Publications by authors named "Lauren Murphy"

75 Publications

Familial thrombocytopenia: The long and short of it.

J Exp Med 2021 Jun 20;218(6). Epub 2021 May 20.

Medical Research Council (MRC) Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, UK.

In this issue, Wahlster, Verboon, and colleagues (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210444) describe a multigenerational family with inherited thrombocytopenia where the causal variant was not identified using conventional genome sequencing approaches. Long-read sequencing and RNA sequencing revealed a complex structural variant, causing overexpression of a pathogenic gain-of-function WAC-ANKRD26 fusion transcript.
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http://dx.doi.org/10.1084/jem.20210604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142280PMC
June 2021

Who Moves after SCI? Individual, Health, and Neighborhood Predictors of Residential Mobility among Participants in the National Spinal Cord Injury Model Systems Database.

Arch Phys Med Rehabil 2021 May 15. Epub 2021 May 15.

Case Western University; MetroHealth System.

Objective: To investigate residential mobility among community-living adults with spinal cord injury (SCI) and the individual, health, and neighborhood factors associated with the propensity to relocate.

Design: Retrospective analysis of data from the National SCI Model Systems (SCIMS) database collected between 2006 and 2018 and linked with the American Community Survey five-year estimates.

Setting: Community.

Interventions: Not applicable.

Participants: People with traumatic SCI who participated in two waves of follow-up and had residential geographic identifiers at the census tract level (N = 4,599).

Main Outcome Measures: Moving was a binary measure reflecting change in residential locations over a five-year interval. Move distance distinguished non-movers from local movers (different tracts within the same county) and long distance movers (to different county or state). Move quality included four categories: stayed/low poverty tract, stayed/high poverty tract, moved/low poverty tract, and moved/high poverty tract.

Results: One in four people moved within a five-year interval (n=1,175). Of the movers, 55% relocated to a different Census tract within the same county and 45% relocated to a different county or state. Thirty-five percent of all movers relocated to a high poverty Census tract. Racial and ethnic minorities, people from low income households, and younger adults were more likely to move, move locally, and relocate to a high poverty neighborhood. High poverty and racial/ethnic segregation in the origin neighborhood predicted an increased risk for remaining in or moving to a high poverty neighborhood.

Conclusions: Although people with SCI relocated at a lower rate than has been reported in the general population, moving was a frequent occurrence post-injury. People from vulnerable groups were more likely to remain in or relocate to socioeconomically disadvantaged neighborhoods, thus increasing the risk for health disparities and poorer long-term outcomes among minorities and people from low income households. These findings inform policy makers' considerations of housing, healthcare, and employment initiatives for persons with SCI and other chronic disabilities.
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http://dx.doi.org/10.1016/j.apmr.2021.03.039DOI Listing
May 2021

The history of medical education: a commentary on race.

J Osteopath Med 2021 Feb;121(2):163-170

A.T. Still University School of Osteopathic Medicine in Arizona , Mesa , AZ, USA.

The institution of medicine was built on a foundation of racism and segregation, the consequences of which still permeate the experiences of Black physicians and patients. To predict the future direction of medical inclusivity, we must first understand the history of medicine as it pertains to race, diversity, and equity. In this Commentary, we review material from publicly available books, articles, and media outlets in a variety of areas, including undergraduate medical education and professional medical societies, where we found an abundance of policies and practices that created a foundation of systemic racism in medical training that carried through the career paths of Black physicians. The objective of this Commentary is to present the history of race in the medical education system and medical society membership, acknowledge the present state of both, and offer concrete solutions to increase diversity in our medical community.
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http://dx.doi.org/10.1515/jom-2020-0212DOI Listing
February 2021

Simultaneous measurement of electrical activity of uterine, abdominal, and pelvic floor muscles during the second and third stages of labor.

Am J Obstet Gynecol MFM 2020 11 3;2(4):100171. Epub 2020 Jul 3.

Department of Obstetrics and Gynecology, Banner University Medical Center, The University of Arizona College of Medicine, Phoenix, AZ.

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http://dx.doi.org/10.1016/j.ajogmf.2020.100171DOI Listing
November 2020

Damage to Orbitofrontal Areas 12 and 13, but Not Area 14, Results in Blunted Attention and Arousal to Socioemotional Stimuli in Rhesus Macaques.

Front Behav Neurosci 2020 8;14:150. Epub 2020 Sep 8.

Department of Psychology, Emory College of Arts and Sciences, Emory University, Atlanta, GA, United States.

An earlier study in monkeys indicated that lesions to the mid-portion of the ventral orbitofrontal cortex (OFC), including Walker's areas 11 and 13 (OFC11/13), altered the spontaneous scanning of still pictures of primate faces (neutral and emotional) and the modulation of arousal. Yet, these conclusions were limited by several shortcomings, including the lesion approach, use of static rather than dynamic stimuli, and manual data analyses. To confirm and extend these earlier findings, we compared attention and arousal to social and nonsocial scenes in three groups of rhesus macaques with restricted lesions to one of three OFC areas (OFC12, OFC13, or OFC14) and a sham-operated control group using eye-tracking to capture scanning patterns, focal attention and pupil size. Animals with damage to the lateral OFC areas (OFC12 and OFC13) showed decreased attention specifically to the eyes of negative (threatening) social stimuli and increased arousal (increased pupil diameter) to positive social scenes. In contrast, animals with damage to the ventromedial OFC area (OFC14) displayed no differences in attention or arousal in the presence of social stimuli compared to controls. These findings support the notion that areas of the lateral OFC are critical for directing attention and modulating arousal to emotional social cues. Together with the existence of face-selective neurons in these lateral OFC areas, the data suggest that the lateral OFC may set the stage for multidimensional information processing related to faces and emotion and may be involved in social judgments.
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http://dx.doi.org/10.3389/fnbeh.2020.00150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506161PMC
September 2020

Review and Study of Uterine Bioelectrical Waveforms and Vector Analysis to Identify Electrical and Mechanosensitive Transduction Control Mechanisms During Labor in Pregnant Patients.

Reprod Sci 2021 03 22;28(3):838-856. Epub 2020 Oct 22.

Department of Biomedical Engineering, Arizona State University, Tempe, AZ, USA.

The bioelectrical signals that produce uterine contractions during parturition are not completely understood. The objectives are as follows: (1) to review the literature and information concerning uterine biopotential waveforms generated by the uterus, known to produce contractions, and evaluate mechanotransduction in pregnant patients using electromyographic (EMG) recording methods and (2) to study a new approach, uterine vector analysis, commonly used for the heart: vectorcardiography analysis. The patients used in this study were as follows: (1) patients at term not in labor (n = 3); (2) patients during the 1st stage of labor at cervical dilations from 2 to 10 cm (n = 30); and (3) patients in the 2nd stage of labor and during delivery (n = 3). We used DC-coupled electrodes and PowerLab hardware (model no. PL2604, ADInstruments, Castle Hill, Australia), with software (LabChart, ADInstruments) for storage and analysis of biopotentials. Uterine and abdominal EMG recordings were made from the surface of each patient using 3 electrode pairs with 1 pair (+ and -, with a 31-cm spacing distance) placed in the right/left position (X position) and with 1 pair placed in an up/down position (Y position, also 31 cm apart) and with the third pair at the front/back (Z position). Using signals from the three X, Y, and Z electrodes, slow (0.03 to 0.1 Hz, high amplitude) and fast wave (0.3 to 1 Hz, low amplitude) biopotentials were recorded. The amplitudes of the slow waves and fast waves were significantly higher during the 2nd stage of labor compared to the 1st stage (respectively, p = 9.54 × e and p = 3.94 × e). When 2 channels were used, for example, the X vs. Y, for 2-D vector analysis or 3 channels, X vs. Y vs. Z, for 3-D analysis, are plotted against each other on their axes, this produces a vector electromyometriogram (EMMG) that shows no directionality for fast waves and a downward direction for slow waves. Similarly, during the 2nd stage of labor during abdominal contractions ("pushing"), the slow and fast waves were enlarged. Manual applied pressure was used to evoke bioelectrical activity to examine the mechanosensitivity of the uterus. Conclusions: (1) Phasic contractility of the uterus is a product of slow waves and groups of fast waves (bursts of spikes) to produce myometrial contractile responses. (2) 2-D and 3-D uterine vector analyses (uterine vector electromyometriogram) demonstrate no directionality of small fast waves while the larger slow waves represent the downward direction of biopotentials towards the cervical opening. (3) Myometrial cell action event excitability and subsequent contractility likely amplify slow wave activity input and uterine muscle contractility via mechanotransduction systems. (4) Models illustrate the possible relationships of slow to fast waves and the association of a mechanotransduction system and pacemaker activity as observed for slow waves and pacemakers in gastrointestinal muscle. (5) The interaction of these systems is thought to regulate uterine contractility. (6) This study suggests a potential indicator of delivery time. Such vector approaches might help us predict the progress of gestation and better estimate the timing of delivery, gestational pathologies reflected in bioelectric events, and perhaps the potential for premature delivery drug and mechanical interventions.
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http://dx.doi.org/10.1007/s43032-020-00358-5DOI Listing
March 2021

Toxicologic Confounders of Brain Death Determination: A Narrative Review.

Neurocrit Care 2021 Jun 30;34(3):1072-1089. Epub 2020 Sep 30.

Department of Emergency Medicine, Oregon Health and Science University, Medical Toxicology, Portland, OR, USA.

The aim of this narrative review is to describe the toxicologic confounders of brain death currently reported in the literature to offer guidance for physicians assessing brain death after a toxic exposure. We established an a priori definition of a "brain death mimic" as an unresponsive, intubated patient missing some, but not all brainstem reflexes. We completed a review of the literature utilizing MEDLINE and EMBASE to find case reports of patients of all ages in English, French, and Spanish meeting the criteria and hand searched the references of the results. We recorded xenobiotic dose, duration of physical exam suggesting brain death, and how the cases failed to meet full brain death criteria, when available. Fifty-six cases representing 19 different substances met the a priori definition of brain death mimic. Xenobiotic toxicities included: snake envenomation (13), baclofen (11), tricyclic antidepressants (8), bupropion (7), alcohols (4), antiepileptic agents (3), barbiturates (2), antidysrhythmics (2), organophosphates (2), and one case each of magnesium, succinylcholine, tetrodotoxin, and zolpidem. All patients except one survived to discharge and the majority at their baseline physical health. The most common means by which the cases failed brain death examination prerequisites was via normal neuroimaging. The xenobiotics in this review should be considered in cases of poisoning resulting in loss of brainstem reflexes and addressed before brain death determination. Brain death diagnosis should not be pursued in the setting of normal cerebral imaging or incomplete evaluation of brain death prerequisites.
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http://dx.doi.org/10.1007/s12028-020-01114-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526708PMC
June 2021

Comparison of pregnancy outcomes following preimplantation genetic testing for aneuploidy using a matched propensity score design.

Hum Reprod 2020 10;35(10):2356-2364

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

Study Question: Does preimplantation genetic testing for aneuploidy (PGT-A) increase the likelihood of live birth among women undergoing autologous IVF who have fertilized embryos?

Summary Answer: PGT-A is associated with a greater probability of live birth among women 35 years old and older who are undergoing IVF.

What Is Known Already: Previous studies evaluating the association between PGT-A and the incidence of live birth may be prone to confounding by indication, as women whose embryos undergo PGT-A may have a lower probability of live birth due to other factors associated with their increased risk of aneuploidy (e.g. advancing age, history of miscarriage). Propensity score matching can reduce bias where strong confounding by indication is expected.

Study Design, Size, Duration: We conducted a retrospective cohort study utilizing data from women who underwent autologous IVF treatment, had their first oocyte retrieval at our institution from 1 January 2011 through 31 October 2017 and had fertilized embryos from this retrieval. If a woman elected to use PGT-A, all good quality embryos (defined as an embryo between Stages 3 and 6 with Grade A or B inner or outer cell mass) were tested. We only evaluated cycles associated with the first oocyte retrieval in this analysis.

Participants/materials, Setting, Methods: Our analytic cohort included 8227 women. We used multivariable logistic regression to calculate a propensity score for PGT-A based on relevant demographic and clinical factors available to the IVF provider at the time of PGT-A or embryo transfer. We used the propensity score to match women who did and did not utilize PGT-A in a 1:1 ratio. We then used log-binomial regression to compare the cumulative incidence of embryo transfer, clinical pregnancy, miscarriage and live birth between women who did and did not utilize PGT-A. Because the risk of aneuploidy increases with age, we repeated these analyses among women <35, 35-37 and ≥38 years old based on the Society for Assisted Reproductive Technology's standards.

Main Results And The Role Of Chance: Overall, women with fertilized embryos who used PGT-A were significantly less likely to have an embryo transfer (risk ratios (RR): 0.78; 95% CI: 0.73, 0.82) but were more likely to have a cycle that resulted in a clinical pregnancy (RR: 1.15; 95% CI: 1.04, 1.28) and live birth (RR: 1.21; 95% CI: 1.08, 1.35) than women who did not use PGT-A. Among women aged ≥38 years, those who used PGT-A were 67% (RR: 1.67; 95% CI: 1.31, 2.13) more likely to have a live birth than women who did not use PGT-A. Among women aged 35-37 years, those who used PGT-A were also more likely to have a live birth (RR: 1.27; 95% CI: 1.05, 1.54) than women who did not use PGT-A. In contrast, women <35 years old who used PGT-A were as likely to have a live birth (RR: 0.91; 95% CI: 0.78, 1.06) as women <35 years old who did not use PGT-A.

Limitations, Reasons For Caution: We were unable to abstract several potential confounding variables from patients' records (e.g. anti-Mullerian hormone levels and prior IVF treatment), which may have resulted in residual confounding. Additionally, by restricting our analyses to cycles associated with the first oocyte retrieval, we were unable to estimate the cumulative incidence of live birth over multiple oocyte retrieval cycles.

Wider Implications Of The Findings: Women aged 35 years or older are likely to benefit from PGT-A. Larger studies might identify additional subgroups of women who might benefit from PGT-A.

Study Funding/competing Interest(s): No funding was received for this study. D.S. reports that he is a member of the Cooper Surgical Advisory Board. The other authors report no conflicts of interest.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deaa161DOI Listing
October 2020

Osteopathic Considerations for the Pregnant Patient with COVID-19.

J Am Osteopath Assoc 2020 Aug 7. Epub 2020 Aug 7.

In any given year, approximately 130 million babies are born worldwide. Previous research has shown that pregnant women may be more severely affected and vulnerable to contracting emerging infections, making them a particularly high-risk population. Therefore, special considerations should be given to treatment methods for pregnant women with COVID-19. In this narrative review, the authors evaluate scholarly journal articles and electronic databases to determine what is known about the pathophysiology of COVID-19 in pregnancy and the associated mortality rate. Osteopathic manipulative treatment techniques to mitigate the underlying pathology were identified, and modifications for use in pregnancy and the critical care setting are described.
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http://dx.doi.org/10.7556/jaoa.2020.112DOI Listing
August 2020

Double trouble? Clinic-specific risk factors for monozygotic twinning.

Fertil Steril 2020 09 1;114(3):587-594. Epub 2020 Jul 1.

Boston IVF, Waltham, Massachusetts.

Objective: To investigate clinic-specific risk factors for monozygotic twinning (MZT) using a large, electronic database.

Design: Retrospective case-control study.

Setting: Infertility clinics.

Patient(s): Using an electronic medical record system, viable clinical pregnancy (confirmation of a gestational sac(s) and presence of at least one fetal pole with a heartbeat on first trimester ultrasound), data were obtained from homologous in vitro fertilization (IVF) cycles after single ET from June 1, 2004, to December 31, 2016. Monozygotic twinning was defined as a pregnancy with two fetal heartbeats on ultrasound with sex concordance at birth.

Intervention(s): None.

Main Outcome Measure(s): Risk factors for MZT including cycle type, method of insemination, and method of cryopreservation.

Result(s): Of the 28,265 IVF cycles that met inclusion criteria over the study period, 8,749 (31.0%) resulted in a viable intrauterine clinical pregnancy. There were 102 (2.7%) MZT in the fresh cycle cohort and 133 (2.7%) in the frozen cycle cohort. Neither cryopreservation nor the method of cryopreservation was a significant risk factor for MZT. However, the use of sequential media was an independent risk factor for MZT in fresh, but not frozen, ETs (odds ratio = 1.72, 95% confidence interval, 1.10-2.68). Significant differences were seen in the incidence of MZT between clinics, and this difference persisted after controlling for known risk factors (clinic 0, reference; clinic 2, odds ratio = 2.22; 95% confidence interval, 1.48-3.32; clinic 3, odds ratio = 1.93; 95% confidence interval, 1.30-2.87).

Conclusion(s): Differences in MZT rates exist between individual IVF clinics, suggesting that variations in practice patterns may contribute to this event. The present study noted the use of sequential media was an independent risk factor for fresh but not frozen cycles.
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http://dx.doi.org/10.1016/j.fertnstert.2020.04.010DOI Listing
September 2020

Associations between a safety prequalification survey and worker safety experiences on commercial construction sites.

Am J Ind Med 2020 09 9;63(9):766-773. Epub 2020 Jun 9.

Department of Health Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts.

Background: While assessment of subcontractors' safety performance during project bidding processes are common in commercial construction, the validation of organizational surveys used in these processes is largely absent.

Methods: As part of a larger research project called Assessment of Contractor Safety (ACES), we designed and tested through a cross-sectional study, a 63-item organizational survey assessing subcontractors' leading indicators of safety performance. We administered the ACES Survey to 43 subcontractors on 24 construction sites. Concurrently, we captured the safety climate of 1426 workers on these sites through worker surveys, as well as injury rates, for the duration of the project.

Results: At the worksite level, higher average ACES scores were associated with higher worker safety climate scores (P < .01) and lower rates of injury involving days away (P < .001). Within subcontracting companies, no associations were observed between ACES and worker safety climate scores and injuries.

Conclusions: These results suggest the overall and collective importance of the construction project and its worksite in mediating worker experiences, perhaps somewhat independent of the individual subcontractor level.
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http://dx.doi.org/10.1002/ajim.23143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641207PMC
September 2020

Impacts of genesurance considerations on genetic counselors' practice and attitudes.

J Genet Couns 2020 12 20;29(6):1210-1220. Epub 2020 May 20.

University of Texas Genetic Counseling Program, University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.

Genesurance counseling has been identified as an integral part of many genetic counseling sessions, but little is known about the workflow impacts and genetic counselor perceptions of genesurance-related tasks. In this study, we aimed to characterize how insurance and billing considerations for genetic testing are being incorporated into genetic counselors' practice in the United States, as well as describe current attitudes and challenges associated with their integration. An electronic survey was sent by email to members of the National Society of Genetic Counselors (NSGC). A total of 325 American Board of Genetic Counselors-certified genetic counselors who provide direct patient care in the United States for at least 50% of their time were included in data analysis. Results showed that the frequency and timing of various insurance- and billing-related tasks were not consistent among respondents, even those practicing in similar settings. Inadequate training to complete tasks was reported by 64% of respondents, and 47% reported a lack of resources from their employer and/or institution to complete genesurance tasks. Additionally, only 38% of respondents agreed that insurance- and billing-related tasks were within the scope of the genetic counseling practice, and there was little consensus on who respondents believe is the most appropriate person to complete these tasks. When asked how genesurance considerations affected job satisfaction, 85% of respondents reported a negative impact. This study found an inconsistent genesurance workflow among genetic counselors practicing in the United States, a lack of consensus on who should be responsible for genesurance tasks, several challenges associated with completing these tasks, and identifies genesurance considerations as potential risk factors for genetic counselor burnout.
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http://dx.doi.org/10.1002/jgc4.1291DOI Listing
December 2020

Interventions to address health outcomes among autistic adults: A systematic review.

Autism 2020 08 11;24(6):1345-1359. Epub 2020 May 11.

Autistic author, presenter, and trainer, USA.

Lay Abstract: Autistic adults have more health problems then their same-aged peers. Yet little research has been conducted that focuses on addressing these health problems. In order to guide future research, it is important to know what intervention studies have been done to improve health outcomes among autistic adults. The project team and student assistants read studies that were published between 2007 and 2018 in the online research database, PubMed. We looked for studies published in English, which were peer-reviewed and included (1) an intervention, (2) an outcome that was related to health, and (3) a study group that included autistic adults. We did not include studies that had outcomes about employment (unless there was a health outcome), studies about caregivers or caregiving, or expert opinions about interventions. Of 778 reviewed articles, 19 studies met all of the criteria above. Within these studies, two approaches were found to have emerging evidence for their use in autistic adults: cognitive behavioral interventions and mindfulness-based approaches for improved mental health outcomes. The remaining intervention approaches did not have enough articles to support their use. Many of the outcomes were about reduced symptoms of co-occurring mental health diagnoses (e.g. reduced anxiety, depression). Most of the participants in these studies were male and did not have intellectual disability. Most study participants were adults younger than 40. There are not many intervention studies that address health outcomes among autistic adults. More research is needed on interventions which are desired by the adult autism community and address preferred health outcomes such as increased quality of life or well-being.
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http://dx.doi.org/10.1177/1362361320913664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787674PMC
August 2020

Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets.

Mol Cell 2020 05;78(3):477-492.e8

Haematopoietic Stem Cell Biology Laboratory, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford OX3 9DS, UK; MRC Molecular Haematology Unit, MRC WIMM, University of Oxford, Oxford OX3 9DS, UK; NIHR Biomedical Research Centre, University of Oxford, Oxford OX4 2PG, UK. Electronic address:

Myelofibrosis is a severe myeloproliferative neoplasm characterized by increased numbers of abnormal bone marrow megakaryocytes that induce fibrosis, destroying the hematopoietic microenvironment. To determine the cellular and molecular basis for aberrant megakaryopoiesis in myelofibrosis, we performed single-cell transcriptome profiling of 135,929 CD34 lineage hematopoietic stem and progenitor cells (HSPCs), single-cell proteomics, genomics, and functional assays. We identified a bias toward megakaryocyte differentiation apparent from early multipotent stem cells in myelofibrosis and associated aberrant molecular signatures. A sub-fraction of myelofibrosis megakaryocyte progenitors (MkPs) are transcriptionally similar to healthy-donor MkPs, but the majority are disease specific, with distinct populations expressing fibrosis- and proliferation-associated genes. Mutant-clone HSPCs have increased expression of megakaryocyte-associated genes compared to wild-type HSPCs, and we provide early validation of G6B as a potential immunotherapy target. Our study paves the way for selective targeting of the myelofibrosis clone and illustrates the power of single-cell multi-omics to discover tumor-specific therapeutic targets and mediators of tissue fibrosis.
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http://dx.doi.org/10.1016/j.molcel.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217381PMC
May 2020

Integrating Urban Adolescent Mental Health Into Urban Sustainability Collective Action: An Application of Shiffman & Smith's Framework for Global Health Prioritization.

Front Psychiatry 2020 20;11:44. Epub 2020 Feb 20.

Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States.

The majority (55%) of the world's population lives in urban environments. Of relevance to global mental health, the rapid growth in urban populations around the world and the attendant risks coincide with the presence of the largest population of adolescents the global community has seen to date. Recent reviews on the effects of the urban environment on mental health report a greater risk of depression, anxiety, and some psychotic disorders among urban dwellers. Increased risk for mental disorders is associated with concentrated poverty, low social capital, social segregation, and other social and environmental adversities that occur more frequently in cities. To address these problems, urban adolescent mental health requires attention from decision makers as well as advocates who seek to establish sustainable cities. We examine opportunities to increase the prominence of urban adolescent mental health on the global health and development agenda using Shiffman and Smith's framework for policy priorities, and we explore approaches to increasing its relevance for urban health and development policy communities. We conclude with suggestions for expanding the community of actors who guide the field and bridging the fields of mental health and urban development to meet urban adolescent mental health needs.
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http://dx.doi.org/10.3389/fpsyt.2020.00044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044235PMC
February 2020

Attention bias towards threat in African American children exposed to early life trauma.

Behav Brain Res 2020 04 25;383:112513. Epub 2020 Jan 25.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, United States. Electronic address:

Background: Attentional bias is linked to a range of mood disorders, including posttraumatic stress disorder (PTSD). The present study examined attention bias patterns in African American children exposed to trauma, in order to better understand potential risk factors for PTSD.

Methods: 31 children (ages 8-14) completed an eye-tracking task to assess gaze bias patterns while viewing pairs of emotional and neutral faces. Trauma exposure and PTSD symptoms were assessed in a subsample of children (n = 24).

Results: Repeated measures analysis of variance (ANOVA) results examining attention bias indices and gender showed greater attention bias toward angry faces than happy faces (p < 0.01) and toward emotional faces in males than females (p < 0.05). Correlational analyses showed attention bias toward angry faces was associated with greater levels of child trauma exposure (p < 0.05). Based on linear regression analysis, child trauma exposure accounted for 17 % of variance in attention bias toward angry versus neutral faces independent of gender or posttraumatic stress symptoms (p < 0.05).

Conclusions: Trauma exposure in children is related to altered attention bias, via enhanced attention towards threatening cues. Results contribute to evidence that males and females may exhibit different attentional patterns. This study highlights the importance of additional research on attention bias patterns and prospective mental health outcomes across gender and through development.
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http://dx.doi.org/10.1016/j.bbr.2020.112513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040527PMC
April 2020

The role of negative affect in the association between attention bias to threat and posttraumatic stress: An eye-tracking study.

Psychiatry Res 2020 02 9;284:112674. Epub 2019 Dec 9.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Georgia, United States of America.

Biased processing of threatening stimuli, including attention toward and away from threat, has been implicated in the development and maintenance of PTSD symptoms. Research examining theoretically-derived mechanisms through which dysregulated processing of threat may be associated with PTSD is scarce. Negative affect, a transdiagnostic risk factor for many types of psychopathology, is one potential mechanism that has yet to be examined. Thus, the present study (n = 92) tested the indirect effect of attention bias on PTSD via negative affect using rigorous eye-tracking methodology in a sample of urban-dwelling, trauma-exposed African-American women. We found support for the hypothesis that attention bias toward threat was indirectly associated with PTSD symptoms through increased negative affect. These results suggest that negative affect may be an important etiological process through which attention bias patterns could impact PTSD symptom severity. Implications for psychological and pharmacological therapeutic interventions targeting threat-related attention biases and negative affect are discussed.
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http://dx.doi.org/10.1016/j.psychres.2019.112674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012707PMC
February 2020

It takes two: uptake of carrier screening among male reproductive partners.

Prenat Diagn 2020 02 2;40(3):311-316. Epub 2019 Dec 2.

Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School at UTHealth, Houston, TX, USA.

Objective: To describe uptake of carrier screening by male reproductive partners of prenatal and preconception patients.

Methods: A retrospective database review of all prenatal and preconception patients seen for genetic counseling in Maternal Fetal Medicine clinics was performed. Descriptive statistics and chi-square analysis were used on the data set.

Results: Within the study period, 6087 patients were seen for genetic counseling, of whom 661 were identified as a carrier of an autosomal recessive disorder by their referring provider or genetic counselor. Despite guidelines recommending partner testing for risk clarification when a woman is known to be a carrier of an autosomal recessive condition, only 41.5% male partners elected carrier screening to clarify the couple's reproductive risk, with a majority of males (75%) having screening consecutively. Of all assessed variables, the only significant predictors of male carrier screening uptake were female parity and earlier gestational age (p < .0001, and p = .001, respectively).

Conclusion: With less than half of male partners pursuing carrier screening when indicated, its utility becomes severely diminished. More research is needed to explore reasons why males elect or decline carrier screening.
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http://dx.doi.org/10.1002/pd.5588DOI Listing
February 2020

Chemogenetic Inhibition of the Amygdala Modulates Emotional Behavior Expression in Infant Rhesus Monkeys.

eNeuro 2019 Sep/Oct;6(5). Epub 2019 Oct 14.

Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329.

Manipulation of neuronal activity during the early postnatal period in monkeys has been largely limited to permanent lesion studies, which can be impacted by developmental plasticity leading to reorganization and compensation from other brain structures that can interfere with the interpretations of results. Chemogenetic tools, such as DREADDs (designer receptors exclusively activated by designer drugs), can transiently and reversibly activate or inactivate brain structures, avoiding the pitfalls of permanent lesions to better address important developmental neuroscience questions. We demonstrate that inhibitory DREADDs in the amygdala can be used to manipulate socioemotional behavior in infant monkeys. Two infant rhesus monkeys (1 male, 1 female) received AAV5-hSyn-HA-hM4Di-IRES-mCitrine injections bilaterally in the amygdala at 9 months of age. DREADD activation after systemic administration of either clozapine--oxide or low-dose clozapine resulted in decreased freezing and anxiety on the human intruder paradigm and changed the looking patterns on a socioemotional attention eye-tracking task, compared with vehicle administration. The DREADD-induced behaviors were reminiscent of, but not identical to, those seen after permanent amygdala lesions in infant monkeys, such that neonatal lesions produce a more extensive array of behavioral changes in response to the human intruder task that were not seen with DREADD-evoked inhibition of this region. Our results may help support the notion that the more extensive behavior changes seen after early lesions are manifested from brain reorganization that occur after permanent damage. The current study provides a proof of principle that DREADDs can be used in young infant monkeys to transiently and reversibly manipulate behavior.
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http://dx.doi.org/10.1523/ENEURO.0360-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791827PMC
May 2020

Hereditary Gastrointestinal Cancer Syndromes: Role of Imaging in Screening, Diagnosis, and Management.

Radiographics 2019 Sep-Oct;39(5):1280-1301. Epub 2019 Aug 2.

From the Department of Radiology, University of Texas Health Science Center, 7703 Floyd Curl Dr, San Antonio, TX 78229 (V.S.K., L.K., L.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (C.O.M.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.); Department of Radiology, University of Wisconsin Medical Center, Madison, Wis (M.G.L.); and Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P.).

Hereditary gastrointestinal (GI) cancer syndromes due to specific germline mutations are characterized by an increased risk of GI tract malignancies, extra-GI tract cancers, and benign abnormalities. These syndromes include Lynch syndrome, familial adenomatous polyposis, juvenile polyposis syndrome, Peutz-Jeghers syndrome, Cowden syndrome, hereditary diffuse gastric cancer, and hereditary pancreatic cancer. Timely identification of the responsible genes will help predict future cancer risks in these patients and their family members. Early detection of cancers is possible with appropriate screening methods; risk-reducing measures will help in cancer prevention. Select malignancies and benign conditions associated with these syndromes have distinctive imaging features that can aid in classifying the syndromes. Imaging also plays a pivotal role in screening and surveillance of patients as well as their at-risk relatives and is invaluable for follow-up of treated malignancies. The American College of Gastroenterology has established specific guidelines for diagnosis and management of hereditary GI cancer syndromes. Knowledge of the imaging features of various pathologic conditions and screening strategies will guide appropriate management of patients and at-risk family members. RSNA, 2019.
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http://dx.doi.org/10.1148/rg.2019180185DOI Listing
May 2020

Psychiatric genetic counseling: A mapping exercise.

Am J Med Genet B Neuropsychiatr Genet 2019 12 20;180(8):523-532. Epub 2019 Jun 20.

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

Psychiatric genetic counseling (PGC) is gradually developing globally, with countries in various stages of development. In some, PGC is established as a service or as part of research projects while in others, it is just emerging as a concept. In this article, we describe the current global landscape of this genetic counseling specialty and this field's professional development. Drawing on information provided by expert representatives from 16 countries, we highlight the following: (a) current understanding of PGC; (b) availability of services for patients; (c) availability of training; (d) healthcare system disparities and cultural differences impacting practice; and (e) anticipated challenges going forward.
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http://dx.doi.org/10.1002/ajmg.b.32735DOI Listing
December 2019

Current genetic counseling practice in the United States following positive non-invasive prenatal testing for sex chromosome abnormalities.

J Genet Couns 2019 08 4;28(4):802-811. Epub 2019 Apr 4.

UTHealth Graduate School of Biomedical Sciences, MD Anderson Cancer Center, The University of Texas, Houston, Texas.

The purpose of this study was to describe current genetic counseling practice in the United States following a non-invasive prenatal testing (NIPT) result positive for a sex chromosome abnormality (SCA). Screening for SCAs can be confounded by confined placental mosaicism, natural loss of the X chromosome from maternal cells during aging, and undiagnosed maternal SCA or copy number variant (CNV). Furthermore, with the exception of 45,X, individuals with SCAs usually have no ultrasound or postnatal findings. This makes follow-up for unresolved positive NIPT necessary; however, there are currently no clinical guidelines. This study used a cross-sectional design with an anonymous questionnaire to survey 176 genetic counselors. The majority of prenatal respondents always offered diagnostic testing (>88%) and anatomy ultrasound (~90%), but the percent consistently offering maternal karyotype (22%-52%) and postnatal evaluation (28%-87%) varied. Maternal karyotype was offered more often when NIPT was positive for 45,X or 47,XXX and patients had normal prenatal diagnostic testing (p < 0.02) or declined testing (p < 0.02). Offer of postnatal evaluation was more likely when diagnostic testing was declined (p < 0.001). The majority of pediatric providers always offered a postnatal karyotype for the newborn (>72%) but the percent offering maternal karyotype (6%-46%) varied widely. With the current inconsistencies, many newborns with undiagnosed SCAs who could benefit from growth hormone therapy, early intervention, and/or targeted surveillance may be missed. Therefore, there is a need for professional guidelines to help improve the consistency of clinical care for patients with NIPT results positive for SCAs.
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http://dx.doi.org/10.1002/jgc4.1122DOI Listing
August 2019

Attention bias toward threatening faces in women with PTSD: eye tracking correlates by symptom cluster.

Eur J Psychotraumatol 2019 13;10(1):1568133. Epub 2019 Feb 13.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.

Maladaptive patterns of attention to emotional stimuli are a common feature of posttraumatic stress disorder (PTSD), with growing evidence supporting sustained attention to threatening stimuli across trauma samples. However, it remains unclear how different PTSD symptom clusters are associated with attentional bias patterns, particularly in urban civilian settings with high rates of trauma exposure and PTSD. The present study examined associations among these variables in 70 traumatized primarily African American women. PTSD was measured using the Clinician Administered PTSD Scale, and eye tracking was used to measure patterns of attention as participants engaged in an attention bias (dot probe) task to emotional faces; average initial fixation (1 s) and dwell duration (overall time spent looking at emotional face versus neutral face across the 5 s task) were used to assess attention bias patterns toward emotional faces. Women with PTSD showed significantly longer dwell duration toward angry faces than women without PTSD (5.16, .05). Bivariate correlation analyses with the PTSD symptom clusters showed a significant association between average initial fixation toward angry faces and higher levels of avoidance symptoms (0.29, .05) as well as sustained attention to angry faces and higher levels of re-experiencing symptoms (0.24, .05). Using separate linear regression models based on initial significant correlations, we found that PTSD avoidance symptoms were significantly related to average initial fixation toward angry faces (= 0.09, .05) and PTSD re-experiencing symptoms were significantly related to dwell duration toward angry faces (= 0.06, .05). These findings contribute to evidence that PTSD is related to both initial vigilance and sustained attention to threat and that certain symptom clusters may either drive or be more impacted by attentional biases, highlighting the benefits of addressing attentional biases within treatment.
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http://dx.doi.org/10.1080/20008198.2019.1568133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374933PMC
February 2019

Association Between Antithrombotic Medication Use After Bioprosthetic Aortic Valve Replacement and Outcomes in the Veterans Health Administration System.

JAMA Surg 2019 02 20;154(2):e184679. Epub 2019 Feb 20.

Health Services Research and Development, Center for Health Information and Communication, Richard L. Roudebush VA Medical Center, Department of Veterans Affairs, Indianapolis, Indiana.

Importance: The recommendations about antithrombotic medication use after bioprosthetic aortic valve replacement (bAVR) vary.

Objectives: To describe the post-bAVR antithrombotic medication practice across the Veterans Health Administration (VHA) and to assess the association between antithrombotic strategies and post-bAVR outcomes.

Design, Setting, And Participants: Retrospective cohort study. Multivariable modeling with propensity scores was conducted to adjust for differences in patient characteristics across the 3 most common antithrombotic medication strategies (aspirin plus warfarin sodium, aspirin only, and dual antiplatelets). Text mining of notes was used to identify the patients with bAVR (fiscal years 2005-2015).

Main Outcomes And Measures: This study used VHA and non-VHA outpatient pharmacy data and text notes to classify the following antithrombotic medications prescribed within 1 week after discharge from the bAVR hospitalization: aspirin plus warfarin, aspirin only, dual antiplatelets, no antithrombotics, other only, and warfarin only. The 90-day outcomes included all-cause mortality, thromboembolism risk, and bleeding events. Outcomes were identified using primary diagnosis codes from emergency department visits or hospital admissions.

Results: The cohort included 9060 veterans with bAVR at 47 facilities (mean [SD] age, 69.3 [8.8] years; 98.6% male). The number of bAVR procedures per year increased from 610 in fiscal year 2005 to 1072 in fiscal year 2015. The most commonly prescribed antithrombotic strategy was aspirin only (4240 [46.8%]), followed by aspirin plus warfarin (1638 [18.1%]), no antithrombotics (1451 [16.0%]), dual antiplatelets (1010 [11.1%]), warfarin only (439 [4.8%]), and other only (282 [3.1%]). Facility variation in antithrombotic prescription patterns was observed. During the 90-day post-bAVR period, adverse events were uncommon, including all-cause mortality in 127 (1.4%), thromboembolism risk in 142 (1.6%), and bleeding events in 149 (1.6%). No differences in 90-day mortality or thromboembolism were identified across the 3 antithrombotic medication groups in either the unadjusted or adjusted models. Patients receiving the combination of aspirin plus warfarin had higher odds of bleeding than patients receiving aspirin only in the unadjusted analysis (odds ratio, 2.58; 95% CI, 1.71-3.89) and after full risk adjustment (adjusted odds ratio, 1.92; 95% CI, 1.17-3.14).

Conclusions And Relevance: These data demonstrate that bAVR procedures are increasingly being performed in VHA facilities and that aspirin only was the most commonly used antithrombotic medication strategy after bAVR. The risk-adjusted results suggest that the combination of aspirin plus warfarin does not improve either all-cause mortality or thromboembolism risk but increases the risk of bleeding events compared with aspirin only.
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http://dx.doi.org/10.1001/jamasurg.2018.4679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439666PMC
February 2019

The Gap Between Tools and Best Practice: An Analysis of Safety Prequalification Surveys in the Construction Industry.

New Solut 2019 02 10;28(4):683-703. Epub 2018 Dec 10.

2 Department of Physical Therapy, Movement, and Rehabilitation Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, MA, USA.

This study characterizes safety prequalification surveys currently in use in the construction industry to identify approaches that include leading indicators of worker safety performance. We collected prequalification surveys available in the public domain from internet searches, construction company websites, published literature, and construction industry partners. We utilized a conceptual framework, based on safety theory and best practices, to categorize survey questions. Fifty-two prequalification surveys were identified containing 112 unique questions. Most included questions related to lagging indicators (83 percent), safety management leadership (75 percent), and worker training (60 percent). Safety management system elements such as hazard prevention and control, program evaluation and improvement, and coordination and communication were notably absent in 90 percent of the surveys. There was little consistency in the surveys available concerning leading indicators of safety. Only a small number of surveys currently in use incorporate all the elements of best practices associated with robust safety management systems.
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http://dx.doi.org/10.1177/1048291118813583DOI Listing
February 2019

To test or not to test? A framework for counselling patients on preimplantation genetic testing for aneuploidy (PGT-A).

Hum Reprod 2019 02;34(2):268-275

Boston IVF, Waltham, MA, USA.

Study Question: What is the treatment path and cumulative live birth (CLB) rate from a single oocyte retrieval of patients who intend to pursue PGT-A at the start of an IVF cycle compared to matched controls?

Summary Answer: The choice of PGT-A at the start of the first IVF cycle decreases the CLB per oocyte retrieval for patients <38 years of age, however patients ≥38 years of age benefit significantly per embryo transfer (ET) when live birth (LB) is evaluated.

What Is Known Already: PGT-A has been shown to reduce the practice of transferring multiple embryos and to confer a higher live birth rate per transfer.

Study Design, Size, Duration: This is a retrospective cohort study from December 2014 to September 2016, involving 600 patients: those intending PGT-A for their first IVF cycle (N = 300) and their matched controls. Post-hoc power calculations (alpha of 0.05, power of 0.80) indicated that our study was powered adequately to demonstrate significant differences in CLB per retrieval and LB per transfer.

Participants/materials, Setting, Methods: The study was performed at a large academically affiliated infertility practice where approximately 80% of patients have insurance coverage for fertility care. Patients were identified through electronic medical records, and those who intended to pursue PGT-A at the start of stimulation were assessed. Patients were matched by age, time of oocyte retrieval and oocyte yield to the same number of controls. CLB outcomes per single retrieval, including the fresh and frozen transfers arising from the initial stimulation cycle, were calculated.

Main Results And The Role Of Chance: PGT-A was not beneficial when CLB rate was assessed per retrieval, however its benefits were significant when LB rate was assessed per transfer. First cycle, <38 year-old patients who intended to have PGT-A had a significantly (P < 0.001) lower CLB rate per oocyte retrieval compared to controls (49.4% vs. 69.1%). Conversely, patients ≥ 38 years in the PGT-A group had similar CLB rates compared to controls per oocyte retrieval, while LB rates per transfer were doubled compared to controls (62.1% vs. 31.7%; P < 0.001). Of the first-cycle PGT-A and control patients, 25.3% and 2.3% failed to achieve a transfer, respectively.

Limitations, Reasons For Caution: This is not a true intention-to-treat study, due to its retrospective nature. Additionally, the number of patients with two or more previous miscarriages was significantly greater in the PGT-A group as compared to controls, however a sub-analysis showed that this failed to impact outcomes.

Wider Implications Of The Findings: The findings indicate that PGT-A may be detrimental for those <38 years old undergoing their first IVF cycle. PGT-A has the greatest clinical impact when a transfer is achieved in the ≥38 years old population. This study evaluates the typical treatment path following a patient's choice to pursue PGT-A at the cycle start, and can be used as a guide for counselling patients in relation to age and cycle number.

Study Funding/competing Interest(s): None.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/dey346DOI Listing
February 2019

Clinical experience with sex chromosome aneuploidies detected by noninvasive prenatal testing (NIPT): Accuracy and patient decision-making.

Prenat Diagn 2018 10 15;38(11):841-848. Epub 2018 Aug 15.

Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, USA.

Objective: The objectives of the study are to assess the accuracy of noninvasive prenatal testing (NIPT) for sex chromosome aneuploidies (SCAs) and to investigate patient decision-making in clinical practice.

Study Design: This is a retrospective cohort study review of positive NIPT results for SCAs from January 2013 to September 2017.

Results: Of the 136 positive NIPT results for SCAs, 73 (53.7%) were positive for 45,X, 62 (45.6%) were a sex chromosome trisomy, and 1 was a sex chromosome tetrasomy. Of the 134 viable pregnancies, 46 (34.3%) elected to pursue prenatal diagnosis. Fewer women underwent invasive prenatal testing when counseled regarding a positive NIPT for monosomy X in the presence of suggestive ultrasound findings (4/23; 17.4%) compared with those who had a positive NIPT result without ultrasound findings (24/46, 52.2%). Abnormal karyotypes consistent with the NIPT result were confirmed in 30/64 (46.9%). Even in the context of ultrasound abnormalities, there was not 100% concordance.

Conclusions: The majority (88/134; 65.7%) of patients in our cohort declined prenatal diagnosis even in the presence of associated ultrasound findings. Comprehensive pretest and posttest counseling is recommended and should address the importance of confirmatory testing and benefits of early diagnosis. Practice guidelines are needed to address provider responsibilities about postnatal testing.
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http://dx.doi.org/10.1002/pd.5339DOI Listing
October 2018

Rapid Decompensation to Systemic Inflammatory Response Syndrome in Children with Osteomyelitis: A Report of Three Cases.

JBJS Case Connect 2018 Apr-Jun;8(2):e27

Grand Rounds Inc., San Francisco, California.

Case: We present 3 pediatric cases of osteomyelitis with delayed diagnosis, which resulted in systemic inflammatory response syndrome (SIRS) and complicated hospital stays.

Conclusion: These 3 cases illustrate that early treatment of osteomyelitis is imperative in order to avoid fatal complications, which can occur with SIRS. Subtle signs and symptoms should not be dismissed. Patients with fever, pain, and no history of trauma should be scrutinized.
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http://dx.doi.org/10.2106/JBJS.CC.17.00151DOI Listing
November 2019

Treatment with epigenetic agents profoundly inhibits tumor growth in leiomyosarcoma.

Oncotarget 2018 Apr 10;9(27):19379-19395. Epub 2018 Apr 10.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Leiomyosarcomas are rare mesenchymal neoplasms characterized by a smooth muscle differentiation pattern. Due to the extremely poor prognosis in patients, the development of novel chemotherapeutic regimens remains critically important. In this study, multiple leiomyosarcoma cell lines, SK-UT1, SK-LMS1, and MES-SA were treated with varying doses of the DNA Methyltransferase Inhibitors (DNMTi) 5-azacitidine (Aza), 5-aza-2-deoxycytidine (DAC), and guadecitabine (SGI-110). The effect of these epigenetic modulators was measured using both and models. Of the three epigenetic modulators, Guadecitabine was the most effective at decreasing cell survival in LMS cell lines. SK-UT1 was found to be the more sensitive to all three epigenetic modulators, while SK-LMS1 and MES-SA were more resistant. The contrast in sensitivity seen was also represented by the increase in apoptosis in Aza and guadecitabine. In parallel with Aza, guadecitabine was observed to also arrest the cell cycle. Treatment with guadecitabine led to a decrease in growth across the spectrum of sensitivity in LMS cell lines, both in a delayed and model; in parallel experiments, apoptotic pathways were activated in sensitive and less sensitive lines. Additional studies are required to explore potential therapeutic applications and mechanisms for leiomyosarcoma treatment.
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http://dx.doi.org/10.18632/oncotarget.25056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922404PMC
April 2018