ABSTRACT
Peer recovery coaches utilize their lived experiences to support overdose survivors, a role gaining prominence across communities. A convergent mixed methods design, informed by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, was used to evaluate the Recovery Opioid Overdose Team Plus (ROOT +), through an iterative evaluation using web-based surveys and qualitative interviews. Reach: Over 27 months, ROOT + responded to 83% of suspected overdose referrals (n = 607) and engaged with 41% of survivors (n = 217) and 7% of survivors' family/friends (n = 38). Effectiveness: Among those initially engaged with ROOT +, 36% of survivors remained engaged, entered treatment, or were in recovery at 90 days post-overdose (n = 77). Adoption: First responders completed 77% of ROOT + referrals (n = 468). Implementation: Barriers included lack of awareness of ROOT + , working phones, and access to treatment from community partner interviews (n = 15). Maintenance: Adaptations to ROOT + were made to facilitate implementation. Peer-led teams are promising models to engage with overdose survivors.
ABSTRACT
Policymakers are exploring ways to expand access to doula care to address persistent inequities in maternal and infant health across the United States. Doulas are non-medical professionals who provide physical, emotional, and informational support to birthing people before, during and after childbirth. Growing evidence supports the role of doulas in improved birth outcomes. Delaware is among several states moving towards Medicaid reimbursement for doula care to serve those most at risk. Objective: To gain an in-depth understanding of key stakeholders' knowledge, attitudes, beliefs and experiences regarding doula training and certification, relationships among providers, and other potential needs related to infrastructure to identify areas of agreement and inform policy change in the state of Delaware. Methods: We conducted focus groups with 11 doulas and key-informant interviews with 12 licensed providers practicing in Delaware, including six nurses, four physicians and two certified nurse midwives. Qualitative data was collected via Zoom (video conferencing) between September 2022 and April 2023. Results: Analysis revealed themes related to training, credentials and competencies of doulas, including cultural competence; logistical, administrative, and financial considerations for policy and practice change; and the whole care team-relationships between doulas and medical partners, and opportunities for growth. Conclusions: Doulas and licensed providers agree on key elements of doula training, the value of certification, the need for financial support, and the importance of relationship-building across the care team. Policy implications: Areas of agreement among stakeholders provide a foundation for state leaders to move forward to ensure the delivery of the most accessible, high quality, and culturally competent doula care for birthing people in Delaware.
ABSTRACT
BACKGROUND: Sepsis alerts commonly used for intensive care unit (ICU) patients can lead to alert fatigue because these patients generally meet 1 or more of the criteria for systemic inflammatory response syndrome. To identify ICU patients at greatest risk for sepsis-related consequences, an ICU-specific sepsis alert was implemented. OBJECTIVE: To evaluate an ICU sepsis alert based on modified criteria for systemic inflammatory response syndrome among critically ill medical patients. METHODS: This retrospective evaluation was conducted at a comprehensive tertiary referral center. Patients included were at least 18 years old, were admitted to the critical care medicine service, and had at least 1 sepsis alert between January 1 and February 29, 2020. The sepsis alert identified patients meeting at least 2 modified systemic inflammatory response syndrome criteria (white blood cell count, <4000/µL or >12 000/µL; body temperature, <36 °C or >38.3 °C; heart rate, >110/min; and respiratory rate, >21/min), with at least 1 of the 2 criteria being white blood cell count or body temperature. RESULTS: For 128 alerts evaluated, the positive predictive value was 72%. Of 713 patients who were admitted to the critical care medicine service and did not have a sepsis alert, 7 received a sepsis diagnosis. The ICU sepsis alert had a negative predictive value of 99%, sensitivity of 92.9%, and specificity of 95.1%. CONCLUSIONS: An ICU sepsis alert using modified systemic inflammatory response syndrome criteria was effective for identifying sepsis in critically ill medical patients.
Subject(s)
Critical Illness , Intensive Care Units , Sepsis , Systemic Inflammatory Response Syndrome , Humans , Retrospective Studies , Male , Female , Middle Aged , Sepsis/diagnosis , Aged , Systemic Inflammatory Response Syndrome/diagnosis , Adult , Alert Fatigue, Health PersonnelABSTRACT
OBJECTIVE: Both Indigenous and non-Indigenous governments and organizations have increasingly called for improved Indigenous health data in order to improve health equity among Indigenous peoples. This scoping review identifies best practices, potential consequences and barriers for advancing Indigenous health data and Indigenous data sovereignty globally. METHODS: A scoping review was conducted to capture the breadth and nature of the academic and grey literature. We searched academic databases for academic records published between 2000 and 2021. We used Google to conduct a review of the grey literature. We applied Harfield's Aboriginal and Torres Strait Islander Quality Appraisal Tool (QAT) to all original research articles included in the review to assess the quality of health information from an Indigenous perspective. RESULTS: In total, 77 academic articles and 49 grey literature records were included. Much of the academic literature was published in the last 12 years, demonstrating a more recent interest in Indigenous health data. Overall, we identified two ways for Indigenous health data to be retrieved. The first approach is health care organizations asking clients to voluntarily self-identify as Indigenous. The other approach is through data linkage. Both approaches to improving Indigenous health data require awareness of the intergenerational consequences of settler colonialism along with a general mistrust in health care systems among Indigenous peoples. This context also presents special considerations for health care systems that wish to engage with Indigenous communities around the intention, purpose, and uses of the identification of Indigenous status in administrative databases and in health care settings. Partnerships with local Indigenous nations should be developed prior to the systematic collection of Indigenous identifiers in health administrative data. The QAT revealed that many research articles do not include adequate information to describe how Indigenous communities and stakeholders have been involved in this research. CONCLUSION: There is consensus within the academic literature that improving Indigenous health should be of high priority for health care systems globally. To address data disparities, governments and health organizations are encouraged to work in collaboration with local Indigenous nations and stakeholders at every step from conceptualization, data collection, analysis, to ownership. This finding highlights the need for future research to provide transparent explanation of how meaningful Indigenous collaboration is achieved in their research.
Subject(s)
Health Services, Indigenous , Humans , Health Services, Indigenous/organization & administration , Indigenous Peoples , Native Hawaiian or Other Pacific IslanderABSTRACT
Objective: The objective of this study is to assess the perceptions of Indigenous medical students on postgraduate admissions through an Indigenous admissions pathway (IAP), and to determine what factors may influence Indigenous medical students' choice of residency training program. Methods: We distributed a survey to self-identified Indigenous students at settler Canadian medical schools. The survey questioned the students' acceptability of an IAP, and what factors would influence application through an IAP. Analysis included descriptive statistics and thematic analysis of open-ended questions. Results: Thirty-six participants responded to the survey. Location and proximity to family or support system were the most important factors in choosing a residency program. Participants identified mentorship from Indigenous physicians and community involvement as being important features of a residency program that has an IAP. Eighty-one percent of participants felt the availability of an IAP would influence their choice of residency program. Fear of judgement or stigma, concern about entrance requirements, and program logistics were identified as barriers to applying to residency through an IAP. All participants believed that an IAP would have a positive influence on the healthcare system more broadly. Conclusions: An IAP appears to be an acceptable residency application format to Indigenous students but cannot exist in isolation. It is important for programs to consider the needs and safety of Indigenous trainees within residency programs.
Objectif: L'objectif de cette étude était d'avoir le point de vue des étudiants en médecine autochtones sur une éventuelle voie d'admission aux études postdoctorales réservée aux candidats autochtones et de relever les facteurs qui influenceraient leur choix de programme de résidence. Méthodes: Nous avons fait parvenir un questionnaire aux étudiants inscrits dans les facultés de médecine canadiennes qui se définissent comme Autochtones. L'enquête portait sur l'acceptabilité par les étudiants d'un programme d'admission pour candidats autochtones (PACA) et sur les facteurs qui influenceraient leur choix de poser leur candidature dans le cadre d'un PACA. Les données ont été évaluées par des méthodes statistiques descriptives et par une analyse thématique des questions ouvertes. Résultats: Trente-six participants ont répondu à l'enquête. Le lieu et la proximité de la famille ou du réseau de soutien ressortent comme les facteurs les plus importants dans le choix d'un programme de résidence. Les répondants attachent également de l'importance à l'existence d'un mentorat de la part de médecins autochtones et à une participation de la communauté dans le cadre d'un programme de résidence doté d'un PACA. Quatre-vingt-un pour cent des participants ont estimé que l'existence d'un PACA influencerait leur choix de programme de résidence. La crainte d'être jugé ou stigmatisé, et une inquiétude par rapport aux conditions d'admission et la logistique du programme ont été identifiées comme des obstacles à la présentation d'une demande de résidence dans le cadre d'un PACA. Les participants sont unanimes quant à l'influence positive d'un tel programme sur le système de soins de santé en général. Conclusions: Les étudiants autochtones trouvent la formule d'une voie d'admission à la résidence réservée aux candidats autochtones acceptable, à condition qu'elle ne soit pas un élément isolé et qu'on tienne compte des besoins et de la sécurité des étudiants dans le cadre des programmes de résidence eux-mêmes.
Subject(s)
Internship and Residency , Students, Medical , Humans , Canada , Surveys and Questionnaires , Schools, MedicalABSTRACT
BACKGROUND: Rapid identification and timely management of sepsis improve survival. Therefore, a bundled approach to care is recommended. LOCAL PROBLEM: In an acute care area of the study institution, a 2016 internal evaluation of 27 patients with sepsis showed a median time to first-dose antibiotic administration of 269 minutes, with no patients receiving antibiotics within the 60-minute target time. Additionally, only one-third of patients received appropriate fluid resuscitation (30-mL/kg bolus of intravenous crystalloids). Given poor bundle compliance, a nurse-driven rapid response team protocol for suspected sepsis was implemented. The purpose of this project was to assess the protocol's impact on the timeliness of treatment for sepsis. METHODS: This retrospective quality improvement evaluation involved patients aged 18 years or older for whom the suspected sepsis protocol was initiated during their acute care area admission. The evaluation focused on improvements in time to intravenous antibiotic administration and volume of fluid resuscitation compared with before protocol implementation. The protocol empowers the rapid response team to initiate sepsis management and includes pertinent laboratory tests, blood cultures, intravenous broad-spectrum antibiotic administration, and a crystalloid bolus (30 mL/kg) if indicated. RESULTS: A total of 32 patients were evaluated. Time to first-dose antibiotic administration was reduced by half (from 269 to 135 minutes). Eighteen patients met criteria for fluid resuscitation, with twice as many receiving appropriate fluid volumes compared with before protocol implementation. CONCLUSION: Implementation of the suspected sepsis protocol demonstrates the substantial role nurses have in optimizing patient care, especially in the timely treatment of sepsis.
Subject(s)
Hospital Rapid Response Team , Sepsis , Anti-Bacterial Agents/therapeutic use , Crystalloid Solutions/therapeutic use , Humans , Retrospective Studies , Sepsis/diagnosis , Sepsis/drug therapyABSTRACT
BACKGROUND: Patients in remote communities who risk premature delivery require transfer to a tertiary care centre for obstetric and neonatal care. Following stabilisation, many patients are candidates for outpatient management but cannot be discharged to their home communities due to lack of neonatal intensive care unit (ICU) support. PROBLEM: Without outpatient accommodation proximal to neonatal ICU, these patients face prolonged hospitalisation-an expensive option with medical, social and psychological consequences. Therefore, we sought to establish an alternative accommodation for out-of-town stable antepartum patients. METHODS: Quality Improvement approaches were used to identify process strengths and opportunities for improvement on the antepartum ward in a tertiary care centre. Physician and patient surveys informed outpatient accommodation programme development by a multidisciplinary team. The intervention was implemented using a plan-do-study-act cycle. Barriers to patient discharge and enrolment in the programme were analysed by completing thematic and strengths-weaknesses-opportunities-threats (SWOT) analysis. RESULTS: Physicians broadly supported safe outpatient management, whereas patients were hesitant to leave the hospital even when physicians assured safety. Our alternative accommodation was pre-existing and cost-effective, however, we encountered significant barriers. The physical space limited family visits and social interaction, lacked desired amenities,and the programme proved inconvenient to patients. The thematic and SWOT analysis identified aspects of the intervention which can be optimised to develop future actionable strategies. CONCLUSION: The utilisation of acute care beds is costly for the healthcare system and must be allocated judiciously. Patient needs, experience and health system barriers need to be considered when establishing alternative outpatient accommodations and strategies for stable antepartum patients.
Subject(s)
Critical Care , Patient Discharge , Delivery of Health Care , Female , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Pregnancy , Tertiary Care CentersABSTRACT
BACKGROUND: Meaningful performance measurement requires indicators to be scientifically robust and strategically focused. For many circumpolar states, indicators aligned with national strategies may ignore the priorities of northern, remote, or Indigenous populations. The aim of this project was to identify contextually appropriate performance indicators for maternity care in circumpolar regions. METHODS: Fourteen maternity care and health systems experts participated in a modified Delphi consensus process. The list of proposed indicators was derived from a previously published scoping review. Fourteen participants rated each proposed indicator according to importance, circumpolar relevance, validity, and reliability and suggested additional indicators for consideration. RESULTS: Consensus was achieved after two rounds, as measured by a Cronbach's alpha of 0.87. Eleven indicators, many of which represented physical health outcomes, were ranked highly on all four criteria. Twenty-nine additional indicators, largely focused on social determinants of health, health care responsiveness, and accessibility, were identified for further research. Travel for care, cultural safety and upstream structural determinants of health were identified as important themes. CONCLUSIONS: This study identified the important gaps between current performance measurement strategies and the context and values that permeate maternal-child health in circumpolar regions. The indicators identified in this study provide an important foundation for ongoing work. We recommend that future work encompass an appreciation for the intersectoral nature of social, structural, and colonial determinants of maternal-child health in circumpolar regions.
Subject(s)
Maternal Health Services , Quality Indicators, Health Care , Child , Consensus , Delphi Technique , Female , Humans , Pregnancy , Reproducibility of ResultsABSTRACT
Forced and coerced sterilization refers to the provision of permanent contraception without true informed consent. In Canada, this topic is particularly relevant to Indigenous Peoples because of this country's history of racialized eugenics programs. In this commentary, we briefly review the history of forced and coerced sterilization in Canada, describe the clinical considerations for health care providers who work with Indigenous patients in this context, and outline calls to action for health care providers and organizations to support the provision of culturally appropriate reproductive health care to Indigenous people.
Subject(s)
Indigenous Peoples , Population Groups , Contraception , Health Personnel , Humans , SterilizationABSTRACT
BACKGROUND: In critically ill patients, maintaining appropriate serum potassium concentrations requires careful supplementation to correct hypokalemia but avoid hyperkalemia. At the study institution, an institution-based, nurse-driven standardized electrolyte replacement protocol is used in critically ill patients with a serum creatinine concentration of 2 mg/dL or less. If the serum creatinine concentration is greater than 2 mg/dL, electrolyte replacement requires a physician order. OBJECTIVE: To determine if standardized potassium supplementation is safe in critically ill patients with renal insufficiency not requiring renal replacement therapy. METHODS: This study was an institutional review board-approved, single-center, retrospective evaluation of critically ill patients receiving intravenous potassium replacement per protocol. Patients were grouped according to serum creatinine concentration (≤ 2 mg/dL or > 2 mg/dL) at the time of replacement. The primary outcome was the incidence of hyperkalemia (potassium concentration ≥ 5 mEq/L) following potassium replacement. Secondary outcomes were the incidence of hyperkalemia, change in serum potassium concentration, and need for hyperkalemia treatment. Outcomes were analyzed using χ2 and t tests. RESULTS: Of 814 patients screened, 145 were included (99 with serum creatinine ≤ 2 mg/dL and 46 with serum creatinine > 2 mg/dL). The incidence of hyperkalemia was not different between groups (P = .57). Five patients experienced hyperkalemia; none received hyperkalemia treatment. Change in serum potassium was similar for patients in the 2 groups (P = .33). CONCLUSIONS: A standardized, nurse-driven electrolyte replacement protocol can be used safely in critically ill patients with renal insufficiency not requiring renal replacement therapy.
Subject(s)
Hyperkalemia , Renal Insufficiency , Critical Illness , Humans , Hyperkalemia/chemically induced , Potassium , Retrospective StudiesABSTRACT
BACKGROUND: Prone positioning is a standard treatment for moderate to severe acute respiratory distress syndrome (ARDS), but the outcomes associated with manual versus automatic prone positioning have not been evaluated. OBJECTIVE: To retrospectively evaluate outcomes associated with manual versus automatic prone positioning as part of a pronation quality improvement project implemented by a multidisciplinary team. METHODS: A retrospective, descriptive-comparative approach was used to analyze data from 24 months of a prone positioning protocol for ARDS. The study involved 37 patients, with 16 undergoing manual and 21 undergoing automatic prone positioning. Descriptive and nonparametric statistical analyses were used to evaluate outcomes associated with manual versus automatic prone positioning. RESULTS: Outcomes were similar between the 2 groups regarding time to initiation of prone positioning, discharge disposition, and length of stay. Manually pronated patients were less likely to experience interruptions in therapy (P = .005) and complications (P = .002). Pressure injuries were the most common type of complication, with the most frequent locations in automatically pronated patients being the head (P = .045), thorax (P = .003), and lower extremities (P = .047). Manual prone positioning resulted in a cost avoidance of $78 617 per patient. CONCLUSION: Manual prone positioning has outcomes similar to those of automatic prone positioning with less risk of interruptions in therapy, fewer complications, and lower expense. Further research is needed to determine whether manual prone positioning is superior to automatic prone positioning in patients with ARDS.
Subject(s)
Patient Positioning , Prone Position , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/therapy , Retrospective StudiesABSTRACT
BACKGROUND: Vulvar trauma is relatively uncommon and typically occurs in accidental or sports-related injuries. There is limited literature for management of penetrating trauma to the vulva. CASE: A 38-year-old G9, P9 woman presented to the gynaecology service for assessment of vulvar injury after a gunshot wound to the right lateral thigh. She underwent initial stabilization and operative management by the Trauma and Plastic Surgery services for predominantly soft-tissue injuries. Multiple gunshot pellets were found embedded in the right labia majora and medial thigh. On assessment, surgical removal was deemed necessary on the basis of symptoms and potential for functional impairment. CONCLUSION: We present the first reported case on the management of vulvar injury secondary to penetrating trauma. The principles of non-obstetrical vulvar trauma management are discussed.
Subject(s)
Soft Tissue Injuries/surgery , Vulva/surgery , Wounds, Penetrating , Adult , Female , Humans , Tomography, X-Ray Computed , Treatment Outcome , Wounds, Gunshot/diagnostic imaging , Wounds, Gunshot/surgeryABSTRACT
This symposium report provides a brief overview of the six programmes and studies on parental education and maternal health services within the circumpolar region presented in the symposium "parental education" at the 17th International Congress of Circumpolar Health in Copenhagen, Denmark, August 2018.
Subject(s)
Maternal Health Services/organization & administration , Parents/education , Arctic Regions , Breast Feeding/ethnology , Child Development , Cultural Competency , Humans , Infant , Infant, Newborn , Maternal Health Services/standards , Mothers/education , Parenting/ethnology , Quality Indicators, Health CareABSTRACT
The 2013 pan-Canadian consensus Report on Resident Duty Hours identified that traditional 24-hour duty periods pose risks to the well-being of residents and should be avoided. In anticipation of duty-hour restrictions, the Obstetrics and Gynaecology Residency Program at the University of Toronto developed and implemented a night float (NF) call model over a three-year span. Quarterly resident surveys have consistently shown that the NF system is preferred to traditional 24-hour call and has resulted in reduced fatigue and improved continuity of patient care. Through many iterations, the NF model achieved levels of resident morale, surgical experience, and impact on family relationships that are comparable to the 24-hour call system. We review here our process for developing an NF call model and the perceptions and experiences of residents, with the goal of providing insight for other residency programs that are considering or instituting NF call systems.
Subject(s)
Attitude of Health Personnel , Gynecology/organization & administration , Internship and Residency/organization & administration , Obstetrics/organization & administration , Physicians , Work Schedule Tolerance , Canada , Female , Humans , Physicians/psychology , Physicians/statistics & numerical dataABSTRACT
BACKGROUND: In circumpolar regions, harsh climates and scattered populations have prompted the centralization of care and reduction of local maternity services. The resulting practice of routine evacuation for birth from smaller towns to larger urban centres points to a potential conflict between the necessity to ensure patient safety and the importance of delivering services that are responsive to the health needs and values of populations served. OBJECTIVE: To identify recommended performance/quality indicators for use in circumpolar maternity care systems. METHODS: We searched Scopus, Ebscohost databases (including Academic Search Complete and CINAHL), the Global Health Database, High North Research Documents, and online grey literature. Articles were included if they focused on maternal health indicators in the population of interest (Indigenous women, women receiving care in circumpolar or remote regions). Articles were excluded if they were not related to pregnancy, birth or the immediate post-partum or neonatal periods. Two reviewers independently reviewed articles for inclusion and extracted relevant data. RESULTS: Twenty-six documents were included. Twelve were government documents, seven were review articles or indicator compilations, four were indicator sets recommended by academics or non-governmental organizations and three were research papers. We extracted and categorized 81 unique health indicators. The majority of indicators reflected health systems processes and outcomes during the antenatal and intra-partum periods. Only two governmental indicator sets explicitly considered the needs of Indigenous peoples. CONCLUSIONS: This review demonstrates that, although most circumpolar health systems engage in performance reporting for maternity care, efforts to capture local priorities and values are limited in most regions. Future work in this area should involve northern stakeholders in the process of indicator selection and development.
Subject(s)
Maternal Health Services/standards , Quality Indicators, Health Care/standards , Arctic Regions , Female , Humans , Inuit , PregnancyABSTRACT
When exposed to high osmolarity, methicillin-resistant Staphylococcus aureus (MRSA) restores its growth and establishes a new steady state by accumulating the osmoprotectant metabolite betaine. Effective osmoregulation has also been implicated in the acquirement of a profound antibiotic resistance by MRSA. Betaine can be obtained from the bacterial habitat or produced intracellularly from choline via the toxic betaine aldehyde (BA) employing the choline dehydrogenase and betaine aldehyde dehydrogenase (BADH) enzymes. Here, it is shown that the putative betaine aldehyde dehydrogenase SACOL2628 from the early MRSA isolate COL (SaBADH) utilizes betaine aldehyde as the primary substrate and nicotinamide adenine dinucleotide (NAD(+)) as the cofactor. Surface plasmon resonance experiments revealed that the affinity of NAD(+), NADH and BA for SaBADH is affected by temperature, pH and buffer composition. Five crystal structures of the wild type and three structures of the Gly234Ser mutant of SaBADH in the apo and holo forms provide details of the molecular mechanisms of activity and substrate specificity/inhibition of this enzyme.
Subject(s)
Betaine-Aldehyde Dehydrogenase/chemistry , Betaine-Aldehyde Dehydrogenase/metabolism , Betaine/analogs & derivatives , NAD/metabolism , Staphylococcus aureus/enzymology , Betaine/metabolism , Binding Sites , Crystallography, X-Ray , Kinetics , Models, Molecular , Protein Binding , Protein Conformation , Substrate SpecificityABSTRACT
Biophysical fragment screening of a thermostabilized ß1-adrenergic receptor (ß1AR) using surface plasmon resonance (SPR) enabled the identification of moderate affinity, high ligand efficiency (LE) arylpiperazine hits 7 and 8. Subsequent hit to lead follow-up confirmed the activity of the chemotype, and a structure-based design approach using protein-ligand crystal structures of the ß1AR resulted in the identification of several fragments that bound with higher affinity, including indole 19 and quinoline 20. In the first example of GPCR crystallography with ligands derived from fragment screening, structures of the stabilized ß1AR complexed with 19 and 20 were determined at resolutions of 2.8 and 2.7 Å, respectively.
Subject(s)
Biophysical Phenomena , Drug Design , Piperazines/chemistry , Piperazines/metabolism , Receptors, Adrenergic, beta-1/metabolism , Drug Evaluation, Preclinical , HEK293 Cells , Humans , Molecular Docking Simulation , Piperazine , Protein Binding , Protein Conformation , Receptors, Adrenergic, beta-1/chemistry , Surface Plasmon ResonanceABSTRACT
We took a different approach to reviewing the commercial biosensor literature this year by inviting 22 biosensor users to serve as a review committee. They set the criteria for what to expect in a publication and ultimately decided to use a pass/fail system for selecting which papers to include in this year's reference list. Of the 1514 publications in 2009 that reported using commercially available optical biosensor technology, only 20% passed their cutoff. The most common criticism the reviewers had with the literature was that "the biosensor experiments could have been done better." They selected 10 papers to highlight good experimental technique, data presentation, and unique applications of the technology. This communal review process was educational for everyone involved and one we will not soon forget.
Subject(s)
Biosensing Techniques/statistics & numerical data , Optical Devices/statistics & numerical data , Peer Review, Research , Data CollectionABSTRACT
Biophysical studies with G-protein-coupled receptors (GPCRs) are typically very challenging due to the poor stability of these receptors when solubilized from the cell membrane into detergent solutions. However, the stability of a GPCR can be greatly improved by introducing a number of point mutations into the protein sequence to give a stabilized receptor or StaR®. Here, we present the utility of StaRs for biophysical studies and the screening of fragment libraries. Two case studies are used to illustrate the methods: first, the screening of a library of fragments by surface plasmon resonance against the adenosine A(2A) receptor StaR, demonstrating how very small and weakly active xanthine fragments can be detected binding to the protein on chips; second, the screening and detection of fragment hits of a larger fragment library in an NMR format called TINS (target-immobilized NMR screening) against the ß(1) adrenergic StaR.