ 3% and 9% who had BSA of ≥ 10%. QoL was poor among nonswitchers. The mean [standard deviation (SD)] DLQI scores for nonswitchers meeting treatment failure criteria, nonswitchers not meeting failure criteria, and switchers were 6.11 (4.55), 2.62 (3.29), and 2.25 (4.23), respectively. CONCLUSION: There is a clear unmet need for more effective oral therapies, and further research into the reasons for patients remaining undertreated, which may include patient preference for oral treatments (despite lack of response), contraindications, or insurance/formulary-related barriers to access, are needed.

Psoriasis is a common skin disease that causes itchy, painful, scaly sores. Patients may feel stigmatized, which can impact their quality of life and productivity. About 1 in 5 patients have severe psoriasis, which is harder to treat and may require pills or shots. Both shots and pills are effective at treating psoriasis; however, many patients choose to continue taking pills, even if their psoriasis worsens, for reasons including a desire to avoid needles. We described patients with moderate-to-severe psoriasis who started on pills and either remained on pills or switched to shots by the time of the survey. We looked at the reasons they gave for switching, as well as at quality of life measures reported by the patients. To do this, we analyzed data from a survey called the Adelphi Real World Psoriasis Disease Specific Programme. This survey was conducted among doctors who treat skin diseases and their patients. Participating doctors and patients from the USA, France, Germany, and the United Kingdom were asked questions about the patients' health and how psoriasis affects their lives. Survey results showed that nearly half of patients switched to shots by 24 months, and most who switched cited treatment failure as the reason. Those who continued to take their pills despite having more severe psoriasis symptoms had more itching and pain and had lower quality of life than those who switched to shots. This suggests that there is a need for more effective oral treatments for patients with psoriasis.

When primary healthcare meets queerstory: community-based system dynamics influencing regional/rural LGBTQ + people's access to quality primary healthcare in Australia.

BACKGROUND: Lesbian, gay, bisexual, transgender, Queer, and people of any other minority sexuality or gender identity (LGBTQ + or "Queer") are often marginalised from accessing quality primary healthcare (PHC) in their local community. This is largely due to Queerphobic, cis-heteronormative/sexist systems pathologising Queer life and identities. The study aims were to: (1) identify key priorities for increasing Queer people's access to quality PHC as told by Queer people themselves, (2) identify the feedback loops that reduce or support Queer people's access to quality PHC in non-metropolitan, regional/rural communities, and (3) identify potential action areas to improve system structures to increase Queer people's access to quality PHC. METHODS: Group Model Building (GMB) workshops were held with a small group (n = 8) of LGBTQ + people in regional Victoria with lived experience of using PHC services. This participatory approach permits exploration and visual mapping of local structures causing behaviour patterns of community concern over time - in this case, Queer people's ability to access quality PHC in the Geelong-Barwon region. This is the first study that specially applies GMB in Queer PHC in the non-metropolitan regional/rural context. RESULTS: Key community identified PHC priorities were: (a) providers' level of Queer Literacy, (b) the responsibility of Queer Advocacy (at individual, systemic, and collective levels), (c) support from safe Queer Spaces, (d) strength from a Queer Presence, and (e) power from Intersectional Queer Life. These priorities interconnected, creating system-level feedback loops reinforcing barriers and enablers to Queer people's access to quality PHC in the Geelong-Barwon region; with potential action areas identified. CONCLUSIONS: Improving Queer people's access to quality PHC in the Geelong-Barwon region requires embedding principles of Queer Literacy, Queer Advocacy, Queer Space, Queer Presence, and Intersectional Queer Life within practices and service systems. The study findings were distilled into a novel, preliminary set of Queer Equity Principles. These need to be taken back to regional Queer communities for further co-design and planning for translation across PHC practices and systems, with potential applicability in other areas of the healthcare spectrum.

LGBTQ+ Loss and Grief in a Cis-Heteronormative Pandemic: A Qualitative Evidence Synthesis of the COVID-19 Literature.

LGBTQ+ people are no stranger to loss and grief, particularly during times of pandemic such as the 1980s-90s HIV/AIDS pandemic and now, the COVID-19 pandemic. Current COVID-19 loss and grief research remains relatively silent on LGBTQ+ peoples' loss and grief experiences. The aim of this research was to conduct a qualitative evidence synthesis of LGBTQ+ people's COVID-19 loss and grief experiences reported in the literature. A systematic search and inclusion strategy identified 22 relevant articles for review. Inductive thematic synthesis resulted in five loss-focused themes across the articles: (1) loss of work and livelihood, (2) loss of social and kinship connection, (3) loss of LGBTQ+ community connection, (4) loss of physical and mental health supports and (5) loss of LGBTQ+ identity authenticity, affirmation and visibility. Discussion of these themes highlights the many layered and often disenfranchised nature of LGBTQ+ people's loss during the COVID-19 pandemic.

Real-world health outcomes in US adult patients with mild to moderate plaque psoriasis taking topical therapy.

BACKGROUND: Limited health outcomes information exists for patients with mild to moderate plaque psoriasis (hereafter, referred to as psoriasis) prescribed topical treatment(s). AIM: We evaluated clinical characteristics of patients with systemic-naïve mild to moderate psoriasis after topical use in the United States. METHODS: Data were drawn from 2017 to 2018 Adelphi Psoriasis Disease Specific Programme™, a point-in-time survey of physicians and adult psoriasis patients, capturing data on topical treatment at time of consultation prescribed to systemic-naïve patients with mild to moderate psoriasis (i.e. body surface area [BSA] ≤ 10%) at current treatment initiation. Patient clinical characteristics before/after topical use were evaluated descriptively. RESULTS: Among 304 patients (median age 43.0 years; 53.6% female), mean time since diagnosis was 60.9 months. After a mean 6.9 months on their current topical, 14.5% of patients achieved ≥75% BSA reduction, 38.9% ≥50% BSA reduction, and 50.2% no BSA reduction. Residual psoriasis symptoms included scaling (76.5%), inflamed skin (65.9%), and itching (60.4%). Most patients (71.2%) had residual psoriasis in special body areas: nails (92.3%), palmoplantar (78.9%), scalp (75.9%), and face (65.8%). CONCLUSION: We found unmet need in topical treatment effectiveness in mild to moderate psoriasis patients, in terms of BSA reduction, symptoms, and special body areas affected.

Patient Characteristics and Treatment Patterns in European Pediatric Patients with Psoriasis: A Real-World, Cross-Sectional Study.

INTRODUCTION: This study evaluated patient characteristics and treatment patterns according to weight in pediatric patients with psoriasis in a real-world setting. METHODS: Primary care and specialist physicians treating pediatric patients with psoriasis aged 6-17 years in five European countries were surveyed in the 2019-2020 Adelphi Real World Pediatric Psoriasis Disease Specific Programme. At least two patients with current or previous biologic use were included per physician. Patient characteristics and treatment patterns were analyzed overall and for patients weighing 25-50 kg or more than 50 kg. RESULTS: Data from 772 patients weighing 25-50 kg and 1147 weighing more than 50 kg were analyzed. Median age at diagnosis was significantly less in lighter than heavier patients (10.0 vs. 14.0 years; p < 0.001), as was median disease duration (2.2 vs. 3.0 years; p < 0.001). Topical treatments were prescribed in 59.0% of patients overall (70.3% of lighter and 51.4% of heavier patients; p < 0.001), and were used to treat mild rather than moderate-to-severe psoriasis. Conventional systemic use was low (10.8% of patients overall) and predominantly for moderate-to-severe psoriasis. In this biologic-enriched sample, most biologics (78.2%) were prescribed in older (> 13 years) patients. Biologic use increased with line of therapy (6.6% of first-line, 18.0% of second-line, 33.7% of third-line, 44.7% of fourth-line treatments). CONCLUSION: Biologics are predominantly prescribed in older (> 13 years) and heavier (> 50 kg) patients, with little first- or second-line use. The low use of biologics in European pediatric patients with psoriasis may represent an unmet treatment need, as topical or conventional systemic agents remain the main treatment option for moderate or severe psoriasis in these patients through the treatment pathway.

This study looked into types of treatments according to body weight in children with psoriasis, since approved dosing regimens for some treatments are based on body weight. Primary care and specialist physicians treating children with psoriasis aged 6­17 years in five European countries completed a survey. Patient information for those receiving specific types of psoriasis treatments were collected. Of the children included, 772 weighed 25­50 kg and 1147 weighed more than 50 kg. Most children received treatments applied to the skin, such as creams and ointments; this occurred in 70% of lighter patients and in 51% of heavier patients. Conventional treatments taken via the mouth were prescribed in a few patients (11% [overall]), while newer biologic drugs were taken to a greater extent in heavier (30%) than lighter (16%) patients. Most biologics (78%) were prescribed in older (> 13 years) patients. Biologic use increased with the number of failed previous treatments, comprising 7%, 18%, 34%, and 45% of first, second, third, and fourth treatments, respectively. We conclude that children with psoriasis who are treated with biologic drugs are predominantly older and heavier, and have more severe psoriasis. Prescriptions for biologics are given after many other treatments have been tried.

Physician-reported Clinical Unmet Needs, Burden and Treatment Patterns of Paediatric Psoriasis Patients: A US and EU Real-world Evidence Study.

This study is a retrospective analysis using data collected from the Adelphi Paediatric Psoriasis Disease-Specific Programme cross-sectional survey. Despite being treated for their psoriasis, a substantial proportion of paediatric patients presented with moderate (18.3%) or severe (1.3%) disease at sampling; 42.9% and 92.0% had a body surface area (BSA) of >10%, and 38.8% and 100.0% had a Psoriasis Area Severity Index (PASI) score >10, respectively. Overall, 69.9% of patients had only ever been treated with a topical therapy for their psoriasis. For patients with moderate or severe disease at sampling, 16.3% and 14.4% were currently receiving conventional systemics or biologic therapy, respectively. There is a clinical unmet need in this paediatric population; a considerable percentage of patients still experienced moderate or severe disease and persistent psoriasis symptoms, with numerous body areas affected. A significant proportion of patients were undertreated, which may explain the high burden of disease observed.

Assessment of the benefit of achieving complete versus almost complete skin clearance in psoriasis: a patient's perspective.

BACKGROUND: Psoriasis is characterized by thick and scaly plaques. The Dermatology Life Quality Index (DLQI) and Physician Global Assessment (PGA) can be used to define its severity. OBJECTIVE: To assess the impact of complete clearance of skin versus almost clear skin across various disease measures. METHODS: Data were collected in a survey of US dermatologists and patients with psoriasis from November 2016-January 2017. Dermatologists completed a 6-point PGA (0 = clear skin, 1 = almost clear skin). Patients completed the DLQI and Work Productivity and Activity Impairment questionnaire (WPAI). Patients with clear and almost clear skin were compared using analysis of covariance for continuous variables, and multivariate logistic regression analysis for categorical variables. RESULTS: Data for 99 and 160 patients with clear and almost clear skin, respectively, were included in the analyses. Patients with clear skin reported less frequent and lower intensity itching, lower total DLQI score (indicating better health-related quality of life), and less impairment of overall work productivity than patients with almost clear skin (all: p < 0.05). LIMITATIONS: Limitations relating to general survey methodology. CONCLUSION: Patients perceived a meaningful difference between clear and almost clear skin. Clear skin is now a realistic treatment target with newer biologics approved in psoriasis.

Factors influencing self-reported adherence to standard precautions among Thai nursing students: A cross sectional study.

AIM: This study explored nursing students' compliance with standard precautions (SPs) and attitudes to SPs in Thailand, to identify factors that may increase adherence to SPs and infection prevention and control best practice. BACKGROUND: In the context of high rates of healthcare associated infections as in Thailand, effective strategies to promote high levels of clinician adherence to SPs is a priority. Nursing students are one group of healthcare workers who play a vital role in caring for patients and constitute the future nursing workforce. DESIGN: A cross-sectional survey design was used. METHODS: A self-reported survey comprising the Compliance with Standard Precautions Scale and the Factors Influencing Adherence to Standard Precautions Scale were distributed to nursing students as a Thai paper-based survey. RESULTS: A total of '533 second' to fourth year nursing students from a tertiary nursing school in Bangkok, Thailand completed the survey. The average nursing student compliance to SPs was 68.5%. Most (91.2%) reported only using water for handwashing and 57.2% reported reuse of surgical masks. The fourth-year students had higher compliance (M=3.90, SD=1.12) on the 'prevention of cross infection from person-to-person' dimension while second-year students reported higher compliance on the 'disposal of sharps' (M=2.67, SD=0.57) dimension. 'Contextual Cues' was identified as the factor (M=3.41, SD=0.40) that had the greatest influence on adherence and 'Practice Culture' (M=1.84, SD=0.66) and 'Justification' (M = 1.35, SD.68 had the lowest influence. Fourth year students identified 'Leadership' (M=2.90, SD=0.49) as an important influence on adherence to SPs. CONCLUSIONS: To increase nursing students' adherence there needs to be greater emphasis on the importance of SPs in theoretical sessions and regular monitoring and feedback on hand hygiene performance and personal protective equipment use while students are on placements. More visible organizational leadership and promotion of high levels of adherence to SPs may assist students to translate their theoretical knowledge into practice.

Mindful energy and information flow: A reflective account of S.E.L.F connection during COVID-19.

Life during the COVID-19 pandemic is uncertain, intense, and traumatic. At the same time, there is room for hope, inspiration, and meaning for social workers through mindfully connecting with energy-information flow as it influences our Safety, Emotions, Loss, and Future - S.E.L.F. As adapted from the Sanctuary Model®, this S.E.L.F connection is an opportunity to discover within ourselves our unwavering core that is grounded, present, and connected and sustain an ethical and compassionate approach to social work practice, education, and research during this time of pandemic. The aim in this reflective essay is to provide an example of S.E.L.F. connection from the perspective of a Buddhist and social work academic at an Australian university during the COVID-19 pandemic. While beneficial, ongoing S.E.L.F. connections are necessary for social workers if we are to stay mindful of energy-information flow and steer this flow towards the creation of a story of relationship, compassion, and connection into the future.

An investigation into nursing students' application of infection prevention and control precautions.

BACKGROUND: Undergraduate education of Health Care Workers is pivotal to ensuring that frontline clinicians have appropriate knowledge and skills in Infection Prevention and Control (IPC). OBJECTIVES: The aim of this study was to describe undergraduate nursing students' self-reported compliance with Standard Precautions and to explore the psychosocial factors that influence adherence in clinical practice. DESIGN: A cross-sectional survey design was used. SETTING: The study was conducted in the School of Nursing and Midwifery at an Australian University. PARTICIPANTS: All undergraduate nursing students were invited to participate in an online survey; 321 participated, mean age 25.7 years (SD = 8.4). The majority, 196 (61%), had no healthcare work experience, 54 (17%) were patient-care assistants, 40 (13%) enrolled nurses, and 31 (9%) were nurses registered overseas. METHODS: Two validated instruments were used: the Compliance with Standard Precautions Scale (CSPS) and the Factors Influencing Adherence to Standard Precautions Scale- Student version (FIASPS-SV). Linear regression was used to measure the impact of psychosocial factors on self-reported compliance. RESULTS: Overall self-reported compliance with prevention of cross-infection was 83%, use of Personal Protective Equipment (81%), correct disposal of sharps (83%) and general waste (75%), and equipment decontamination (69%). The predominant factors endorsed on the FIASPS-SV were 'Leadership' (M = 15.21 SD = 5.28) and 'Contextual cues' (M = 19.09 SD = 6.37). Multivariate linear regression demonstrated that after adjusting for age, gender and years of nursing study, the Leadership factor predicted participants' self-reported compliance on the 'prevention of cross-infection' (p < .001), 'use of PPE' (p < .001), 'waste disposal' (p = .021), and 'decontamination of equipment' (p < .001) sub-domains of the CSPS. CONCLUSIONS: These findings highlight that strong clinical leadership and role modelling are essential to ensure all healthcare students prioritise rigorous adherence with infection prevention and control guidelines.

Determinants of patient and physician treatment satisfaction in moderate-to-severe psoriasis: a multinational survey of psoriasis patients.

There is a lack of validated information of both physician and patient-reported treatment satisfaction, and association with outcomes in psoriasis. Data from the 2015 Adelphi Psoriasis Disease Specific Programme were used to compare self-reported satisfaction with biologic and non-biologic therapy for psoriasis in physicians and their consulting patients in the United States (USA) and five European countries (EU5). Disease severity and health-related quality of life (HRQoL) were assessed using Body Surface Area (BSA) affected by psoriasis and the Dermatology Life Quality Index (DLQI), respectively. Patients satisfied with biologic therapy reported better HRQoL than unsatisfied patients, whereas a greater proportion of unsatisfied patients on biologic therapy had moderate-to-severe psoriasis (USA: 95.1% versus 52.4%, EU5; 86.4% versus 43.1%, P<0.0001). Multivariate logistic regression indicated that having a BSA affected by psoriasis of >10% was associated with lower likelihoods of physician and patient treatment satisfaction versus <3% (P<0.0001). A one-unit increase in the DLQI score lowered the likelihood of a patient being satisfied by approximately 20% (P<0.0001). Patients were ~60% more likely to be satisfied on biologic therapy than non-biologic therapy (P=0.0012). Physician and patient-reported treatment satisfaction was associated with greater HRQoL and lesser disease severity.

COVID-19 distress and worries: The role of attitudes, social support, and positive coping during social isolation.

As the COVID-19 pandemic accelerates, one public health response has been for governments to impose quarantine 'lockdowns' which require people to socially isolate. In this study, we explored the level of psychological distress that people experienced in social isolation and the factors which might ameliorate or exacerbate it. Two hundred and thirteen participants (69% female) with a mean age of 37.82 years participated in an online study. They completed a series of questions designed as part of a larger cross-national study. A positive attitude towards social isolation introduced by government as a strategy to reduce the transmission of COVID-19 was predictive of positive coping strategies, and both attitude and coping predicted reduced psychological distress. Participants' worries about contagion of COVID-19, their financial status, and the economic and political impact of the COVID-19 pandemic predicted increases in their psychological distress. Social support from family and work colleagues was not significant in reducing worries or psychological distress but it did positively predict engagement in coping. The findings and recommendations are discussed. PRACTITIONER POINTS: Fostering a positive attitude towards social isolation in clients: reduces psychological distress, fosters engagement in positive coping behaviours. Enhancing clients' level of social support received will serve to increase positive coping and indirectly reduce psychological distress during social isolation. Strategies to reduce clients' COVID-19 worries are important as worry contributes to their overall level of psychological distress.

The Factors Influencing Adherence to Standard Precautions Scale - Student version (FIASP- SV): A psychometric validation.

BACKGROUND: Standard Precautions have been demonstrated to limit infection transmission in the healthcare setting. Despite their mandated use, adherence by healthcare professionals remains suboptimal. A nursing curriculum embedding infection prevention and control is essential in equipping future healthcare professionals with the skills and knowledge to improve patient safety. There are no psychometrically-validated tools that specifically assess influences on nursing students' adherence to standard precautions. METHODS: The aim in this study was to determine the reliability and validity of the five-factor Factors Influencing Adherence to Standard Precautions within a sample of undergraduate nursing students studying at one Australian University. RESULTS: Data from 321 participants were used to test the 5 factors structure, using Confirmatory Factor Analysis. The goodness of fit indices did not support adequate fit of the data and the data were submitted to a random split-half sample factor analysis process. A four-factor solution was extracted with good to acceptable internal reliabilities (α = .66 -.80). CONCLUSION: There are distinctive differences in the factors that influence student versus registered nurses' behaviour and clinical decision-making in relation to use of SP. The Factors Influencing Adherence to Standard Precautions (Student Version) has good psychometric properties and is suitable for use with nursing students. Having measures specific to students is essential as measures developed for healthcare professionals might not be applicable to a nursing student population.

Clinical practice guidelines: Oral health care for children and adults living with epidermolysis bullosa.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a genetic disorder characterized by skin fragility and unique oral features. AIMS: To provide (a) a complete review of the oral manifestations in those living with each type of inherited EB, (b) the current best practices for managing oral health care of people living with EB, (c) the current best practices on dental implant-based oral rehabilitation for patients with recessive dystrophic EB (RDEB), and (d) the current best practice for managing local anesthesia, principles of sedation, and general anesthesia for children and adults with EB undergoing dental treatment. METHODS: Systematic literature search, panel discussion including clinical experts and patient representatives from different centers around the world, external review, and guideline piloting. RESULTS: This article has been divided into five chapters: (i) general information on EB for the oral health care professional, (ii) systematic literature review on the oral manifestations of EB, (iii) oral health care and dental treatment for children and adults living with EB-clinical practice guidelines, (iv) dental implants in patients with RDEB-clinical practice guidelines, and (v) sedation and anesthesia for adults and children with EB undergoing dental treatment-clinical practice guidelines. Each chapter provides recommendations on the management of the different clinical procedures within dental practice, highlighting the importance of patient-clinician partnership, impact on quality of life, and the importance of follow-up appointments. Guidance on the use on nonadhesive wound care products and emollients to reduce friction during patient care is provided. CONCLUSIONS: Oral soft and hard tissue manifestations of inherited EB have unique patterns of involvement associated with each subtype of the condition. Understanding each subtype individually will help the professionals plan long-term treatment approaches.

New computational protein design methods for de novo small molecule binding sites.

Protein binding to small molecules is fundamental to many biological processes, yet it remains challenging to predictively design this functionality de novo. Current state-of-the-art computational design methods typically rely on existing small molecule binding sites or protein scaffolds with existing shape complementarity for a target ligand. Here we introduce new methods that utilize pools of discrete contacts between protein side chains and defined small molecule ligand substructures (ligand fragments) observed in the Protein Data Bank. We use the Rosetta Molecular Modeling Suite to recombine protein side chains in these contact pools to generate hundreds of thousands of energetically favorable binding sites for a target ligand. These composite binding sites are built into existing scaffold proteins matching the intended binding site geometry with high accuracy. In addition, we apply pools of side chain rotamers interacting with the target ligand to augment Rosetta's conventional design machinery and improve key metrics known to be predictive of design success. We demonstrate that our method reliably builds diverse binding sites into different scaffold proteins for a variety of target molecules. Our generalizable de novo ligand binding site design method provides a foundation for versatile design of protein to interface previously unattainable molecules for applications in medical diagnostics and synthetic biology.

Exploration of Acetylation as a Base-Labile Protecting Group in Escherichia coli for an Indigo Precursor.

Biochemical protecting groups are observed in natural metabolic pathways to control reactivity and properties of chemical intermediates; similarly, they hold promise as a tool for metabolic engineers to achieve the same goals. Protecting groups come with costs: lower yields from carbon, metabolic load to the production host, deprotection catalyst costs and kinetics limitations, and wastewater treatment of the group. Compared to glycosyl biochemical protection, such as glucosyl groups, acetylation can mitigate each of these costs. As an example application where these benefits could be valuable, we explored acetylation protection of indoxyl, the reactive precursor to the clothing dye, indigo. First, we demonstrated denim dyeing with chemically sourced indoxyl acetate by deprotection with base, showing results comparable to industry-standard denim dyeing. Second, we modified an Escherichia coli production host for improved indoxyl acetate stability by the knockout of 14 endogenous hydrolases. Cumulatively, these knockouts yielded a 67% reduction in the indoxyl acetate hydrolysis rate from 0.22 mmol/g DCW/h to 0.07 mmol/g DCW/h. To biosynthesize indoxyl acetate, we identified three promiscuous acetyltransferases which acetylate indoxyl in vivo. Indoxyl acetate titer, while low, was improved 50%, from 43 µM to 67 µM, in the hydrolase knockout strain compared to wild-type E. coli. Unfortunately, low millimolar concentrations of indoxyl acetate proved to be toxic to the E. coli production host; however, the principle of acetylation as a readily cleavable and low impact biochemical protecting group and the engineered hydrolase knockout production host should prove useful for other metabolic products.

Treatment patterns among patients with moderate-to-severe ulcerative colitis in the United States and Europe.

OBJECTIVE: The aim of the present study is to examine how moderate-to-severe ulcerative colitis (UC) is currently managed in real-world clinical practice across the United States (US) and European Union Five (EU5; France, Germany, Italy, Spain, and the United Kingdom). METHODS: Data from the 2017 Adelphi Inflammatory Bowel-Disease Specific Programme (IBD-DSP) were used. The IBD-DSP is a database of patient chart information abstracted by selected gastroenterologists across the US and EU5. Eligible gastroenterologists who agreed to participate were asked to complete patient record forms for the next seven consecutive eligible adult patients with UC. Only charts from patients with moderate-to-severe UC were included in the analysis (defined as those with documented administration of either an immunosuppressant [IM] or a biologic). Treatment patterns were reported descriptively. RESULTS: 411 and 1191 patient charts were included in the US and EU5 (mean ages 44.2 and 39.6 years; 53.0% and 43.5% female), respectively. For those with complete treatment history, 40.7% and 52.9% used either an IM or biologic as their first treatment (with or without steroids). Usage of these therapies increased in subsequent lines. The percentage of patients treated with combination therapy (i.e., biologic therapy with a concomitant IM) in first line generally varied between 10-20% (e.g., US: adalimumab (ADA), 10.8%; infliximab (IFX), 18.2%; EU5: ADA, 12.5%; IFX, 19.9%), though increased in later lines in the EU5. Among patients currently using a biologic therapy, between 10-40% of patients used a higher than indicated dose or greater than indicated dosing frequency during maintenance (e.g., US: IFX, 37.1%; ADA, 13.4%; EU5: IFX, 39.1%; ADA, 36.1%). In both the US and EU5, the primary reason for switching therapy was efficacy-related. CONCLUSIONS: In this analysis, many patients with moderate-to-severe UC use an IM or biologic as their first therapy after diagnosis. Combination therapy and dose escalation are also common, and underscore the challenges with managing this patient population.

The association between disease activity and patient-reported outcomes in patients with moderate-to-severe ulcerative colitis in the United States and Europe.

BACKGROUND: Patients with ulcerative colitis (UC) experience periods of recurring and episodic clinical signs and symptoms. This study sought to establish the association between disease activity and health-related quality of life (HRQoL) and other patient-reported outcomes. METHODS: United States (US) and European Union 5 ([EU5]; i.e., France, Germany, Italy, Spain, and the United Kingdom) data from the 2015 and 2017 Adelphi Inflammatory Bowel Disease-Specific Programme (IBD-DSP) were used. The IBD-DSP is a database of retrospective patient chart information integrated with patient survey data (EuroQoL-5 Dimensions [EQ-5D], Short Quality of Life in Inflammatory Bowel Disease Questionnaire [SIBDQ], and Work Productivity and Activity Impairment-Ulcerative Colitis [WPAI-UC] questionnaire). Using available chart information, physicians classified their moderate-to-severe patients into one of the following categories: remission with a Mayo endoscopic score = 0 ("deep remission"), remission without a Mayo endoscopic score = 0 ("remission"), or active disease. Differences among disease activity categories with respect to patient-reported outcomes were analyzed using generalized linear models, controlling for confounding variables. RESULTS: N = 289 and N = 1037 patient charts with linked surveys were included from the US and EU5, respectively. The disease activity distribution was as follows: active disease = 40.1% (US) and 33.6% (EU5); remission = 48.0 and 53.0%; deep remission = 11.9 and 13.3%. Patients with active disease reported significantly lower levels of EQ-5D health state utilities (adjusted mean [AdjM] = 0.87 [US] and 0.78 [EU5]) compared with remission (AdjM = 0.92 and 0.91) and deep remission (AdjM = 0.93 and 0.91) (all P < 0.05 compared with active disease within each region). Similar findings were observed with the scores from the SIBDQ and the WPAI-UC. No significant differences were observed between remission categories. CONCLUSIONS: Among patients with moderate-to-severe UC in the US and EU5, active disease was associated with significant impairments in HRQoL, work and leisure activities. These results reinforce the importance, to both the patient and society, of achieving some level of remission to restore generic and disease-related HRQoL and one's ability to work productively.