Παρασκευή, 20 Ιουλίου 2018

Inhibition and attentional control in pedophilic child sexual offenders – An event-related potential study

Publication date: September 2018

Source: Clinical Neurophysiology, Volume 129, Issue 9

Author(s): Timm Rosburg, Gunnar Deuring, Coralie Boillat, Patrick Lemoine, Michael Falkenstein, Marc Graf, Ralph Mager

Abstract
Objective

Impaired response inhibition might play a role in child sexual offences. Recording of event-related potentials (ERPs) can help to clarify whether child sexual offenders (CSOs) show an altered processing of stop signals and commission errors.

Methods

In the current ERP study, we investigated these processes in a Go/Nogo task on two groups of CSOs, pedophilic contact CSOs and non-contact CSOs (child pornography offenders), as well as on non-offenders as controls.

Results

Behaviorally, CSOs showed a slight, but non-significant increase of the false alarm rate to Nogo cues, as compared to controls. The amplitudes of the ERP components N2 and P3 to Nogo cues followed by correctly withhold responses did not vary between CSOs and controls. The analysis of the ERPs to committed errors showed that the Ne amplitudes (reflecting error detection) did not differ between the groups either, whereas the Pe amplitudes (reflecting error evaluation and error awareness) were strongly diminished in CSOs. This diminishment was primarily found in contact CSOs.

Conclusions

The findings suggest that response inhibition, processing of stop signals, and error detection are not necessarily impaired in CSOs. However, CSOs appear to dedicate less cognitive resources to the evaluation of committed errors.

Significance

This selective alteration could reflect a reduced sense of responsibility for misconduct in this offender group, which might contribute to their delinquent behavior.



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Growth, Body Composition and Micronutrient Abnormalities During and After Weaning Off Home Parenteral Nutrition

Objectives: To assess growth, body composition and micronutrient abnormalities in children with intestinal failure (IF) over time, both during and after weaning off parenteral nutrition (PN). Methods: Retrospective study in children on home PN between 2001 and 2015. Weight-for-age (WFA) and height-for-age (HFA) SD scores (SDS) were calculated, as well as fat mass (FM) and fat free mass (FFM) SDS obtained by DEXA. The course of growth parameters and body composition was analyzed with linear mixed models. All micronutrient measurements during the study period were obtained. Results: Fifty-two patients were included with a median follow-up of 3.4 years. Seventy-one % weaned off after a median PN duration of 0.9 years. One year after the start of PN, 28 patients were still PN-dependent with median WFA-SDS of -0.66 and median HFA-SDS of -0.96, both significantly lower than zero. Catch-up growth was achieved during PN, but HFA-SDS decreased after weaning (p = 0.0001). At a median age of 6.2 years, median %FM SDS was 0.30 and FFM SDS was -1.21, the latter significantly lower than zero. Frequent micronutrient abnormalities during PN were vitamin A (90%), zinc (87%) and iron (76%) and after weaning vitamin A (94%), E (61%) and 25-OH vitamin D (59%). Conclusion: Children with IF demonstrate abnormal growth and body composition and frequent micronutrient abnormalities. Longitudinal evaluation showed that catch-up growth occurs during PN, but height SDS decreases after weaning. This underlines the need for close monitoring, also after reaching enteral autonomy. Address correspondence and reprint requests to Jessie Hulst, PhD, MD, Department of Pediatric Gastroenterology, Erasmus Medical Center – Sophia Children's Hospital, Room Sp3435, PO BOX 2060, 3000 CB Rotterdam, the Netherlands (e-mail: j.hulst@erasmusmc.nl) Received 16 April, 2018 Accepted 23 June, 2018 Conflicts of interest and source of funding: none declared Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Is the WHO Creating Unnecessary Confusion Over Breast Milk Substitutes?

A recent statement by WHO that "breast milk substitutes should be understood to include any milks …that are specifically marketed for feeding infants and young children up to the age of 3 years" differs significantly from the definition in the International Code which states "a breast milk substitute is any food being marketed or otherwise presented as a partial or total replacement for breast milk, whether or not suitable for that purpose." The new interpretation, which lacks consultation and endorsement, is also ambiguous, with the boundaries between breast milk substitutes and complementary foods being blurred during the first 3 years of life. The logical definitions of breast milk substitutes and complementary foods contained within the Code should be maintained and inappropriate promotion of foods and fluids for infants and young children should be addressed through effective regulation of composition and labelling standards. Address correspondence and reprint requests to Stewart Forsyth, MD, 1 Ellieslea Road, West Ferry, Dundee, DD5 1JG (e-mail: stewartforsyth@btinternet.com). Received 24 April, 2018 Accepted 19 June, 2018 Conflicts of Interest and Source of Funding – SF has received research grants from government, charitable organisations, and industry; and consultancy fees and honoraria from government and industry, including companies that produce infant formula. He currently receives consultancy fees from DSM Nutritional Products, an international ingredient supplier. No funding related to this manuscript © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Liver Biopsy can be Safely Performed in Pediatric Acute Liver Failure to Aid in Diagnosis and Management

Objectives: Liver biopsy can be a valuable tool to help determine the etiology of pediatric acute liver failure (PALF), but is often not performed due to safety concerns. The primary aim was to describe the incidence of major complications after liver biopsy performed in the setting of PALF. Methods: Medical records from 2006–2016 were reviewed. Patients age 0–17 years, who met criteria for PALF, and had a liver biopsy performed while their international normalized ratio (INR) was ≥1.5 were included. Results: 26 cases of liver biopsy in the setting of PALF were identified. The majority (n = 22, 85%) of patients had primary liver disease. Most biopsies (n = 17, 65%) were performed by the transjugular route, with 5 (19%) performed percutaneously under ultrasound guidance and 4 (15%) during a surgical procedure. Median INR prior to biopsy was 2.1 (IQR = 1.73–2.9). Blood products were given prior to or during the procedure in 23 (88%) cases. One patient (3.8%) had a major complication of biopsy-associated bleeding requiring a blood transfusion. An additional 3 patients had a hemoglobin decrease of 2.1–2.9 g/dL post-biopsy that was attributed to the procedure but no interventions were necessary. Biopsy results contributed to establishing a diagnosis in 62% (n = 16) of cases, and influenced treatment decisions in 9 of those cases. Conclusions: Liver biopsy is safe in the majority of patients with PALF and associated with infrequent major complications. Clinicians should consider performing liver biopsy in this setting, especially when the transjugular approach is feasible, since findings may guide diagnosis and therapy. Address correspondence and reprint requests to Catherine A. Chapin, MD, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Ave Box 65, Chicago, IL 60610 (E-mail cchapin@luriechildrens.org). Received 10 January, 2018 Accepted 22 June, 2018 Author contributions: Catherine A Chapin, MD and Estella M Alonso, MD were involved in study concept and design; acquisition of data; analysis and interpretation of data; drafting of the initial manuscript; critical revision of the manuscript for important intellectual content; and study supervision. Saeed Mohammad, MD, Sarah A Taylor, MD, Lee M Bass, MD, and Susan Kelly, RN were involved in study concept and design; analysis and interpretation of data; and critical revision of the manuscript. Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to disclose. There are no sources of funding to declare for this work. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Real-time observation of nucleoplasmin-mediated DNA decondensation and condensation reveals its specific functions as a chaperone

Publication date: August 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 8

Author(s): Xin-Mei Huo, Li-feng Meng, Tao Jiang, Ming Li, Fang-Zhen Sun, Bo Sun, Jian-Ke Li

Abstract

Fertilization requires decondensation of promatine-condensed sperm chromatin, a dynamic process serving as an attractive system for the study of chromatin reprogramming. Nucleoplasmin is a key factor in regulating nucleosome assembly as a chaperone during fertilization process. However, knowledge on nucleoplasmin in chromatin formation remains elusive. Herein, magnetic tweezers (MT) and a chromatin assembly system were used to study the nucleoplasmin-mediated DNA decondensation/condensation at the single-molecular level in vitro. We found that protamine induces DNA condensation in a stepwise manner. Once DNA was condensed, nucleoplasmin, polyglutamic acid, and RNA could remove protamine from the DNA at different rates. The affinity binding of the different polyanions with protamine suggests chaperone-mediated chromatin decondensation activity occurs through protein–protein interactions. After decondensation, both RNA and polyglutamic acid prevented the transfer of histones onto the naked DNA. In contrast, nucleoplasmin is able to assist the histone transfer process, even though it carries the same negative charge as RNA and polyglutamic acid. These observations imply that the chaperone effects of nucleoplasmin during the decondensation/condensation process may be driven by specific spatial configuration of its acidic pentamer structure, rather than by electrostatic interaction. Our findings offer a novel molecular understanding of nucleoplasmin in sperm chromatin decondensation and subsequent developmental chromatin reprogramming at individual molecular level.



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Tandem Duplicate Genes in Maize Are Abundant and Date to Two Distinct Periods of Time

Tandem duplicate genes are proximally duplicated and as such occur in similar genomic neighborhoods. Using the maize B73 and PH207 de novo genome assemblies, we identified thousands of tandem gene duplicates that account for ~10% of the annotated genes. These tandem duplicates have a bimodal distribution of ages, which coincide with ancient allopolyploidization and more recent domestication. Tandem duplicates are smaller on average and have a higher probability of containing LTR elements than other genes, suggesting origins in nonhomologous recombination. Within relatively recent tandem duplicate genes, ~26% appear to be undergoing degeneration or divergence in function from the ancestral copy. Our results show that tandem duplicates are abundant in maize, arose in bursts throughout maize evolutionary history under multiple potential mechanisms, and may provide a substrate for novel phenotypic variation.



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2018 Hooley Awards winners named

Three individuals were named 2018 Hooley Awards winners at the 10th annual ImageTrend Connect Conference on July 19

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Table of Contents, Volume 176A, Number 7, July 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1537-1540, July 2018.


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Publication schedule for 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1541-1541, July 2018.


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Introducing in AJMG Part A: Case reports in diverse populations

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1547-1548, July 2018.


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Autosomal‐dominant biventricular arrhythmogenic cardiomyopathy in a large family with a novel in‐frame DSP nonsense mutation

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1622-1626, July 2018.


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Cover Image, Volume 176A, Number 7, July 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page i-i, July 2018.


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A novel FBXO28 frameshift mutation in a child with developmental delay, dysmorphic features, and intractable epilepsy: A second gene that may contribute to the 1q41‐q42 deletion phenotype

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1549-1558, July 2018.


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Ocular albinism with infertility and late‐onset sensorineural hearing loss

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1587-1593, July 2018.


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In This Issue

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1544-1545, July 2018.


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Diagnostic clarity of exome sequencing following negative comprehensive panel testing in the neonatal intensive care unit

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1688-1691, July 2018.


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Molecular Signature at Birth Associated With Genetic Burden for Autism

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1543-1544, July 2018.


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Further delineation of Aymé‐Gripp syndrome and use of automated facial analysis tool

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1648-1656, July 2018.


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Hyperactive SHP2 Mutants Impair Chondrocyte Differentiation During Endochondral Bone Growth in Noonan Syndrome

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1546-1546, July 2018.


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Novel phenotype of achondroplasia due to biallelic FGFR3 pathogenic variants

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1675-1679, July 2018.


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Patterns of care and outcomes in oesophageal cancer

The optimal treatment for oesophageal cancer is a matter of debate. The aim of this study was to describe patterns of care and survival in a well-defined population for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the oesophagus.

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SYSTEMATIC REVIEW: FEATURES, DIAGNOSIS, MANAGEMENT AND PROGNOSIS OF HEPATIC HEMATOMA, A RARE COMPLICATION OF ERCP

Hepatic Hematoma (HH) is a rare but severe adverse event following endoscopic retrograde cholangiopancreatography (ERCP).

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Autonomic dysreflexia as a potential adverse effect of duloxetine and amitriptyline combination therapy: A case report

Pharmacologic triggers of autonomic dysreflexia (AD) have rarely been described. We present a 31 year-old woman with T3 AIS A spinal cord injury who developed recurrent AD while receiving duloxetine and amitriptyline combination therapy for neuropathic pain. After excluding other AD generators, duloxetine was discontinued and the AD episodes resolved. While secondary hypertension is a known side effect of amitriptyline and duloxetine, neither drug has been previously associated with AD. One potential mechanism for inhibition of duloxetine metabolism is discussed.

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Acute Spinal Epidural Hematoma as a Complication of Dry Needling: A Case Report

Dry needling is a procedure commonly performed for the relief of myofascial pain disorders. The procedure is generally well tolerated. Adverse events often are mild, but severe complications have been reported. This case report describes an acute spinal epidural hematoma as a complication of dry needling. It is a reminder to the performing physician or therapist to take specific precautions when placing a needle near the spine. Sudden onset of neuropathic pain post-needling therapy in and around the spine should prompt emergent assessment with possibly advanced spine imaging to evaluate the integrity of the spinal cord.

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Walking Stability During Normal Walking And Its Association With Slip Intensity Among Individuals With Incomplete Spinal Cord Injury

Ambulatory individuals with incomplete spinal cord injury (iSCI) experience frequent falls suggesting impairments in their balance control. Individuals with iSCI are more stable during normal walking as compared to able-bodied individuals; however, it is not known whether this increased stability helps prevent hazardous slips.

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Patterns of care and outcomes in oesophageal cancer

The optimal treatment for oesophageal cancer is a matter of debate. The aim of this study was to describe patterns of care and survival in a well-defined population for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the oesophagus.

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SYSTEMATIC REVIEW: FEATURES, DIAGNOSIS, MANAGEMENT AND PROGNOSIS OF HEPATIC HEMATOMA, A RARE COMPLICATION OF ERCP

Hepatic Hematoma (HH) is a rare but severe adverse event following endoscopic retrograde cholangiopancreatography (ERCP).

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Your dedication, our appreciation

New AT&T First Responder Appreciation offer gives local Law Enforcement, Fire, EMS exclusive discounts on AT&T Unlimited &More wireless plans, TV and Internet. Discounts available to eligible first responders include: 25% off the monthly plan charge on AT&T Unlimited &More wireless plans $15 off DIRECTV $15 off AT&T Internet Certain restrictions apply. Learn more about...

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Tackling the quandary of the late-night call to increase retention

Our co-hosts discuss a recent article on the topic of late-night fatigue in EMS and how addressing those issues can lead to increased retention rates in the industry

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New smartwatch engages user and notifies first responders

The watch also has built-in GPS that alerts responders or a designated contact to the patient's exact location

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System Concepts - Part 1- What is a System?

maxresdefault.jpg

This vlog post is the first in a series about the concept of systems. We begin with a discussion of the definition of a system and introduce the idea of systems thinking. We then look at how that applies to improving clinical quality and economic efficiency in systems of care, particularly for high-risk time-sensitive conditions like cardiac arrest. This post features an excerpt from an amazing lecture given by the late Dr. Russell Ackoff – a major contributor to the field of systems thinking. Duration = 9 min 5 sec Link to CSI webpage - https://ift.tt/2mviom3

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System Concepts - Part 1- What is a System?

maxresdefault.jpg

This vlog post is the first in a series about the concept of systems. We begin with a discussion of the definition of a system and introduce the idea of systems thinking. We then look at how that applies to improving clinical quality and economic efficiency in systems of care, particularly for high-risk time-sensitive conditions like cardiac arrest. This post features an excerpt from an amazing lecture given by the late Dr. Russell Ackoff – a major contributor to the field of systems thinking. Duration = 9 min 5 sec Link to CSI webpage - https://ift.tt/2mviom3

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System Concepts - Part 1- What is a System?

maxresdefault.jpg

This vlog post is the first in a series about the concept of systems. We begin with a discussion of the definition of a system and introduce the idea of systems thinking. We then look at how that applies to improving clinical quality and economic efficiency in systems of care, particularly for high-risk time-sensitive conditions like cardiac arrest. This post features an excerpt from an amazing lecture given by the late Dr. Russell Ackoff – a major contributor to the field of systems thinking. Duration = 9 min 5 sec Link to CSI webpage - https://ift.tt/2mviom3

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System Concepts - Part 1- What is a System?

maxresdefault.jpg

This vlog post is the first in a series about the concept of systems. We begin with a discussion of the definition of a system and introduce the idea of systems thinking. We then look at how that applies to improving clinical quality and economic efficiency in systems of care, particularly for high-risk time-sensitive conditions like cardiac arrest. This post features an excerpt from an amazing lecture given by the late Dr. Russell Ackoff – a major contributor to the field of systems thinking. Duration = 9 min 5 sec Link to CSI webpage - https://ift.tt/2mviom3

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Neural correlates underlying spatial and verbal working memory in children with different mathematics achievement levels: An event-related potential study

Publication date: Available online 20 July 2018

Source: International Journal of Psychophysiology

Author(s): I-hsuan Shen, Pei-yi Liu, Chia-ling Chen



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Analysis of the relationship binding in situ gamma count rates and soil sample activities: Implication on radionuclide inventory and uncertainty estimates due to spatial variability

Publication date: December 2018

Source: Journal of Environmental Radioactivity, Volume 192

Author(s): Huong Liên Nguyen, Chantal de Fouquet, Christelle Courbet, Rodolfo Gurriaran, Valery Kashparov, Sviatoslav Levchuk, Evelyne Barker

Abstract

The paper strives to identify through geostatistical simulations the parameters which build up a correlation between radionuclide activity concentrations measured on core samples and corresponding in situ total gamma count rates measured into boreholes drilled within the contaminated soil. This numerical exercise demonstrates that a linear relationship should exist between logarithmic values of in situ count rates and logarithmic values of activity concentrations when the contamination is strongly structured through space. A sensitivity analysis to some parameters (geostatistical range of the contamination structure, core sampling method, soil water content, multiple gamma-emitter contamination, etc.) is undertaken to identify which situations may impede the use of such a correlation. Then this approach is applied on Chernobyl measurements undertaken in 2015 and compared to the co-kriging method which considers the localization of the measurements and the additional measurements. It appears that co-kriging is a better estimator than linear regression, but the latter remains an acceptable way of estimating activity from gamma emitters and presents better results than lognormal regression. Therefore, total gamma logging measurements performed into boreholes of porous media contaminated by gamma-emitting radionuclides can be used for characterizing contamination and dealing with its spatial variability with the use of co-kriging.

Graphical abstract

Image 1



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Peculiarities of Hematopoiesis in small rodents from the Chornobyl Exclusion Zone on the background of extreme environment

Publication date: Available online 20 July 2018

Source: Journal of Environmental Radioactivity

Author(s): Оlena О. Burdo, Аlla I. Lypska, Nataliia M. Riabchenko, Olena A. Sova

Abstract

Radiobiological investigations of natural populations of Myodes glareolus (bank vole) from the Chornobyl Exclusion Zone, namely within a highly radioactive site of the Red Forest were carried out. The complex of hematological and cytogenetic parameters of the bank voles inhabiting the contaminated site was studied before the site was flooded, in 2012, and after it drained, in 2015. A significant increase in micronucleated polychromatic erythrocytes, alterations in bone marrow and peripheral blood cell counts were observed in the population of 2015 in comparison with the group of 2012 and animals from the reference site. It is supposed that prolonged flooding has affected the features of radionuclide contamination of the experimental site as well as population characteristics and resulted in the increase of the genotoxic effects observed in the renewed population of bank voles exposed to chronic radiation.



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How to recover mentally and emotionally after an act of mass violence

By Amy Morgan, MSC, Executive Training Director at Academy Hour and IPSA Mental Health Committee Member If you were attacked and bitten violently by a dog when you were a kid, you would most likely have an adverse reaction throughout adulthood every time you see a similar dog. At a minimum, you would feel a heightened sense of caution and awareness. Any disturbing, traumatic or high-risk event that ...

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Do Subspecialists Ask About and Refer Families with Psychosocial Concerns? A Comparison with General Pediatricians

Abstract

Objectives Calls for pediatricians to tend to children's psychosocial concerns have existed for decades because they are known to negatively impact child health. Children with chronic illnesses frequently have child- and family-level psychosocial concerns that complicate the care provided by their pediatric subspecialists. This study compares pediatricians who exclusively practice general pediatrics with subspecialists regarding their inquiring/screening and referring for psychosocial concerns. Physician and practice characteristics associated with these behaviors were examined. Methods We conducted a cross-sectional study using the 2013 American Academy of Pediatrics Periodic Survey of Fellows. Respondents included 304 pediatricians who exclusively practice general pediatrics and 147 subspecialists. The primary analysis compared the current practices of generalists vs. subspecialists with regard to inquiring/screening and referring children with 10 different psychosocial concerns. Covariates included socio-demographics, practice characteristics, and training experiences. Weighted univariate, bivariate and multivariable analyses were performed. Results Less than half of all pediatricians in the sample reported routinely inquiring/screening for most psychosocial concerns, and 2/3 of subspecialists failed to routinely inquire/screen for most of these conditions. Pediatricians who practice general pediatrics exclusively were more likely to inquire/screen (incident rate ratio (IRR) 1.41, p < .05) and refer (IRR 1.59, p < .001) for a greater number of psychosocial concerns than subspecialists, after adjusting for provider and practice characteristics. Having attended a child or adolescent mental health (MH) lecture/conference in the past 2 years was also related to inquiring/screening (IRR 1.24, p < .05). Conclusions Pediatricians infrequently inquire/screen and refer psychosocial concerns, with subspecialists addressing these concerns even less frequently.



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A Systematic Approach to Translating Evidence into Practice to Reduce Infant Mortality

Abstract

Purpose To provide recommendations for improving rates of infant mortality in a U.S. southeastern city using a collective impact approach. Description A convening organization and its academic partner devised a systematic process involving national experts and local stakeholders. Assessment A panel of infant mortality experts reached consensus on eight recommendations and three key overarching principles. Local stakeholder groups advanced four recommendations, of which three aligned closely with expert panel recommendations: (1) increasing access to, and use of 17-alpha hydroxyprogesterone caproate (17P); (2) reshaping housing policy using a health lens, and (3) supporting pre-conception health, intra-conception health and family planning. Conclusion The dynamic process of recommendation development occurred within a larger collective impact framework and can be used to shape a community-based approach to infant mortality. Other communities interested in improving rates of infant mortality or tackling other challenging public health issues could engage in a similar process.



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KRAB-containing zinc finger protein ZNF496 inhibits breast cancer cell proliferation by selectively repressing ERα activity

Publication date: Available online 20 July 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Jinlong Wang, Xiuyuan Zhang, Jiming Ling, Yun Wang, Xiaolin Xu, Yuchen Liu, Chaozhi Jin, Jiyu Ju, Yanzhi Yuan, Fuchu He, Chunling Zhao, Jian Wang, Chunyan Tian

Abstract

KRAB-containing zinc finger proteins (KZNF) constitute the largest family of transcriptional regulators in humans and play critical roles in normal development and tumorigenesis. However, the function and mechanism of most KZNFs remain unclear. Here, we report that ZNF496, a KZNF family member, interacts with the DNA binding domain (DBD) of estrogen receptor alpha (ERα) via its C2H2 domain. This interaction decreases ERα binding to chromatin DNA and results in the repression of ERα transactivation, the selective suppression of ERα target genes, and ultimately in a reduction of ERα-positive cell growth in the presence of E2. An analysis of clinical data revealed that the downregulation of ZNF496 expression is observed only in ERα-positive and not in ERα-negative breast cancer tissues when compared with that in matched adjacent tissues. Lastly, we also observed that the downregulation of ZNF496 is associated with poor recurrence-free survival among patients with breast cancer. Collectively, our findings demonstrate that ZNF496 is a novel ERα-binding protein that acts as a target gene-specific ERα corepressor and inhibits the growth of ERα-positive breast cancer cells.

Graphical abstract

Unlabelled Image



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Sleep disturbances can be prospectively observed in patients with an inactive inflammatory bowel disease

Digestive Diseases and Sciences

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The gentamicin-collagen implant and the risk of distant metastases of rectal cancer following short-course radiotherapy and curative resection: The long-term outcomes of a randomized study

International Journal of Colorectal Disease

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Role of diagnostic preoperative upper gastrointestinal endoscopy in radiologically confirmed gastric volvulus

Digestive Diseases and Sciences

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Perioperative radiotherapy is an independent risk factor for major LARS: A cross-sectional observational study

International Journal of Colorectal Disease

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The incidence of colorectal cancer in patients with previously removed polyp(s): A cross-sectional study

Journal of Gastrointestinal Oncology

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Macroscopic serosal invasion and small tumor size as independent prognostic factors in stage IIA colon cancer

International Journal of Colorectal Disease

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Meta-analysis of the prognostic value of CpG island methylator phenotype in rectal cancer

International Journal of Colorectal Disease

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The prognostic value of tumour stroma ratio and tumour budding in stage II colon cancer. A nationwide population-based study

International Journal of Colorectal Disease

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Short- and long-term outcomes after colorectal anastomotic leakage is affected by surgical approach at reoperation

International Journal of Colorectal Disease

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Long-term follow-up of hepatic adenoma and adenomatosis: Analysis of size change on imaging with histopathological correlation

Clinical Radiology

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The 10 fundamental principles of lay resuscitation: Recommendations by the German Resuscitation Council

No abstract available

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Natural History of Barrett’s Esophagus

Abstract

Barrett's esophagus (BE) is a very common condition. We have obtained fairly profound knowledge of the natural history of this condition. This results from many cross-sectional and cohort studies, many describing patients undergoing long-term surveillance. Their consent to use their clinical data has improved our knowledge to the benefit of these same and other patients. The prevalence of BE increases with age both in men and in women. This increase starts at a younger age in men than in women. The incidence of high-grade dysplasia and cancer in BE depends on segment length, gender, and age. The latter two likely indicate the duration of the presence of BE in an individual patient. Other factors that influence the incidence of dysplasia and cancer are smoking behavior and use of certain medications such as PPIs, statins, and NSAIDs. Surveillance of BE and treatment of dysplasia can impact the incidence of and mortality due to esophageal adenocarcinoma. This is of major benefit to a subgroup of BE patients. The epidemiology and burden of disease ask for further efforts to develop targeted screening, surveillance, and intervention techniques in coming years.



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Clinical Guidelines Update on the Diagnosis and Management of Barrett’s Esophagus

Abstract

Barrett's esophagus is a condition in which metaplastic columnar epithelium replaces stratified squamous epithelium in the distal esophagus. This condition occurs due to chronic gastroesophageal reflux disease and is a risk factor for the development of esophageal adenocarcinoma. Multiple clinical guidelines have been published around the world in recent years to assist gastroenterologists in the management of these patients and have evolved as new data have become available. While some information such as surveillance technique has not drastically changed, there has been an evolution over the years in diagnostic criteria, screening and endoscopic therapy with a variety of subtle differences among the different guidelines. Herein, we highlight areas of agreement and disagreement on definitions, screening, surveillance, and treatment techniques among these guidelines for the optimal management of Barrett's esophagus patients.



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Are Gastric and Esophageal Metaplasia Relatives? The Case for Barrett’s Stemming from SPEM

Abstract

Chronic injury and inflammation in the esophagus can cause a change in cellular differentiation known as metaplasia. Most commonly, the differentiation changes manifest as Barrett's esophagus (BE), characterized by the normal stratified squamous epithelium converting into a cuboidal–columnar, glandular morphology. BE cells can phenotypically resemble specific normal cell types of the stomach or intestine, or they can have overlapping phenotypes in disorganized admixtures. The stomach can also undergo metaplasia characterized by aberrant gastric or intestinal differentiation patterns. In both organs, it has been argued that metaplasia may represent a recapitulation of the embryonic or juvenile gastrointestinal tract, as cells access a developmental progenitor genetic program that can help repair damaged tissue. Here, we review the normal development of esophagus and stomach, and describe how BE represents an intermixing of cells resembling gastric pseudopyloric (SPEM) and intestinal metaplasia. We discuss a cellular process recently termed "paligenosis" that governs how mature, differentiated cells can revert to a proliferating progenitor state in metaplasia. We discuss the "Cyclical Hit" theory in which paligenosis might be involved in the increased risk of metaplasia for progression to cancer. However, somatic mutations might occur in proliferative phases and then be warehoused upon redifferentiation. Through years of chronic injury and many rounds of paligenosis and dedifferentiation, eventually a cell with a mutation that prevents dedifferentiation may arise and clonally expand fueling stable metaplasia and potentially thereafter acquiring additional mutations and progressing to dysplasia and cancer.



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How Should We Report Endoscopic Results in Patient’s with Barrett’s Esophagus?

Abstract

Barrett's esophagus is the only known pre-cancerous lesion for esophageal adenocarcinoma and is diagnosed by high-definition white light endoscopy demonstrating a columnar-lined esophagus along with biopsy evidence of intestinal metaplasia. With accurate performance and reporting of the endoscopic procedure, an evidence-based management strategy can be developed for treatment of Barrett's dysplasia. However, cross-sectional data demonstrate that there is still inconsistency among gastroenterologists in performance and reporting of endoscopic findings in patients with Barrett's esophagus. Here, we present an evidence-based review of how to report endoscopic findings in Barrett's esophagus.



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A Goblet (Cell) Half Full: What Do We Really Know About Barrett’s Esophagus—A Tribute to Emmet Keeffe



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Origins of Metaplasia in the Esophagus: Is This a GE Junction Stem Cell Disease?

Abstract

The incidence of esophageal adenocarcinoma (EAC) and its precursor lesion Barrett's esophagus (BE) has been increasing steadily in the western world in recent decades. Understanding the cellular origins of BE and the conditions responsible for their malignant transformation would greatly facilitate risk assessment and identification of patients at risk of progression, but this topic remains a source of debate. Here, we review recent findings that have provided support for the gastroesophageal junction (GEJ) as the main source of stem cells that give rise to BE and EAC. These include both gastric cardia cells and transitional basal cells. Furthermore, we discuss the role of chronic injury and inflammation in a tumor microenvironment as a major factor in promoting stem cell expansion and proliferation as well as transformation of the GEJ-derived stem cells and progression to EAC. We conclude that there exists a large amount of empirical support for the GEJ as the likely source of BE stem cells. While BE seems to resemble a successful adaptation to esophageal damage, carcinogenesis appears as a consequence of natural selection at the level of GEJ stem cells, and later glands, that expand into the esophagus wherein the local ecology creates the selective landscape for cancer progression.



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Is Barrett’s-Associated Esophageal Adenocarcinoma a Clonal Disease?

Abstract

In this study, we argue that the basic clonal unit that makes up the Barrett's segment is at the level of the gland. There is expansion of this clonal unit, the gland, by fission, and there is evidence that the Barrett's segment is itself a clonal proliferation. Barrett's esophagus arises from both goblet cell-containing metaplasia and non-goblet cell-containing metaplasia and may arise from a stable clone, but the genomic changes occurring are subject to selection, usually with little or no evolution, appearing indolent from the evolutionary perspective. Genomic changes leading to dysplastic phenotypes are selected, but without any single clone predominating within the segment.



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Cardiac Metaplasia: Follow, Treat, or Ignore?

Abstract

Over the past two decades, evidence has accumulated to challenge the traditional view that cardiac mucosa, which is comprised exclusively of mucus glands, is the normal lining of the most proximal portion of the stomach (the gastric cardia). There is now considerable evidence to suggest that cardiac mucosa develops as a GERD-induced, squamous-to-columnar esophageal metaplasia in some, if not all, cases. Although cardiac mucosa lacks the goblet cells commonly required for a histologic diagnosis of intestinal metaplasia, cardiac mucosa has many molecular features of an intestinal-type mucosa, and appears to be the precursor of intestinal metaplasia with goblet cells. In apparently normal individuals, cardiac mucosa is commonly found in a narrow band, less than 3 mm in extent, on the columnar side of the squamo-columnar junction at the end of the esophagus. A greater extent of cardiac mucosa can be found in GERD patients, and the magnitude of that extent appears to be an index of GERD severity. Presently, the risk of adenocarcinoma imposed by cardiac mucosa is not clear, but appears to be far less than that of intestinal metaplasis with goblet cells. The British Society of Gastroenterology accepts an esophagus lined by cardiac mucosa as a "Barrett's esophagus". However, if one defines Barrett's esophagus as a metaplasia that predisposes to cancer, then only intestinal metaplasia clearly fulfills that criterion at this time. Well-designed, prospective studies are needed to establish the malignant potential of cardiac mucosa.



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Mucosal Ablation in Patients with Barrett’s Esophagus: Fry or Freeze?

Abstract

The management of Barrett's esophagus and early esophageal adenocarcinoma has shifted away from esophagectomy and toward endoscopic techniques, including endoscopic resection and ablative therapies. The most commonly used ablative therapies are radiofrequency ablation and cryotherapy. Radiofrequency ablation has risen to the top of the management algorithm due to its favorable safety profile and established track record of efficacy in patients with dysplastic Barrett's. Cryotherapy offers early promise as an alternatively safe and effective ablative modality. We review radiofrequency ablation and cryotherapy techniques, and updated data regarding their efficacy and safety as well as their roles in the management of Barrett's esophagus.



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Point–Counterpoint: Screening and Surveillance for Barrett’s Esophagus, Is It Worthwhile?

Abstract

The exponential rise in incidence of esophageal adenocarcinoma (EAC), paired with persistently poor survival, continues to drive efforts to improve and optimize screening and surveillance practices. While advancements in endoscopic therapy have generated a shift in management and significantly improved the outcomes of patients with early-stage EAC, the majority of prevalent EAC continues to be diagnosed at advanced stages, remaining ineligible for curative therapy. Barrett's esophagus (BE) screening, when applied to high-yield target populations, using minimally or noninvasive accurate tests, followed by endoscopic surveillance to detect prevalent or incident dysplasia/EAC (which can then be treated successfully) is the cornerstone of the current BE management paradigm. While supported by some empiric evidence and attractive, this approach faces a number of challenges, which are also balanced by numerous recent advances in these areas. In this manuscript, we review the rationale, supportive evidence, current challenges, and recent progress in BE screening and surveillance.



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Barrett’s Esophagus and Esophageal Adenocarcinoma: How Common Are They Really?

Abstract

Since the early 1970s, the incidence of esophageal adenocarcinoma (EA) has increased dramatically in most Western populations while the incidence of esophageal squamous cell carcinoma has decreased. As a result, EA has become the predominant subtype of esophageal cancer in North America and Europe and is an important contributor to overall cancer mortality. Barrett's esophagus (BE), a metaplastic columnar epithelium of the distal esophagus, is the known precursor lesion for EA. EA and BE occur more frequently in white men over 50 years old, as well as in people with frequent symptoms of gastroesophageal reflux, in smokers, and in people who are obese. Conversely, EA and BE are less common in persons using nonsteroidal anti-inflammatory drugs and in person with Helicobacter pylori infection. The 5-year survival rate for patients with EA, although generally poor, has improved during the past decade, and long-term survival is increasingly possible for patients with early or locally advanced disease. This review combines a synthesis of published studies with an analysis of data from the United States National Cancer Institute's Surveillance, Epidemiology, and End Results program to discuss the change in incidence of EA and summarize current knowledge of risk factors.



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Screening and Surveillance for Barrett’s Esophagus: Is It Cost-Effective?

Abstract

The cost-effectiveness of screening and surveillance for Barrett's esophagus continues to evolve as the incidence of esophageal adenocarcinoma increases, biomarkers enhance the identification of individuals at highest risk for developing cancer, and endoscopic eradication of Barrett's esophagus improves. Screening to detect Barrett's esophagus may be cost-effective in selected high-risk groups based on age, race, sex and other factors such as symptoms of heartburn. Currently, endoscopic eradication therapy for Barrett's esophagus and high-grade dysplasia is a cost-effective intervention, while endoscopic therapy for non-dysplastic Barrett's esophagus is not a cost-effective strategy. As diagnosis of low-grade dysplasia improves, endoscopic eradication therapy may also prove to be a cost-effective intervention.



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Management of Early-Stage Adenocarcinoma of the Esophagus: Endoscopic Mucosal Resection and Endoscopic Submucosal Dissection

Abstract

Barrett's esophagus with high-grade dysplasia and early-stage adenocarcinoma is amenable to curative treatment by endoscopic resection. Histopathological correlation has established that mucosal cancer has minimal risk of nodal metastases and that long-term complete remission can be achieved. Although surgery is the gold-standard treatment once there is submucosal involvement, even T1sm1 (submucosal invasion ≤ 500 μm) cases without additional risk factors for nodal metastases might also be cured with endoscopic resection. Endoscopic resection is foremost an initial diagnostic procedure, and once histopathological assessment confirms that curative criteria are met, it will be considered curative. Endoscopic resection may be achieved by endoscopic mucosal resection, which, although easy to perform with relatively low risk, is limited by an inability to achieve en bloc resection for lesions of size more than 1.5 cm. Conversely, the technique of endoscopic submucosal dissection is more technically demanding with higher risk of complications but is able to achieve en bloc resection for lesions larger than 1.5 cm. Endoscopic submucosal dissection would be particularly important in specific situations such as suspected submucosal invasion and lesion size more than 1.5 cm. In other situations, since endoscopic resection would always be combined with radiofrequency ablation to ablate the remaining Barrett's epithelium, piecemeal endoscopic mucosal resection would suffice since any remnant superficial invisible dysplasia would be ablated.



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Natural History of the Post-ablation Esophagus

Abstract

Endoscopic ablative therapy including radiofrequency ablation (RFA) represents the preferred management strategy for dysplastic Barrett's esophagus (BE) and appears to diminish the risk of developing esophageal adenocarcinoma (EAC). Limited data describe the natural history of the post-ablation esophagus. Recent findings demonstrate that recurrent intestinal metaplasia (IM) following RFA is relatively frequent. However, dysplastic BE and EAC subsequent to the complete eradication of intestinal metaplasia (CEIM) are uncommon. Moreover, data suggest that the risk of recurrent disease is probably highest in the first year following CEIM. Recurrent IM and dysplasia are usually successfully eradicated with repeat RFA. Future studies may refine surveillance intervals and inform the length of time surveillance should be conducted following RFA with CEIM. Further data will also be necessary to understand the utility of chemopreventive strategies, including NSAIDs, in reducing the risk of recurrent disease.



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Chemoprevention of Barrett’s Esophagus and Esophageal Adenocarcinoma

Abstract

Barrett's esophagus is common in Western countries, but progression to esophageal adenocarcinoma is uncommon. Chemoprevention therefore needs to consider whether benefits outweigh risks given an otherwise healthy population. This will depend on the particular population at risk and the relative safety of a potential preventive agent. Most evidence regarding the potential benefit of chemoprevention of Barrett's esophagus and prevention of progression to esophageal adenocarcinoma is based on observational studies such as case–control and cohort studies. Given the potential benefits and relatively low risks, patients with BE should receive once-daily PPI therapy, but routine use of twice-daily PPI is not recommended unless necessitated by poor control of reflux symptoms or esophagitis. Recent data suggest that the inverse associations between aspirin/NSAID use and esophageal adenocarcinoma may be the result of reducing neoplastic progression (from metaplasia to dysplasia and carcinoma) rather than initiation of Barrett's esophagus. While substantial associative data suggest a potential benefit of aspirin and nonaspirin NSAIDs in reducing the risk of progression of Barrett's esophagus, the low risk of progression and the potential risks (gastrointestinal bleeding, complicated ulcer disease, hemorrhagic stroke) do not warrant routine use, unless dictated by cardiovascular risk. Chemoprevention after mucosal ablation in those at highest risk of post-ablation recurrence (dysplastic Barrett's) is currently under investigation.



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Origins of Metaplasia in Barrett’s Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease?

Abstract

The incidence of esophageal adenocarcinoma has been increasing in Western countries over the past several decades. Though Barrett's esophagus, in which the normal esophageal squamous epithelium is replaced with metaplastic intestinalized columnar cells due to chronic damage from gastroesophageal reflux, is accepted as the requisite precursor lesion for esophageal adenocarcinoma, the Barrett's esophagus cell of origin and the molecular mechanism underlying esophageal epithelial metaplasia remain controversial. Much effort has been dedicated towards identifying the Barrett's esophagus cell of origin since this could lead to more effective prevention and treatment strategies for both Barrett's esophagus and esophageal adenocarcinoma. Previously, it was hypothesized that terminally differentiated esophageal squamous cells might undergo direct conversion into specialized intestinal columnar cells via the process of transdifferentiation. However, there is increasing evidence that stem and/or progenitor cells are molecularly reprogrammed through the process of transcommitment to differentiate into the columnar cell lineages that characterize Barrett's esophagus. Given that Barrett's esophagus originates at the gastroesophageal junction, the boundary between the distal esophagus and gastric cardia, potential sources of these stem and/or progenitor cells include columnar cells from the squamocolumnar junction or neighboring gastric cardia, native esophageal squamous cells, native esophageal cuboidal or columnar cells from submucosal glands or ducts, or circulating bone marrow-derived cells. In this review, we focus on native esophageal specific stem and/or progenitor cells and detail molecular mediators of transcommitment based on recent insights gained from novel mouse models and clinical observations from patients.



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Molecular Evolution of Metaplasia to Adenocarcinoma in the Esophagus

Abstract

Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a condition where the normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. In a minority of individuals, BE can progress to low- and high-grade dysplasia and eventually to intra-mucosal and then invasive carcinoma. BE provides researchers with a unique model to characterize the process by which a carcinoma arises from its precursor lesion. Molecular studies of BE have demonstrated that it is not simply a metaplastic tissue, but rather it harbors frequent alterations that are also present in dysplastic BE and in EAC. Both BE and EAC are characterized by loss of heterozygosity, aneuploidy, specific genetic mutations, and clonal diversity. Epigenetic abnormalities, primary alterations in DNA methylation, are also frequently seen in BE and EAC. Candidate gene and array-based approaches have demonstrated that numerous tumor suppressor genes exhibit aberrant promoter methylation, and some of these altered genes are associated with the neoplastic progression of BE. It has also been shown that the BE and EAC epigenomes are characterized by hypomethylation of intragenic and non-coding regions Recent studies have also provided new insight into the evolutionary forces underlying the molecular alterations seen in BE and EAC and into the molecular pathogenesis of EAC.



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Biomarkers of Barrett’s Esophagus: From the Laboratory to Clinical Practice

Abstract

The currently recommended approach to managing cancer risk for patients with Barrett's esophagus is endoscopic surveillance including a biopsy protocol to sample the esophageal tissue randomly to detect dysplasia. However, there are numerous limitations in this practice that rely on the histopathological grading of dysplasia alone to make clinical decisions. The availability of in silico models demonstrating the potential cost-effectiveness of biomarker-based stratification has increased interest in finding a clinically relevant "Barrett's biomarker." The success of endoscopic eradication therapy in preventing neoplastic progression of dysplastic Barrett's esophagus has promoted the desire to stratify non-dysplastic Barrett's esophagus to those with "high risk" that may benefit from endotherapy. Furthermore, on the other end of the spectrum, there is interest in searching for a "low risk" marker that may identify those that would not likely benefit from endoscopy screening or surveillance. This review highlights recent data from the genomics (r)evolution revealing new genetic biomarkers of susceptibility to the development of Barrett's esophagus and novel pathways for its neoplastic progression, addresses the development of new modes of tissue sampling and imaging to detect early neoplasia in Barrett's esophagus, and discusses current progress in moving biomarkers from the laboratory into clinical practice in the era of precision medicine.



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