Weight stigma and binge eating related to poorer perceptions of healthcare provider interaction quality in a community-based sample.

BACKGROUND: Weight stigma refers to the social rejection, discrimination, and ideological devaluation of individuals because of body size and is a direct result of weight bias and anti-fat attitudes. Individuals with higher weight may be less likely to seek healthcare due to weight stigma, and if or when they do present for care, medical providers with weight bias may fail to provide high quality care. Little, however, is known about the intersectionality of weight stigma and perceptions of healthcare interactions as experienced by individuals who also binge eat. METHODS: Community-based adults completed online self-report questionnaires regarding generalized weight stigma (Attitudes Towards Obese Persons1), healthcare interaction quality (Patient Perceptions of Healthcare Provider Interaction Quality; PPH), and disordered eating (Eating Disorder Examination-Questionnaire) via Amazon's Mechanical Turk platform. For this cross-sectional study, participants were categorized by the presence and absence of regular binge episodes. Pearson's correlations, T-tests, ANOVA/ANCOVA, and a multivariate regression were used to examine relationships among demographic variables, weight stigma, disordered eating, and the PPH. RESULTS: Participants (N = 648) primarily identified as female (65.4%) and White, non-Hispanic (72.7%). Participants' average age and body mass index (BMI) were 37.5 (SD = 12.3) years old and 27.3 (SD = 6.9) kg/m2, respectively. Higher healthcare provider interaction quality ratings (PPH) were significantly related to lower BMI (r(648)=-0.098,p = 0.012), less weight stigma (r(648) = 0.149,p < 0.001), and identifying as a woman (t(514) = 2.09, p = 0.037, Cohen's d = 0.165) or White, non-Hispanic (t(646)=-2.73, p = 0.007, Cohen's d=-0.240). Participants reporting regular binge eating endorsed significantly worse perceptions of healthcare provider quality than those who did not, even after accounting for BMI, F(1, 645) = 8.42, p = 0.004, η2 = 0.013. A multivariate linear regression examining the PPH as dependent, and weight stigma and binge eating as independent, variable/s, was significant even after accounting for covariates (sex, race, BMI), F(95, 640) = 7.13,p < 0.001, R2 = 0.053 (small effect). CONCLUSIONS: More negative experiences with healthcare providers was associated with worse weight stigma, higher BMI, regular binge eating and overall disordered eating, and for participants identifying as male or a Person of Color. These data have implications for non-clinical community populations and are particularly important as experiencing poorer quality of interactions with healthcare providers may decrease individuals' likelihood of seeking needed care for both disordered eating and health-related concerns. TRIAL REGISTRATION: N/A.

Weight stigma refers to the discrimination towards individuals because of body size. Individuals who identify as a Person of Color and who experience binge eating may experience additional discrimination, resulting in barriers to receiving healthcare. To examine these relationships, a community-based sample (N = 648) completed health- and eating-related questionnaires online. Participants who had higher weight rated their perceptions of their interactions with healthcare providers as lower quality. People of Color and men reported lower quality of perceptions of their healthcare provider interactions compared to White, non-Hispanic and female participants, respectively. Participants reporting less weight stigma also reported more positive interactions with their healthcare providers. Participants who reported regular binge eating episodes reported worse quality of interactions with their healthcare providers compared to those who did not report regular binge eating, regardless of their weight. Participants endorsing more stigmatizing views of individuals with higher weight and those reporting regular binge eating were more likely to report poorer perceived quality of interactions with healthcare providers, regardless of their weight, race/ethnicity, or sex. These findings are of particular importance as experiencing poor quality interactions with healthcare providers may be a barrier to receiving needed healthcare.

Engagement in binge eating and fasting associated with poorer sleep quality in an online sample of adults.

OBJECTIVES: Both disordered eating and disturbed sleep represent significant threats to mental health. Accumulating evidence suggests that disordered eating behaviors and sleep problems co-occur. A majority of current research, however, has focused on these behaviors as components of eating disorder diagnoses, rather than investigating the independent associations of transdiagnostic disordered eating behaviors and sleep. The present study sought to examine fasting, binge eating, self-induced vomiting, laxative or diuretic misuse, and driven exercise as predictors of sleep quality complaints. METHOD: An online sample of 648 U.S. adults completed the Eating Disorder Examination - Questionnaire, the Pittsburgh Sleep Quality Index, and the Patient Health Care Questionnaire-2 as part of a larger parent study. RESULTS: Results of a hierarchical linear regression revealed that, collectively, disordered eating behaviors predicted worse sleep quality [R2 = 0.30, F(7, 640) = 31.21, p < .001], and that both binge eating and fasting, but not other compensatory behaviors, accounted for unique variance in sleep quality after controlling for BMI and depression. CONCLUSIONS: Overall, findings suggest that transdiagnostic disordered eating behaviors are associated with sleep quality complaints. Improved understanding of the specific relationships between individual eating behaviors and sleep characteristics can help refine the identification of individuals at high risk for sleep disturbance and address the potential reciprocal influence of sleep quality on disordered eating behaviors.

Physician homicide: Reports in the National Violent Death Reporting System (2003-2018).

OBJECTIVE: To explore the occurrence, demographics, and circumstances of homicides of physicians. METHOD: Authors interrogated the National Violent Death Reporting System (NVDRS), the Centers for Disease Control and Prevention's surveillance system tracking violent deaths between 2003 and 2018 which integrates data from law enforcement and coroner/medical examiner reports. Authors identified cases of homicide decedents whose profession was physician, surgeon, or psychiatrist. Data collected included decedents' demographics as well as circumstances of death. RESULTS: Data were provided by 7-41 states as participating states increased over time. Fifty-six homicides were reported, most were male (73.2%) and white (76.8%). Most (67.9%) identified assailants reportedly knew decedents: 23.2% were perpetrated by partners/ex-partners; 10.7% by patients/patients' family members. Deaths were mainly due to gunshot wounds (44.6%), stabbing (16.1%), and blunt force trauma (16.1%). More (58.9%) homicides occurred at victims' homes than work (16.1%). CONCLUSIONS: Physician homicides are relatively rare and occur at lower rates than in the general population. Physicians were more frequently killed by partners or ex-partners than by patients. Most homicides occurred away from the workplace. Broader efforts are needed to promote interventions throughout America's violent society to reduce domestic/partner violence and gun violence.

Trait impulsivity influences behavioural and physiological responses to threat in a virtual environment.

Trait impulsivity represents a tendency to take action without forethought or consideration of consequences. This trait is multifaceted and can be decomposed into attentional, motor and non-planning subtypes of impulsivity. The purpose of the current study was to investigate how subtypes of trait impulsivity responded to different degrees of threat within room-scale virtual reality (VR) with respect to behaviour and level of physiological activation. Thirty-four participants were required to negotiate a virtual environment (VE) where they walked at height with the continuous threat of a virtual 'fall.' Behavioural measures related to the speed of movement, interaction frequency and risk were collected. Participants also wore ambulatory sensors to collect data from electrocardiogram (ECG) and electrodermal activity (EDA). Our results indicated that participants who scored highly on non-planning impulsivity exhibited riskier behaviour and higher skin conductance level (SCL). Participants with higher motor impulsivity interacted with more objects in the VE when threat was high, they also exhibited contradictory indicators of physiological activation. Attentional impulsivity was associated with a greater number of falls across the VE. The results demonstrate that subtypes of trait impulsivity respond to threats via different patterns of behaviour and levels of physiological activation, reinforcing the multifaceted nature of the trait.

Sleep is the best medicine: assessing sleep, disordered eating, and weight-related functioning.

Sleep quality is linked to disordered eating, obesity, depression, and weight-related functioning. Most research, however, has focused on clinical populations. The current study investigated relationships between sleep quality, disordered eating, and patterns of functioning in a community sample to better understand relationships among modifiable health behaviors. Participants (N = 648) recruited from Amazon Mechanical Turk completed assessments of eating, depression, weight-related functioning, and sleep. Self-reported height and weight were used to calculate body mass index (M = 27.3, SD = 6.9). Participants were on average 37.6 years (SD = 12.3), primarily female (65.4%), and White, not Hispanic (72.7%). Over half of participants endorsed poor sleep quality, and average sleep scores were above the clinical cutoff for poor sleep quality. Sleep scores were significantly positively correlated with disordered eating, depression, and weight-related functioning, even after adjusting for age, body mass index, and sex. Multivariate regression models predicting weight-related functioning and depression showed that both sleep quality and disordered eating independently predicted depression. Sleep quality did not independently predict weight-related functioning; however, disordered eating did. To the best of our knowledge, this is the first study to assess sleep behaviors, disordered eating, and weight-related functioning in a community sample of weight diverse participants. Results indicate that most participants endorsed poor sleep quality, which was associated with disordered eating patterns, including binge eating and poorer weight-related functioning, even after controlling for body mass index, highlighting that this relationship exists across the weight spectrum. These results speak to the importance of health behavior assessment and intervention within nonclinical samples.Level of evidence Level III: evidence obtained from well-designed cohort or case-control analytic studies.

Homicides of psychologists, physicians, nurses, pharmacists, social workers, and other health professionals: National Violent Death Reporting System data 2003-2020.

OBJECTIVE: Homicide is the extreme endpoint along the continuum of interpersonal violence. Violence in healthcare settings and directed toward healthcare workers has been a growing concern. Analysis of health professionals' homicides is needed to inform prevention interventions. METHODS: Decedent numbers, age, and sex in the National Violent Death Reporting System are reported for 10 types of health professionals: advance practice registered nurses, dentists, nurses, pharmacists, physicians, physician assistants, psychiatrists, psychologists, social workers, and veterinarians. RESULTS: Between 2003 and 2020, 944 homicides of these professionals were reported to the NVDRS. Nearly 80% of victims were women; 53% of homicides involved guns. Nurses, social workers, physicians, and pharmacists comprised the most victims. In 2020, nurses, social workers, pharmacists, and psychologists had the highest homicide rates relative to their workforce size. Few of these homicides were related to professionals' work. The number of homicides within these professions correlated highly with the size of professions' workforces. CONCLUSIONS: Health professionals' homicides constitute a small proportion of US homicides generally at lower rates than seen in the general population. Age is likely one of the protective factors. Future, more comprehensive data will provide greater insights into emerging trends to inform strategies to mitigate homicide risk in health professionals. Prevention needs to go beyond healthcare settings and address societal roots of violence.

Eating disorders in weight-related therapy (EDIT): Protocol for a systematic review with individual participant data meta-analysis of eating disorder risk in behavioural weight management.

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

Early Use of Iloprost in Nonfreezing Cold Injury.

Nonfreezing cold injury (NFCI) is caused by prolonged exposure to cold, usually wet conditions and represents a separate pathological entity from frostbite. The pathophysiology of NFCI is characterized by vasoconstriction and microcirculatory disturbance. Iloprost, a synthetic prostaglandin analogue with vasodilatory properties is a recognized adjuvant treatment in frostbite; however, its role in NFCI is unclear. We present a case of a 29-y-old man with severe NFCI to both forefeet after prolonged immersion in cold seawater. Initial treatment with passive rewarming, analgesia and aspirin was initiated. Infusion of iloprost was used within 24 h from presentation and was well tolerated. This resulted in reduced tissue loss compared to the apparent tissue damage documented during the initial assessment. Delayed surgical intervention allowed minor debridement and minor toe amputations, maintaining the patient's ability to ambulate. This case demonstrates the safe use of iloprost in acute NFCI and highlights the importance of delayed surgical intervention in patients presenting with severe NFCI.

Characterization of Poor Visual Outcomes of Diabetic Macular Edema: The Fight Retinal Blindness! Project.

PURPOSE: To investigate the incidence, characteristics, and baseline predictors of poor visual outcomes in eyes with diabetic macular edema (DME) receiving intravitreal therapy in routine clinical practice. DESIGN: Observational study. PARTICIPANTS: Treatment-naïve eyes starting intravitreal therapy for DME between 2014 and 2018 tracked in the Fight Retinal Blindness! registry. We examined 2 groups with poor visual outcomes: (1) those with sustained vision loss of > 10 letters from baseline without recovery of visual acuity (VA); and (2) those with a VA of < 55 letters at 2 years. Respective controls were eyes that did not experience poor visual outcomes. METHODS: Kaplan-Meier curves analyzed the proportion of eyes that experienced poor outcomes. Cox proportional hazards models evaluated the potential baseline predictors of poor outcomes. MAIN OUTCOME MEASURES: The proportion of eyes that experienced poor visual outcomes within 2 years of treatment initiation and its baseline predictors. RESULTS: The proportion of eyes with sustained VA of ≥ 10 letter loss was 14% at 2 years; 16% of eyes had VA of ≤ 55 letters 2 years after starting intravitreal therapy. Initial treatment with intravitreal corticosteroid was independently associated with a higher incidence of ≥ 10 letter loss (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.60-6.44; P < 0.01). No improvement in the VA at 3 months after starting treatment was associated with ≥ 10 letter loss (HR, 6.81; 95% CI, 4.11-11.27; P < 0.01) and VA of ≤ 55 letters at 2 years (HR, 4.28; 95% CI, 2.66-6.89; P < 0.01). The other factors related to higher risk of VA of ≤ 55 letters were older age (HR, 1.02 per year; 95% CI, 1-1.04; P = 0.04) and poor baseline VA (HR, 0.68 per 5 letters; 95% CI, 0.65-0.72, P < 0.001). CONCLUSIONS: Fourteen percent of eyes managed with intravitreal therapy in routine clinical care experienced ≥ 10 letter loss and 16% had VA of ≤55 letters 2 years after starting the treatment for DME. The identification of the incidence and predictors of poor outcomes provides a more accurate assessment of the potential benefit from intravitreal therapy.

Extended-course antibiotic prophylaxis in lower limb amputation: randomized clinical trial.

BACKGROUND: Lower limb amputation (LLA) is typically described as 'clean surgery', but surgical-site infection (SSI) rates are high and there is significant variation in antibiotic prophylaxis practice. This study aimed to determine whether an extended period of antibiotic prophylaxis (5-day course) is superior to a short course (24 h) in preventing SSI in patients undergoing minor and major LLA. METHODS: Patients undergoing minor and major amputation from a single vascular unit were recruited and randomized to receive either a 5-day or a 24-h prophylactic course of antibiotics. Patients with significant baseline infection were excluded. Outcomes included the incidence of SSI and impaired wound healing (IWH), both measured using ASEPSIS criteria, the need for further surgery, duration of hospital stay, and mortality up to 1 year. RESULTS: Some 161 patients were recruited to the study, and 152 were included in the analysis. A 5-day course of antibiotics was associated with a lower incidence of SSI (11.8 versus 39.5 per cent; P < 0.001) and lower incidence of IWH (22.4 versus 58 per cent; P < 0.001). Fewer patients receiving the 5-day course required amputation revisional surgery (6.6 versus 21 per cent; P = 0.010). Duration of hospital stay and mortality rates were similar. The presence of SSI (odds ratio (OR) 5.14, 95 per cent c.i. 1.96 to 13.45; P < 0.001) and IWH (OR 4.62, 1.68 to 12.72; P = 0.003) increased the need for revisional surgery. SSI increased the duration of hospital stay: median 28 (i.q.r. 16-40) versus 14 (9-21) days (P = 0.045). CONCLUSION: SSI and IWH are common after LLA and have a significant impact on outcome. A 5-day course of antibiotic prophylaxis was associated with a reduction in both SSI and IWH compared with a 24-h course, and this reduced the need for further surgery. Registration number: NCT02018094 (http://www.clinicaltrials.gov); EudraCT 2012-003146-32 (https://www.clinicaltrialsregister.eu).

Ethnic and racial comparisons of weight-loss treatment utilization history and outcomes in patients with obesity and binge-eating disorder.

BACKGROUND: This study examined ethnic/racial differences in reported utilization of weight-loss methods/treatments and weight loss among adults with binge-eating disorder (BED) with co-existing obesity. METHODS: Participants were 400 adults (non-Hispanic Black: n = 99, Hispanic: n = 38, non-Hispanic White: n = 263) seeking treatment for BED in Connecticut from 2007 to 2012. Participants were asked about prior weight-loss methods/treatments and resulting weight losses. RESULTS: Overall, self-help diets were utilized most; mental-health services were utilized least. While non-significant differences for most methods/treatments were observed by ethnicity/race, significant differences emerged for self-help diets and supervised programs with non-Hispanic Whites, in general, utilizing these diets more frequently and losing more weight on these types of diets. CONCLUSIONS: Among treatment-seeking patients with BED and obesity, non-Hispanic White patients reported histories of greater weight-loss treatment utilization and weight loss than non-White patients for supervised and self-help diets. Findings highlight the need for greater understanding of treatment utilization and outcomes among minority patients with obesity and BED.

Digital self-harm is associated with disordered eating behaviors in adults.

PURPOSE: Eating-disorder psychopathology is associated with self-harm behaviors. With much time spent and many social interactions taking place online, self-cyberbullying has emerged as a new form of self-harm that is digital. The current study examined digital self-harm in adults and its associations with eating-disorder psychopathology and behaviors. METHODS: Participants were adults (N = 1794) who completed an online cross-sectional survey. Participants reported whether they had ever posted mean things about themselves online, whether they had ever anonymously bullied themselves online and completed measures of eating-disorder psychopathology and disordered eating behaviors. RESULTS: Digital self-harm was reported by adults across demographic characteristics and across the lifespan, although there were some significant differences in demographic characteristics associated with reported digital self-harm. Participants who engaged in digital self-harm were younger than those denying digital self-harm. Eating-disorder psychopathology and disordered eating behaviors were significantly higher among individuals reporting digital self-harm compared with age-matched controls. CONCLUSIONS: This was the first study to examine digital self-harm among adults and the first study to examine associations of digital self-harm with eating-disorder psychopathology and disordered eating behaviors. Importantly, digital self-harm is reported by adults and therefore is not limited to youth. Our findings that digital self-harm is associated with disordered eating suggests that digital self-harm is a clinically significant topic that needs further research to inform clinical practice and clinical research. LEVEL OF EVIDENCE: Level III, Evidence obtained from well-designed cohort or case-controlled analytic studies.

Influence of Nutritional Status and Leptin Action on Agrp and Pomc Co-Expression in Hypothalamic Melanocortin System Neurons.

OBJECTIVES: The control of energy balance relies on the counterbalancing release of neuropeptides encoded by the pro-opiomelanocortin (Pomc) and agouti-related protein (Agrp) genes, expressed by 2 distinct neuronal populations of the arcuate (ARC) nucleus of the hypothalamus. Although largely segregated, single-cell resolution techniques demonstrate some degree of co-expression. We studied whether challenges to the control of energy balance influence the degree of Agrp and Pomc co-expression in ARC melanocortin neurons. METHODS: We used fluorescence-activated cell sorting followed by quantitative polymerase chain reaction and fluorescent in situ hybridization to measure Pomc and Agrp gene co-expression in POMC or AGRP neurons in response to (1) acute or chronic calorie restriction, or (2) obesity due to loss of leptin receptor expression or chronic high-fat diet feeding in male mice. RESULTS: Melanocortin ARC neurons of fed mice exhibited low, yet detectable, levels of Pomc and Agrp gene co-expression. Calorie restriction significantly increased and decreased total Agrp and Pomc expression, respectively, and reduced the expression of Pomc relative to Agrp in AGRP neurons. Leptin-deficient db/db mice showed increased total Agrp levels and decreased Pomc expression, as well as significantly increased Agrp expression relative to Pomc in POMC neurons. Expression or co-expression levels did not differ between diet-induced obese mice and lean controls. CONCLUSIONS: Changes in Agrp and Pomc co-expression within POMC and AGRP neurons following chronic calorie restriction or in db/db mice suggest an additional mechanism to further suppress the melanocortin signaling during conditions of severely reduced leptin action.

Bevacizumab for diabetic macular oedema: one-year treatment outcomes from the Fight Retinal Blindness! Registry.

OBJECTIVES: This study evaluated the 1-year treatment outcomes of bevacizumab for diabetic macular oedema (DMO) in routine clinical practice. METHODS: A retrospective analysis was performed on 298 eyes of 220 patients with DMO that received intra-vitreal bevacizumab between 1 September 2013 and 31 August 2018 that were tracked by a prospectively designed, web-based observational registry-the Fight Retinal Blindness! Registry. RESULTS: The mean visual acuity (95% confidence interval [CI]) at 1-year was 3 (2, 5) letters better than a mean (SD) of 68 (15) letters at study entry. Nearly a quarter of eyes achieved ≥20/40. Eyes presenting with better vision (≥20/40) tended to maintain that vision during the period of observation, whereas those presenting with worse vision (<20/40) gained a mean (95% CI) of 9 (5, 13) letters. A mean reduction in the macular thickness was observed over the study period with the central subfield improving by 29 µm (95% CI 17, 40) from a mean (SD) of 402 (109) µm at study entry. Eyes that completed 1 year of follow-up received a median (Q1, Q3) of 7 (4, 9) bevacizumab injections. Sixty-two eyes, ~20%, that started with bevacizumab changed to either another VEGF inhibitor or steroid (triamcinolone) during the period of observation. This did not lead to functional improvement for eyes changed to either ranibizumab or aflibercept despite a further reduction in macular thickness. An improvement in vision and reduction in macular thickness was noted in the 13 eyes that subsequently received triamcinolone. Approximately 10% of eyes dropped out over 12 months, even though their mean visual acuity had improved by seven letters from the initial visit. CONCLUSIONS: Bevacizumab is an effective treatment for DMO in unselected populations.

Examining impairment and distress from food addiction across demographic and weight groups.

Rates of food addiction (FA) vary across weight and demographic groups. Factors influencing discrepant prevalence rates are largely unknown. Rates of clinically significant distress or impairment also vary across demographic groups, yet prior studies have overlooked the diagnostic significance of distress/impairment in heterogenous groups. We tested if weight and demographic groups differed in their likelihood of endorsing distress/impairment from FA. Participants (N = 1832) recruited from Amazon Mechanical Turk completed the modified Yale Food Addiction Scale 2.0 (mYFAS). The mYFAS includes 11 dichotomous symptom indicators and one dichotomous distress/impairment indicator. Differences in distress/impairment were tested across weight, sex, racial/ethnic, and educational groups using logistic regression. FA severity was controlled for using FA symptom count. There were no differences among racial/ethnic and educational groups (p > 0.05). Compared to men, women were more likely to report distress/impairment (aOR = 1.96, 95% CI = 1.28-3.03). People with obesity were more likely to report distress/impairment compared to people with overweight (aOR = 2.20, 95% CI = 1.39-3.49) or normal weight (aOR = 1.99, 95% CI = 1.26-3.13). Individual characteristics (i.e., sex, weight) may influence reporting of distress/impairment from FA. Further inquiry may be appropriate for men and people with normal weight or overweight presenting with FA symptoms who otherwise deny distress/impairment.

Anti-schistosomal activities of quinoxaline-containing compounds: From hit identification to lead optimisation.

Schistosomiasis is a neglected disease of poverty that is caused by infection with blood fluke species contained within the genus Schistosoma. For the last 40 years, control of schistosomiasis in endemic regions has predominantly been facilitated by administration of a single drug, praziquantel. Due to limitations in this mono-chemotherapeutic approach for sustaining schistosomiasis control into the future, alternative anti-schistosomal compounds are increasingly being sought by the drug discovery community. Herein, we describe a multi-pronged, integrated strategy that led to the identification and further exploration of the quinoxaline core as a promising anti-schistosomal scaffold. Firstly, phenotypic screening of commercially available small molecules resulted in the identification of a moderately active hit compound against Schistosoma mansoni (1, EC50 = 4.59 µM on schistosomula). Secondary exploration of the chemical space around compound 1 led to the identification of a quinoxaline-core containing, non-genotoxic lead (compound 22). Compound 22 demonstrated substantially improved activities on both intra-mammalian (EC50 = 0.44 µM, 0.20 µM and 84.7 nM, on schistosomula, juvenile and adult worms, respectively) and intra-molluscan (sporocyst) S. mansoni lifecycle stages. Further medicinal chemistry optimisation of compound 22, resulting in the generation of 20 additional analogues, improved our understanding of the structure-activity relationship and resulted in considerable improvements in both anti-schistosome potency and selectivity (e.g. compound 30; EC50 = 2.59 nM on adult worms; selectivity index compared to the HepG2 cell line = 348). Some derivatives of compound 22 (e.g. 31 and 33) also demonstrated significant activity against the two other medically important species, Schistosoma haematobium and Schistosoma japonicum. Further optimisation of this class of anti-schistosomal is ongoing and could lead to the development of an urgently needed alternative to praziquantel for assisting in schistosomiasis elimination strategies.

Inter-laboratory automation of the in vitro micronucleus assay using imaging flow cytometry and deep learning.

The in vitro micronucleus assay is a globally significant method for DNA damage quantification used for regulatory compound safety testing in addition to inter-individual monitoring of environmental, lifestyle and occupational factors. However, it relies on time-consuming and user-subjective manual scoring. Here we show that imaging flow cytometry and deep learning image classification represents a capable platform for automated, inter-laboratory operation. Images were captured for the cytokinesis-block micronucleus (CBMN) assay across three laboratories using methyl methanesulphonate (1.25-5.0 µg/mL) and/or carbendazim (0.8-1.6 µg/mL) exposures to TK6 cells. Human-scored image sets were assembled and used to train and test the classification abilities of the "DeepFlow" neural network in both intra- and inter-laboratory contexts. Harnessing image diversity across laboratories yielded a network able to score unseen data from an entirely new laboratory without any user configuration. Image classification accuracies of 98%, 95%, 82% and 85% were achieved for 'mononucleates', 'binucleates', 'mononucleates with MN' and 'binucleates with MN', respectively. Successful classifications of 'trinucleates' (90%) and 'tetranucleates' (88%) in addition to 'other or unscorable' phenotypes (96%) were also achieved. Attempts to classify extremely rare, tri- and tetranucleated cells with micronuclei into their own categories were less successful (≤ 57%). Benchmark dose analyses of human or automatically scored micronucleus frequency data yielded quantitation of the same equipotent concentration regardless of scoring method. We conclude that this automated approach offers significant potential to broaden the practical utility of the CBMN method across industry, research and clinical domains. We share our strategy using openly-accessible frameworks.

12 Months later: Motivational interviewing plus nutrition psychoeducation for weight loss in primary care.

PURPOSE: Motivational interviewing (MI) weight-loss interventions have garnered much attention, particularly in primary care. Few studies, however, have examined long-term outcomes of MI for weight loss in primary care. This study sought to examine the longer-term outcomes of a combination approach comprising MI and nutrition psychoeducation (MINP) with a publically available web-support component (i.e., livestrong.com). METHODS: Thirty-one adults with overweight/obesity were enrolled in a 3-month MINP treatment delivered in primary care by medical assistants. Weight, blood pressure, and depression (beck depression inventory) were assessed at baseline and 1-year following treatment cessation (i.e., 15 months total). RESULTS: Participants' average BMI was significantly lower 12-months following treatment. Approximately one-third of participants (34.8%) maintained 5% or more weight loss. Participants also experienced significant decreases in diastolic blood pressure, resting heart rate, and depression symptoms, but not systolic blood pressure or waist circumference. CONCLUSION: The scalable (2.5 h total) MINP intervention delivered in primary care by medical assistants resulted in significant weight (medium effect size) and psychological improvements 12 months later. These findings complement previous RCT findings that MI or nutrition psychoeducation interventions, delivered separately, resulted in small weight loss effects after 12 months, with 5% and 17% of participants, respectively, maintaining 5% weight loss. It remains unclear, however, if implementing MI in primary care for weight loss is cost effective beyond providing nutrition psychoeducation alone. CLINICAL TRIAL REGISTRATION: The clinical trial registration number is NCT02578199. LEVEL OF EVIDENCE: IV, uncontrolled trial.

Characterizing fear of weight gain and sensitivity to weight gain in individuals seeking weight loss treatment.

PURPOSE: Weight concern, including fear of weight gain and sensitivity to weight gain, is indicative of disordered eating in individuals with underweight or healthy weight. It is unknown, however, whether or how these constructs present in individuals with excess weight, particularly among those with binge-eating disorder (BED). This study sought to characterize fear of weight gain and sensitivity to weight gain and examine their relationship with disordered eating and depression symptoms, in individuals seeking weight loss treatment, both with and without BED. METHODS: Adults seeking weight loss treatment in an urban primary care clinic (N = 131) completed the Eating Disorder Examination interview and Beck Depression Inventory. Height and weight were collected. RESULTS: Clinical levels of fear of weight gain and sensitivity to weight gain were present in this sample. Individuals with BED reported experiencing fear of weight gain (48.6%), significantly more than those without BED (20.9%); both groups reported similar and clinically elevated sensitivity to weight gain. Both constructs were related to greater levels of disordered eating and depression symptoms, at times based on BED status. Fear of weight gain was associated with overvaluation of weight and shape for those without BED only. Objective and subjective bulimic episodes were unrelated to fear of weight gain or sensitivity to weight gain, regardless of BED status. CONCLUSION: Fear of weight gain and sensitivity to weight gain were common in this sample and may be maladaptive, as evidenced by associations with elevated eating psychopathology. Future studies should examine these variables within larger samples and should employ longitudinal designs. LEVEL OF EVIDENCE: Level III: case-control analytic study.