Exploring Decisional Conflict Experienced by Individuals Considering Metoidioplasty and Phalloplasty Gender-affirming Surgery.

Background: Metoidioplasty and phalloplasty gender-affirming surgery (MaPGAS) is increasingly performed and requires patients to make complex decisions that may lead to decisional uncertainty. This study aimed to evaluate decisional conflict in individuals considering MaPGAS. Methods: We administered a cross-sectional survey to adult participants assigned female sex at birth and considering MaPGAS, recruited via social media platforms and community health centers. We collected data on demographics, medical and surgical history, MaPGAS type considered, and the Decisional Conflict Scale (DCS). DCS scores range from 0 to 100 (>37.5 indicates greater decisional conflict). Demographic characteristics and DCS scores were compared between subgroups, using descriptive and chi-square statistics. Participants commented on MaPGAS uncertainty, and their comments were evaluated and thematically analyzed. Results: Responses from 264 participants were analyzed: mean age 29 years; 64% (n = 168) trans men, 80% (n = 210) White, 78% (n = 206) nonrural, 45% (n = 120) privately insured, 56% (n = 148) had 4 or more years of college, 23% (n = 84) considering metoidioplasty, 24% (n = 87) considering phalloplasty, and 26% (n = 93) considering metoidioplasty and phalloplasty. DCS total scores were significantly higher (39.8; P < 0.001) among those considering both MaPGAS options, as were mean ratings on the Uncertainty subscale [64.1 (SD 25.5; P < 0.001)]. Concerns surrounding complications were the top factor contributing to uncertainty and decisional conflict. Conclusions: In a cross-sectional national sample of individuals seeking MaPGAS, decisional uncertainty was the highest for those considering both MaPGAS options compared with metoidioplasty or phalloplasty alone. This suggests this cohort would benefit from focused decision support.

An acyl-CoA thioesterase is essential for the biosynthesis of a key dauer pheromone in C. elegans.

Methyl ketone (MK)-ascarosides represent essential components of several pheromones in Caenorhabditis elegans, including the dauer pheromone, which triggers the stress-resistant dauer larval stage, and the male-attracting sex pheromone. Here, we identify an acyl-CoA thioesterase, ACOT-15, that is required for the biosynthesis of MK-ascarosides. We propose a model in which ACOT-15 hydrolyzes the ß-keto acyl-CoA side chain of an ascaroside intermediate during ß-oxidation, leading to decarboxylation and formation of the MK. Using comparative metabolomics, we identify additional ACOT-15-dependent metabolites, including an unusual piperidyl-modified ascaroside, reminiscent of the alkaloid pelletierine. The ß-keto acid generated by ACOT-15 likely couples to 1-piperideine to produce the piperidyl ascaroside, which is much less dauer-inducing than the dauer pheromone, asc-C6-MK (ascr#2, 1). The bacterial food provided influences production of the piperidyl ascaroside by the worm. Our work shows how the biosynthesis of MK- and piperidyl ascarosides intersect and how bacterial food may impact chemical signaling in the worm.

Organizational Intent, Organizational Structures, and Reviewer Mental Models Influence Mortality Review Processes.

Objective: To identify the factors that influence the mortality review process at health systems, including how mortality review is conducted, cases are adjudicated, and results are used. Methods: We conducted a qualitative analysis of the mortality review processes of 6 US health systems from February 1, 2021 to June 31, 2021. The data sources included individual and small-group semi-structured interviews with mortality review team members and a content analysis of site artifacts (eg, guiding principles, chart abstraction forms, review workflows, and clinical pathways developed from past mortality reviews). We analyzed each site's mortality review process, goals and incentives for mortality review, historical and evolving aspects of mortality review, personnel involved, and post-review use of findings. Results: Across the 6 systems, we interviewed a total of 24 mortality review experts and analyzed 26 site documents. We identified 3 thematic factors that influence mortality review processes: organizational intent, organizational structures for mortality review, and the mental models of individuals involved in the review process. Two subthemes emerged within organizational intent: (1) identifying preventable deaths to lower (clinical or financial) risk and (2) using death cases to guide system improvement. Sites varied in governance and decision rights concerning mortality review and adjudication, with 2 subthemes within organizational structures: (1) centralized-hierarchical and (2) decentralized or multidisciplinary. The analysis of mental models of participating reviewers revealed 2 themes: (1) confirmation of preventability and (2) identification of patterns or "signals." Conclusion: Understanding the factors that influence mortality review allows health systems to better leverage mortality review for institutional improvement and to develop training that builds shared mental models to enhance the review process.

Five state factors control progressive stages of freshwater salinization syndrome.

Factors driving freshwater salinization syndrome (FSS) influence the severity of impacts and chances for recovery. We hypothesize that spread of FSS across ecosystems is a function of interactions among five state factors: human activities, geology, flowpaths, climate, and time. (1) Human activities drive pulsed or chronic inputs of salt ions and mobilization of chemical contaminants. (2) Geology drives rates of erosion, weathering, ion exchange, and acidification-alkalinization. (3) Flowpaths drive salinization and contaminant mobilization along hydrologic cycles. (4) Climate drives rising water temperatures, salt stress, and evaporative concentration of ions and saltwater intrusion. (5) Time influences consequences, thresholds, and potentials for ecosystem recovery. We hypothesize that state factors advance FSS in distinct stages, which eventually contribute to failures in systems-level functions (supporting drinking water, crops, biodiversity, infrastructure, etc.). We present future research directions for protecting freshwaters at risk based on five state factors and stages from diagnosis to prognosis to cure.

Structure and integration of specialty palliative care in three NCI-designated cancer centers: a mixed methods case study.

INTRODUCTION: Early access to specialty palliative care is associated with better quality of life, less intensive end-of-life treatment and improved outcomes for patients with advanced cancer. However, significant variation exists in implementation and integration of palliative care. This study compares the organizational, sociocultural, and clinical factors that support or hinder palliative care integration across three U.S. cancer centers using an in-depth mixed methods case study design and proposes a middle range theory to further characterize specialty palliative care integration. METHODS: Mixed methods data collection included document review, semi-structured interviews, direct clinical observation, and context data related to site characteristics and patient demographics. A mixed inductive and deductive approach and triangulation was used to analyze and compare sites' palliative care delivery models, organizational structures, social norms, and clinician beliefs and practices. RESULTS: Sites included an urban center in the Midwest and two in the Southeast. Data included 62 clinician and 27 leader interviews, observations of 410 inpatient and outpatient encounters and seven non-encounter-based meetings, and multiple documents. Two sites had high levels of "favorable" organizational influences for specialty palliative care integration, including screening, policies, and other structures facilitating integration of specialty palliative care into advanced cancer care. The third site lacked formal organizational policies and structures for specialty palliative care, had a small specialty palliative care team, espoused an organizational identity linked to treatment innovation, and demonstrated strong social norms for oncologist primacy in decision making. This combination led to low levels of specialty palliative care integration and greater reliance on individual clinicians to initiate palliative care. CONCLUSION: Integration of specialty palliative care services in advanced cancer care was associated with a complex interaction of organization-level factors, social norms, and individual clinician orientation. The resulting middle range theory suggests that formal structures and policies for specialty palliative care combined with supportive social norms are associated with greater palliative care integration in advanced cancer care, and less influence of individual clinician preferences or tendencies to continue treatment. These results suggest multi-faceted efforts at different levels, including social norms, may be needed to improve specialty palliative care integration for advanced cancer patients.

Decision making in metoidioplasty and phalloplasty gender-affirming surgery: a mixed methods study.

BACKGROUND: Gender-affirming surgical procedures, such as metoidioplasty and phalloplasty for those assigned female at birth, are complex and multistaged and involve risks. Individuals considering these procedures experience greater uncertainty or decisional conflict, compounded by difficulty finding trustworthy information. AIM: (1) To explore the factors contributing to decisional uncertainty and the needs of individuals considering metoidioplasty and phalloplasty gender-affirming surgery (MaPGAS) and (2) to inform development of a patient-centered decision aid. METHODS: This cross-sectional study was based on mixed methods. Adult transgender men and nonbinary individuals assigned female at birth at various stages of MaPGAS decision making were recruited from 2 study sites in the United States to participate in semistructured interviews and an online gender health survey, which included measures of gender congruence, decisional conflict, urinary health, and quality of life. Trained qualitative researchers conducted all interviews with questions to explore constructs from the Ottawa decision support framework. OUTCOMES: Outcomes included goals and priorities for MaPGAS, expectations, knowledge, and decisional needs, as well as variations in decisional conflict by surgical preference, surgical status, and sociodemographic variables. RESULTS: We interviewed 26 participants and collected survey data from 39 (24 interviewees, 92%) at various stages of MaPGAS decision making. In surveys and interviews, affirmation of gender identity, standing to urinate, sensation, and the ability to "pass" as male emerged as highly important factors for deciding to undergo MaPGAS. A third of survey respondents reported decisional conflict. Triangulation of data from all sources revealed that conflict emerged most when trying to balance the strong desire to resolve gender dysphoria through surgical transition against the risks and unknowns in urinary and sexual function, appearance, and preservation of sensation post-MaPGAS. Insurance coverage, age, access to surgeons, and health concerns further influenced surgery preferences and timing. CLINICAL IMPLICATIONS: The findings add to the understanding of decisional needs and priorities of those considering MaPGAS while revealing new complexities among knowledge, personal factors, and decisional uncertainty. STRENGTHS AND LIMITATIONS: This mixed methods study was codeveloped by members of the transgender and nonbinary community and yielded important guidance for providers and individuals considering MaPGAS. The results provide rich qualitative insights for MaPGAS decision making in US contexts. Limitations include low diversity and sample size; both are being addressed in work underway. CONCLUSIONS: This study increases understanding of the factors important to MaPGAS decision making, and results are being used to guide development of a patient-centered surgical decision aid and informed survey revision for national distribution.

A chemical signal that promotes insect survival via thermogenesis.

Cold-activated thermogenesis of brown adipose tissues (BAT) is vital for the survival of animals under cold stress and also inhibits the development of tumours. The development of small-molecule tools that target thermogenesis pathways could lead to novel therapies against cold, obesity, and even cancer. Here, we identify a chemical signal that is produced in beetles in the winter to activate fat thermogenesis. This hormone elevates the basal body temperature by increasing cellular mitochondrial density and uncoupling in order to promote beetle survival. We demonstrate that this hormone activates UCP4- mediated uncoupled respiration through adipokinetic hormone receptor (AKHR). This signal serves as a novel fat-burning activator that utilizes a conserved mechanism to promote thermogenesis not only in beetles, nematode and flies, but also in mice, protecting the mice against cold and tumor growth. This hormone represents a new strategy to manipulate fat thermogenesis.

Pathogenic bacteria modulate pheromone response to promote mating.

Pathogens generate ubiquitous selective pressures and host-pathogen interactions alter social behaviours in many animals1-4. However, very little is known about the neuronal mechanisms underlying pathogen-induced changes in social behaviour. Here we show that in adult Caenorhabditis elegans hermaphrodites, exposure to a bacterial pathogen (Pseudomonas aeruginosa) modulates sensory responses to pheromones by inducing the expression of the chemoreceptor STR-44 to promote mating. Under standard conditions, C. elegans hermaphrodites avoid a mixture of ascaroside pheromones to facilitate dispersal5-13. We find that exposure to the pathogenic Pseudomonas bacteria enables pheromone responses in AWA sensory neurons, which mediate attractive chemotaxis, to suppress the avoidance. Pathogen exposure induces str-44 expression in AWA neurons, a process regulated by a transcription factor zip-5 that also displays a pathogen-induced increase in expression in AWA. STR-44 acts as a pheromone receptor and its function in AWA neurons is required for pathogen-induced AWA pheromone response and suppression of pheromone avoidance. Furthermore, we show that C. elegans hermaphrodites, which reproduce mainly through self-fertilization, increase the rate of mating with males after pathogen exposure and that this increase requires str-44 in AWA neurons. Thus, our results uncover a causal mechanism for pathogen-induced social behaviour plasticity, which can promote genetic diversity and facilitate adaptation of the host animals.

Problematic Integration: Racial Discordance in End-of-Life Decision Making.

We describe racially discordant oncology encounters involving EOL decision-making. Fifty-eight provider interviews were content analyzed using the tenets of problematic integration theory. We found EOL discussions between non-Black providers and their Black patients were often complex and anxiety-inducing. That anxiety consisted of (1) ontological uncertainty in which providers characterized the nature of Black patients as distrustful, especially in the context of clinical trials; (2) ontological and epistemological uncertainty in which provider intercultural incompetency and perceived lack of patient health literacy were normalized and intertwined with provider assumptions about patients' religion and support systems; (3) epistemological uncertainty as ambivalence in which providers' feelings conflicted when deciding whether to speak with family members they perceived as lacking health literacy; (4) divergence in which the provider advised palliative care while the family desired surgery or cancer-directed medical treatment; and (5) impossibility when an ontological uncertainty stance of Black distrust was seen as natural by providers and therefore impossible to change. Some communication strategies used were indirect stereotyping, negotiating, asking a series of value questions, blame-guilt framing, and avoidance. We concluded that provider perceptions of Black distrust, religion, and social support influenced their ability to communicate effectively with patients.

Adoption of Telemedicine in a Rural US Cancer Center Amid the COVID-19 Pandemic: Qualitative Study.

BACKGROUND: The COVID-19 pandemic necessitated a rapid shift to telemedicine to minimize patient and provider exposure risks. While telemedicine has been used in a variety of primary and specialty care settings for many years, it has been slow to be adopted in oncology care. Health care provider and administrator perspectives on factors affecting telemedicine use in oncology settings are not well understood, and the conditions associated with the COVID-19 pandemic offered the opportunity to study the adoption of telemedicine and the resulting provider and staff perspectives on its use. OBJECTIVE: The aim of this paper is to study the factors that influenced telemedicine uptake and sustained use in outpatient oncology clinics at a US cancer center to inform future telemedicine practices. METHODS: We used purposive sampling to recruit a mix of oncology specialty providers, practice managers, as well as nursing and administrative staff representing 5 outpatient oncology clinics affiliated with the Dartmouth Cancer Center, a large regional cancer center in the northeast of United States, to participate in semistructured interviews conducted over 6 weeks in spring 2021. The interview guide was informed by the 5 domains of the Consolidated Framework for Implementation Research, which include inner and outer setting factors, characteristics of the intervention (ie, telemedicine modality), individual-level factors (eg, provider and patient characteristics), and implementation processes. In total, 11 providers, 3 leaders, and 6 staff participated following verbal consent, and thematic saturation was reached across the full sample. We used a mixed deductive and inductive qualitative analysis approach to study the main influences on telemedicine uptake, implementation, and sustainability during the first year of the COVID-19 pandemic across the 5 settings. RESULTS: The predominant influencers of telemedicine adoption in this study were individual provider experiences and assumptions about patient preference and accessibility. Providers' early telemedicine experiences, especially if negative, influenced preferences for telephone over video and affected sustained use. Telemedicine was most favorably viewed for lower-acuity cancer care, visits less dependent on physical exam, and for patient and caregiver education. A lack of clinical champions, leadership guidance, and vision hindered the implementation of standardized practices and were cited as essential for telemedicine sustainability. Respondents expressed anxiety about sustaining telemedicine use if reimbursements for telephonic visits diminished or ceased. Opportunities to enhance future efforts include a need to provide additional guidance supporting telemedicine use cases and evidence of effectiveness in oncology care and to address provider concerns with communication quality. CONCLUSIONS: In a setting of decentralized care processes, early challenges in telemedicine implementation had an outsized impact on the nature and amount of sustained use. Proactively designed telemedicine care processes with attention to patient needs will be essential to support a sustained role for telemedicine in cancer care.

Patient Empowerment Among Adults With Arthritis: The Case for Emotional Support.

OBJECTIVE: This study aimed to identify differences in patient empowerment based on biopsychosocial patient-reported measures, the magnitude of those differences, and which measures best explain differences in patient empowerment. METHODS: This was a cross-sectional observational study of 6918 adults with arthritis in the US. Data were collected from March 2019 to March 2020 through the Arthritis Foundation Live Yes! INSIGHTS program. Patient empowerment, measured by the Health Care Empowerment Questionnaire, included 2 scales: Patient Information Seeking and Healthcare Interaction Results. Patient-reported outcomes were measured using the Patient Reported Outcomes Measurement Information System (PROMIS)-29 and PROMIS emotional support scale. ANOVA assessed differences between groups, and Spearman rank correlation assessed correlations between variables. Hierarchical regression analysis determined the contributions of sociodemographic characteristics, arthritis type, and patient-reported health measures in explaining patient empowerment (α = 0.05). RESULTS: Empowerment was lower among those who were male, older, less educated, or who had lower income, osteoarthritis, less emotional support, or better physical function, although the effect was small-to-negligible for most of these variables in the final regression models. Empowerment did not differ by race/ethnicity in unadjusted or adjusted analysis. In final regression models, emotional support contributed the most to explaining patient empowerment. CONCLUSION: Emotional support is important for patient empowerment. This suggests that programs that seek to improve patient empowerment should target and measure effects on emotional support.

Chemical Signaling Regulates Axon Regeneration via the GPCR-Gqα Pathway in Caenorhabditis elegans.

Chemical communication controls a wide range of behaviors via conserved signaling networks. Axon regeneration in response to injury is determined by the interaction between the extracellular environment and intrinsic growth potential. In this study, we investigated the role of chemical signaling in axon regeneration in Caenorhabditis elegans We find that the enzymes involved in ascaroside pheromone biosynthesis, ACOX-1.1, ACOX-1.2, and DAF-22, participate in axon regeneration by producing a dauer-inducing ascaroside, ascr#5. We demonstrate that the chemoreceptor genes, srg-36 and srg-37, which encode G-protein-coupled receptors for ascr#5, are required for adult-specific axon regeneration. Furthermore, the activating mutation in egl-30 encoding Gqα suppresses axon regeneration defective phenotype in acox-1.1 and srg-36 srg-37 mutants. Therefore, the ascaroside signaling system provides a unique example of a signaling molecule that regulates the regenerative pathway in the nervous system.SIGNIFICANCE STATEMENT In Caenorhabditis elegans, axon regeneration is positively regulated by the EGL-30 Gqα-JNK MAP kinase cascade. However, it remains unclear what signals activate the EGL-30 pathway in axon regeneration. Here, we show that SRG-36 and SRG-37 act as upstream G-protein-coupled receptors (GPCRs) that activate EGL-30. C. elegans secretes a family of small-molecule pheromones called ascarosides, which serve various functions in chemical signaling. SRG-36 and SRG-37 are GPCRs for the dauer-inducing ascaroside ascr#5. Consistent with this, we found that ascr#5 activates the axon regeneration pathway via SRG-36/SRG-37 and EGL-30. Thus, ascaroside signaling promotes axon regeneration by activating the GPCR-Gqα pathway.

Mapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan.

Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) hybrid systems typically use complex protein-protein interactions to facilitate direct transfer of intermediates between these multimodular megaenzymes. In the canal-associated neurons (CANs) of Caenorhabditis elegans, PKS-1 and NRPS-1 produce the nemamides, the only known hybrid polyketide-nonribosomal peptides biosynthesized by animals, through a poorly understood mechanism. Here, we use genome editing and mass spectrometry to map the roles of individual PKS-1 and NRPS-1 enzymatic domains in nemamide biosynthesis. Furthermore, we show that nemamide biosynthesis requires at least five additional enzymes expressed in the CANs that are encoded by genes distributed across the worm genome. We identify the roles of these enzymes and discover a mechanism for trafficking intermediates between a PKS and an NRPS. Specifically, the enzyme PKAL-1 activates an advanced polyketide intermediate as an adenylate and directly loads it onto a carrier protein in NRPS-1. This trafficking mechanism provides a means by which a PKS-NRPS system can expand its biosynthetic potential and is likely important for the regulation of nemamide biosynthesis.

Neuronal control of maternal provisioning in response to social cues.

Mothers contribute cytoplasmic components to their progeny in a process called maternal provisioning. Provisioning is influenced by the parental environment, but the molecular pathways that transmit environmental cues between generations are not well understood. Here, we show that, in Caenorhabditis elegans, social cues modulate maternal provisioning to regulate gene silencing in offspring. Intergenerational signal transmission depends on a pheromone-sensing neuron and neuronal FMRFamide (Phe-Met-Arg-Phe)-like peptides. Parental FMRFamide-like peptide signaling dampens oxidative stress resistance and promotes the deposition of mRNAs for translational components in progeny, which, in turn, reduces gene silencing. This study identifies a previously unknown pathway for intergenerational communication that links neuronal responses to maternal provisioning. We suggest that loss of social cues in the parental environment represents an adverse environment that stimulates stress responses across generations.

Modular Platform for the Development of Recombinant Hemoglobin Scavenger Biotherapeutics.

Cell-free hemoglobin (Hb) is a driver of disease progression in conditions with intravascular or localized hemolysis. Genetic and acquired anemias or emergency medical conditions such as aneurysmal subarachnoid hemorrhage involve tissue Hb exposure. Haptoglobin (Hp) captures Hb in an irreversible protein complex and prevents its pathophysiological contributions to vascular nitric oxide depletion and tissue oxidation. Preclinical proof-of-concept studies suggest that human plasma-derived Hp is a promising therapeutic candidate for several Hb-driven diseases. Optimizing the efficacy and safety of Hb-targeting biotherapeutics may require structural and functional modifications for specific indications. Improved Hp variants could be designed to achieve the desired tissue distribution, metabolism, and elimination to target hemolytic disease states effectively. However, it is critical to ensure that these modifications maintain the function of Hp. Using transient mammalian gene expression of Hp combined with co-transfection of the pro-haptoglobin processing protease C1r-LP, we established a platform for generating recombinant Hp-variants. We designed an Hpß-scaffold, which was expressed in this system at high levels as a monomeric unit (mini-Hp) while maintaining the key protective functions of Hp. We then used this Hpß-scaffold as the basis to develop an initial proof-of-concept Hp fusion protein using human serum albumin as the fusion partner. Next, a hemopexin-Hp fusion protein with bispecific heme and Hb detoxification capacity was generated. Further, we developed a Hb scavenger devoid of CD163 scavenger receptor binding. The functions of these proteins were then characterized for Hb and heme-binding, binding of the Hp-Hb complexes with the clearance receptor CD163, antioxidant properties, and vascular nitric oxide sparing capacity. Our platform is designed to support the generation of innovative Hb scavenger biotherapeutics with novel modes of action and potentially improved formulation characteristics, function, and pharmacokinetics.

CREB mediates the C. elegans dauer polyphenism through direct and cell-autonomous regulation of TGF-ß expression.

Animals can adapt to dynamic environmental conditions by modulating their developmental programs. Understanding the genetic architecture and molecular mechanisms underlying developmental plasticity in response to changing environments is an important and emerging area of research. Here, we show a novel role of cAMP response element binding protein (CREB)-encoding crh-1 gene in developmental polyphenism of C. elegans. Under conditions that promote normal development in wild-type animals, crh-1 mutants inappropriately form transient pre-dauer (L2d) larvae and express the L2d marker gene. L2d formation in crh-1 mutants is specifically induced by the ascaroside pheromone ascr#5 (asc-ωC3; C3), and crh-1 functions autonomously in the ascr#5-sensing ASI neurons to inhibit L2d formation. Moreover, we find that CRH-1 directly binds upstream of the daf-7 TGF-ß locus and promotes its expression in the ASI neurons. Taken together, these results provide new insight into how animals alter their developmental programs in response to environmental changes.

Toward Improved Identification of Parental Substance Misuse: An Examination of Current Practices and Gaps in One US State.

INTRODUCTION: The use of illicit substances, including opioids, is a serious public health issue in the United States. While there are reports of the impact of the ongoing opioid crisis on adults, a new focus has emerged on how parental substance misuse (PSM) affects children. This study explored existing screening and assessment practices and services for children and families affected by PSM across different service sectors in one state. The purpose of the study was to identify opportunities for training, policy development, and practice improvement related to identifying PSM and linking children and parents to services. METHODS: Interviews (n = 15) with professionals from five service sectors (mental health, primary care, schools, community programs, and law enforcement) were used to inform development of a state-wide survey of the same groups (n = 498) to assess current practices, attitudes, knowledge, and training needs related to child screening of PSM. The survey was piloted using cognitive interviewing (n = 9) before it was distributed. RESULTS: Fewer than 20% of survey respondents reported using standardized tools specific to screening PSM. Informal assessment practices predominate, though 60% of respondents saw value in adopting more standardized PSM screening. Attitudes about PSM and screening varied among sectors but interest in training was high. DISCUSSION: Results indicate a need for more systematic PSM screening, cross-sector training and practice discussions, and policies to support early identification of children affected by PSM. Ramifications of these findings and recommendations are discussed.

Psychometric characteristics of the health care empowerment questionnaire in a sample of patients with arthritis and rheumatic conditions.

BACKGROUND: Patient empowerment can improve health-related outcomes and is important in chronic conditions, such as arthritis. This study aimed to validate the Health Care Empowerment Questionnaire (HCEQ), a patient-reported experience measure of empowerment, for use with patients with arthritis and other rheumatic diseases. METHODS: The HCEQ measures Patient Information Seeking (or Involvement in Decisions) and Healthcare Interaction Results (or Involvement in Interactions) and asks respondents to answer questions in two ways: whether they feel something happened and its importance to them. Face validity was assessed through qualitative data (n = 8, nominal group technique; n = 55, focus groups). Measure structure was assessed through confirmatory factor analysis (CFA); internal consistency was also assessed (n = 9226). Test-retest reliability was assessed with sub-sample of participants (n = 182). RESULTS: We found adequate face validity of the HCEQ for patients with arthritis. The CFA indicated good fit to the data for the two-factor structure of the HCEQ (RMSEA = 0.075; CFI = 0.987; TLI = 0.978; SRMR = 0.026). Internal consistency was strong (α=0.94 for both subscales). Test-retest reliability was moderate for Patient Information Seeking (ICC=0.67) and good for Healthcare Interaction Results (ICC=0.77). CONCLUSIONS: The HCEQ, with modifications, demonstrated promising psychometric properties within this sample, laying the foundation for further assessment. This work supports the HCEQ as an appropriate instrument for examining experiences with and perceived importance of empowerment in individuals with arthritis and other rheumatic conditions. PATIENT CONTRIBUTION: Patients contributed to the assessment of face validity. As a measure of patient empowerment, the HCEQ's use can enable further participation of patients in health care.

A novel soluble complement receptor 1 fragment with enhanced therapeutic potential.

Human complement receptor 1 (HuCR1) is a pivotal regulator of complement activity, acting on all three complement pathways as a membrane-bound receptor of C3b/C4b, C3/C5 convertase decay accelerator, and cofactor for factor I-mediated cleavage of C3b and C4b. In this study, we sought to identify a minimal soluble fragment of HuCR1, which retains the complement regulatory activity of the wildtype protein. To this end, we generated recombinant, soluble, and truncated versions of HuCR1 and compared their ability to inhibit complement activation in vitro using multiple assays. A soluble form of HuCR1, truncated at amino acid 1392 and designated CSL040, was found to be a more potent inhibitor than all other truncation variants tested. CSL040 retained its affinity to both C3b and C4b as well as its cleavage and decay acceleration activity and was found to be stable under a range of buffer conditions. Pharmacokinetic studies in mice demonstrated that the level of sialylation is a major determinant of CSL040 clearance in vivo. CSL040 also showed an improved pharmacokinetic profile compared with the full extracellular domain of HuCR1. The in vivo effects of CSL040 on acute complement-mediated kidney damage were tested in an attenuated passive antiglomerular basement membrane antibody-induced glomerulonephritis model. In this model, CSL040 at 20 and 60 mg/kg significantly attenuated kidney damage at 24 h, with significant reductions in cellular infiltrates and urine albumin, consistent with protection from kidney damage. CSL040 thus represents a potential therapeutic candidate for the treatment of complement-mediated disorders.