Unraveling the Gordian knot of coronary pressure-flow autoregulation.

The coronary circulation has the inherent ability to maintain myocardial perfusion constant over a wide range of perfusion pressures. The phenomenon of pressure-flow autoregulation is crucial in response to flow-limiting atherosclerotic lesions which diminish coronary driving pressure and increase risk of myocardial ischemia and infarction. Despite well over half a century of devoted research, understanding of the mechanisms responsible for autoregulation remains one of the most fundamental and contested questions in the field today. The purpose of this review is to highlight current knowledge regarding the complex interrelationship between the pathways and mechanisms proposed to dictate the degree of coronary pressure-flow autoregulation. Our group recently likened the intertwined nature of the essential determinants of coronary flow control to the symbolically unsolvable "Gordian knot". To further efforts to unravel the autoregulatory "knot", we consider recent challenges to the local metabolic and myogenic hypotheses and the complicated dynamic structural and functional heterogeneity unique to the heart and coronary circulation. Additional consideration is given to interrogation of putative mediators, role of K+ and Ca2+ channels, and recent insights from computational modeling studies. Improved understanding of how specific vasoactive mediators, pathways, and underlying disease states influence coronary pressure-flow relations stands to significantly reduce morbidity and mortality for what remains the leading cause of death worldwide.

Climate change is an important predictor of extinction risk on macroevolutionary timescales.

Anthropogenic climate change is increasing rapidly and already impacting biodiversity. Despite its importance in future projections, understanding of the underlying mechanisms by which climate mediates extinction remains limited. We present an integrated approach examining the role of intrinsic traits versus extrinsic climate change in mediating extinction risk for marine invertebrates over the past 485 million years. We found that a combination of physiological traits and the magnitude of climate change is necessary to explain marine invertebrate extinction patterns. Our results suggest that taxa previously identified as extinction resistant may still succumb to extinction if the magnitude of climate change is great enough.

Clinical, Radiographic, and Patient-Reported Outcomes of First Metatarsophalangeal Interposition Arthrodesis Using Porous Titanium Wedges.

BACKGROUND: First metatarsophalangeal (MTP) arthrodesis is a common surgical procedure for addressing hallux MTP pathology. In the setting of revision procedures with significant bone loss, porous titanium wedges may provide an alternative to structural bone autograft or allograft. OBJECTIVE: The purpose of this study is to report the clinical and radiographic outcomes achieved in first MTP interposition arthrodesis using porous titanium wedges. METHODS: A retrospective analysis of 9 patients with a mean age 65.4 years (45-82 years) who underwent first MTP interposition arthrodesis with the use of porous titanium wedges from February 2014 to September 2017 was performed. Outcomes were assessed using both plain-film radiographs and computed tomography (CT) scans, as well as patient-reported outcome measures, including Foot and Ankle Ability Measure (FAAM) (Sports and Activities of Daily Living), pain Visual Analogue Scale (VAS), and 36-Item Short Form Survey (SF-36). Average follow-up time was 34.2 months (14-72 months). RESULTS: At final follow-up, the average FAAM score was 91.1 ± 14.7 (75.1 ± 5.3 FAAM Activities of Daily Living; 17.9 ± 9.9 FAAM Sports). Average pain VAS score was 1.9 ± 1.7. Postoperative computed tomography (CT) imaging was obtained for 5 patients, all of which demonstrated good bony apposition or osseous integration of the wedge. Four patients underwent subsequent surgical procedures, including 3 isolated dorsal fixation revisions, and 1 complete MTP arthrodesis revision. CONCLUSION: To our knowledge, this study represents the first reported clinical and radiographic outcomes in patients undergoing first MTP interposition arthrodesis with use of porous titanium wedges. While we found this technique to be a viable alternative to bone grafting for this difficult problem, further research should focus on comparative data with other commonly performed operative techniques. LEVEL OF EVIDENCE: Level IV: Case series.

A Milky Way-like barred spiral galaxy at a redshift of 3.

The majority of massive disk galaxies in the local Universe show a stellar barred structure in their central regions, including our Milky Way1,2. Bars are supposed to develop in dynamically cold stellar disks at low redshift, as the strong gas turbulence typical of disk galaxies at high redshift suppresses or delays bar formation3,4. Moreover, simulations predict bars to be almost absent beyond z = 1.5 in the progenitors of Milky Way-like galaxies5,6. Here we report observations of ceers-2112, a barred spiral galaxy at redshift zphot ≈ 3, which was already mature when the Universe was only 2 Gyr old. The stellar mass (M★ = 3.9 × 109 M⊙) and barred morphology mean that ceers-2112 can be considered a progenitor of the Milky Way7-9, in terms of both structure and mass-assembly history in the first 2 Gyr of the Universe, and was the closest in mass in the first 4 Gyr. We infer that baryons in galaxies could have already dominated over dark matter at z ≈ 3, that high-redshift bars could form in approximately 400 Myr and that dynamically cold stellar disks could have been in place by redshift z = 4-5 (more than 12 Gyrs ago)10,11.

A lipid-associated macrophage lineage rewires the spatial landscape of adipose tissue in early obesity.

Adipose tissue macrophage (ATM) infiltration is associated with adipose tissue dysfunction and insulin resistance in mice and humans. Recent single-cell data highlight increased ATM heterogeneity in obesity but do not provide a spatial context for ATM phenotype dynamics. We integrated single-cell RNA-Seq, spatial transcriptomics, and imaging of murine adipose tissue in a time course study of diet-induced obesity. Overall, proinflammatory immune cells were predominant in early obesity, whereas nonresident antiinflammatory ATMs predominated in chronic obesity. A subset of these antiinflammatory ATMs were transcriptomically intermediate between monocytes and mature lipid-associated macrophages (LAMs) and were consistent with a LAM precursor (pre-LAM). Pre-LAMs were spatially associated with early obesity crown-like structures (CLSs), which indicate adipose tissue dysfunction. Spatial data showed colocalization of ligand-receptor transcripts related to lipid signaling among monocytes, pre-LAMs, and LAMs, including Apoe, Lrp1, Lpl, and App. Pre-LAM expression of these ligands in early obesity suggested signaling to LAMs in the CLS microenvironment. Our results refine understanding of ATM diversity and provide insight into the dynamics of the LAM lineage during development of metabolic disease.

Understanding the Experiences of Latinx LGBTQ Texans at the Beginning of the COVID-19 Pandemic.

Marginalized communities have been disproportionately affected by COVID-19, including both racial/ethnic minority and sexual minority populations. To date, there has been little research examining the impact of the COVID-19 pandemic at the intersections of marginalized identities. Furthermore, available national data on COVID-19 outcomes may obscure our understanding of region-specific outcomes, particularly in the U.S. South. Using an intersectional approach, we explore differences in worries over COVID-19, preventative behaviors, and COVID-19 outcomes in the early months of the pandemic in a diverse sample of LGBTQ people (N = 1076) living in Texas. Our findings indicated that LGBTQ Latinx people in Texas reported more COVID-19 related worries and adverse outcomes than non-Latinx LGBTQ people. These findings are in line with previous research that found that the increased risk to Latinx and LGBTQ populations in public health crises is often overlooked and can be attributed to many factors such as socioeconomic status, occupational propensity, disparities in physical health, and barriers to healthcare access. Furthermore, our findings suggest the necessity of utilizing an intersectional approach when examining the disproportionate burden marginalized communities face in public health crises.

Awareness of social care needs in people with epilepsy and intellectual disability.

BACKGROUND: Nearly a quarter of people with intellectual disability (ID) have epilepsy with large numbers experiencing drug-resistant epilepsy, and premature mortality. To mitigate epilepsy risks the environment and social care needs, particularly in professional care settings, need to be met. PURPOSE: To compare professional care groups as regards their subjective confidence and perceived responsibility when managing the need of people with ID and epilepsy. METHOD: A multi-agency expert panel developed a questionnaire with embedded case vignettes with quantitative and qualitative elements to understand training and confidence in the health and social determinants of people with ID and epilepsy. The cross-sectional survey was disseminated amongst health and social care professionals working with people with ID in the UK using an exponential non-discriminative snow-balling methodology. Group comparisons were undertaken using suitable statistical tests including Fisher's exact, Kruskal-Wallis, and Mann-Whitney. Bonferroni correction was applied to significant (p < 0.05) results. Content analysis was conducted and relevant categories and themes were identified. RESULTS: Social and health professionals (n = 54) rated their confidence to manage the needs of people with ID and epilepsy equally. Health professionals showed better awareness (p < 0.001) of the findings/recommendations of the latest evidence on premature deaths and identifying and managing epilepsy-related risks, including the relevance of nocturnal monitoring. The content analysis highlighted the need for clearer roles, improved care pathways, better epilepsy-specific knowledge, increased resources, and better multi-disciplinary work. CONCLUSIONS: A gap exists between health and social care professionals in awareness of epilepsy needs for people with ID, requiring essential training and national pathways.

Service user perspectives on social prescribing services for mental health in the UK: a systematic review.

AIM: To thematically synthesise adult service users' perspectives on how UK-based social prescribing services support them with their mental health management. METHODS: Nine databases were systematically searched up to March 2022. Eligible studies were qualitative or mixed methods studies involving participants aged ⩾ 18 years accessing social prescribing services primarily for mental health reasons. Thematic synthesis was applied to qualitative data to create descriptive and analytical themes. RESULTS: 51,965 articles were identified from electronic searches. Six studies were included in the review (n = 220 participants) with good methodological quality. Five studies utilised a link worker referral model, and one study a direct referral model. Modal reasons for referral were social isolation and/or loneliness (n = 4 studies). Two analytical themes were formulated from seven descriptive themes: (1) person-centred care was key to delivery and (2) creating an environment for personal change and development. CONCLUSIONS: This review provides a synthesis of the qualitative evidence on service users' experiences of accessing and using social prescribing services to support their mental health management. Adherence to principles of person-centred care and addressing the holistic needs of service users (including devoting attention to the quality of the therapeutic environment) are important for design and delivery of social prescribing services. This will optimise service user satisfaction and other outcomes that matter to them.

Lameness recovery rates following treatment of dairy cattle with claw horn lameness in the Waikato region of New Zealand.

AIMS: To describe the time in days for lame dairy cows to recover after diagnosis and treatment of claw horn lameness, and to investigate whether cure rates differed between farms. METHODS: Five dairy farms in the Waikato region were conveniently enrolled into a descriptive epidemiological study. Three of these farms had dairy cattle enrolled over two consecutive seasons, while two farms enrolled for one year. Lame cattle diagnosed by the farmers were enrolled into the study if they had a lameness score (LS ≥ 2 on a 0-3 scale) and claw horn lesions. All enrolled animals were treated by a single veterinarian following a consistent methodology, and subsequently assessed for LS at a median frequency of 4 days from enrolment until they were sound (LS = 0). The times (days) taken for animals to become sound and non-lame (LS < 2) were reported for all animals, and Kaplan-Meier survival curves used to present the results. A Cox-proportional hazard model was used to assess if the hazard of soundness was associated with farm, age, breed, lesion, number of limbs involved, and LS at enrolment. RESULTS: A total of 241 lame cattle with claw horn lesions were enrolled across the five farms. White line disease was the predominant pain-causing lesion in 225 (93%) animals, and blocks were applied to 205 (85%) of enrolled animals. The overall median days from enrolment to becoming sound was 18 (95% CI = 14-21) days, and 7 (95% CI = 7-8) days to become non-lame. A difference in the hazards of lameness cure between farms was identified (p = 0.007), with median days to lameness cure between farms ranging from 11 to 21 days. No associations were identified between age, breed, limb, or LS at enrolment on the lameness cure rates. CONCLUSIONS: Treatment of claw horn lameness following industry-standard guidelines in dairy cattle on five New Zealand dairy farms resulted in rapid cure, although cure rates differed between farms. CLINICAL RELEVANCE: Following industry best-practice lameness treatment guidelines, including frequent use of blocks, can result in rapid lameness cure rates in New Zealand dairy cows. This study also suggests that management of lame cattle on pasture can positively benefit their welfare and recovery times. The reported cure rates provide veterinarians with benchmarks on the length of time after which a lame animal should be re-examined, and in the investigation of poor treatment response rates at the herd level.

Radiation dose to staff from medical X-ray scatter in the orthopaedic theatre.

PURPOSE: Given the growing demand for intraoperative imaging, there is increased concern for radiation dose for orthopaedic surgical staff. This study sought to determine the distribution of scatter radiation from fluoroscopic imaging in the orthopaedic surgical environment, with particular emphasis on the positions of personnel and the type of orthopaedic surgery performed. METHODS: A radiation survey detector was deployed at various angles and distances around an anthropomorphic phantom. The scatter dose rate in microsieverts per hour (µSv/h) was recorded using consistent exposure parameters for five common surgical procedures. A C-arm unit produced radiation for the hip arthroscopy, hip replacement and knee simulations, whilst a mini C-arm unit produced fluoroscopy for the foot and hand simulations. RESULTS: Readings were tabulated, and coloured heatmaps were generated from scatter measurements for each of the five procedures. Positions corresponding to the typical location of the surgical staff (surgeon, surgical assistant, anaesthetist, instrument (scrub) nurse, circulation (scout) nurse and anaesthetic nurse) were superimposed on heatmaps. The surgeon's proximity to the radiation source meant this position experienced the greatest amount of radiation in all five surgical procedures. Mini C-arm doses were considered low in all procedures for positions, with and without lead protection. CONCLUSION: This investigation demonstrated the distribution of scattered radiation dose experienced at different positions within the orthopaedic surgical theatre. It reinforces the importance of staff increasing their distance from the primary beam where possible, reducing exposure time and increasing shielding with lead protection.

Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure.

The coronary circulation has an innate ability to maintain constant blood flow over a wide range of perfusion pressures. However, the mechanisms responsible for coronary autoregulation remain a fundamental and highly contested question. This study interrogated the local metabolic hypothesis of autoregulation by testing the hypothesis that hypoxemia-induced exaggeration of the metabolic error signal improves the autoregulatory response. Experiments were performed on open-chest anesthetized swine during stepwise changes in coronary perfusion pressure (CPP) from 140 to 40 mmHg under normoxic (n = 15) and hypoxemic (n = 8) conditions, in the absence and presence of dobutamine-induced increases in myocardial oxygen consumption (MVO2) (n = 5-7). Hypoxemia (PaO2 < 40 mmHg) decreased coronary venous PO2 (CvPO2) ~ 30% (P < 0.001) and increased coronary blood flow ~ 100% (P < 0.001), sufficient to maintain myocardial oxygen delivery (P = 0.14) over a wide range of CPPs. Autoregulatory responsiveness during hypoxemia-induced reductions in CvPO2 were associated with increases of autoregulatory gain (Gc; P = 0.033) but not slope (P = 0.585) over a CPP range of 120 to 60 mmHg. Preservation of autoregulatory Gc (P = 0.069) and slope (P = 0.264) was observed during dobutamine administration ± hypoxemia. Reductions in coronary resistance in response to decreases in CPP predominantly occurred below CvPO2 values of ~ 25 mmHg, irrespective of underlying vasomotor reserve. These findings support the presence of an autoregulatory threshold under which oxygen-sensing pathway(s) act to preserve sufficient myocardial oxygen delivery as CPP is reduced during increases in MVO2 and/or reductions in arterial oxygen content.

Body image, self-compassion, and sexual distress in individuals living with endometriosis.

OBJECTIVE: Extensive psychological burden is associated with the experience of living with endometriosis, including negative changes to body image and sexual functioning. Emerging evidence suggests that potential protective factors such as body appreciation and self-compassion may help mitigate these adverse impacts of endometriosis. This study aimed to investigate the association of body image, both positive (body appreciation) and negative (body image disturbance) dimensions, with sexual distress and the potential buffering effect of self-compassion on the body image-sexual distress link. METHODS: Data were collected via an online cross-sectional survey (N = 471) assessing body image disturbance, body appreciation, self-compassion and sexual distress in individuals with endometriosis. A series of hierarchical linear regression analyses were conducted to explore the relationship between key variables. RESULTS: >80% of the sample reported clinically significant sexual distress and high levels of body image disturbance. Regression analyses indicated a moderate positive effect of body image disturbance with sexual distress, and a weaker inverse effect of self-compassion with sexual distress. Body appreciation was not associated with sexual distress, and no moderating effects of self-compassion were evident. CONCLUSION: The high prevalence of sexual distress identified in this sample, along with the finding that body image disturbance was strongly associated with sexual distress, suggest that psychosocial interventions addressing body image may help ameliorate sexual distress in individuals with endometriosis.

Developing an Entrustable Professional Activity to Improve the Care of LGBTQ+ Youth.

Despite the multitude of health inequities often experienced by lesbian, gay, bisexual, transgender, and queer (LGBTQ)+ youth, few training programs consistently and comprehensively address these disparities through education and assessment of learners. Over the past decade, programs have begun to incrementally increase the number of hours dedicated to LGBTQ+ health training; however, the lack of standardization for curricula and assessment remains a significant barrier. As medical education shifts to a competency-based approach, focusing on patient outcomes and the competencies trainees must achieve to meet those outcomes, we must take this opportunity to develop curricula and assessment tools that emphasize inclusive, affirming, equitable, and culturally humble care for LGBTQ+ youth. Entrustable professional activities (EPA) are increasingly used to educate and assess trainees on their progression from full supervision to unsupervised practice. Given their multifaceted use to standardize curricula, assess learners, and highlight programmatic gaps in education, we believe an EPA is the ideal tool to systematically improve LGBTQ+ health training in graduate medical education. Our team of national experts in this field developed an LGBTQ+ health EPA. We describe our methods of development, the functions and curricular components of the EPA, and the many applications for widespread program use.

Chronic high-rate pacing induces heart failure with preserved ejection fraction-like phenotype in Ossabaw swine.

The lack of pre-clinical large animal models of heart failure with preserved ejection fraction (HFpEF) remains a growing, yet unmet obstacle to improving understanding of this complex condition. We examined whether chronic cardiometabolic stress in Ossabaw swine, which possess a genetic propensity for obesity and cardiovascular complications, produces an HFpEF-like phenotype. Swine were fed standard chow (lean; n = 13) or an excess calorie, high-fat, high-fructose diet (obese; n = 16) for ~ 18 weeks with lean (n = 5) and obese (n = 8) swine subjected to right ventricular pacing (180 beats/min for ~ 4 weeks) to induce heart failure (HF). Baseline blood pressure, heart rate, LV end-diastolic volume, and ejection fraction were similar between groups. High-rate pacing increased LV end-diastolic pressure from ~ 11 ± 1 mmHg in lean and obese swine to ~ 26 ± 2 mmHg in lean HF and obese HF swine. Regression analyses revealed an upward shift in LV diastolic pressure vs. diastolic volume in paced swine that was associated with an ~ twofold increase in myocardial fibrosis and an ~ 50% reduction in myocardial capillary density. Hemodynamic responses to graded hemorrhage revealed an ~ 40% decrease in the chronotropic response to reductions in blood pressure in lean HF and obese HF swine without appreciable changes in myocardial oxygen delivery or transmural perfusion. These findings support that high-rate ventricular pacing of lean and obese Ossabaw swine initiates underlying cardiac remodeling accompanied by elevated LV filling pressures with normal ejection fraction. This distinct pre-clinical tool provides a unique platform for further mechanistic and therapeutic studies of this highly complex syndrome.

Geospatial Reach of the Maryland COVID-19 School Meals Response: Spring 2020.

OBJECTIVE: Examine characteristics of pandemic meal site (n = 602) location and meals served per site in Maryland, Spring 2020, following federal/state waivers for local meal site placement decision-making. METHODS: Using geographic information systems, we connected meal sites to census tract-level data and generated service areas from sites and distances from population-weighted census tract centroids to the closest pandemic meal site. Regression analysis determined associations of census tract pandemic meal site count and meals served per site with socioeconomic and demographic variables. RESULTS: Census tracts with more meal sites were urban (P < 0.001), food deserts (P < 0.001), and had higher percentages of children in poverty (P < 0.001). Sites serving fewer meals were in food deserts (P < 0.001) and areas with more children in poverty (P < 0.001). CONCLUSIONS AND IMPLICATIONS: Waivers allowing local meal site placement decision-making supported meal sites in high-need areas. Geospatial approaches could optimize site locations to ensure maximum reach to populations in need. Additional supports may be needed to ensure children in poverty areas receive meals distributed at these sites.

Health Literacy Perceptions and Knowledge in Pediatric Continuity Practices.

BACKGROUND: Low health literacy affects one-third of adults in the United States and can have a negative effect on health behavior and outcomes. OBJECTIVE: The goal of this study was to examine attitudes and knowledge of health literacy among pediatric residents and faculty in pediatric resident continuity clinics across the country. METHODS: An online mixed-methods survey was distributed to pediatric faculty and residents through the Academic Pediatric Association's Continuity Research Network. The 20-question survey included questions about the participants' health literacy knowledge and health literacy practices in continuity clinics, such as use of universal health literacy precautions. Categorical answer choices were dichotomized into positive and negative groupings and resident and faculty responses were compared using the Chi-squared test (significance p < .05). Qualitative data were analyzed using emergent coding and grounded theory to determine themes. KEY RESULTS: Responses were received from 402 individuals at 24 pediatric residency programs. Most participants agreed or strongly agreed that they could correctly identify participants with low health literacy (76% residents vs. 53% faculty). Only 19% of residents and 26% of faculty were familiar with universal health literacy precautions. Many residents and faculty had received no training in health literacy (37% residents vs. 38% faculty). Barriers and challenges around health literacy included time, language, limited training or resources, low literacy, disease mismanagement, and fixed misconceptions. CONCLUSION: Despite ample evidence in the literature to the contrary, most respondents believed they could correctly identify individuals with low health literacy. Additionally, most participants had not heard of universal health literacy precautions and were unaware of their usage in their practice setting. This is not consistent with current expert recommendations. These findings are troubling as they are from academic residency programs, indicating an educational deficit. These findings point toward a next step in health literacy education for pediatric residents. [HLRP: Health Literacy Research and Practice. 2022;6(1):e51-e60.] Plain Language Summary: Pediatric residents and faculty in continuity clinics were surveyed about their opinions, health literacy knowledge, ability, and practices in continuity clinics. Despite evidence to the contrary, most respondents believed they could correctly identify individuals with low health literacy and had not heard of universal health literacy precautions. These findings highlight the need for more health literacy education for pediatric residents.

An exploration of the impact of SARS-CoV-2 (COVID-19) restrictions on marginalised groups in the UK.

BACKGROUND: To contain the spread of COVID-19 within the UK over the past year, there have been a series of local and national lockdowns. These restrictions are likely to have impacted upon the health and well-being of marginalised groups who rely on now closed social and community support services to stay healthy. An understanding of the experiences of marginalised people is important; therefore, this study aimed to explore the impact of the COVID-19 restrictions on the health and well-being of marginalised groups in the UK. METHODS: In summer 2020, a rapid telephone survey was conducted by trained, trusted volunteers with 76 participants who were from marginalised groups. As part of this survey, 64 participants consented to describe their experience of lockdown. These case studies were thematically analysed to identify patterns of meaning. RESULTS: Findings indicate that lockdown led to the deterioration of health of participants, impacted adversely on their socio-economic positions and affected access to food and essential supplies. In addition, government public health messaging was considered confusing and inadequate. CONCLUSIONS: This study highlights the need for pathways into services which support marginalised groups to remain accessible during periods of restrictions and essential supplies and food to be mapped and protected for marginalised individuals within our local communities.

Delineating sociodemographic, medical and quality of life factors associated with psychological distress in individuals with endometriosis.

STUDY QUESTION: What is the relationship between specific quality of life domains and depression, anxiety and stress in the endometriosis population? SUMMARY ANSWER: Psychosocial domains of quality of life, such as a perception of social support and self-image, are more strongly associated with depression, anxiety and stress than pain and medical factors. WHAT IS KNOWN ALREADY: Prior research indicates a high prevalence of anxiety and depression in individuals with endometriosis. Pain is thought to be critical in the development of psychological distress, however prior research has investigated this association without consideration of psychosocial quality of life domains such as social functioning, perceived social support and self-image. STUDY DESIGN, SIZE, DURATION: This study is a cross-sectional analysis of baseline data collected in a longitudinal study exploring psychological distress in endometriosis (n = 584). PARTICIPANTS/MATERIALS, SETTING, METHODS: Individuals living with endometriosis participated in this study and were recruited via online platforms of community organizations and support groups. Demographic and medical information concerning endometriosis treatment and diagnosis was self-reported. Psychological distress and quality of life was measured using the Depression, Anxiety and Stress Scale (DASS-21), Endometriosis Health Profile-30 (EHP-30) and the Short Form Survey (SF-36v2). A series of linear regression analyses explored the relationship between specific quality of life domains and the primary outcomes of depression, anxiety and stress. MAIN RESULTS AND THE ROLE OF CHANCE: Approximately half of the participants in this sample reported moderate to severe anxiety, depression and stress. Quality of life domains, particularly perceived social support, social functioning and self-image, were more strongly associated with psychological distress than medical or demographic factors. Pain was associated with anxiety, but not depression or stress. A greater number of endometriosis symptoms was only associated with depression. LIMITATIONS, REASONS FOR CAUTION: These data are cross-sectional and, therefore, causality cannot be inferred from this analysis. Information about endometriosis diagnosis and treatment was self-reported, and not verified against medical records. WIDER IMPLICATIONS OF THE FINDINGS: This study indicates that psychosocial factors may be more salient factors underlying depression, anxiety and stress in the endometriosis population than pain and medical factors. There is a need for interventions that target psychological distress in this population with a focus on the broader impact of endometriosis beyond pain and physical symptomatology. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Research Training Program (RTP) Scholarship awarded to C.S.M. by Macquarie University. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER: ACTRN12619001508167.

Urinary complement proteins and risk of end-stage renal disease: quantitative urinary proteomics in patients with type 2 diabetes and biopsy-proven diabetic nephropathy.

PURPOSE: To investigate the association between urinary complement proteins and renal outcome in biopsy-proven diabetic nephropathy (DN). METHODS: Untargeted proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass spectrometry was performed to determine the abundance of urinary complement proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and patients with T2DM and biopsy-proven DN. The abundance of each urinary complement protein was individually included in Cox proportional hazards models for predicting progression to end-stage renal disease (ESRD). RESULTS: Untargeted proteomic and functional analysis using the KEGG showed that differentially expressed urinary proteins were primarily associated with the complement and coagulation cascades. Subsequent urinary complement proteins quantification using PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) correlated negatively with annual estimated glomerular filtration rate (eGFR) decline, while urinary abundances of C5, decay-accelerating factor (DAF), and CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher urinary abundance of CFAH and lower urinary abundance of DAF were independently associated with greater risk of progression to ESRD. Urinary abundance of CFAH and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, or any pathological parameter. Moreover, the model that included CFAH or DAF had a larger AUC than that with only clinical or pathological parameters. CONCLUSION: Urinary abundance of complement proteins was significantly associated with ESRD in patients with T2DM and biopsy-proven DN, indicating that therapeutically targeting the complement pathway may alleviate progression of DN.