A multi-lesional analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a single-centre analysis.

AIM: To conduct a multi-lesional computed tomography (CT) analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) patients to determine volumetric changes in lesions over 5 years. MATERIALS AND METHODS: A retrospective case-note review was undertaken to identify 16 patients with histological and radiological features of DIPNECH between 2012-2021. Area and volume were calculated for 17 sets of lesions identified on high-resolution CT. Clinical data were extracted from electronic patient records, which included demographic data, outpatient clinic letters, histology reports, and imaging reports. RESULTS: One hundred and twenty-eight lesions were identified in 16 patients (one male, 15 female) and followed-up annually over a median 1,985 days (range 1,450-2,290). At year 1 follow-up, lesion area ranged from 1-48 mm2, and lesion volume ranged from 8-18,380 mm3; lesion area ranged from 1-45mm2 and lesion volume ranged from 11-17,800 mm3 and year 5. Half (8/16) of the patients had concomitant typical carcinoid tumours and one patient had an atypical carcinoid tumour. No statistically significant correlation (p<0.05) was found between lesion cross-sectional area or volume and duration of follow-up (years and days). No metastatic spread was observed at the time of analysis. CONCLUSIONS: No significant increase was observed in the size of over 100 lesions in patients with DIPNECH over a 5-year period and no metastasis occurred during the study period affirming the relatively indolent course of the disease.

Partner bereavement when parenting dependent children: What factors influence adjustment?

Little is known about those who are widowed while raising dependent children. This study aimed to explore the factors which influence adjustment to partner death. Seven fathers and five mothers were interviewed, and constructivist grounded theory was used. Three interrelated themes were identified: Interpersonal influences, Intrapersonal influences, and Contextual influences. Dependent children meant sole responsibility and increased demands, yet ultimately provided widowed parents a purpose. Participants highlighted the need for increased awareness of young widowhood at a systemic and cultural level, to improve communication around death and young widowhood. Implications included social, financial and therapeutic interventions.

The validation of contemporary body composition methods in various races and ethnicities.

Few investigations have evaluated the validity of current body composition technology among racially and ethnically diverse populations. This study assessed the validity of common body composition methods in a multi-ethnic sample stratified by race and ethnicity. One hundred and ten individuals (55 % female, age: 26·5 (sd 6·9) years) identifying as Asian, African American/Black, Caucasian/White, Hispanic, Multi-racial and Native American were enrolled. Seven body composition models (dual-energy X-ray absorptiometry (DXA), air displacement plethysmography (ADP), two bioelectrical impedance devices (BIS, IB) and three multi-compartment models) were evaluated against a four-compartment criterion model by assessing total error (TE) and standard error of the estimate. For the total sample, measures of % fat and fat-free mass (FFM) from multi-compartment models were all excellent to ideal (% fat: TE = 0·94-2·37 %; FFM: TE = 0·72-1·78 kg) compared with the criterion. % fat measures were very good to excellent for DXA, ADP and IB (TE = 2·52-2·89 %) and fairly good for BIS (TE = 4·12 %). For FFM, single device estimates were good (BIS; TE = 3·12 kg) to ideal (DXA, ADP, IB; TE = 1·21-2·15 kg). Results did not vary meaningfully between each race and ethnicity, except BIS was not valid for African American/Black, Caucasian/White and Multi-racial participants for % fat (TE = 4·3-4·9 %). The multi-compartment models evaluated can be utilised in a multi-ethnic sample and in each individual race and ethnicity to obtain highly valid results for % fat and FFM. Estimates from DXA, ADP and IB were also valid. The BIS may demonstrate greater TE for all racial and ethnic cohorts and results should be interpreted cautiously.

Evaluating suitability of saliva to measure steroid concentrations in grey seal pups.

Measurement of steroids in wild pinnipeds can facilitate assessment of breeding, nutritional and stress status, and is useful in understanding behavioral responses. Even in young animals, sex steroids may be important in behavioral interactions and immune modulation. Use of saliva can avoid the large fluctuations seen in some steroids in plasma, and can negate the need for venipuncture, making it a potentially useful matrix in the wildlife. However, its utility in estimating steroid levels in wild young pinnipeds has not been evaluated. Here, we investigated the suitability of saliva for steroid hormone analysis in wild grey seal pups during their suckling and post-weaning fast periods. We collected saliva (n = 38) and plasma (n = 71) samples during the breeding season on the Isle of May, Scotland, 2012. We investigated success of sample collection, ease of preparation, accuracy and precision of analysis, and, where possible, comparability of measurements (n = 27) from saliva and plasma. Plasma sampling was rapid, whereas sampling saliva took up to five times longer. Analytical performance criteria (parallelism, accuracy, and precision (intra and inter assay co-efficient of variation (% CV)) of commercial ELISA kits to measure estradiol, testosterone and cortisol in both matrices were assessed. Estradiol and cortisol assays performed well and can be used in plasma and saliva. However, we could not confidently validate testosterone for either matrix. Saliva estradiol correlated with levels in plasma. Saliva sample preparation was faster and simpler than plasma preparation because it did not require extraction. However, given the additional time taken to obtain saliva in the wild, the possibility of blood contamination from oral damage and the lower success rate in obtaining sufficient sample for analysis, we recommend that this matrix only be used as an alternative to plasma sampling measurement in pinnipeds when animals are anaesthetized, tolerate mouth swabbing, or have been trained to accept saliva sampling in captivity.

Stability of hippocampal subfield volumes after trauma and relationship to development of PTSD symptoms.

BACKGROUND: The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus' functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0. METHODS: Two-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability. RESULTS: After controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl - T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure. CONCLUSION: Our study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).

Shock Ignition Laser-Plasma Interactions in Ignition-Scale Plasmas.

We use a subignition scale laser, the 30 kJ Omega, and a novel shallow-cone target to study laser-plasma interactions at the ablation-plasma density scale lengths and laser intensities anticipated for direct drive shock-ignition implosions at National Ignition Facility scale. Our results show that, under these conditions, the dominant instability is convective stimulated Raman scatter with experimental evidence of two plasmon decay (TPD) only when the density scale length is reduced. Particle-in-cell simulations indicate this is due to TPD being shifted to lower densities, removing the experimental back-scatter signature and reducing the hot-electron temperature. The experimental laser energy-coupling to hot electrons was found to be 1%-2.5%, with electron temperatures between 35 and 45 keV. Radiation-hydrodynamics simulations employing these hot-electron characteristics indicate that they should not preheat the fuel in MJ-scale shock ignition experiments.

Psychosexual distress following routine primary human papillomavirus testing: a longitudinal evaluation within the English Cervical Screening Programme.

OBJECTIVE: To assess psychosexual distress over a 12-month period among women receiving different human papillomavirus (HPV) and cytology results in the context of the English HPV primary screening pilot. DESIGN: Longitudinal, between-group study. SETTING: Five sites in England where primary HPV testing was piloted. POPULATION: Women aged 24-65 years (n = 1133) who had taken part in the NHS Cervical Screening Programme. METHODS: Women were sent a postal questionnaire soon after receiving their screening results (baseline) and 6 and 12 months later. Data were analysed using linear regression models to compare psychosexual outcomes between groups receiving six possible combinations of HPV and cytology screening results, including a control group with normal cytology and no HPV test. MAIN OUTCOME MEASURES: Psychosexual distress, assessed using six items from the Psychosocial Effects of Abnormal Pap Smears Questionnaire (PEAPS-Q). RESULTS: At all time points, there was an association between screening result group and psychosexual distress (all P < 0.001). At baseline, mean psychosexual distress score (possible range: 1-5) was significantly higher among women with HPV and normal cytology (B = 1.15, 95% CI 0.96-1.34), HPV and abnormal cytology (B = 1.02, 95% CI: 0.78-1.27) and persistent HPV (B = 0.90, 95% CI 0.70-1.10) compared with the control group (all P < 0.001). At the 6 and 12 month follow ups the pattern of results were similar, but coefficients were smaller. CONCLUSIONS: Our findings suggest receiving an HPV-positive result can cause psychosexual distress, particularly in the short-term. Developing interventions to minimise the psychosexual burden of testing HPV-positive will be essential to avoid unnecessary harm to the millions of women taking part in cervical screening. TWEETABLE ABSTRACT: Receiving an HPV-positive result following primary HPV testing can cause psychosexual distress, particularly in the short-term.

Adolescents' knowledge of a peer's non-suicidal self-injury and own non-suicidal self-injury and suicidality.

OBJECTIVE: Some research suggests that suicidal ideation and attempt among adolescents may be contagious - that is adolescents who are exposed to peers' suicidal behaviour are more likely to experience suicidal ideation or attempt suicide themselves. Less is known about the potential contagion effect of non-suicidal self-injury (NSSI). Our objective was to determine whether knowledge of a friend's NSSI is associated with adolescent's own non-suicidal self-injury and suicidal behaviours. METHODS: Data from 1483 youth ages 14-17 years were obtained from the 2014 Ontario Child Health Study, a cross-sectional population-based survey of children and adolescents in Ontario, Canada. Logistic regression models were used to examine associations between knowledge of a friend's NSSI and adolescents' own self-reported self-injurious and suicidal behaviours. Interactions with gender, age group and presence of a mental disorder were investigated. RESULTS: Knowledge of a friend's non-suicidal self-injury was significantly associated with the adolescent's own non-suicidal self-injury (OR = 2.03, 95% CI 1.05-3.90), suicidal ideation (OR = 3.08, 95% CI 1.50-6.30) and suicide attempt (OR = 2.87, 95% CI 1.20-6.87). CONCLUSION: These findings suggest an apparent contagion effect for non-suicidal self-injury. Awareness of a friend's self-injurious behaviours is associated with an adolescent's own self-injury and suicidality. Interventions aimed at preventing NSSI and suicidality should consider prevention of possible contagion at the school and/or community level.

Polypharmacy Rates among Patients over 45 years

Polypharmacy, defined as receipt of ≥5 medications in any one month, is often associated with potentially inappropriate prescribing and adverse drug interactions. High levels of polypharmacy have been observed internationally and in Ireland. The Health Service Executive Primary Care Reimbursement Services (HSE-PCRS) pharmacy claims database for the GMS eligible population was used. We conducted Chi-square tests to determine the statistical significance of perceived differences in medication use among patients aged ³ 45 years. Our results establish a national benchmark for polypharmacy in gender and various age categories in the HSE-PCRS. Of the 794,628 individuals aged ≥45 years with at least one claim in 2013, 64.3% (510,946) had polypharmacy, with higher rates among women (67.0% - 293,886 - compared to 60.8% of men - 216,444). Patients aged 45-54 years were less likely to have polypharmacy (38.6% - 69,934) compared to those aged 75 years old (82.6% - 197,565). The high levels of polypharmacy are of interest, and suggest that monitoring and evaluation of patients' medication regimes may be required to ensure appropriateness.

De novo vitamin D supplement use post-diagnosis is associated with breast cancer survival.

PURPOSE: Experimental laboratory data have indicated a protective effect of vitamin D on breast cancer progression, while epidemiological evidence is growing. Using pharmacy claims data, this study investigates the association between vitamin D supplement use initiated after a breast cancer diagnosis and associated mortality. METHODS: Women aged 50-80 years with a record of invasive breast cancer were identified on the National Cancer Registry Ireland database (n = 5417). Initiation of de novo vitamin D post-diagnosis was identified from linked national prescription data (n = 2581, 49%). Multivariate Cox proportional hazards models were used to estimate adjusted HRs (95% CIs) for breast cancer-specific mortality. RESULTS: There was a 20% reduction in breast cancer-specific mortality in de novo vitamin D users (modelled as a time-varying variable) compared to non-users (HR 0.80; 95% CI 0.64-0.99, p = 0.048) and the reduction was greater at 49% (HR 0.51; 95% CI 0.34-0.74, p < 0.001), if vitamin D was initiated soon after the breast cancer diagnosis (within 6 months). CONCLUSIONS: In this large national breast cancer cohort, de novo vitamin D use post-diagnosis was found to be associated with a reduction in breast cancer-specific mortality. Vitamin D, therefore, has the potential as a non-toxic and inexpensive agent to improve survival in breast cancer patients. Findings support the need for RCTs exploring the effect of vitamin D supplementation on breast cancer survival.

The impact of didactic read-aloud action cards on the performance of cannula cricothyroidotomy in a simulated 'can't intubate can't oxygenate' scenario.

Significant benefits have been demonstrated with the use of peri-operative checklists. We assessed whether a read-aloud didactic action card would improve performance of cannula cricothyroidotomy in a simulated 'can't intubate, can't oxygenate' scenario. A 17-step action card was devised by an expert panel. Participants in their first 4 years of anaesthetic training were randomly assigned into 'no-card' or 'card' groups. Scenarios were video-recorded for analysis. Fifty-three participants (27 no-card and 26 card) completed the scenario. The number of steps omitted was mean (SD) 6.7 (2.0) in the no-card group vs. 0.3 (0.5); p < 0.001 in the card group, but the no-card group was faster to oxygenation by mean (95% CI) 35.4 (6.6-64.2) s. The Kappa statistic was 0.84 (0.73-0.95). Our study demonstrated that action cards are beneficial in achieving successful front-of-neck access using a cannula cricothyroidotomy technique. Further investigation is required to determine this tool's effectiveness in other front-of-neck access situations, and its role in teaching or clinical management.

Predicting the health impact of lowering salt consumption in Turkey using the DYNAMO health impact assessment tool.

OBJECTIVE: To estimate the impact of three daily salt consumption scenarios on the prevalence and incidence of ischaemic heart disease (IHD) and cerebrovascular disease in 2025 in the Turkish population aged ≥30 years using the DYNAMO Health Impact Assessment tool. STUDY DESIGN: Statistical disease modelling study. METHODS: DYNAMO health impact assessment was populated using data from Turkey to estimate the prevalence and incidence of IHD and cerebrovascular disease in 2025. TurkSTAT data were used for demographic data, and national surveys were used for salt consumption and disease-specific burden. Three salt consumption scenarios were modelled: (1) reference scenario: mean salt consumption stays the same from 2012-2013 until 2025; (2) gradual decline: daily salt intake reduces steadily by 0.47 g per year by lowering salt intake from bread by 50% and from table salt by 40% by 2025; and (3) World Health Organization (WHO) advice: daily salt intake of 5 g per day from 2013 until 2025. RESULTS: The gradual decline scenario would lead to a decrease in the prevalence of IHD and cerebrovascular disease by 0.3% and 0.2%, respectively, and a decrease in the incidence by 0.6 and 0.4 per 1000, respectively. Following WHO's advice would lead to a decrease in the prevalence of IHD and cerebrovascular disease by 0.8% and 0.5%, respectively, and a decrease in the incidence by 1.0 and 0.7 per 1000, respectively. CONCLUSION: This model indicates that Turkey can lower its future cardiovascular disease burden by following the gradual decline scenario. Following WHO's advice would achieve an even greater benefit.

Periconception HIV Risk Behavior Among Men and Women Reporting HIV-Serodiscordant Partners in KwaZulu-Natal, South Africa.

HIV-infected men and women who choose to conceive risk infecting their partners. To inform safer conception programs we surveyed HIV risk behavior prior to recent pregnancy amongst South African, HIV-infected women (N = 209) and men (N = 82) recruited from antenatal and antiretroviral clinics, respectively, and reporting an uninfected or unknown-HIV-serostatus pregnancy partner. All participants knew their HIV-positive serostatus prior to the referent pregnancy. Only 11 % of women and 5 % of men had planned the pregnancy; 40 % of women and 27 % of men reported serostatus disclosure to their partner before conception. Knowledge of safer conception strategies was low. Around two-thirds reported consistent condom use, 41 % of women and 88 % of men reported antiretroviral therapy, and a third of women reported male partner circumcision prior to the referent pregnancy. Seven women (3 %) and two men (2 %) reported limiting sex without condoms to peak fertility. None reported sperm washing or manual insemination. Safer conception behaviors including HIV-serostatus disclosure, condom use, and ART at the time of conception were not associated with desired pregnancy. In light of low pregnancy planning and HIV-serostatus disclosure, interventions to improve understandings of serodiscordance and motivate mutual HIV-serostatus disclosure and pregnancy planning are necessary first steps before couples or individuals can implement specific safer conception strategies.

Antidepressant prescribing in Irish children: secular trends and international comparison in the context of a safety warning.

BACKGROUND: In 2003, the Irish Medicines Board (IMB) warned against the treatment of childhood depression with selective serotonin reuptake inhibitors (SSRIs) due to increased risk of suicide. This study examined the effect of this warning on the prevalence of anti-depressants in Irish children and compared age and gender trends and international comparisons of prescription rates. METHODS: A retrospective cohort study of the Irish Health Service Executive (HSE) pharmacy claims database for the General Medical Services (GMS) scheme for dispensed medication. Data were obtained for 2002-2011 for those aged ≤ 15 years. Prevalence of anti-depressants per 1000 eligible population, along with 95% confidence intervals, were calculated. A negative binomial regression analysis was used to investigate trends and compare rates across years, sex and age groups (0-4, 5-11, 12-15 years). International prescribing data were retrieved from the literature. RESULTS: The prevalence of anti-depressants decreased from 4.74/1000 population (95% CI: 4.47-5.01) in 2002 to 2.61/1000 population (95% CI: 2.43-2.80) in 2008. SSRI rates decreased from 2002 to 2008. Prescription rates for contra-indicated SSRIs paroxetine, sertraline and citralopram decreased significantly from 2002 to 2005, and, apart from paroxetine, only small fluctuations were seen from 2005 onwards. Fluoxetine was the most frequently prescribed anti-depressant and rates increased between 2002 and 2011. Anti-depressant rates were higher for younger boys and older girls. The Irish prevalence was lower than the US, similar to the U.K. and higher than Germany and Denmark. CONCLUSIONS: The direction and timing of these trends suggest that medical practitioners followed the IMB advice.

The Budget Impact of Hepatitis C Treatment in Ireland 2001-2012.

Chronic Hepatitis C (HCV) is estimated to infect 20,000 to 50,000 people in Ireland. National estimates of the number of patients who have been treated for HCV, their demographics and the cost associated with that treatment have not been published. Prescriptions for the treatment of HCV from 2000-2012 were established by interrogating the records of the High-Tech Drug Scheme and the pharmacy records of the Genitourinary Medicine and Infectious Diseases department of St. James Hospital. 2320 patients were initiated on treatment for HCV. Over €27 million was spent on HCV treatment. €25.5 million was spent on anti-viral therapy and €2 million was spent on haematological growth factor support for the management of adverse effects. The budget impact of HCV treatment has been significant in Ireland. New agents for HCV will have a greater budget impact but should require less spend on adverse event management.

A Survey of GPs Awareness and Use of Risk Assessment Tools and Cardiovascular Disease Prevention Guidelines.

Cardiovascular disease (CVD) is the leading cause of death worldwide. This study aimed to benchmark awareness and use of CVD risk assessment (RA) tools and prevention guidelines in Irish general practice. 493 (18%) Irish general practitioners (GPs) were invited to participate in a cross-sectional study in 2011. 213 (43%) GPs responded with most being male (n = 128, 58.2%) and aged ≥ 45 years (n = 124, 56.8%). While 197 (92.5%) GPs were aware of at least one RA tool, only 69 (32.4%) GPs reported frequent use. 187 (87.8%) GPs were aware of one or more CVD prevention guidelines with 115 (54.0%) GPs reporting frequent use of at least one guideline. No age or gender difference observed. Barriers to implementation of CVD prevention guidelines were lack of remuneration, too many CVD guidelines and time constraints. Most Irish GPs were aware of RA tools and CVD prevention guidelines with half reporting frequent use of guidelines.

A cohort study investigating aspirin use and survival in men with prostate cancer.

BACKGROUND: Aspirin use has been associated with reduced mortality from cancer including prostate cancer in some studies. A number of anti-cancer mechanisms of aspirin have been proposed, including the inhibition of the cyclooxygenase enzymes, through which aspirin mediates both anti-platelet and anti-inflammatory activities. This cohort study examines associations between pre-diagnostic aspirin use (overall and by dose and dosing intensity) and mortality in men with localised prostate cancer. PATIENTS AND METHODS: Men with stage I-III prostate cancer were identified from Irish National Cancer Registry records, which have been linked to national prescribing data from the Irish General Medical Services scheme. Aspirin use in the year preceding prostate cancer diagnosis was identified from this linked prescription-claims data. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for associations between aspirin use and all-cause and prostate cancer-specific mortality. Associations between prescribed dose and dosing intensity were examined. The presence of effect modification by the type of treatment received and tumour characteristics was also assessed. RESULTS: Two thousand nine hundred and thirty-six men with a diagnosis of stage I-III prostate cancer (2001-2006) were identified (aspirin users, n = 1131). The median duration of patient follow-up was 5.5 years. In adjusted analyses, aspirin use was associated with a small, but non-significant, reduced risk of prostate cancer-specific mortality (HR = 0.88, 95% CI 0.67-1.15). In dose-response analyses, stronger associations with prostate cancer-specific mortality were observed in men with higher aspirin dosing intensity (HR = 0.73, 95% CI 0.51-1.05) and in men receiving >75 mg of aspirin (HR = 0.61, 95% CI 0.37-0.99). Analyses of effect modification by treatment type or tumour characteristics were non-significant. CONCLUSIONS: Consistent with prior studies, aspirin use was associated with a non-significant reduced risk of prostate cancer-specific mortality in men with localised prostate cancer. Men receiving higher doses of aspirin had a statistically significant reduced risk of prostate cancer-specific mortality. These findings regarding an aspirin dose require further investigation.

Principles and methods for automated palynology.

Pollen grains are microscopic so their identification and quantification has, for decades, depended upon human observers using light microscopes: a labour-intensive approach. Modern improvements in computing and imaging hardware and software now bring automation of pollen analyses within reach. In this paper, we provide the first review in over 15 yr of progress towards automation of the part of palynology concerned with counting and classifying pollen, bringing together literature published from a wide spectrum of sources. We consider which attempts offer the most potential for an automated palynology system for universal application across all fields of research concerned with pollen classification and counting. We discuss what is required to make the datasets of these automated systems as acceptable as those produced by human palynologists, and present suggestions for how automation will generate novel approaches to counting and classifying pollen that have hitherto been unthinkable.

Bisphenol A affects larval growth and advances the onset of metamorphosis in Drosophila melanogaster.

Exposure to Bisphenol A (BPA) has been reported to dysregulate endocrine pathways in a wide array of vertebrate species. The effects of BPA on invertebrate species are less well understood. We tested the effects of BPA on growth and development in Drosophila as these processes are governed by well-studied endocrine pathways. In this study, we tested the effects of three concentrations of BPA (0.1mg/L, 1mg/L or 10mg/L) and found a statistically significant increase in larval growth for the low dose treatment group (0.1mg/L), but not statistically significant for the high dose treatment group (10mg/L). BPA exposure resulted in an increased body size in treated animals at 48, 72 and 96h after egg laying (AEL). This finding reflects a non-monotonic dose-response that has been observed for an increasing number of endocrine disrupting compounds. The increase in growth rate found for all treatment groups was associated with a statistically significant increase in food intake observed at 72h AEL. Furthermore, we observed that the increased growth rate was coupled with an earlier onset of pupariation consistent with previously reported phenotypes resulting from increased activity of insulin/insulin growth factor signaling (IIS) in Drosophila. Since the timing of the onset of pupariation in Drosophila is controlled through the complex interaction of the IIS and the ecdysone signaling pathways, our findings suggest that BPA exerts its effects through disruption of endocrine signaling in Drosophila.

A systematic review and meta-analysis of environmental contaminant exposure impacts on weight loss and glucose regulation during calorie-restricted diets in preclinical studies: Persistent organic pollutants may impede glycemic control.

Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or restoration of glycemic control during calorie restricted diets. Few human studies examine this hypothesis. This systematic review and clustered meta-analysis examines preclinical evidence that exposure to anthropogenic environmental contaminants impedes weight loss and resumption of glycemic control during calorie restriction. Of five eligible papers from 212 unique citations, four used C57BL/6 mice and one used Sprague Dawley rats. In four the animals received high fat diets to induce obesity and impaired glycemic control. All examined persistent organic pollutants (POPs). Polychlorinated biphenyl (PCB) 77 exposure did not affect final mass (standardised mean difference (SMD) = -0.35 [-1.09, 0.39]; n = 5 (experiments); n = 3 (papers)), or response to insulin in insulin tolerance tests (SMD = -1.54 [-3.25, 0.16] n = 3 (experiments); n = 2 (papers)), but impaired glucose control in glucose tolerance tests (SMD = -1.30 [-1.96, -0.63]; n = 6 (experiments); n = 3 (papers)). The impaired glycemic control following perfluoro-octane sulphonic acid (PFOS) exposure and enhanced mass loss following dichlorodiphenyltrichloroethane (DDT) exposure have not been replicated. Animal studies thus suggest some chemical groups, especially PCB and PFOS, could impair glucose control management during calorie restriction, similar to conclusions from limited existing clinical studies. We discuss the research that is urgently required to inform weight management services that are now the mainstay prevention initiative for T2DM.