The prescription and monitoring of conventional synthetic disease-modifying anti-rheumatic drugs: British Society for Rheumatology guideline scope.

This guideline will provide up-to-date, evidence-based recommendations on the safe use of non-biologic DMARDs, also called conventional synthetic DMARDs (csDMARD), across the full spectrum of autoimmune rheumatic diseases. The guideline will update the guideline published in 2017 and will be expanded to include people of all ages. Updated information on the monitoring of DMARDs and vaccinations will be included. The guideline will be developed using the methods and processes described in the British Society for Rheumatology's 'Creating clinical guidelines: our protocol', updated 2023.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients.

Background: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results: Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions: CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.

Effectiveness of digital health interventions on adherence and control of hypertension: a systematic review and meta-analysis.

BACKGROUND: Hypertension, a risk factor for developing cardiovascular disease, is becoming increasingly prevalent worldwide. Digital health is now widely utilized for hypertension management, and numerous studies have assessed its effectiveness. OBJECTIVE: The review aims to analyse the effectiveness of digital health (i.e., mobile health (mHealth), telehealth, and the combination of mHealth & telehealth) on hypertensive patients, concerning three key areas: clinical outcomes, medication adherence, and adherence to lifestyle changes, as compared to standard care. METHODS: The review followed the PRISMA framework. Eight electronic databases were scanned for randomized control trials focusing on the effects of mHealth or telehealth on hypertensive patients, published between 2010 and 2023. All processes were conducted by the first two authors independently. A meta-analysis was conducted for quantitative data, while a narrative synthesis was conducted for qualitative data. RESULTS: In total, 74 studies involving 92 686 participants were identified. The meta-analysis favoured the interventions, revealing a significant decrease in systolic blood pressure and diastolic blood pressure for mHealth, telehealth and mHealth & telehealth groups. Nevertheless, medication adherence showed improvement only in the mHealth group, while blood pressure control showed improvement in both mHealth and mHealth & telehealth groups, and BMI showed improvement only in the mHealth group. Evidence for adherence to physical activity and DASH diet/salt intake remained inconclusive. CONCLUSION: In general, mHealth and telehealth have demonstrated their merits in improving the clinical outcomes of hypertensive patients.

Performance of Tumor Surveillance for Children With Cancer Predisposition.

Importance: Pediatric oncology patients are increasingly recognized as having an underlying cancer predisposition syndrome (CPS). Surveillance is often recommended to detect new tumors at their earliest and most curable stages. Data on the effectiveness and outcomes of surveillance for children with CPS are limited. Objective: To evaluate the performance of surveillance across a wide spectrum of CPSs. Design, Setting, and Participants: This cohort study reviewed surveillance outcomes for children and young adults from birth to age 23 years with a clinical and/or molecular CPS diagnosis from January 1, 2009, through September 31, 2021. Patients were monitored using standard surveillance regimens for their corresponding CPS at a specialty pediatric oncology center. Patients with hereditary retinoblastoma and bone marrow failure syndromes were excluded. Data were analyzed between August 1, 2021, and December 6, 2023. Exposure: Cancer predisposition syndrome. Main Outcomes and Measures: Outcomes of surveillance were reviewed to evaluate the incidence, spectrum, and clinical course of newly detected tumors. Surveillance modalities were classified for accuracy and assessed for common strengths and weaknesses. Results: A total of 274 children and young adults (mean age, 8 years [range, birth to 23 years]; 144 female [52.6%]) with 35 different CPSs were included, with a median follow-up of 3 years (range, 1 month to 12 years). During the study period, 35 asymptomatic tumors were detected in 27 patients through surveillance (9.9% of the cohort), while 5 symptomatic tumors were detected in 5 patients (1.8% of the cohort) outside of surveillance, 2 of whom also had tumors detected through surveillance. Ten of the 35 tumors (28.6%) were identified on first surveillance imaging. Malignant solid and brain tumors identified through surveillance were more often localized (20 of 24 [83.3%]) than similar tumors detected before CPS diagnosis (71 of 125 [56.8%]; P < .001). Of the 24 tumors identified through surveillance and surgically resected, 17 (70.8%) had completely negative margins. When analyzed across all imaging modalities, the sensitivity (96.4%), specificity (99.6%), positive predictive value (94.3%), and negative predictive value (99.6%) of surveillance were high, with few false-positive (6 [0.4%]) or false-negative (5 [0.3%]) findings. Conclusions and Relevance: These findings suggest that standardized surveillance enables early detection of new tumors across a wide spectrum of CPSs, allowing for complete surgical resection and successful treatment in the majority of patients.

Factors Related to, and Effective Interventions for, Vaccination Uptake Among Older Adults in Two Asia-Pacific Countries: A Rapid Review.

This rapid review aims to present a comprehensive overview of barriers, facilitators, and effective interventions that promote vaccination uptake by older adults in the Asia-Pacific region. Rapid review methodology was applied, using two databases (PubMed, Embase). Articles were included if studies were conducted in Australia, Singapore, Indonesia, and the Philippines; included human population ≥50 years of age, and was published from 2016 to August 2022. Related articles were not found from Indonesia and Philippines. A total of 23 articles met the inclusion criteria, with 19 reporting on barriers and facilitators, whereas, four articles reported effective interventions to promote vaccination uptake. Among the 19 studies that identified barriers and facilitators to vaccination uptake, the more common factors were social influences (n = 8/19), perceived benefits of vaccine (n = 7/19), and perceived vaccine safety (n = 6/19). Interventions that focused on supporting clinicians were found to be effective in leading them to recommend vaccinations among older adults, such as creating awareness on the low baseline vaccination rates among older adults, provision of structured health assessment, and nurse reminders. More studies are needed to ascertain the barriers and facilitators to uptake, as well as to identify effective interventions influencing vaccine uptake among older adults in the Asia-Pacific region.

Association of Vitamin A and D Deficiencies with Infectious Outcomes in Children Undergoing Intensive Induction Therapy for Acute Lymphoblastic Leukemia.

OBJECTIVE: To evaluate the association between deficiency of vitamin A or D at diagnosis of pediatric acute lymphoblastic leukemia (ALL) and subsequent infectious complications during induction therapy. STUDY DESIGN: An IRB-approved, retrospective cohort study of children diagnosed with newly-diagnosed ALL from 2007 to 2017 at St. Jude Children's Research Hospital. We measured vitamin D, vitamin D binding protein, retinol binding protein as a surrogate for vitamin A, and immunoglobulin isotypes in serum obtained at ALL diagnosis, and we assessed the association between vitamin deficiencies or levels and infection-related complications during the 6-week induction phase using Cox regression models. RESULTS: Among 378 evaluable participants, vitamin A and D deficiencies were common (43% and 17% respectively). Vitamin D deficiency was associated with higher risks of febrile neutropenia (adjusted hazard ratio [aHR] 1.7; p=0.0072), clinically-documented infection (aHR 1.73; p=0.025), and likely bacterial infection (aHR 1.86; p=0.008). Conversely, vitamin A deficiency was associated solely with a reduced risk of sepsis (aHR 0.19; p=0.027). CONCLUSIONS: In this retrospective study, vitamin D deficiency was associated with an increased risk of common infection-related complications during induction therapy for ALL. Additional studies are warranted to evaluate whether vitamin D supplementation could mitigate this effect.

Psychosocial factors in knee osteoarthritis: Scoping review of evidence and future opportunities.

OBJECTIVE: Identify, describe and produce an evidence map of studies investigating psychosocial factors association with, or effect on, clinical outcomes for people with knee osteoarthritis. METHODS: Scoping review of interventional and observational studies was performed. Medline (Ovid), Embase (Ovid), Cumulated Index in Nursing and Allied Health Literature, PsycInfo and Web of Science were searched on the 15th May 2023. Screening, data extraction and analysis was performed by two independent researchers. Extracted information included characteristics of studies plus which psychosocial factors were used to investigate association with, or effect on, clinical outcome(s). Descriptive statistics summarized the study design, temporal trend, geographic distribution, frequency of each psychosocial factor and whether associations/effects were observed. RESULTS: 23,065 records were screened, with 108 studies selected. Eighty-two percent of studies (n = 89/108) were cross-sectional in design. Number of studies increased over time and spanned 28 countries. Most research originated from the Americas region (55 %, 59/108). Twenty-four psychosocial factors (11 psychological, 13 social) were identified. Depression (47 %, n = 48/102) and education (28 %, n = 29/102) were the most frequently reported psychological and social factors, respectively. Psychological factors were often reported to have an association with/effect on pain (81 %, n = 71/88) and physical function (75 %, n = 56/74). Social factors were less frequently reported to have an association with or effect on pain (57 %, n = 46/81) and physical function (50 %, n = 18/36). CONCLUSION: Psychosocial factors are often associated with clinical outcomes for people with knee osteoarthritis. High-quality longitudinal studies examining a wide range of psychosocial factors across diverse cultural and geographical settings are key to continue informing the development of biopsychosocial models of care.

Risk assessment and the use of personal protective equipment in an emergency department: Differing perspectives of emergency and infection control clinicians. A video-vignette survey.

BACKGROUND: The use of personal protective equipment (PPE) in emergency departments (EDs) is an important defense during infectious disease emergencies. However, what counts as appropriate PPE in EDs is contentious and inconsistently implemented in practice. METHODS: An online scenario-based video survey was distributed through purposive sampling, and completed by 270 ED and infection prevention and control clinicians in Australia. A descriptive content analysis was performed on the data, and differences between groups were tested using Fisher exact test. RESULTS: Participants agreed that most items were required in both scenarios. Eye protection, mask use, and hand hygiene frequency were more contentious. Physicians were more likely than nurses, and ED clinicians more likely than infection prevention and control clinicians, to regard items or actions as optional rather than essential. Many ED clinicians, particularly physicians, regarded sequences as too time-consuming to be practical in a busy ED. DISCUSSION: Our findings likely reflect differences in professional roles, competing priorities, and risks, and highlight important contextual characteristics of EDs, such as diagnostic uncertainty, equipment inaccessibility, and resource constraints. CONCLUSIONS: To be feasible, practicable, and thereby effective, PPE guidance in the ED must be designed collaboratively with frontline ED staff, and reflects the complexities of their practice.

Developing a Mental Health Screening Questionnaire in an Asian Children's Hospital Emergency Setting.

INTRODUCTION: Mental health concerns among adolescents are increasingly prevalent, yet underrecognized. Adolescents with psychological distress often present to the emergency department (ED) with somatic symptoms. Due to inadequate time for rapport building and lack of familiarity of ED clinicians with psychosocial evaluation, these concerns often get missed. We describe the development and implementation of the Youth Well Being (YWB) questionnaire, a self-administered psychosocial screening tool that aims to overcome the communication barriers to psychosocial evaluation. METHODS: A multidisciplinary team used a Delphi-like approach to develop the questionnaire, using the home, education, activities/peers, drugs/alcohol, suicidality, emotions/behavior, discharge resources (HEADS-ED) questionnaire as the main reference. Modifications were made based on panel members' clinical experience and adapted to suit local sociocultural context. The YWB questionnaire is administered to adolescents aged 10 to 19 years presenting to the KK Women's and Children's Hospital ED with possible psychosomatic symptoms and behavioral or mental health issues. Positive findings prompt further targeted face-to-face interviews by the clinicians to facilitate appropriate psychosocial referral. RESULTS: The 9 domains in the YWB questionnaire explore potential psychosocial difficulties that affect the adolescent's well-being and aim to uncover potential issues that could account for the adolescent's symptoms. We discuss the rationale behind the questions and response options in the YWB questionnaire. CONCLUSIONS: The YWB questionnaire is the first initiative in Singapore to enable efficient psychosocial screening of at-risk adolescents in the ED. This communication tool can potentially be used in other health care settings to enable early recognition and intervention for adolescents distressed by psychosocial problems.

MDSCs are important osteoclast precursors primed by B cells in rheumatoid arthritis.

Osteoclast-mediated bone erosion and deformation represent significant pathological features in rheumatoid arthritis (RA). Myeloid-derived suppressor cells (MDSCs) and B cells have emerged as key contributors to the progression of RA. Nevertheless, their involvement, especially the interaction in RA osteoclastogenesis remains elusive. In this study, our results revealed a marked expansion of MDSCs in RA patients, and importantly, their abundance was positively correlated with radiographic damage evaluated by the Sharp/van der Heijde score. Notably, MDSCs derived from both RA patients and arthritic mice exhibited a heightened propensity to differentiate into osteoclasts compared with those from healthy individuals. Intriguingly, we observed that B cells from RA patients could augment the osteoclastogenic potential of MDSCs, which was also observed in arthritic mice. The impact of B cells on MDSC-mediated osteoclastogenesis was found to be most pronounced in switched memory B cells, followed by CD21low B cells and naïve B cells. MDSCs from B-cell-deficient mice exhibited diminished capacity to differentiate into osteoclasts, accompanied by distinct gene expression profiles associated with osteoclastogenesis. Taken together, our findings suggested that MDSCs were important osteoclast precursors primed by B cells in RA, serving as novel therapeutic targets for the persistent disease.

Combined analysis of metabolomics and 16S rRNA sequencing for ankylosing spondylitis patients before and after secukinumab therapy.

OBJECTIVE: Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to investigate changes in gut microbiota and metabolites in individuals with AS before and after treatment with secukinumab, to identify the biological characteristics specific to AS patients and investigate the potential biomarkers, for optimizing therapeutic strategies more effectively. METHODS: Fecal microbiome data were collected from 30 AS patients before and after secukinumab therapy and compared with data from 40 healthy controls (HC). Additionally, we analyzed the metabolic profile of both groups from plasma. RESULTS: Findings indicated that the treatment-induced changes in the composition of several crucial bacterial groups, including Megamonas, Prevotella_9, Faecalibacterium, Roseburia, Bacteroides, and Agathobacter. Post-treatment, these groups exhibited a distribution more akin to that of the healthy populations compared with their pretreatment status. We identified three gut microbial taxa, namely Prevotellaceae_bacterium_Marseille_P2831, Prevotella_buccae, and Elusimicrobiota, as potential biomarkers for diagnosing individuals at a higher risk of developing AS and assessing disease outcomes. Plasma metabolomics analysis revealed 479 distinct metabolites and highlighted three disrupted metabolic pathways. Integration of microbiome and metabolomics datasets demonstrated a significant degree of correlation, underscoring the impact of the microbiome on metabolic activity. CONCLUSION: Secukinumab can restore the balance of the gut microbiome and metabolites in AS patients, rendering them more similar to those found in the healthy population. The analysis of microbiome and metabolomics data have unveiled some candidate biomarkers capable of evaluating treatment efficacy.

Caregiver reported long-term outcomes in children with major trauma and traumatic brain injuries: A single-centre retrospective study.

Introduction: We aim to investigate the functional outcomes and long-term health-related quality of life (HRQOL) in children with major trauma associated with traumatic brain injury (TBI). Method: We performed a retrospective review of records among patients >2 and ≤16 years old in a tertiary paediatric hospital between January 2014 and October 2019 with major trauma (Injury Severity Score of ≥16) and TBI of all severities. We recorded each child's Glasgow Outcome Scale-Extended Pediatric Version (GOS-E Peds) at 12 months post-injury and Pediatric Quality of Life Inventory (PedsQL) scores at 6 and 12 months post-injury based on the parent proxy-report scales. Results: We included 53 patients with a median age of 9.0 years old (interquartile range 2.3-15.5). Most injuries were due to falls (30, 56.6%) or road traffic collisions (15, 28.3%); 41 patients (77.3%) required intensive care while 30 patients (56.6%) underwent neurosurgical intervention. Most patients (43, 81.1%) had GOS-E Peds scores of ≤2 at 12 months post-injury. We reported a significant mean difference between the 6- and 12-month parent-reported scores for physical functioning (6.6, 95% confidence interval [CI] 0.3-12.8, P=0.041), psychosocial functioning (4.1, 95% CI 1.0-7.2, P=0.012) and overall scores (5.0, 95% CI 1.4-8.7, P=0.008). Compared with the validated PedsQL scores, our mean scores were higher across all domains at 12 months. Conclusion: With current standard of care, parents of children with major trauma and TBI reported gains in quality of life, physical, psychosocial and overall function between 6 and 12 months post-injury.

Physician perceptions of medically unexplained symptoms in adolescent patients presenting to the emergency department.

INTRODUCTION: Adolescents presenting with medically unexplained symptoms (MUS) in non-mental healthcare settings, particularly Emergency Departments (EDs), pose diagnostic challenges necessitating a comprehensive bio-psycho-social approach. Amid the youth mental health crisis, recognising psychological distress is imperative. This study delved into physicians' perceptions and diagnostic tendencies regarding such cases, exploring the potential overshadowing of psychosomatic presentations by medicalized diagnoses in EDs. METHODS: Our study involved 74 physicians, representing 82% of eligible respondents in the Paediatric Emergency Medicine Department, and was conducted using an online questionnaire examining perceptions of case scenarios with psychosomatic presentations. RESULTS: Results disclosed a prevalent inclination toward medical diagnoses, with less than 10% of physicians considering psychosomatic conditions in specific scenarios. Interestingly, psychosomatic diagnoses were more probable for symptoms like headaches, shortness of breath, and chest pain. The study uncovered a possible bias among physicians towards medical diagnoses in EDs for adolescents with MUS, possibly stemming from physicians' focus on physical care, diagnostic uncertainties, cognitive biases, and concerns about stigmatisation. CONCLUSION: Adolescents with MUS seeking assistance in non-mental health settings may encounter delayed mental health diagnoses and interventions. Psychosomatic symptoms could signify stressors or underlying mental health disorders. Recognising psychosocial distress early on is crucial for optimal mental health outcomes. Consequently, the study advocates for a paradigm shift towards a holistic bio-psychosocial approach in both medical education and practice.

Immunological role of Gas6/TAM signaling in hemostasis and thrombosis.

The immune system is an emerging regulator of hemostasis and thrombosis. The concept of immunothrombosis redefines the relationship between coagulation and immunomodulation, and the Gas6/Tyro3-Axl-MerTK (TAM) signaling pathway builds the bridge across them. During coagulation, Gas6/TAM signaling pathway not only activates platelets, but also promotes thrombosis through endothelial cells and vascular smooth muscle cells involved in inflammatory responses. Thrombosis appears to be a common result of a Gas6/TAM signaling pathway-mediated immune dysregulation. TAM TK and its ligands have been found to be involved in coagulation through the PI3K/AKT or JAK/STAT pathway in various systemic diseases, providing new perspectives in the understanding of immunothrombosis. Gas6/TAM signaling pathway serves as a breakthrough target for novel therapeutic strategies to improve disease management. Many preclinical and clinical studies of TAM receptor inhibitors are in process, confirming the pivotal role of Gas6/TAM signaling pathway in immunothrombosis. Therapeutics targeting the TAM receptor show potential both in anticoagulation management and immunotherapy. Here, we review the immunological functions of the Gas6/TAM signaling pathway in coagulation and its multiple mechanisms in diseases identified to date, and discuss the new clinical strategies that may generated by these roles.

'But it's not in their book': An interview study exploring the contextual factors influencing senior midwives' facilitation of students' clinical experiences of perinatal loss'.

PROBLEM: Midwifery students are seldom afforded experiences of perinatal loss care, potentially depriving them the confidence and competence to provide effective and supportive care in such circumstances. BACKGROUND: Perinatal loss care is predominantly provided by midwives. Students depend on midwives to provide clinical learning experiences of perinatal loss, preparing them for registered independent practice. The reasons behind midwives' decisions regarding the provision of clinical experiences to students remains unexplored. AIM: To identify the contextual factors identified by midwives as influencing the involvement of student midwives in clinical experiences of perinatal loss. METHODS: A qualitative interview study, using semi-structured interviews with 20 senior midwives in New South Wales, Australia. FINDINGS: Four themes describing the contextual factors were identified: 1) it's not in their book, 2) unwritten rules, 3) activity, acuity, and 'the numbers', and 4) teaching the teachers. DISCUSSION: The contextual factors influencing decisions of midwives around this issue are complex and interrelated. Commonly held beliefs within the workplace, and hesitancy to challenge the status quo, are complicated by lack of confidence in 'what to do' with a student in the space of perinatal loss. Lack of direction from governing bodies regarding requirements of students in this space, and pressures on staffing, also play key roles. CONCLUSION: Midwives need support, guidance, mentorship, and supervision in what is for many, a new practice. Our findings suggest systems-level changes are needed, to allow midwives the time and space to learn and reflect on this new skill.

Collaborative model of care between orthopaedics and allied healthcare professionals (CONNACT) in knee osteoarthritis: Effectiveness-implementation hybrid randomized controlled trial of a community-based, multidisciplinary, stratified intervention.

OBJECTIVE: To compare the clinical and cost effectiveness of the Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT), a community-based, stratified, multidisciplinary intervention consisting of exercise, education, psychological and nutrition delivered through a chronic care model to usual hospital care in adults with knee osteoarthritis (OA). METHODS: Pragmatic, parallel-arm, single-blinded superiority RCT trial. Community-dwelling, ambulant adults with knee OA (Kellgren-Lawrence grade > 1; Knee Injury and OA Outcome Score (KOOS4) ≤75) were enrolled. Primary outcome was KOOS4 at 12-months; secondary outcomes included: quality of life, physical performance measures, symptom satisfaction, psychological outcomes, dietary habits, and global perceived effect. Intention-to-treat analysis using generalized linear model (GLM) and regression modeling were conducted. Economic evaluation through a societal approach was embedded. RESULTS: 110 participants (55 control, 55 intervention) were randomized. No between-group difference found for the primary outcome (MD [95%CI]: -1.86 [-9.11. 5.38]), although both groups demonstrated within-group improvement over 12-months. Among the secondary outcomes, the CONNACT group demonstrated superior dietary change (12 months) and physical performance measures (3 months), and global perceived effect (6 months). While there was no between-group difference in total cost, significant productivity gains (reduced indirect cost) were seen in the CONNACT group. CONCLUSION: CONNACT was not superior to usual care at 1 year. Further efforts are needed to understand the underlying contextual and implementation factors in order to further improve and refine such community-based, stratified care models moving forward. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03809975. Registered January 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03809975.

Engineering the cyanobacterial ATP-driven BCT1 bicarbonate transporter for functional targeting to C3 plant chloroplasts.

The ATP-driven bicarbonate transporter 1 (BCT1), a four-component complex in the cyanobacterial CO2-concentrating mechanism, could enhance photosynthetic CO2 assimilation in plant chloroplasts. However, directing its subunits (CmpA, CmpB, CmpC and CmpD) to three chloroplast sub-compartments is highly complex. Investigating BCT1 integration into Nicotiana benthamiana chloroplasts revealed promising targeting strategies using transit peptides from the intermembrane space protein Tic22 for correct CmpA targeting, while the transit peptide of the chloroplastic ABCD2 transporter effectively targeted CmpB to the inner envelope membrane. CmpC and CmpD were targeted to the stroma by RecA and recruited to the inner envelope membrane by CmpB. Despite successful targeting, expression of this complex in CO2-dependent Escherichia coli failed to demonstrate bicarbonate uptake. We then used rational design and directed evolution to generate new BCT1 forms that were constitutively active. Several mutants were recovered, including a CmpCD fusion. Selected mutants were further characterized and stably expressed in Arabidopsis thaliana, but the transformed plants did not have higher carbon assimilation rates or decreased CO2 compensation points in mature leaves. While further analysis is required, this directed evolution and heterologous testing approach presents potential for iterative modification and assessment of CO2-concentrating mechanism components to improve plant photosynthesis.

Heat and Acupuncture to Manage Osteoarthritis of the Knee (HARMOKnee): Protocol for an Effectiveness-Implementation Hybrid Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates. OBJECTIVE: Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone. METHODS: A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability. RESULTS: Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals. CONCLUSIONS: The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models. TRIAL REGISTRATION: ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54352.