Bacterial enrichment prior to third-generation metagenomic sequencing improves detection of BRD pathogens and genetic determinants of antimicrobial resistance in feedlot cattle.

Introduction: Bovine respiratory disease (BRD) is one of the most important animal health problems in the beef industry. While bacterial culture and antimicrobial susceptibility testing have been used for diagnostic testing, the common practice of examining one isolate per species does not fully reflect the bacterial population in the sample. In contrast, a recent study with metagenomic sequencing of nasal swabs from feedlot cattle is promising in terms of bacterial pathogen identification and detection of antimicrobial resistance genes (ARGs). However, the sensitivity of metagenomic sequencing was impeded by the high proportion of host biomass in the nasal swab samples. Methods: This pilot study employed a non-selective bacterial enrichment step before nucleic acid extraction to increase the relative proportion of bacterial DNA for sequencing. Results: Non-selective bacterial enrichment increased the proportion of bacteria relative to host sequence data, allowing increased detection of BRD pathogens compared with unenriched samples. This process also allowed for enhanced detection of ARGs with species-level resolution, including detection of ARGs for bacterial species of interest that were not targeted for culture and susceptibility testing. The long-read sequencing approach enabled ARG detection on individual bacterial reads without the need for assembly. Metagenomics following non-selective bacterial enrichment resulted in substantial agreement for four of six comparisons with culture for respiratory bacteria and substantial or better correlation with qPCR. Comparison between isolate susceptibility results and detection of ARGs was best for macrolide ARGs in Mannheimia haemolytica reads but was also substantial for sulfonamide ARGs within M. haemolytica and Pasteurella multocida reads and tetracycline ARGs in Histophilus somni reads. Discussion: By increasing the proportion of bacterial DNA relative to host DNA through non-selective enrichment, we demonstrated a corresponding increase in the proportion of sequencing data identifying BRD-associated pathogens and ARGs in deep nasopharyngeal swabs from feedlot cattle using long-read metagenomic sequencing. This method shows promise as a detection strategy for BRD pathogens and ARGs and strikes a balance between processing time, input costs, and generation of on-target data. This approach could serve as a valuable tool to inform antimicrobial management for BRD and support antimicrobial stewardship.

Studying the Feasibility and Acceptability of an Interactive Web-based Lethal Means Safety Decision Aid for Hospitalized Adults With Suicide Risk (Lock to Live).

OBJECTIVE: Lock to Live is an interactive web-based lethal means safety decision aid that promotes temporary storage of firearms and medications. It has primarily been provided to suicidal patients in emergency department settings. The goal of this study was to evaluate the feasibility and acceptability of the Lock to Live decision aid with hospitalized adults at increased risk of suicide. METHODS: Subjects provided demographic information and completed the Columbia-Suicide Severity Rating Scale after which they completed the Lock to Live program followed by a survey. RESULTS: Twenty participants were recruited for this study, 5 of whom had access to firearms and 19 of whom had access to medications. Lock to Live was feasible to use as the mean length of time to complete the program was 10.0±5.3 minutes. It was acceptable to most participants as 75% of participants found it to be easy to use, and 65% of participants agreed that Lock to Live was helpful in making a decision about changing access to firearms/medications. CONCLUSION: Lock 2 Live decision aid appears to be a feasible and acceptable tool for hospitalized patients at risk for suicide.

Words Matter: Stylistic Writing Strategies for Racial Health Equity in Academic Medicine.

Many racialized health inequities in the USA have been known for decades. However, academic medicine, individual clinicians, and larger healthcare systems have not yet supported action towards sufficient and meaningful solutions, as evidenced by the persistence of racialized health inequities over time. Recently, academic medicine is increasing efforts to unequivocally identify systemic racism as a public health crisis because it drives health inequity to racially minoritized groups. A health equity emphasis in clinical education, practice, and research differs from a disparities approach because it seeks to dismantle the systems of racism that create inequitable health outcomes in the first place. Therefore, medical education, practice, and research are slowly transitioning from a lens of health disparities to one of health equity. In order to support this transition, authors and journals must restructure the depiction of health inequities caused by racism. Based upon the principles of the social medicine pioneer, Dr. Rudolph Virchow, the knowledge conveyed by scientific and medical academic writing must clearly name the drivers of social disease - which is generalized to the American landscape of racialized health inequity for the purposes of this manuscript - in order to inform action capable of stopping socially mediated health inequity. Yet, the language and construction of health disparities literature perpetuates colorblind and aversive racism by stylistically omitting the driver of inequity quite frequently, which renders such knowledge unable to support action. In this article, three academicians across the spectrum of social justice education identify and classify common writing styles of health disparities research in order to demonstrate how a writing style of racial health equity better supports true progress towards equity.

Management of SIADH-related hyponatremia due to psychotropic medications - An expert consensus from the Association of Medicine and Psychiatry.

OBJECTIVE: Hyponatremia is the most common electrolyte imbalance encountered in clinical practice and is associated with negative healthcare outcomes and cost. SIADH is thought to account for one third of all hyponatremia cases and is typically an insidious process. Psychotropic medications are commonly implicated in the etiology of drug induced SIADH. There is limited guidance for clinicians on management of psychotropic-induced SIADH. METHODS: After an extensive review of the existing literature, clinical-educators from the Association of Medicine and Psychiatry developed expert consensus recommendations for management of psychotropic-induced SIADH. A risk score was proposed based on risk factors for SIADH to guide clinical decision-making. RESULTS: SSRIs, SNRIs, antipsychotics, carbamazepine, and oxcarbazepine have moderate to high level of evidence demonstrating their association with SIADH. Evaluation for an avoidance of medications that cause hyponatremia is particularly important. Substitution with medication that is less likely to cause SIADH should be considered when appropriate. We propose an algorithmic approach to monitoring hyponatremia with SIADH and corresponding treatment depending on symptom severity. CONCLUSIONS: The proposed algorithm can help clinicians in determining whether psychotropic medication should be stopped, reduced or substituted where SIADH is suspected with recommendations for sodium (Na+) monitoring. These recommendations preserve a role for clinical judgment in the management of hyponatremia with consideration of the risks and benefits, which may be particularly relevant for complex patients that present with medical and psychiatric comorbidities. Further studies are needed to determine whether baseline and serial Na+ monitoring reduces morbidity and mortality.

CaptureSeq: Hybridization-Based Enrichment of cpn60 Gene Fragments Reveals the Community Structures of Synthetic and Natural Microbial Ecosystems.

BACKGROUND: The molecular profiling of complex microbial communities has become the basis for examining the relationship between the microbiome composition, structure and metabolic functions of those communities. Microbial community structure can be partially assessed with "universal" PCR targeting taxonomic or functional gene markers. Increasingly, shotgun metagenomic DNA sequencing is providing more quantitative insight into microbiomes. However, both amplicon-based and shotgun sequencing approaches have shortcomings that limit the ability to study microbiome dynamics. METHODS: We present a novel, amplicon-free, hybridization-based method (CaptureSeq) for profiling complex microbial communities using probes based on the chaperonin-60 gene. Molecular profiles of a commercially available synthetic microbial community standard were compared using CaptureSeq, whole metagenome sequencing, and 16S universal target amplification. Profiles were also generated for natural ecosystems including antibiotic-amended soils, manure storage tanks, and an agricultural reservoir. RESULTS: The CaptureSeq method generated a microbial profile that encompassed all of the bacteria and eukaryotes in the panel with greater reproducibility and more accurate representation of high G/C content microorganisms compared to 16S amplification. In the natural ecosystems, CaptureSeq provided a much greater depth of coverage and sensitivity of detection compared to shotgun sequencing without prior selection. The resulting community profiles provided quantitatively reliable information about all three domains of life (Bacteria, Archaea, and Eukarya) in the different ecosystems. The applications of CaptureSeq will facilitate accurate studies of host-microbiome interactions for environmental, crop, animal and human health. CONCLUSIONS: cpn60-based hybridization enriched for taxonomically informative DNA sequences from complex mixtures. In synthetic and natural microbial ecosystems, CaptureSeq provided sequences from prokaryotes and eukaryotes simultaneously, with quantitatively reliable read abundances. CaptureSeq provides an alternative to PCR amplification of taxonomic markers with deep community coverage while minimizing amplification biases.

Clinicians' Racial Bias Contributing to Disparities in Electroconvulsive Therapy for Patients From Racial-Ethnic Minority Groups.

Patients from racial-ethnic minority groups undergo disparate electroconvulsive therapy (ECT) treatment compared with Caucasian peers. One leading hypothesis is that clinicians may unknowingly display racial bias when considering ECT for patients of color. Studies have consistently shown that patients of color face numerous racially driven, provider-level interpersonal and perceptual biases that contribute to clinicians incorrectly overdiagnosing them as having a psychotic-spectrum illness rather than correctly diagnosing a severe affective disorder. A patient's diagnosis marks the entry to evidence-based service delivery, and ECT is best indicated for severe affective disorders rather than for psychotic disorders. As a consequence of racially influenced clinician misdiagnosis, patients from racial-ethnic minority groups are underrepresented among those given severe affective diagnoses, which are most indicated for ECT referral. Evidence also suggests that clinicians may use racially biased treatment rationales when considering ECT after they have given a diagnosis of a severe affective or psychotic disorder, thereby producing secondary inequities in ECT referral. Increasing the use of gold-standard treatment algorithms when considering ECT for patients of color is contingent on clinicians transcending the limitations posed by aversive racism to develop culturally unbiased, clinically indicated diagnostic and treatment rationales.

Coping with Racism: a Perspective of COVID-19 Church Closures on the Mental Health of African Americans.

Academic medical literature and news outlets extensively document how older individuals in communities of color, especially African American communities, are dying disproportionately of COVID-19 due to ongoing societal, racial, and healthcare disparities. Fear of death and suffering are acutely elevated in Black communities; yet, African Americans have been facing, coping with, and overcoming American societal racism and subsequent detriments to our mental health for centuries. Predominately African American churches (hereafter referred to as the "Black Church") have always served a historical, cultural, contextual, and scientifically validated role in the mental health well-being of African American communities coping with American racism. Nonetheless, buildings of worship closed due to the COVID-19 pandemic in mid-March 2020. This article is a first-hand perspective of five Black internists/psychiatrists who are deeply involved in both academic medicine and leadership positions within the Black Church. It will explore how the physical closure of Black Churches during this period of increased mental stress, as caused by healthcare inequities revealed by the COVID-19 epidemic, is likely to be uniquely taxing to the mental health of African Americans, particularly older African Americans, who must cope with American racism without physical access to the Black Church for the first time in history.

"There's always something else": Patient perspectives on improving the implementation of obesity guidelines in general practice.

OBJECTIVES: The prevalence of obesity in Australia is rising. National guidelines for the management of overweight and obesity exist but our previous work demonstrates poor implementation of key elements in general practice. The aim of this study was to describe patient perspectives on the implementation of obesity guidelines in general practice. METHODS: Qualitative study of 40 people living with obesity (PwO) who were recruited through general practices in Melbourne, Australia. PwO had a recorded BMI in the overweight range or above (>25), had attended a consultation in the last 6 months and had a diagnosis of at least one of the following: diabetes, kidney disease, hyperlipidemia, hypertension, or cardiovascular disease. Semi-structured telephone interviews were conducted with patients. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: While a strong general practitioner (GP)-patient relationship enabled conversation to occur about weight management there was uncertainty as to whether patients or GPs should broach the topic of weight. Patients described complacency regarding their weight and often being unprepared to take up GP advice. Other health issues were felt to take precedence, and patients described inconsistent provision of information and resources to assist them in tackling their weight problems. CONCLUSIONS: It is imperative to take into account patient perspectives on obesity management in general practice in order to improve health outcomes. This study provides valuable insights into how PwO can be better managed. Interventions should also include strategies to help patients maintain motivation in making lifestyle changes to support healthy weight loss.

Achieving Equity in Informed Consent: A Culturally-Informed Perspective for the Consideration and Consent of Minority Patients for Electroconvulsive Therapy.

Electroconvulsive therapy (ECT) is highly efficacious to treat severe depression in older adults. Yet, patients of ethnic and racial minorities are consistently underrepresented amongst those who receive ECT across all age groups. One strong hypothesis to explain this disparity is that minority patients are less likely to trust medical professionals and are therefore less likely to consent for ECT. Increasing participation of depressed, elderly, minority patients is uniquely challenging. Senior minority individuals have survived decades of medical and social injustices that no other demographic, specifically younger minorities or clinically-matched Caucasian peers, can truly comprehend from a first-hand perspective. This article provides a perspective based in cultural translational science to conversations of informed consent for ECT that removes our self-imposed stigma against discussing past and ongoing injustices with minority patients. Reducing disparities to geriatric minorities through equity of informed consent means that clinicians must validate the unique minority experience in medicine as it pertains to agreeing to a treatment modality as emotionally, socially, and historically laden as ECT.

Sigmoid Perforation Secondary to Accidental Ingestion of a Chicken Bone.

Presentation We describe an unusual presentation of sigmoid colon perforation secondary to an ingested chicken bone. Diagnosis The patient presented with a 4 day history of abdominal pain and distension. On examination there were signs of peritonism. Inflammatory markers were raised. Computed tomography revealed a linear density projecting through the wall of the colon. Treatment The patient underwent emergency laparotomy and a Hartmann's procedure. A chicken bone was found to be the causative foreign object. Conclusion Foreign body ingestion is an uncommon cause of sigmoid perforation which may mimic more common surgical presentations such as diverticulitis.

Perinatal fluoxetine exposure results in social deficits and reduced monoamine oxidase gene expression in mice.

Perinatal antidepressant drug exposure increases risk for autism spectrum disorder, yet the molecular and neurobehavioral effects of maternal antidepressant drug use on offspring remain poorly understood. In this study, we administered the selective serotonin reuptake inhibitor (SSRI) fluoxetine non-invasively to female mice throughout gestation and early lactation, and then examined social interaction behaviors in offspring. In addition, we measured whole brain gene expression levels of monoamine oxidase A (MAOA), the primary metabolizing enzyme for serotonin. We found deficits in sociability and social novelty-seeking behavior in the juvenile offspring of SSRI-treated mice, and these behaviors persisted into young adulthood. Furthermore, we found decreased MAOA expression in the brains of offspring of SSRI-treated mice. Our findings suggest that exposure to antidepressants during the prenatal and early postnatal period may negatively affect social development. Moreover, reduced MAOA expression may play a role in the mechanistic pathway linking SSRI exposure and behavioral deficits symptomatic of autism.

"90% of the time, it's not just weight": General practitioner and practice staff perspectives regarding the barriers and enablers to obesity guideline implementation.

OBJECTIVE: To identify the views of GPs and general practice staff regarding barriers and enablers to implementation of obesity guideline recommendations in general practice. METHODS: Twenty general practitioners (GPs) and 18 practice staff from inner-eastern Melbourne, Australia, participated in semi-structured telephone interviews. The interview schedule was informed by the Theoretical Domains Framework (TDF). Interviews were audio-recorded, transcribed verbatim and underwent thematic analysis. RESULTS: Participants lacked familiarity with and knowledge of the NHMRC obesity guidelines. Barriers and enablers were predominantly related to five theoretical domains: (1) environmental context and resources, (2) knowledge, (3) emotion, (4) beliefs about consequences, and (5) motivation and goals. Time pressures in consultations, costs for the patient, reluctance to add to patient burden particularly in those with comorbidities such as mental health issues, lack of awareness about services to refer patients to and GPs' fear of embarrassing patients and losing them were significant barriers. Enablers included having a strong doctor-patient relationship and a sense of responsibility to the patient to address weight. CONCLUSIONS: Obesity guidelines and policy makers need to better engage with issues of multimorbidity, socioeconomic disadvantage and workforce issues if recommendations are to be widely adopted in general practice. Tasksharing, teamwork and technology are potential solutions to some of the barriers. Patient perspectives and approaches to being able to overcome stigma and legitimise obesity management in primary care consultations could also assist.

Embolus Analog Trajectory Paths Under Physiological Flowrates Through Patient-Specific Aortic Arch Models.

Atrial fibrillation (AF) is the most common irregular heartbeat among the world's population and is a major contributor to cardiogenic embolisms and acute ischemic stroke (AIS). However, the role AF flow plays in the trajectory paths of cardiogenic emboli has not been experimentally investigated. A physiological simulation system was designed to analyze the trajectory patterns of bovine embolus analogs (EAs) (n = 720) through four patient-specific models, under three flow conditions: steady flow, normal pulsatile flow, and AF pulsatile flow. It was seen that EA trajectory paths were proportional to the percentage flowrate split of 25-31% along the branching vessels. Overall, AF flow conditions increased trajectories through the left- (LCCA) and right (RCCA)-common carotid artery by 25% with respect to normal pulsatile flow. There was no statistical difference in the distribution of clot trajectories when the clot was released from the right, left, or anterior positions. Significantly, more EAs traveled through the brachiocephalic trunk (BCT) than through the LCCA or the left subclavian. Yet of the EAs that traveled through the common carotid arteries, there was a greater affiliation toward the LCCA compared to the RCCA (p < 0.05).

The Mechanical Characterisation of Bovine Embolus Analogues Under Various Loading Conditions.

Embolus Analogues (EAs) can provide understanding of the mechanical characteristics of blood clots of cardiac origin. Bovine EAs (n = 29) were fabricated with varying concentrations of thrombin (0-20 NIHU/ml blood). Histological staining confirmed that EA composition compared sufficiently with human samples reported in literature. EAs were mechanically described under seven testing conditions: tensile, compression, shear wave ultrasound elastography (SWE), parallel plate rheometry, indentation, creep and relaxation. The Young modulus of bovine EAs in tension varied from 7 kPa (5% strain) to 84 kPa (50% strain). The compressive Young modulus increased with increasing thrombin concentration, which was in agreement with the SWE results. There was no significant difference in Young modulus throughout the clot (p < 0.05). The EAs displayed a non-linear response under parallel plate rheometry, creep and stress relaxation. The 3rd order Mooney-Rivlin constitutive equation and Standard Linear Solid model were used to fit the non-linear stress-strain response and time-dependent properties, respectively. This is the first study in which bovine EAs, with and without addition of thrombin, are histologically and mechanically described with corresponding proposed constitutive equations. The equations and experimental data determined can be applied for future numerical and experimental testing of mammalian EAs and cardiac source clots.

The internet as a source of support for youth with chronic conditions: A qualitative study.

BACKGROUND: Adolescents living with chronic conditions often portray themselves as "healthy" online, yet use the Internet as one of their top sources of health information and social communication. There is a need to develop online support programs specific to adolescents with chronic conditions in order to provide a private space to discuss concerns. This paper endeavors to increase our understanding of the online support needs and wants of these adolescents and their interest in and preferences for an online support program. METHODS: A qualitative descriptive study using semistructured interviews was completed. Stratified purposive sampling was utilized to ensure a representative sample based on age and diagnosis. English speaking adolescents (aged 12-18 years) diagnosed with a chronic condition were recruited from clinic and inpatient areas across 3 paediatric hospitals in Canada. RESULTS: Thirty-three participants aged 15.3 ± 1.8 years (64% female) completed the study. The main topics identified were (a) the purpose of current online activity, (b) the benefits and challenges of existing online supports, and (c) a description of ideal online resources. The purpose of online activity was social networking, information, online gaming, and social support. When accessing health information online, participants prioritized websites that were easy to access and understand despite the trustworthiness of the site. The reported benefits and challenges varied across participants with many areas perceived as both a benefit and a challenge. The majority of participants were interested in participating in an online support program that included both accurate disease-related information and a community of other adolescents to provide social support. CONCLUSIONS: Adolescents with chronic conditions are interested in online support that encompasses health information and social support that is flexible and easy to navigate. Findings can be used to develop or adapt existing online support programs for adolescents with chronic conditions to help increase engagement and utilization.

Feasibility of using self-reported ethnicity in pregnancy according to the gestation-related optimal weight classification: a cross-sectional study.

OBJECTIVE: To evaluate the feasibility of self-reported ethnicity using the gestation-related optimal growth (GROW) classification in a contemporary multicultural antenatal population. DESIGN: Cross-sectional study. SETTING: Tertiary obstetric hospital in Melbourne, Australia. POPULATION: Pregnant women attending the antenatal clinic. METHODS: We surveyed pregnant women during April-June 2016 regarding their understanding of the term 'ethnicity', and how they would classify the ethnicity of themselves, their partner, and family members according to the Australian GROW classification. RESULTS: Two hundred and thirty-five women completed the survey. When describing 'ethnicity', most women (103, 44%) chose multiple descriptors, most frequently country of birth (54%) and region of ancestry (47%). Interpretation of 'ethnicity' varied significantly between ethnic groups: those choosing 'country of birth' were more likely to identify as Indian (odds ratio, OR 3.5, P = 0.03), whereas those choosing 'physical appearance' were more likely to identify as Chinese (OR 3.0, P = 0.047). Thirty participants (13%) were unable to describe their ethnicity from the available GROW options. Sixty-one (26%) respondents' ethnicity was inconsistent with that of their parents' heritage. A further 35% had a partner of different ethnicity. The agreement between country of birth and self-reported ethnicity was only fair (kappa 0.73, 95% confidence interval, 95% CI 0.64-0.82). CONCLUSION: This study confirms the complexity of defining ethnicity in contemporary multicultural settings. Self-reported ethnicity is often inaccurate, concepts of ethnicity vary by ethnic group, and country of birth is a poor descriptive surrogate. Adjustment for maternal ethnicity should be undertaken with caution in the customised assessment of fetal growth. TWEETABLE ABSTRACT: Is self-reported maternal ethnicity reliable? We think not.

A mobile health intervention promoting healthy gestational weight gain for women entering pregnancy at a high body mass index: the txt4two pilot randomised controlled trial.

OBJECTIVE: To determine the feasibility and effectiveness of an mHealth intervention promoting healthy diet, physical activity and gestational weight gain in pregnant women. DESIGN: Randomised controlled trial (RCT). SETTING: Australian tertiary obstetric hospital. POPULATION: One hundred pregnant women who were overweight or obese prior to pregnancy. METHODS: Women recruited at the first antenatal clinic visit were randomised to either an intervention or a control group. The intervention consisted of a tailored suite of strategies delivered (from first antenatal visit until 36 weeks' gestation) via multiple modalities available on mobile devices. MAIN OUTCOME MEASURES: The primary outcome was intervention feasibility and secondary outcomes were objectively measured changes in gestational weight gain (GWG) and self-reported dietary intake and physical activity. RESULTS: Ninety-one women completed the study. Delivery to protocol provides evidence of program feasibility. Most women engaged regularly with the program, with the majority (97.6%) reporting that the intervention was helpful. Secondary outcomes demonstrated a significantly lower GWG in the intervention group (7.8 kg ± 4.7 versus 9.7 kg ± 3.9; P =0.041) compared with the control group at intervention completion. Intervention group women reported significantly smaller reductions in total, light- and moderate-intensity physical activity from baseline to completion of the intervention (P = 0.001) compared with the control group, but no differences in consumption frequencies of key food groups. CONCLUSION: An intervention that aimed to deliver healthy diet, physical activity and GWG guidance utilising innovative technology can be feasibly implemented and produce positive physical activity and GWG outcomes. TWEETABLE ABSTRACT: txt4two mHealth study improved gestational weight gain and physical activity in pregnant women with high BMIs.

Microparticle subpopulations are potential markers of disease progression and vascular dysfunction across a spectrum of connective tissue disease.

OBJECTIVE: Microparticles (MPs) are membrane-bound vesicles derived from vascular and intravascular cells such as endothelial cells (EMPs) and platelets (PMPs). We investigated EMP and PMP numbers across a spectrum of autoimmune rheumatic diseases (AIRDs) with the aim of comparing the levels of, and relationship between, EMPs and PMPs. METHODS: Patients with Systemic Lupus Erythematosus (SLE) (n = 24), Systemic Sclerosis (SSc) (n = 24), Primary Raynauds Phenomenon (RP) (n = 17) and "other CTD" (n = 15) (Primary Sjogrens Syndrome, UCTD or MCTD) as well as 15 healthy controls were recruited. EMPs and PMPs were quantified using flow cytometry. Associations between MP levels and objective functional vascular assessments were evaluated. RESULTS: SLE patients had significantly higher EMPs compared with healthy controls and SSc patients. Higher PMP levels were noted in SSc and primary RP when compared to healthy controls and 'other CTD' patients. A modest correlation was noted between EMP and PMP levels in healthy controls (Spearman r = 0.6, p = 0.017). This relationship appeared stronger in SLE (r = 0.72, p < 0.0001) and other CTD patients (r = 0.75, p < 0.0001). The association between EMPs and PMPs was notably less strong in SSc (r = 0.45, p = 0.014) and RP (r = 0.37, p = 0.15). A significantly lower EMP/PMP ratio was detected in SSc/RP patients in comparison to both healthy controls and SLE/other CTD patients. Higher EMP and PMP levels were associated with higher digital perfusion following cold challenge in SSc. In contrast, higher PMP (but not EMP) levels were associated with lower digital perfusion at both baseline and following cold challenge in primary RP. Higher PMP levels were associated with greater endothelial-independent dilation in patients with SLE. CONCLUSION: MP populations differ across the spectrum of AIRDS, possibly reflecting differences in vascular cell injury and activation. MP levels are associated with functional assessments of vascular function and might have a role as novel vascular biomarkers in AIRDs. SIGNIFICANCE AND INNOVATIONS: Levels of circulating endothelial and platelet microparticles differ between SSc/primary RP compared with SLE and other CTDs (UCTD, MCTD and Primary Sjogrens). MP release may occur within different vascular sites across these disease groups (macrovascular and microvascular). The association between circulating MP levels and objective assessment of macro- and microvascular dysfunction within these disease areas suggests that MPs might have a useful role as novel circulating biomarkers of vascular disease within the CTDs.

Impact of maternal, antenatal and birth-associated factors on iron stores at birth: data from a prospective maternal-infant birth cohort.

BACKGROUND/OBJECTIVES: Low serum ferritin concentrations at birth, which reflect neonatal iron stores, track through to early childhood and have been associated with poorer neurodevelopmental outcomes. We aimed to identify maternal, antenatal and birth-associated factors that influence iron stores at birth in a prospective maternal-infant birth cohort. SUBJECTS/METHODS: In a population-based, longitudinal, birth cohort in Ireland, 413 maternal-infant dyads with prospectively collected lifestyle and clinical data from 15 weeks' gestation had umbilical cord serum ferritin concentrations measured. Regression models were developed to identify independent factors associated with cord ferritin concentrations. RESULTS: Median (IQR) cord ferritin concentrations were 185.7 (131.7, 385.5) µg/l, and 8% (n=33) of infants had low iron stores (ferritin <76 µg/l) at birth. Maternal obesity (BMI ⩾30 kg/m2) at 15 weeks' gestation (adj. estimate (95% confidence interval (CI)): -66.4 (-106.9, -25.9) µg/l, P<0.0001) and delivery by caesarean section (-38.8 (-70.2, -7.4) µg/l, P=0.016) were inversely associated with cord ferritin concentrations. In addition, maternal smoking at 15 weeks' gestation (adj. odds ratio (95% CI): 2.9 (1.2, 7), P=0.020) and being born small-for-gestational age (3.4 (1.3, 8.9), P=0.012) were associated with an increased risk of low iron stores (ferritin <76 µg/l) at birth. CONCLUSIONS: We have identified a number of potentially modifiable lifestyle factors that influence iron stores at birth, with the important role of overall maternal health and lifestyle during pregnancy highlighted. Public health policies targeting women of child-bearing age to improve nutrition and health outcomes should be prioritised for the health of the next generation.