A major locus confers triclabendazole resistance in Fasciola hepatica and shows dominant inheritance.

Fasciola hepatica infection is responsible for substantial economic losses in livestock worldwide and poses a threat to human health in endemic areas. The mainstay of control in livestock and the only drug licenced for use in humans is triclabendazole (TCBZ). TCBZ resistance has been reported on every continent and threatens effective control of fasciolosis in many parts of the world. To date, understanding the genetic mechanisms underlying TCBZ resistance has been limited to studies of candidate genes, based on assumptions of their role in drug action. Taking an alternative approach, we combined a genetic cross with whole-genome sequencing to localise a ~3.2Mbp locus within the 1.2Gbp F. hepatica genome that confers TCBZ resistance. We validated this locus independently using bulk segregant analysis of F. hepatica populations and showed that it is the target of drug selection in the field. We genotyped individual parasites and tracked segregation and reassortment of SNPs to show that TCBZ resistance exhibits Mendelian inheritance and is conferred by a dominant allele. We defined gene content within this locus to pinpoint genes involved in membrane transport, (e.g. ATP-binding cassette family B, ABCB1), transmembrane signalling and signal transduction (e.g. GTP-Ras-adenylyl cyclase and EGF-like protein), DNA/RNA binding and transcriptional regulation (e.g. SANT/Myb-like DNA-binding domain protein) and drug storage and sequestration (e.g. fatty acid binding protein, FABP) as prime candidates for conferring TCBZ resistance. This study constitutes the first experimental cross and genome-wide approach for any heritable trait in F. hepatica and is key to understanding the evolution of drug resistance in Fasciola spp. to inform deployment of efficacious anthelmintic treatments in the field.

Philadelphia Latine Immigrant Birthing People's Perspectives on Mitigating the Chilling Effect on Prenatal Care Utilization.

RESEARCH DESIGN: Community-engaged qualitative study using inductive thematic analysis of semistructured interviews. OBJECTIVE: To understand Latine immigrants' recent prenatal care experiences and develop community-informed strategies to mitigate policy-related chilling effects on prenatal care utilization. BACKGROUND: Decreased health care utilization among immigrants due to punitive immigration policies (ie, the "chilling effect") has been well-documented among Latine birthing people both pre and postnatally. PATIENTS AND METHODS: Currently or recently pregnant immigrant Latine people in greater Philadelphia were recruited from an obstetric clinic, 2 pediatric primary care clinics, and 2 community-based organization client pools. Thematic saturation was achieved with 24 people. Participants' pregnancy narratives and their perspectives on how health care providers and systems could make prenatal care feel safer and more comfortable for immigrants. RESULTS: Participants' recommendations for mitigating the chilling effect during the prenatal period included training prenatal health care providers to sensitively initiate discussions about immigrants' rights and reaffirm confidentiality around immigration status. Participants suggested that health care systems should expand sources of information for pregnant immigrants, either by partnering with community organizations to disseminate information or by increasing access to trusted individuals knowledgeable about immigrants' rights to health care. Participants also suggested training non-medical office staff in the use of interpreters. CONCLUSION: Immigrant Latine pregnant and birthing people in greater Philadelphia described ongoing fear and confusion regarding the utilization of prenatal care, as well as experiences of discrimination. Participants' suggestions for mitigating immigration-related chilling effects can be translated into potential policy and programmatic interventions which could be implemented locally and evaluated for broader applicability.

Parental communication satisfaction with the clinical team in the paediatric cardiac ICU.

INTRODUCTION: Understanding parents' communication preferences and how parental and child characteristics impact satisfaction with communication is vital to mitigate communication challenges in the cardiac ICU. METHODS: This cross-sectional survey was conducted from January 2019 to March 2020 in a paediatric cardiac ICU with parents of patients admitted for at least two weeks. Family satisfaction with communication with the medical team was measured using the Communication Assessment Tool for Team settings. Clinical characteristics were collected via Epic, Pediatric Cardiac Critical Care Consortium local entry and Society for Thoracic Surgeons Congenital Heart Surgery Databases. Associations between communication score and parental mood, stress, perceptions of clinical care, and demographic characteristics along with patient demographic and clinical characteristics were examined. Multivariable ordinal models were conducted with characteristics significant in bivariate analysis. RESULTS: In total, 93 parents of 84 patients (86% of approached) completed surveys. Parents were 63% female and 70% White. Seventy per cent of patients were <6 months old at admission, 25% had an extracardiac abnormality, and 80% had a cardiac surgery this admission. Parents of children with higher pre-surgical risk of mortality scores (OR 2.875; 95%CI 1.076-7.678), presence of surgical complications (72 [63.0, 75.0] vs. 64 [95%CI 54.6, 73] (p = 0.0247)), and greater satisfaction with care in the ICU (r = 0.93922; p < 0.0001) had significantly higher communication scores. CONCLUSION: These findings can prepare providers for scenarios with higher risk for communication challenges and demonstrate the need for further investigation into interventions that reduce parental anxiety and improve communication for patients with unexpected clinical trajectories.

Impact of COVID-19 on Infants followed after Discharge from the Neonatal Intensive Care Unit Using a Telemedicine Model.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) continues to have a profound impact on infant health care and health outcomes. In this study, we aimed to characterize the social impact of the first COVID-19 lockdown on families in a neonatal follow-up program (NFP). Given the ongoing increased use of telehealth across the medicine, we also evaluated for patient-level differences in virtual visit rates to identify patients at risk of follow-up challenges. STUDY DESIGN: To assess the impact of virtual health care utilization, we conducted a retrospective cohort study to describe challenges associated with telemedicine use in this vulnerable patient population during our telemedicine epoch (March 13, 2020-July 31, 2020). We also looked for patient-level factors associated with attending NFP visits as scheduled. Finally, we summarized caregiver responses to a COVID-19 Obstacles Assessment Survey and assessed for racial disparities in these responses. RESULTS: When comparing patients who completed their virtual visit to those who did not, we found no differences by infants' sex, birthweight, gestational age at birth, or caregiver self-reported race and ethnicity. However, infants whose visits did not occur were more often discharged with equipment or covered by public insurance. Nine percent of families reported food insecurity. CONCLUSION: During the initial COVID-19 lockdown, families with infants discharged from a neonatal intensive care unit (NICU) faced significant obstacles caring for their infants and attending scheduled follow-up visits. Infants in families with lower socioeconomic status or with increased medical complexity faced increased challenges in attending virtual follow-up visits during this epoch. Given the ongoing reliance on telemedicine in health care and the need to better prepare for future epidemics/pandemics, this study offers critical information that can assist neonatal teams in bolstering transitions to home and creating stronger safety nets for their patients after discharge. KEY POINTS: · Telemedicine works well for high-risk neonatal populations.. · Infant medical complexity may be a risk factor for challenges attending neonatal follow-up visits.. · NICUs should work to prevent food insecurity postdischarge..

Risk of Extreme, Moderate, and Late Preterm Birth by Maternal Race, Ethnicity, and Nativity.

OBJECTIVES: To explore the relative risks of preterm birth-both overall and stratified into 3 groups (late, moderate, and extreme prematurity)-associated with maternal race, ethnicity, and nativity (ie, birthplace) combined. STUDY DESIGN: This was a retrospective cross-sectional cohort study of women delivering a live birth in Pennsylvania from 2011 to 2014 (n = 4 499 259). Log binomial and multinomial regression analyses determined the relative risks of each strata of preterm birth by racial/ethnic/native category, after adjusting for maternal sociodemographic, medical comorbidities, and birth year. RESULTS: Foreign-born women overall had lower relative risks of both overall preterm birth and each strata of prematurity when examined en bloc. However, when considering maternal race, ethnicity, and nativity together, the relative risk of preterm birth for women in different racial/ethnic/nativity groups varied by preterm strata and by race. Being foreign-born appeared protective for late prematurity. However, only foreign-born White women had lower adjusted relative risks of moderate and extreme preterm birth compared with reference groups. All ethnic/native sub-groups of Black women had a significantly increased risk of extreme preterm births compared with US born non-Hispanic White women. CONCLUSIONS: Race, ethnicity, and nativity contribute differently to varying levels of prematurity. Future research involving birth outcome disparities may benefit by taking a more granular approach to the outcome of preterm birth and considering how nativity interacts with race and ethnicity.

Streamlining Universal Prenatal Screening for Risk for Adverse Birth Outcomes.

OBJECTIVE: Many of the medical risk factors for adverse birth outcomes (e.g., preeclampsia) are regularly monitored in prenatal care. However, many of the psychosocial risk factors associated with adverse birth outcomes (e.g., maternal stress, anxiety, depression, intimate partner violence) are not regularly addressed during routine prenatal care. Comprehensive prenatal screening for psychosocial risk factors for adverse birth outcomes can improve maternal and neonatal outcomes. In this study, we examine an existing tool for opportunities to streamline and improve screening. METHODS: We reviewed medical records for 528 mother-infant dyads, recording maternal responses to a 21-item prenatal risk screening tool, and gestational age/birth weight of infants. Multiple approaches to scoring were used to predict likelihood of adverse birth outcome. RESULTS: Women who answered yes to any of the top four interrelated items were 3.32 times more likely to have an adverse birth outcome. Sensitivity and specificity were 68% and 65%, respectively. CONCLUSION FOR PRACTICE: We identified a short surveillance tool to identify women who are at highest risk and require more in-depth screening, and to rule out women who are at very low risk of an adverse birth outcome.

Epidemiology and management of appendicular fractures occurring in neonatal intensive care patients.

AIM: To describe the epidemiology and management of appendicular fractures occurring in the neonatal ICU in a large series of patients treated a single, quaternary care neonatal intensive care unit. METHODS: Patients <1 years old with appendicular fractures treated from 2012 to 2016 at a quaternary-level NICU were identified. Bivariate testing compared fractures, work-up and management based on designated mechanism (presumed birth-related vs unknown). In patients with unknown mechanism, factors with potential fracture association were analysed in a descriptive fashion. RESULTS: Eighty-five fractures (54 patients) were included. Mechanistic cohorts differed by birthweight (P < .001) and gestational age at birth (P < .001). Presumed birth-related fractures were more commonly upper extremity (P < .001), solitary (P = .001) and radiographically diagnosed in the acute state (<.001). The biochemical profile of the cohorts differed significantly. The prevalence of factors with potential fracture association was high in patients with unknown mechanism. Only one patient required surgery, while all others resolved with minimal orthopaedic intervention. CONCLUSION: Findings indicate these injuries rarely require operative intervention and that two distinct injury profiles appear to exist based on fracture mechanism. Steroid use, ventilation use, diuretic use, nutritional supplementation and recent bedside procedures were common among patients without known fracture mechanism. LEVEL OF EVIDENCE: Level III-Retrospective Cohort Study.

Implications of the vaginal microbiome and potential restorative strategies on maternal health: a narrative review.

The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women's health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women's cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus-dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs.

New Strategies to Tackle the Combined Biological and Social Context of Preterm Birth.

OBJECTIVE: Preterm birth rates in the population and associated racial inequities have remained relatively unchanged in the United States despite research aimed at prevention. This is potentially the result of the multifactorial pathophysiologic pathways that result in preterm birth, where biological and social drivers intersect in unique ways for different women. The field of dissemination and implementation (D&I) science may address this issue by promoting the contextually-aware uptake of science into health and health care delivery. STUDY DESIGN: In this paper, we describe how the field of D&I science may afford new perspectives on preterm birth prevention to researchers and tools to design studies that translate clinical trial data into measurable changes at the level of the population. We discuss key examples where the perspectives and tools of D&I science have been used in conjunction with quality improvement methodology to change preterm birth rates in large population studies. We build on these case studies and suggest future D&I science-informed studies that could be explored. CONCLUSION: Incorporating D&I scientific principles into the design of studies to prevent preterm birth may allow future research to better address the varied ways in which social forces comingle with biological risk factors to result in preterm birth.

Isolation of Mycobacterium lepromatosis and Development of Molecular Diagnostic Assays to Distinguish Mycobacterium leprae and M. lepromatosis.

BACKGROUND: Mycobacterium leprae was thought to be the exclusive causative agent of leprosy until Mycobacterium lepromatosis was identified in a rare form of leprosy known as diffuse lepromatous leprosy (DLL). METHODS: We isolated M. lepromatosis from a patient with DLL and propagated it in athymic nude mouse footpads. Genomic analysis of this strain (NHDP-385) identified a unique repetitive element, RLPM, on which a specific real-time quantitative polymerase chain reaction assay was developed. The RLPM assay, and a previously developed RLEP quantitative polymerase chain reaction assay for M. leprae, were validated as clinical diagnostic assays according to Clinical Laboratory Improvement Amendments guidelines. We tested DNA from archived histological sections, patient specimens from the United States, Philippines, and Mexico, and US wild armadillos. RESULTS: The limit of detection for the RLEP and RLPM assays is 30 M. leprae per specimen (0.76 bacilli per reaction; coefficient of variation, 0.65%-2.44%) and 122 M. lepromatosis per specimen (3.05 bacilli per reaction; 0.84%-2.9%), respectively. In histological sections (n = 10), 1 lepromatous leprosy (LL), 1 DLL, and 3 Lucio reactions contained M. lepromatosis; 2 LL and 2 Lucio reactions contained M. leprae; and 1 LL reaction contained both species. M. lepromatosis was detected in 3 of 218 US biopsy specimens (1.38%). All Philippines specimens (n = 180) were M. lepromatosis negative and M. leprae positive. Conversely, 15 of 47 Mexican specimens (31.91%) were positive for M. lepromatosis, 19 of 47 (40.43%) were positive for M. leprae, and 2 of 47 (4.26%) contained both organisms. All armadillos were M. lepromatosis negative. CONCLUSIONS: The RLPM and RLEP assays will aid healthcare providers in the clinical diagnosis and surveillance of leprosy.

Defining and distinguishing infant behavioral states using acoustic cry analysis: is colic painful?

BACKGROUND: To characterize acoustic features of an infant's cry and use machine learning to provide an objective measurement of behavioral state in a cry-translator. To apply the cry-translation algorithm to colic hypothesizing that these cries sound painful. METHODS: Assessment of 1000 cries in a mobile app (ChatterBabyTM). Training a cry-translation algorithm by evaluating >6000 acoustic features to predict whether infant cry was due to a pain (vaccinations, ear-piercings), fussy, or hunger states. Using the algorithm to predict the behavioral state of infants with reported colic. RESULTS: The cry-translation algorithm was 90.7% accurate for identifying pain cries, and achieved 71.5% accuracy in discriminating cries from fussiness, hunger, or pain. The ChatterBaby cry-translation algorithm overwhelmingly predicted that colic cries were most likely from pain, compared to fussy and hungry states. Colic cries had average pain ratings of 73%, significantly greater than the pain measurements found in fussiness and hunger (p < 0.001, 2-sample t test). Colic cries outranked pain cries by measures of acoustic intensity, including energy, length of voiced periods, and fundamental frequency/pitch, while fussy and hungry cries showed reduced intensity measures compared to pain and colic. CONCLUSIONS: Acoustic features of cries are consistent across a diverse infant population and can be utilized as objective markers of pain, hunger, and fussiness. The ChatterBaby algorithm detected significant acoustic similarities between colic and painful cries, suggesting that they may share a neuronal pathway.

Preliminary examination of insulin and amylin levels in women with purging disorder.

OBJECTIVE: This preliminary study explored whether differences in meal-stimulated insulin or amylin release are linked to altered ingestive behaviors in individuals with bulimia nervosa (BN) or purging disorder (PD). METHOD: Women with BN (n = 15), PD (n = 16), or no eating disorder (n = 18) underwent structured clinical interviews and assessments of gut hormone and subjective responses to a fixed test meal. Multilevel model analyses were used to explore whether gut hormone responses contribute to subjective responses to the test meal and whether these associations differed by group. RESULTS: Insulin and amylin levels significantly increased following the test meal. Women with PD showed greater insulin release compared to those with BN, but not controls. Multilevel models support significant group X insulin interactions predicting subjective ratings of nausea and urge to vomit, with a stronger association between higher insulin responses and higher nausea and urge to vomit in women with PD and BN. Amylin responses did not differ by group. CONCLUSION: Increased sensitivity to the effects of insulin on nausea and urge to vomit may be linked to purging in both PD and BN. Differences in postprandial insulin levels may be linked to purging behavior in the absence versus presence of binge eating.

Stimulation of bovine monocyte-derived macrophages with lipopolysaccharide, interferon-É£, Interleukin-4 or Interleukin-13 does not induce detectable changes in nitric oxide or arginase activity.

BACKGROUND: Bacterial lipopolysaccharide and interferon-γ stimulation of rodent macrophages in vitro induces up-regulation of inducible nitric oxide synthase, whereas interleukin-4 stimulation results in increased activity of arginase-1. Thus different stimulants result in differing macrophage phenotypes, appropriate for responses to a range of pathogens. The current study was conducted in order to determine whether bovine macrophages derived from monocytes and spleen respond similarly. RESULTS: Lipopolysaccharide and interferon-γ did not induce detectable increases in nitric oxide production by bovine monocyte-derived or splenic macrophages in vitro. Similarly, interleukin-4 and interleukin-13 did not affect arginase activity. However, changes in transcription of genes coding for these products were detected. CONCLUSION: Differences between macrophage activation patterns exist between cattle and other species and these differences may occur during the post-transcription phase.

Dairy Heifers Naturally Exposed to Fasciola hepatica Develop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation.

Fasciola hepatica is a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacies are variable. Evidence from experimental infection suggests that vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response to F. hepatica following natural exposure. Hence, we analyzed the immune responses over time in calves naturally exposed to F. hepatica infection. Cohorts of replacement dairy heifer calves (n = 42) with no prior exposure to F. hepatica, on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through an F. hepatica-specific serum antibody enzyme-linked immunosorbent assay (ELISA) and fluke egg counts. Concurrent changes in peripheral blood leukocyte subpopulations, lymphocyte proliferation, and cytokine responses were measured. Relationships between fluke infection and immune responses were analyzed by using multivariable linear mixed-effect models. All calves from one farm showed evidence of exposure, while cohorts from the remaining two farms remained negative over the grazing season. A type 2 immune response was associated with exposure, with increased interleukin-4 (IL-4) production, IL-5 transcription, and eosinophilia. Suppression of parasite-specific peripheral blood mononuclear cell (PBMC) proliferation was evident, while decreased mitogen-stimulated gamma interferon (IFN-γ) production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated toward a nonproliferative type 2 state following natural challenge with F. hepatica This has implications in terms of the timing of the administration of vaccination programs and for host susceptibility to coinfecting pathogens.

Intragastric nutrient infusion reduces motivation for food in male and female rats.

The idea that gut-derived satiation signals influence food reward has recently gained traction, but this hypothesis is largely based on studies focused on neural circuitry, not the peripherally released signals. Here, we directly tested the hypothesis that intragastric (IG) nutrient infusion can suppress motivation for food. In a series of experiments, IG sucrose infusion (15 kcal) significantly and reliably reduced operant responding for a sucrose reward on a progressive ratio (PR) schedule. Moreover, food deprivation for 24 h before the test session did not prevent the suppressive effect of nutrients. The suppressive effect of IG sucrose on fixed ratio 5 (FR5) operant responding was also assessed as a comparison. The effect of IG nutrients to reduce motivation was not limited to sucrose; IG Ensure infusion (9.3 kcal) also significantly reduced PR operant responding for sucrose pellets. To verify that these effects were not secondary to the osmotic challenge of concentrated nutrients, we tested IG infusion of noncaloric saline solutions equiosmolar to 40% sucrose or Ensure and found no effect. Finally, we focused on glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) as candidate mediators for the effect of IG nutrients. Pretreatment with exendin-9, a GLP-1 receptor antagonist, delivered intraperitoneally, significantly attenuated the ability of IG nutrients to suppress PR responding and breakpoint in males, but not in females, whereas pretreatment with devazepide, a CCKA receptor antagonist, failed to do so in both sexes. Together, these data support the idea that nutrient-induced satiation signals influence food reward and may implicate GLP-1 in this process.

Dapsone Resistance in Leprosy Patients Originally from American Samoa, United States, 2010-2012.

Skin biopsies from US leprosy patients were tested for mutations associated with drug resistance. Dapsone resistance was found in 4 of 6 biopsies from American Samoa patients. No resistance was observed in patients from other origins. The high rate of dapsone resistance in patients from American Samoa warrants further investigation.

Lateral septum growth hormone secretagogue receptor affects food intake and motivation for sucrose reinforcement.

The hormone ghrelin promotes eating and is widely considered to be a hunger signal. Ghrelin receptors, growth hormone secretagogue receptors (GHSRs), are found in a number of specific regions throughout the brain, including the lateral septum (LS), an area not traditionally associated with the control of feeding. Here we investigated whether GHSRs in the LS play a role in the control of food intake. We examined the feeding effects of ghrelin and the GHSR antagonists ([d-Lys3]-growth hormone-releasing peptide-6 and JMV-2959) at doses subthreshold for effect when delivered to the lateral ventricle. Intra-LS ghrelin significantly increased chow intake during the midlight phase, suggesting that pharmacological activation of LS GHSRs promotes feeding. Conversely, GHSR antagonist delivered to the LS shortly before dark onset significantly reduced chow intake. These data support the hypothesis that exogenous and endogenous stimulation of GHSRs in the LS influence feeding. Ghrelin is known to affect motivation for food, and the dorsal subdivision of LS (dLS) has been shown to play a role in motivation. Thus, we investigated the role of dLS GHSRs in motivation for food reward by examining operant responding for sucrose on a progressive ratio (PR) schedule. Intra-dLS ghrelin increased PR responding for sucrose, whereas blockade of LS GHSRs did not affect responding in either a fed or fasted state. Together these findings for the first time substantiate the LS as a site of action for ghrelin signaling in the control of food intake.

Development and validation of a protocol to identify and recruit participants into a large scale study on liver fluke in cattle.

BACKGROUND: Liver fluke infection caused by the parasite Fasciola hepatica is a major cause of production losses to the cattle industry in the UK. To investigate farm-level risk factors for fluke infection, a randomised method to recruit an appropriate number of herds from a defined geographical area into the study was required. The approach and hurdles that were encountered in designing and implementing this study are described. The county of Shropshire, England, was selected for the study because of the variation between farms in exposure to fluke infection observed in an earlier study. RESULTS: From a sampling list of 569 holdings in Shropshire randomly drawn from the RADAR cattle population dataset, 396 (69.6%) holdings were successfully contacted by telephone and asked if they would be interested in taking part in the study. Of 296 farmers who agreed to receive information packs by post, 195 (65.9%) agreed to take part in the study. Over the period October 2014 - April 2015 visits were made to 100 dairy and 95 non-dairy herds. During the farm visits 40 faecal samples +/- bulk-tank milk samples were collected and a questionnaire administered. Composite faecal samples were analysed for the presence of F. hepatica eggs by sedimentation and bulk tank milk samples were tested with an antibody ELISA for F. hepatica. Forty-five (49%) of non-dairy herds were positive for liver fluke infection as determined by the finding of one or more fluke eggs, while 36 (36%) dairy herds had fluke positive faecal samples and 41 (41%) dairy herds were positive for F. hepatica antibody. Eighty-seven (45.8%) farmers said that they monitored their cattle for liver fluke infection and 118 (62.1%) reported that they used flukicide drugs in their cattle. CONCLUSIONS: Using a protocol of contacting farmers directly by telephone and subsequently sending information by post, 79% of the target sample size was successfully recruited into the study. A dataset of farm-specific information on possible risk factors for liver fluke infection and corresponding liver-fluke infection status was generated for the development of statistical models to identify risk factors for liver fluke infection at the farm-level.

Estradiol modulates the anorexic response to central glucagon-like peptide 1.

Estrogens suppress feeding in part by enhancing the response to satiation signals. Glucagon-like peptide 1 (GLP-1) acts on receptor populations both peripherally and centrally to affect food intake. We hypothesized that modulation of the central GLP-1 system is one of the mechanisms underlying the effects of estrogens on feeding. We assessed the anorexic effect of 0, 1, and 10µg doses of GLP-1 administered into the lateral ventricle of bilaterally ovariectomized (OVX) female rats on a cyclic regimen of either 2µg ß-estradiol-3-benzoate (EB) or oil vehicle 30min prior to dark onset on the day following hormone treatment. Central GLP-1 treatment significantly suppressed food intake in EB-treated rats at both doses compared to vehicle, whereas only the 10µg GLP-1 dose was effective in oil-treated rats. To follow up, we examined whether physiologic-dose cyclic estradiol treatment influences GLP-1-induced c-Fos in feeding-relevant brain areas of OVX females. GLP-1 significantly increased c-Fos expression in the area postrema (AP) and nucleus of the solitary tract (NTS), and the presence of estrogens may be required for this effect in the paraventricular nucleus of the hypothalamus (PVN). Together, these data suggest that modulation of the central GLP-1 system may be one of the mechanisms by which estrogens suppress food intake, and highlight the PVN as a region of interest for future investigation.

Weight suppression and bulimic syndrome maintenance: Preliminary findings for the mediating role of leptin.

OBJECTIVE: Longitudinal studies support a prospective relationship between weight suppression (WS) and bulimic syndrome (BN-S) maintenance. Although biobehavioral mechanisms have been proposed to explain this link, such mechanisms have yet to be identified. Given that weight loss would reduce leptin levels which may influence eating, this study examined whether reduced leptin levels mediate the link between greater WS and longer illness duration. METHOD: Women (N = 53), ages 18-45 years, were recruited from the community if they met criteria for a BN-S, including either DSM-5 bulimia nervosa (BN; n = 33) or purging disorder (PD: n = 20), and fell within a healthy weight range (18.5-26.5 kg/m2 ). Participants completed clinical assessments and provided blood samples to measure circulating leptin. RESULTS: Significant associations were found among greater WS, lower leptin concentrations, and longer duration of illness. Mediation analyses using bootstrapping procedures indicated all paths were significant and that leptin mediated the link between WS and illness duration. An alternative model in which longer illness duration contributed to leptin, via greater WS, was not supported. DISCUSSION: Longitudinal research is needed to support temporal associations and explore behavioral mechanisms linking leptin to illness trajectory.