UW Neurological Surgery Recent PubMed Publications

Changes in Salmonella Contamination in Meat and Poultry Since the Introduction of the Pathogen Reduction and Hazard Analysis and Critical Control Point Rule.

J Food Prot. 2020 Oct 01;83(10):1707-1717

Authors: Williams MS, Ebel ED, Saini G, Nyirabahizi E

Abstract
ABSTRACT: In 1996, the Food Safety and Inspection Service (FSIS) published its pathogen reduction and hazard analysis and critical control point (PR-HACCP) rule. The intention of this program was to reduce microbial contamination on meat, poultry, and egg products. The program was implemented in stages between January 1998 and January 2000, with sampling for Escherichia coli O157:H7 and/or Salmonella in large production establishments beginning in 1998. As the PR-HACCP program begins its third decade, it is reasonable to question whether there have been reductions in the frequency of pathogen-contaminated meat and poultry products reaching consumers. This study summarizes the results for over 650,000 samples collected by FSIS between 2000 and 2018 in slaughter and processing establishments across the United States and compares these results to the roughly 100,000 retail samples collected by the U.S. Food and Drug Administration between 2002 and 2017. The data demonstrate that there has been an overall reduction in the occurrence of Salmonella on meat and poultry products, but the direction and magnitude of change has not been consistent over time or across commodities. Although the available data do not support the identification of causal factors for the observed changes, a historical review of the timing of various factors and policy decisions generates potential hypotheses for the observed changes.
HIGHLIGHTS:

PMID: 32421826 [PubMed - indexed for MEDLINE]

Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart.

Apoptosis. 2020 May 16;:

Authors: Chandrasekera DNK, Neale JPH, van Hout I, Rawal S, Coffey S, Jones GT, Bunton R, Sugunesegran R, Parry D, Davis P, Manning P, Williams MJA, Katare R

Abstract
Type 2 diabetes has a strong association with the development of cardiovascular disease, which is grouped as diabetic heart disease (DHD). DHD is associated with the progressive loss of cardiovascular cells through the alteration of molecular signalling pathways associated with cell death. In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated with accentuated apoptosis. RT-PCR analysis showed a significant increase in miR-532 expression in the right atrial appendage tissue of type 2 diabetic patients undergoing coronary artery bypass graft surgery. This was associated with marked downregulation of its anti-apoptotic target protein apoptosis repressor with caspase recruitment domain (ARC) and increased TUNEL positive cardiomyocytes. Further analysis showed a positive correlation between apoptosis and miR-532 levels. Time-course experiments in a mouse model of type 2 diabetes showed that diabetes-induced activation of miR-532 occurs in the later stage of the disease. Importantly, the upregulation of miR-532 preceded the activation of pro-apoptotic caspase-3/7 activity. Finally, inhibition of miR-532 activity in high glucose cultured human cardiomyocytes prevented the downregulation of ARC and attenuated apoptotic cell death. Diabetes induced activation of miR-532 plays a critical role in accelerating cardiomyocytes apoptosis. Therefore, miR-532 may serve as a promising therapeutic agent to overcome the diabetes-induced loss of cardiomyocytes.

PMID: 32418060 [PubMed - as supplied by publisher]

Segesterone Acetate and Ethinyl Estradiol Vaginal Ring (Annovera) for Contraception.

Am Fam Physician. 2020 05 15;101(10):618-620

Authors: Lee AL

PMID: 32412221 [PubMed - indexed for MEDLINE]

Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets.

Acta Neuropathol Commun. 2020 May 13;8(1):68

Authors: Prince E, Whelan R, Donson A, Staulcup S, Hengartner A, Vijmasi T, Agwu C, Lillehei KO, Foreman NK, Johnston JM, Massimi L, Anderson RCE, Souweidane MM, Naftel RP, Limbrick DD, Grant G, Niazi TN, Dudley R, Kilburn L, Jackson EM, Jallo GI, Ginn K, Smith A, Chern JJ, Lee A, Drapeau A, Krieger MD, Handler MH, Hankinson TC, Advancing Treatment for Pediatric Craniopharyngioma Consortium

Abstract
Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential therapies identified through the study of pediatric ACP may also have a role in adult ACP. Using our compiled transcriptome dataset of 27 pediatric and 9 adult ACPs, obtained through the Advancing Treatment for Pediatric Craniopharyngioma Consortium, we interrogated potential age-related transcriptional differences using several rigorous mathematical analyses. These included: canonical differential expression analysis; divisive, agglomerative, and probabilistic based hierarchical clustering; information theory based characterizations; and the deep learning approach, HD Spot. Our work indicates that there is no therapeutically relevant difference in ACP gene expression based on age. As such, potential therapeutic targets identified in pediatric ACP are also likely to have relvance for adult patients.

PMID: 32404202 [PubMed - in process]

Prevalence, Evolution, and Extent of Impaired Cerebral Autoregulation in Children Hospitalized With Complex Mild Traumatic Brain Injury.

Pediatr Crit Care Med. 2019 04;20(4):372-378

Authors: Lele AV, Watanitanon A, Lakireddy V, Clark-Bell C, Moore A, Zimmerman JJ, Chesnut RM, Armstead W, Vavilala MS

Abstract
OBJECTIVES: To examine cerebral autoregulation in children with complex mild traumatic brain injury.
DESIGN: Prospective observational convenience sample.
SETTING: PICU at a level I trauma center.
PATIENTS: Children with complex mild traumatic brain injury (trauma, admission Glasgow Coma Scale score 13-15 with either abnormal head CT, or history of loss of consciousness).
INTERVENTIONS: Cerebral autoregulation was tested using transcranial Doppler ultrasound between admission day 1 and 8.
MEASUREMENTS AND MAIN RESULTS: The primary outcome was prevalence of impaired cerebral autoregulation (autoregulation index < 0.4),determined using transcranial Doppler ultrasonography and tilt testing. Secondary outcomes examined factors associated with and evolution and extent of impairment. Cerebral autoregulation testing occurred in 31 children 10 years (SD, 5.2 yr), mostly male (59%) with isolated traumatic brain injury (91%), median admission Glasgow Coma Scale 15, Injury Severity Scores 14.2 (SD, 7.7), traumatic brain injury due to fall (50%), preadmission loss of consciousness (48%), and abnormal head CT scan (97%). Thirty-one children underwent 56 autoregulation tests. Impaired cerebral autoregulation occurred in 15 children (48.4%) who underwent 19 tests; 68% and 32% of tests demonstrated unilateral and bilateral impairment, respectively. Compared with children on median day 6 of admission after traumatic brain injury, impaired autoregulation was most common in the first 5 days after traumatic brain injury (day 1: relative risk, 3.7; 95% CI, 1.9-7.3 vs day 2: relative risk, 2.7; 95% CI, 1.1-6.5 vs day 5: relative risk, 1.33; 95% CI, 0.7-2.3). Children with impaired autoregulation were older (12.3 yr [SD, 1.3 yr] vs 8.7 yr [SD, 1.1 yr]; p = 0.04) and tended to have subdural hematoma (64% vs 44%), epidural hematoma (29% vs 17%), and subarachnoid hemorrhage (36% vs 28%). Eight children (53%) were discharged home with ongoing impaired cerebral autoregulation.
CONCLUSIONS: Impaired cerebral autoregulation is common in children with complex mild traumatic brain injury, despite reassuring admission Glasgow Coma Scale 13-15. Children with complex mild traumatic brain injury have abnormal cerebrovascular hemodynamics, mostly during the first 5 days. Impairment commonly extends to the contralateral hemisphere and discharge of children with ongoing impaired cerebral autoregulation is common.

PMID: 30575699 [PubMed - indexed for MEDLINE]

Factors Impacting Differential Outcomes in the Definitive Radiation Treatment of Anal Cancer Between HIV-Positive and HIV-Negative Patients.

Oncologist. 2020 May 10;:

Authors: Susko M, Wang CJ, Lazar AA, Kim S, Laffan A, Feng M, Ko A, Venook AP, Atreya CE, Van Loon K, Anwar M

Abstract
BACKGROUND: Anal squamous cell carcinoma (ASCC) is uncommon, yet seen more frequently in the setting of HIV. Chemoradiotherapy is the definitive modality of treatment for patients with ASCC; this study examines factors impacting clinical outcomes in a large cohort of human immunodeficiency virus (HIV)-positive and -negative patients.
METHODS: A retrospective review was conducted of patients treated for nonmetastatic ASCC at a single institution between 2005 and 2018. Freedom from local recurrence (FFLR), freedom from distant metastasis, and overall survival (OS) were calculated using the Kaplan-Meier method, and univariate and multivariate analysis were performed using the Cox proportional hazards model.
RESULTS: During the study period, 111 patients initiated definitive treatment for ASCC. Median age of the entire cohort was 56.7 years (interquartile range, 51.5-63.5), with 52 patients (46.8%) being HIV-positive. At median follow-up of 28.0 months, the 2- and 5-year FFLR were 78.2% (95% confidence interval [CI], 70.4-87.0) and 74.6% (95% CI, 65.8-84.5), respectively. Multivariate analysis revealed time from diagnosis to treatment initiation (median, 8 weeks; hazard ratio, 1.06; 95% CI, 1.03-1.10) to be significantly associated with worse FFLR and OS. HIV-positive patients had a trend toward worse FFLR (log-ranked p = .06). For HIV-positive patients with post-treatment CD4 less than 150 cells per mm3 , there was significantly worse OS (log-ranked p = .015).
CONCLUSION: A trend toward worse FFLR was seen in HIV-positive patients, despite similar baseline disease characteristics as HIV-negative patients. Worse FFLR and OS was significantly associated with increased time from diagnosis to treatment initiation. Poorer OS was seen in HIV-positive patients with a post-treatment CD4 count less than 150 cells per mm3 .
IMPLICATIONS FOR PRACTICE: Human immunodeficiency virus (HIV)-positive patients with anal squamous cell carcinoma can represent a difficult clinical scenario. Definitive radiation with concurrent chemotherapy is highly effective, but can result in significant toxicity and decrease in CD4 count that could predispose to HIV-related complications. As HIV-positive patients have largely been excluded from prospective clinical trials, this study seeks to provide greater understanding of their outcomes with radiation therapy, potential predictors of worse local control and overall survival, and those most at risk of after completion of treatment.

PMID: 32390297 [PubMed - as supplied by publisher]

Anti-inflammatory therapy for preventing stroke and other vascular events after ischaemic stroke or transient ischaemic attack.

Cochrane Database Syst Rev. 2020 May 11;5:CD012825

Authors: Coveney S, McCabe JJ, Murphy S, O'Donnell M, Kelly PJ

Abstract
BACKGROUND: An increasing body of evidence suggests that inflammation plays a key role in stroke, in particular stroke of atherosclerotic origin. Anti-inflammatory medications are a widely heterogeneous group of drugs that are used to suppress the innate inflammatory pathway and thus prevent persistent or recurrent inflammation. Anti-inflammatory agents have the potential to stabilise atherosclerotic plaques by impeding the inflammatory pathway. By targeting specific cytokines, the inflammatory pathway may be interrupted at various stages.
OBJECTIVES: To assess the benefits and harms of anti-inflammatory medications plus standard care versus standard care with or without placebo for prevention of vascular events (stroke, myocardial infarction (MI), non-fatal cardiac arrest, unstable angina requiring revascularisation, vascular death) and all-cause mortality in people with a prior history of ischaemic stroke or transient ischaemic attack (TIA).
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; last searched 29 May 2019); MEDLINE (1948 to 29 May 2019); Embase (1980 to 29 May 2019); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 29 May 2019); and Scopus (1995 to 29 May 2019). In an effort to identify additional published, unpublished, and ongoing trials, we searched several grey literature sources (last searched 30 May 2019). We incorporated all identified studies into the results section. We applied no restrictions with respect to language, date of publication, or study setting.
SELECTION CRITERIA: We considered randomised controlled trials (RCTs) and cluster-randomised controlled trials that evaluated anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed for inclusion titles and abstracts of studies identified by the search. Two review authors independently reviewed full-text articles for inclusion in this review. We planned to assess risk of bias and to apply the GRADE method.
MAIN RESULTS: We identified no studies that met the inclusion criteria.
AUTHORS' CONCLUSIONS: There is currently a paucity of evidence on the use of anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA. RCTs are needed to assess whether use of anti-inflammatory medications in this setting is beneficial.

PMID: 32392374 [PubMed - indexed for MEDLINE]

Commentary: Mature Imaging-Based Outcomes Supporting Local Control for Complex Reirradiation Salvage Spine Stereotactic Body Radiotherapy.

Neurosurgery. 2020 09 15;87(4):E498-E499

Authors: Vellayappan BA, Foote M, Chang EL, Suh JH, Saigal R, Hofstetter CP, Lo SS

PMID: 32386215 [PubMed - indexed for MEDLINE]

Low Chlamydia and Gonorrhea Testing Rates Among Men Who Have Sex With Men in Guangdong and Shandong Provinces, China.

Sex Transm Dis. 2019 04;46(4):260-265

Authors: Wu D, Li KT, Tang W, Ong JJ, Huang W, Fu H, Lee A, Wei C, Tucker JD

Abstract
BACKGROUND: Although periodic chlamydia and gonorrhea testing is recommended for men who have sex with men (MSM), little is known about testing rates in China. This study examines chlamydia and gonorrhea testing rates and testing correlates among Chinese MSM.
METHODS: An online survey of MSM was conducted in August 2017. Men 16 years or older who had ever had sex with a man were enrolled through a gay social networking mobile application. We asked men about their sexual behaviors, community engagement in sexual health, and previous testing for chlamydia, gonorrhea, and HIV. Multivariable logistic regressions were used to examine the association of testing with community engagement and recent HIV testing.
RESULTS: Of 1031 men, 819 (79.5%) were younger than 30 years, and 263 (25.5%) reported condomless sex in the past 3 months. In total, 294 (28.5%) men tested for chlamydia, 315 (30.6%) men tested for gonorrhea, and 817 (79.2%) men tested for HIV. One hundred twenty-five (42.5%) men who received chlamydia testing and 134 (42.5%) men who received gonorrhea testing had substantial community engagement. Compared with men with no/minimal community engagement, men with substantial community engagement had greater odds of chlamydia testing (adjusted odds ratio [AOR], 2.8; 95% confidence interval [CI], 1.9-4.3) and gonorrhea testing (AOR, 2.9; 95% CI, 2.0-4.4). Men with recent HIV testing were more likely to have received chlamydia testing (AOR, 1.5; 95% CI, 1.1-2.0) and gonorrhea testing (AOR, 1.6; 95% CI, 1.2-2.1).
CONCLUSIONS: Chlamydia and gonorrhea testing levels are low among Chinese MSM. Integrating chlamydia and gonorrhea test promotion strategies into HIV prevention programs that engage MSM communities may help bridge the gap.

PMID: 30601282 [PubMed - indexed for MEDLINE]

Ethics of controlled human infection to address COVID-19.

Science. 2020 05 22;368(6493):832-834

Authors: Shah SK, Miller FG, Darton TC, Duenas D, Emerson C, Lynch HF, Jamrozik E, Jecker NS, Kamuya D, Kapulu M, Kimmelman J, MacKay D, Memoli MJ, Murphy SC, Palacios R, Richie TL, Roestenberg M, Saxena A, Saylor K, Selgelid MJ, Vaswani V, Rid A

PMID: 32381590 [PubMed - indexed for MEDLINE]

Home-Time After Discharge Among Patients With Type 2 Myocardial Infarction.

J Am Heart Assoc. 2020 May 08;:e015978

Authors: McCarthy CP, Murphy S, Rehman S, Jones-O'Connor M, Olshan DS, Cohen JA, Cui J, Singh A, Vaduganathan M, Januzzi JL, Wasfy JH

Abstract
Background Home-time, defined as the time spent alive outside of a healthcare institution, has emerged as a patient-centered health outcome. The discharge locations and distribution of home-time after a type 2 myocardial infarction are unknown. Methods and Results Patients with a type 2 myocardial infarction between October 2017 and May 2018 at Massachusetts General Hospital were included. Patients discharged to hospice or without follow-up data were excluded. Our primary outcome was home-time defined as the number of days lived outside of a hospital, long-term acute care facility, skilled nursing facility, or rehabilitation facility. We identified 359 patients with type 2 myocardial infarction over the study period. Of those discharged alive (N=321), 62.9% were discharged home, and the remainder went to a facility or hospice. Among those with available follow-up data (N=289), the median home-time was 30 (interquartile range [IQR], 16-30) days at 30 days, 171 (IQR, 133-180) days at 180 days, and 347 (IQR, 203-362) days at 365 days. At 1 year, 29 patients (10%) with type 2 myocardial infarction had spent no time at home and only 57 patients (19.7%) spent the entire year alive and at home. At 1 year, postdischarge all-cause mortality was 23.2%, all-cause readmission was 69.2%, and major adverse cardiovascular events (composite of all-cause mortality, recurrent myocardial infarction, or stroke) was 34.9%. Home-time through 1 year correlated strongly with time-to-event all-cause mortality (τ=0.54, P<0.001) and major adverse cardiovascular events (τ=0.52, P<0.001) and modestly with a composite of all-cause mortality or readmission (τ=0.44, P<0.001). Conclusions Home-time is low after a hospitalization for type 2 myocardial infarction and correlates strongly with mortality and major adverse cardiovascular events.

PMID: 32384008 [PubMed - as supplied by publisher]

Situational Intracranial Pressure Management: An Argument Against a Fixed Treatment Threshold.

Crit Care Med. 2020 May 01;:

Authors: Chesnut RM, Videtta W

PMID: 32371613 [PubMed - as supplied by publisher]

Looking Into the Future - The Journal of Neurophysiology.

J Neurophysiol. 2020 May 06;:

Authors: Ramirez JM

PMID: 32374209 [PubMed - as supplied by publisher]

Corrigendum to The Cost of Inflammatory Bowel Disease: An Initiative From the Crohn's & Colitis Foundation.

Inflamm Bowel Dis. 2020 May 06;:

Authors: Park KT, Ehrlich OG, Allen JI, Meadows P, Szigethy EM, Henrichsen K, Kim SC, Lawton RC, Murphy SM, Regueiro M, Rubin DT, Engel-Nitz NM, Heller CA

PMID: 32374862 [PubMed - as supplied by publisher]

Vancomycin improves Plasmodium yoelii malaria parasite in vitro liver stage cultures by controlling Elizabethkingia anophelis, a bacterium in the microbiome of lab-reared Anopheles mosquitoes.

Mol Biochem Parasitol. 2020 05;237:111279

Authors: Shears MJ, Murphy SC

Abstract
Studies of Plasmodium sporozoites and liver stages require dissection of Anopheles mosquitoes to obtain sporozoites for experiments. Sporozoites from the rodent parasite P. yoelii are routinely used to infect hepatocytes for liver stage culture, but sometimes these cultures become contaminated. Using standard microbiological techniques, a single colony type of Gram-negative rod-shaped bacteria was isolated from contaminated cultures. Mass spectrometry and sequencing of the bacterial 16S ribosomal RNA gene identified the contaminant as Elizabethkingia spp. Based on sequence comparison and published studies of the Anopheles microbiome, the best match was E. anophelis. Culture contamination was not ameliorated by density gradient purification of sporozoites. However, the addition of vancomycin to the culture media consistently reduced contamination and improved culture outcomes as measured by liver stage parasite size. Thus, mosquito salivary gland-derived E. anophelis is identified a potential contaminant of Plasmodium liver stage cultures that can be mitigated by the addition of antibiotics.

PMID: 32360511 [PubMed - indexed for MEDLINE]

Multiple Sclerosis in Patients with Intracranial Aneurysms: Coincidence or Correlation?

Clin Neurol Neurosurg. 2020 Apr 20;195:105864

Authors: Walker M, Young CC, Levitt MR, Saal-Zapata G

PMID: 32361026 [PubMed - as supplied by publisher]

Letter: Considerations for Performing Emergent Neurointerventional Procedures in a COVID-19 Environment.

Neurosurgery. 2020 May 02;:

Authors: Pandey AS, Ringer AJ, Rai A, Kan PT, Jabbour PM, Siddiqui A, Levy E, Snyder KV, Riina HA, Tanweer O, Levitt MR, Kim LJ, Veznedaroglu E, Binning M, Arthur AS, Mocco J, Schirmer CM, Thompson BG, Langer D, Endovascular Neurosurgery Research Group (ENRG)

PMID: 32358606 [PubMed - as supplied by publisher]

Pilchard orthomyxovirus (POMV). II. Causative agent of salmon orthomyxoviral necrosis, a new disease of farmed Atlantic salmon Salmo salar.

Dis Aquat Organ. 2020 Apr 30;139:51-68

Authors: Godwin SE, Morrison RN, Knowles G, Cornish MC, Hayes D, Carson J

Abstract
Since 2012, an orthomyxo-like virus has been consistently linked to epizootics in marine farmed Atlantic salmon in Tasmania, Australia. Here we describe the properties of the virus, designated the pilchard orthomyxovirus (POMV), in cell culture and present data verifying its direct role in a disease of Atlantic salmon. In infected cells, viral RNA was detectable in both the nucleus and cytoplasm, consistent with the replication cycle of an orthomyxovirus. Viral replication in vitro was temperature-dependent (within a range of 10-20°C), and yields of virus were typically in excess of 107 TCID50 ml-1. In controlled infection trials, cell culture-derived POMV produced significant morbidity in Atlantic salmon fry, pre-smolt and post-smolt. In all cases, the development of disease was rapid, with moribund fish detected within 5 d of direct exposure to POMV, and maximum cumulative morbidity occurring within 4 wk. The experimentally infected fish developed a characteristic suite of gross and microscopic pathological changes, which were consistent with those observed in Atlantic salmon overtly affected by POMV-associated disease on sea farms. These included necrotic lesions across multiple organs that were directly associated with the presence of the virus. Together, our observations indicate that POMV is an endemic virus likely transmitted from wild fish to farmed Atlantic salmon in Tasmania. The virus is pathogenic to Atlantic salmon in freshwater and marine environments and causes a disease that we have named salmon orthomyxoviral necrosis.

PMID: 32351236 [PubMed - indexed for MEDLINE]

Medication treatment for opioid use disorder in expectant mothers (MOMs): Design considerations for a pragmatic randomized trial comparing extended-release and daily buprenorphine formulations.

Contemp Clin Trials. 2020 Apr 27;:106014

Authors: Winhusen T, Lofwall M, Jones HE, Wilder C, Lindblad R, Schiff DM, Wexelblatt S, Merhar S, Murphy SM, Greenfield SF, Terplan M, Wachman EM, Kropp F, Theobald J, Lewis M, Matthews AG, Guille C, Silverstein M, Rosa C

Abstract
Opioid use disorder (OUD) in pregnant women has increased significantly in recent years. Maintaining these women on sublingual (SL) buprenorphine (BUP) is an evidence-based practice but BUP-SL is associated with several disadvantages that an extended-release (XR) BUP formulation could eliminate. The National Drug Abuse Treatment Clinical Trials Network (CTN) is conducting an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial, Medication treatment for Opioid-dependent expectant Mothers (MOMs), to compare mother and infant outcomes of pregnant women with OUD treated with BUP-XR, relative to BUP-SL. A second aim is to determine the relative economic value of utilizing BUP-XR. Approximately 300 pregnant women with an estimated gestational age (EGA) of 6-30 weeks, recruited from 12 sites, will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, EGA, and BUP-SL status (taking/not taking) at the time of randomization. Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum. Participants will be invited to participate in two sub-studies to evaluate the: 1) mechanisms by which BUP-XR may improve mother and infant outcomes; and 2) effects of prenatal exposure to BUP-XR versus BUP-SL on infant neurodevelopment. This paper describes the key design decisions for the main trial made during protocol development. This Investigational New Drug (IND) trial uniquely uses pragmatic features where feasible in order to maximize external validity, hence increasing the potential to inform clinical practice guidelines and address multiple knowledge gaps for treatment of this patient population.

PMID: 32353544 [PubMed - as supplied by publisher]

Exposure to the environmental pollutant bisphenol A diglycidyl ether (BADGE) causes cell over-proliferation in Drosophila.

Environ Sci Pollut Res Int. 2020 Jul;27(20):25261-25270

Authors: Williams MJ, Cao H, Lindkvist T, Mothes TJ, Schiöth HB

Abstract
Bisphenol A diglycidyl ether (BADGE), a derivative of bisphenol A (BPA), is widely used in the manufacture of epoxy resins as well as a coating on food containers. Recent studies have demonstrated the adverse effects of BADGE on reproduction and development in rodents and amphibians, but how BADGE affects biological activity is not understood. To gain a better understanding of the biological effects of BADGE exposure during development, we used the model organism Drosophila melanogaster and performed whole transcriptome sequencing. Interestingly, when Drosophila are raised on food containing BADGE, genes having significantly increased transcript numbers are enriched for those involved in regulating cell proliferation, including DNA replication and cell cycle control. Furthermore, raising larvae on BADGE-containing food induces hemocyte (blood cell) over-proliferation. This effect can be stimulated with even lower concentrations of BADGE if the hemocytes are already primed for cell proliferation by the expression of dominant active Ras GTPase. We conclude that chronic exposure to the xenobiotic BADGE throughout development can induce cell proliferation.

PMID: 32347502 [PubMed - indexed for MEDLINE]