bluuebunny/crossref_metadata_2025 huggingface dataset:
Celiac Diasease–associated lncRNA Named HCG14 Regulates NOD1 Expression in Intestinal Cells
Authors: Santin Izortze , Jauregi‐Miguel Amaia , Velayos Teresa , Castellanos‐Rubio Ainara , Garcia‐Etxebarria Koldo , Romero‐Garmendia Irati , Fernandez‐Jimenez Nora , Irastorza Iñaki , Castaño Luis , Bilbao Jose Ramón
Published: March 2018

Objective:

The aim of the study is to identify additional celiac disease associated loci in the major histocompatibility complex (MHC) independent from classical HLA risk alleles (HLA‐DR3‐DQ2) and to characterize their potential functional impact in celiac disease pathogenesis at the intestinal level.

Methods:

We performed a high‐resolution single‐nucleotide polymorphism (SNP) genotyping of the MHC region, comparing HLA‐DR3 homozygous celiac patients and non‐celiac controls carrying a single copy of the B8‐DR3‐DQ2 conserved extended haplotype. Expression level of potential novel risk genes was determined by RT‐PCR in intestinal biopsies and in intestinal and immune cells isolated from control and celiac individuals. Small interfering RNA‐driven silencing of selected genes was performed in the intestinal cell line T84.

Results:

MHC genotyping revealed 2 associated SNPs, one located in TRIM27 gene and another in the non‐coding gene HCG14. After stratification analysis, only HCG14 showed significant association independent from HLA‐DR‐DQ loci. Expression of HCG14 was slightly downregulated in epithelial cells isolated from duodenal biopsies of celiac patients, and eQTL analysis revealed that polymorphisms in HCG14 region were associated with decreased NOD1 expression in duodenal intestinal cells.

Conclusions:

We have successfully employed a conserved extended haplotype‐matching strategy and identified a novel additional celiac disease risk variant in the lncRNA HCG14. This lncRNA seems to regulate the expression of NOD1 in an allele‐specific manner. Further functional studies are needed to clarify the role of HCG14 in the regulation of gene expression and to determine the molecular mechanisms by which the risk variant in HCG14 contributes to celiac disease pathogenesis.
Proton Pump Inhibitors and Infant Pneumonia/Other Lower Respiratory Tract Infections
Authors: Blank Mei‐Ling , Parkin Lianne , Zeng Jiaxu , Barson David
Published: March 2018

Objective:

The possible association between the use of proton pump inhibitors (PPIs) and community‐acquired pneumonia (CAP) or another lower respiratory tract infection (LRTI) remains uncertain. We conducted a nested case‐control study using routinely collected national health and drug dispensing data in New Zealand to examine the risk of CAP or another LRTI resulting in hospitalization or death in infants dispensed a PPI.

Study Design:

The cohort included 21,991 patients without a history of CAP or another LRTI who were born between 1 January 2005 and 31 December 2012 and were dispensed omeprazole, lansoprazole, or pantoprazole (the PPIs available in New Zealand during the study period) on at least one occasion during the first year of life. Cases had a first diagnosis after cohort entry (first PPI dispensing) of CAP (n = 65) validated by hospital discharge letter or death record, and chest radiography; or LRTI (including CAP) (n = 566) validated by hospital discharge letter or death record, with or without chest radiography. Up to 10 controls, matched by sex and date of birth, were randomly selected for each case. We conducted complete case analyses for the fully adjusted models.

Results:

In the adjusted analysis based on CAP cases and their controls, the matched odds ratio for current versus past use of PPIs was 0.88 (95% confidence interval 0.36–2.16). For all LRTI cases and their controls, the matched odds ratio was 1.13 (0.87–1.48).

Conclusion:

In otherwise healthy community‐dwelling infants, current use of a PPI does not appear to increase the risk of CAP or other LRTIs.
Communicating Nutrition and Other Science: It’s a Management Issue
Authors: Rowe Sylvia B. , Alexander Nick
Published: March 2018

Health, nutrition, and other science communicators, for some time, have been frustrated over the inability or reluctance of policy makers and significant portions of the public to accept scientific messages around topics such as nutrition, obesity, biotechnology, genetic, vaccine, and climate science, as well as other controversial topics of public interest. To date, experts in communication have relied on their experience in developing best practices to overcome antiscience doubts and deliver accurate scientific messages. The National Academies of Science has endorsed a new approach. More than a year ago, the National Academies of Science launched a rigorous project to identify research gaps and ultimately to formulate best guidance for science communicators, particularly in communicating around controversial issues. The present article explores interim findings presented at a November 2017 conference on the Science of Science Communication.
Sudden Unexpected Death in Epilepsy
Authors: Ellis Steven P. , Szabó Charles Ákos
Published: March 2018

Epilepsy is a common neurological disorder associated with increased morbidity and mortality, including premature death from different causes. Sudden unexpected death in epilepsy, or SUDEP, is one of the most common causes of death in people with epilepsy and originally brought to light by medical examiners. It accounts for 5% to 30% of all deaths in individuals with epilepsy and up to 50% in individuals with medically refractory epilepsy. It is commonly associated with a history of generalized tonic-clonic seizures and may be mitigated by other electroclinical risk factors, such as postictal electroencephalographic suppression, prone position, altered heart rate variability, conduction abnormalities, gender, or antiepileptic medications, to name a few. More recently, potential neuroimaging biomarkers have also been identified. Still, despite the increased mortality risk in people with epilepsy due to SUDEP, little is known about its underlying pathophysiology. The pathogenesis is likely to be multifactorial, resulting in neurogenic pulmonary edema or, in some cases, fatal cardiac arrhythmias. Medical examiners can provide an important role in our understanding of the magnitude of the problem and ongoing research into the underlying mechanisms. In this review, we discuss diagnostic criteria, incidence, risk factors, and current theories regarding the pathophysiology of SUDEP.
Electronic Medical Record in the ED
Authors: Franco Marleny , Baird Janette , Brown Linda L. , Overly Frank L.
Published: March 2018

Objectives

The aims of this study were to describe current practices in nursing documentation of trauma and medical resuscitations across emergency departments (EDs) and explore physicians' and nurses' perceptions of electronic medical record (EMR) use for nursing documentation of resuscitations.

Methods

An anonymous Web-based survey was developed and distributed to a convenience sample of ED physicians and nurses in the United States.

Results

Of 438 respondents, 154 were nurses; 97.2% of respondents reported that their EDs use EMR generally. Of those, 51.2% use EMR to document resuscitations. When describing documentation processes, 19% (95% confidence interval [CI], 15%–23%) reported direct documentation on EMR, 18% (95% CI, 14%–21%) reported documenting on paper before transferring to EMR, and 22% (95% CI, 18%–26%) reported simultaneously documenting on EMR and paper. Thirty-seven percent of respondents reported that the “documentor” frequently performs other tasks during resuscitations. Few nurses (39.6%) and physicians (26.4%) perceived EMR as more efficient than paper. Nurses (66.2%) and physicians (51.8%) perceived paper as more complete than EMR. Few nurses (31.6%) and physicians (25.6%) agreed that paper would facilitate continuity of care better than EMR. No associations between nurses' perceptions of EMR, professional experience, or technology use were found.

Conclusions

Although EMR adoption was common among respondents, only half reported using EMR to document resuscitations. Even fewer reported documenting directly on EMR, whereas a significant proportion reported processes that may be inefficient, redundant, or prone to errors. Respondents endorsed mostly negative perceptions of EMR. Our findings suggest that there may be factors inherent to resuscitations and the existing EMR interfaces that render documenting resuscitations on EMR uniquely challenging.
Adolescent Sexual Behavior and Emergency Department Use
Authors: Weisman Julie , Chase Alyse , Badolato Gia M. , Teach Stephen J. , Trent Maria E. , Chamberlain James M. , Goyal Monika K.
Published: March 2018

Objectives

The objective of this study was to determine whether adolescents in emergency departments (EDs) who report engaging in high-risk sexual behaviors are less likely to identify a primary care provider (PCP) and more likely to access the ED than their sexually inexperienced peers.

Methods

This was a secondary analysis of adolescents presenting to a pediatric ED with non–sexually transmitted infection (STI)–related complaints who completed surveys to assess sexual behavior risk and health care access. We measured differences in self-reported PCP identification, preferential use of the ED, and number of ED visits over a 12-month period by sexual experience. Secondary outcomes included clinician documented sexual histories and STI testing.

Results

Of 758 patients meeting inclusion criteria, 341 (44.9%) were sexually experienced, and of those, 129 (37.8%) reported engaging in high-risk behavior. Participants disclosing high-risk behavior were less likely to identify a PCP (adjusted odds ratio, 0.5; 95% confidence interval [CI], 0.3–0.9), more likely to prefer the ED for acute care issues (adjusted odds ratio, 1.6; 95% CI, 1.0–2.6), and had a higher rate of ED visits (adjusted relative risk, 1.2; 95% CI, 1.0–1.3) compared with sexually inexperienced peers. Among patients disclosing high-risk behavior, 10.9% had clinician-documented sexual histories and 2.6% underwent STI testing.

Conclusion

Adolescents who reported engaging in high-risk sexual behaviors were less likely to identify a PCP, as well as more likely to prefer ED-based care and make more ED visits. However, ED clinicians infrequently obtained sexual histories and performed STI testing in asymptomatic youth, thereby missing opportunities to screen high-risk adolescents who may lack access to preventive care.
Intimate Partner Violence Educational Materials in the Acute Care Setting
Authors: Randell Kimberly A. , Sherman Ashley , Walsh Irene , O'Malley Donna , Dowd Mary Denise
Published: March 2018

Objectives

This study aimed to determine acceptability of intimate partner violence (IPV) materials and effect of the materials on caregiver attitudes toward IPV screening.

Methods

We used an anonymous computerized survey to assess approval of IPV materials and screening, and willingness to disclose IPV in response to screening among mothers bringing a child to an urban pediatric emergency department or 2 suburban pediatric urgent care centers affiliated with a free-standing academic children's hospital. We compared responses between participants recruited before and after display of the IPV materials, as well as between subgroups, using χ2 tests.

Results

A total of 522 participated (predisplay, n = 261; postdisplay, n = 261). More subjects in the postdisplay group approved of display of IPV materials in pediatric emergency department/urgent care center restrooms (94% pre vs 98% post, P = 0.04) and examination rooms (94% pre vs 98% post, P = 0.01). We found no differences in acceptability of IPV screening between the pre and post groups (73% pre and post, P = 0.92). Willingness to disclose IPV in response to screening was higher in the postdisplay group for those with a personal IPV history (55% pre, 73% post; P = 0.02), African Americans (60% pre, 78% post; P = 0.02), and those with a high school degree or less education (66% pre, 77% post; P = 0.04).

Conclusions

Intimate partner violence materials in this study were acceptable to most participants and did not negatively impact attitudes toward IPV screening or willingness to disclose IPV. Display of IPV materials should be considered as a component of IPV intervention.
Rising Clinical Burden of Psychiatric Visits on the Pediatric Emergency Department
Authors: Nadler Ariella , Avner Deena , Khine Hnin , Avner Jeffrey R. , Fein Daniel M.
Published: March 2018

Objective

The mental health epidemic in pediatrics has resulted in a growing clinical burden on the health care system, including pediatric emergency departments (PED). Our objective was to describe the changing characteristics of visits to an urban PED, in particular length of stay, for emergency psychiatric evaluations (EPEs) over a 10-year period.

Methods

A retrospective study of children with an EPE in the PED at a large urban quaternary care children's hospital was performed during two discrete periods a decade apart: July 1, 2003–June 30, 2004 (period 1) and July 1, 2013–June 30, 2014 (period 2). Visit information, including length of stay and demographic data, were compared between groups.

Results

There was a significant increase in the percentage of PED visits for EPE from period 1 to period 2 (1.1% vs 2.2% P < 0.0001). Overall, the median (interquartile range [IQR]) length of stay for children requiring an EPE increased significantly for all visits (5.3 [3.2–15.4] hours vs 17.0 [6.0–26.0] hours, P < 0.0001), including for patients who were admitted (17.8 [7.4–24.6] hours vs 27.0 [21.0–36.0] hours, P < 0.0001) and for those who were discharged (4.5 [2.8–7.7] hours vs 8 [5–20] hours, P < 0.0001).

Conclusions

Over a decade, the percentage of children with an EPE has doubled, with a significant increase in the amount of time spent in the PED. This highlights a continued surge in the utilization of PED resources for EPE.
Liquid Biopsies and Cancer Immunotherapy
Authors: Thompson Jonathan R. , Menon Smitha P.
Published: March 2018

Cancer immunotherapy has recently undergone rapid advances and has become an integral part of the treatment armamentarium in various malignancies. However, tissue-based biomarker development in this arena has been slow, and valid biomarker identification to guide immunotherapeutic management is desperately needed. “Liquid” or blood-based biopsies potentially offer more convenient and efficient means to judge the immune milieu of individual patients and identify who will benefit most from immunotherapy. The following review highlights the current literature regarding the application of liquid biopsies to cancer immunotherapy.
Future of Liquid Biopsies With Growing Technological and Bioinformatics Studies: Opportunities and Challenges in Discovering Tumor Heterogeneity With Single-Cell Level Analysis
Authors: Ramalingam Naveen , Jeffrey Stefanie S.
Published: March 2018

Liquid biopsy provides minimally invasive and readily obtainable access to tumor-associated biological material in blood or other body fluids. These samples provide important insights into cancer biology, such as primary tumor heterogeneity; real-time tumor evolution; response to therapy, including immunotherapy; and mechanisms of cancer metastasis. Initial biological materials studied were circulating tumor cells and circulating nucleic acids, including circulating tumor DNA and microRNAs; more recently, studies have expanded to investigate extracellular vesicles, such as exosomes, microvesicles, and large oncosomes; tumor-derived circulating endothelial cells; and tumor-educated platelets. Even with an ongoing ambitious investment effort to develop liquid biopsy as an early cancer detection test in asymptomatic individuals, current challenges remain regarding how to access and analyze rare cells and tumor-derived nucleic acids in cancer patients. Technologies and associated bioinformatics tools are continuously evolving to capture these rare materials in an unbiased manner and to analyze them with high confidence. After first presenting recent applications of liquid biopsy, this review discusses aspects affecting the field, including tumor heterogeneity, single-cell analyses, and associated computational tools that will shape the future of liquid biopsy, with resultant opportunities and challenges.
Plastic Surgery Complications from Medical Tourism Treated in a U.S. Academic Medical Center
Authors: Ross Kimberly M. , Moscoso Andrea V. , Bayer Lauren R. , Rosselli-Risal Liliana , Orgill Dennis P.
Published: March 2018

Background:

Medical tourism is a growing, multi–billion dollar industry fueled by improvements in the global transportation infrastructure. The authors studied patients living in the United States who travel to other countries for plastic surgical procedures and returned to have their complications treated in the authors’ center.

Methods:

A retrospective patient evaluation was performed. Patients who had presented to an urban tertiary academic hospital plastic surgery service with complications or complaints associated with plastic surgery performed in a developing country were studied. The authors collected demographic information, types of surgery performed, destinations, insurance coverage, and complications.

Results:

Seventy-eight patients were identified over 7 years. Most commonly, complications were seen following abdominoplasty (n = 35), breast augmentation (n = 25), and foreign body injections (n = 15). Eighteen patients underwent multiple procedures in one operative setting. The most common destination country was the Dominican Republic (n = 59). Complications included surgical-site infections (n = 14), pain (n = 14), and wound healing complications (n = 12). Eighty-six percent of patients (n = 67) relied on their medical insurance to pay for their follow-up care or manage their complications, with the most common type of health insurance coverage being Massachusetts Medicaid (n = 48).

Conclusions:

Cosmetic surgery performed in developing countries can carry substantial risks of complications that can be challenging to patients, primary care providers, insurers, and plastic surgical teams not associated with the original surgery. These complications pose significant burdens on our public health systems.
Outcome of Palate Re-repair with Radical Repositioning of the Levator Muscle Sling as a First-Line Strategy in Postpalatoplasty Velopharyngeal Incompetence Management Protocol
Authors: Elsherbiny Ahmed , Amerson Meghan , Sconyers Laura , Grant John H.
Published: March 2018

Background:

Palatal re-repair aims to improve velar function by retropositioning the levator muscles. Although it has become a popular procedure, very few studies document its efficacy. To date, this is the largest series reported to clarify its indications and efficacy.

Methods:

One hundred eighty-three consecutive cleft patients presenting with velopharyngeal incompetence and evidence of abnormally oriented levator muscles underwent palate re-repair (regardless of the gap size) performed by a single surgeon from 2000 to 2015. Perceptual speech assessment was performed using the Pittsburgh Weighted Speech Score. Other patients’ demographic data were collected.

Results:

Complete records of 111 patients were available. Eighteen cases were syndromic (18.9 percent). Postoperatively, there was highly significant improvement (p < 0.001) in nasal emission (from 2.24 to 0.64), nasality (from 3.44 to 1.27), articulation (from 5.32 to 2.01), and total score (from 11.29 to 4.11). Speech became normal/borderline normal, improved or did not improve in 66.7, 24.3, and 9 percent of patients, respectively. An initial diagnosis of isolated cleft palate, Caucasians, intravelar veloplasty in the primary repair, older patients, and nonsyndromic cases were associated with better outcome. There were no reported cases of postoperative fistula or new obstructive sleep apnea.

Conclusions:

This large series study provides confirmatory evidence of the effectiveness and safety of the re-repair procedure. It is recommended as a first-line procedure in all velopharyngeal incompetence cases with abnormally oriented levator muscles regardless of gap size, even if the primary operation included prior muscle dissection. The pharyngoplasty rate could be significantly reduced with the current protocol.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Surgical Approach to Injuries of the Cervical Plexus and Its Peripheral Nerve Branches
Authors: Brown David L. , Dellon A. Lee
Published: March 2018

Background:

Located in the neck beneath the sternocleidomastoid muscle, the cervical plexus comprises a coalition of nerves originating from C1 through C4, which provide input to four cutaneous, seven motor, and three cranial nerves and the sympathetic trunk. Sporadic instances of injury to these superficial nerves have been reported. Nevertheless, this specific anatomical cause of neurogenic pain remains incompletely described and underrecognized.

Methods:

Twelve patients presented with pain and were diagnosed with various combinations of injury to the lesser occipital, great auricular, transverse cervical, and supraclavicular nerves. Inciting events included prior face lift, migraine, and thoracic outlet procedures; and traumatic events including seatbelt trauma, a fall, and a clavicular fracture. History and examination suggested injury to the cervical plexus, and nerve blocks confirmed the diagnoses. Neurectomy with intramuscular transposition was performed for three nerve branches in one patient, two branches in two patients, and one branch in the remaining nine patients.

Results:

Nine of the twelve patients had complete relief of their cervical plexus–related pain. The three failures were in patients with pain after previous face-lift surgery. Residual perception of neck tightness and choking sensation persisted despite relief of cheek and ear pain.

Conclusions:

Knowledge of the cervical plexus anatomy and its branches is crucial for surgeons operating in this area to minimize iatrogenic nerve injury. In addition, neuromas should be considered a likely cause of pain and dysesthesia following surgery or injury. Proper diagnosis and surgical intervention can have a significantly positive effect on these debilitating problems.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Comparison of Cartilage-Scoring and Cartilage-Sparing Otoplasty: A Retrospective Analysis of Complications and Aesthetic Outcome of 1060 Ears
Authors: Smittenberg Marije N. , Marsman Martijn , Veeger Nic J. G. M. , Moues Chantal M.
Published: March 2018

Background:

Various techniques are used to correct prominent ears. The authors describe their experience with four different otoplasty techniques in 565 patients with congenital deformities of the ears (1060 ears) that were performed in their hospital during an 11-year period (2002 to 2012).

Methods:

The authors divided the techniques into two groups: group I, cartilage-sparing techniques (i.e., IA, Mustardé; and IB, Furnas); and group II, cartilage-cutting techniques (i.e., IIA, Chongchet; and IIB, concha shell reduction). The authors compared early and late and minor and major complications, recurrence rates, and revision surgery. Furthermore, aesthetic outcome was scored by three different groups (consultant plastic surgeons, plastic surgery residents, and laymen) on a visual analogue scale using a blinded random selection of preoperative and postoperative photographs.

Results:

The percentage of complications without the need for reoperation was 20 percent and 21 percent in the cartilage-sparing and cartilage-cutting groups, respectively (p = 0.44). In 6 percent of all cases, a reoperation of the otoplasty was required (7 percent and 6 percent in the cartilage-sparing and cartilage-cutting groups, respectively). Aesthetic postoperative results showed that the cartilage-cutting group scored significantly lower on postoperative shape (p = 0.04), result (p = 0.03), and satisfaction (p = 0.04) compared with the cartilage-sparing group.

Conclusions:

The study shows that patients who have undergone operations with cartilage-sparing or cartilage-cutting techniques have a similar rate of complications and need for reoperation. However, the cartilage-sparing techniques have a better aesthetic outcome, as judged by the different groups.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Factors Affecting Women’s Success in Academic and Private Practice Plastic Surgery
Authors: Shah Amita R. , Haws Melinda J. , Kalliainen Loree K.
Published: March 2018

Because plastic surgery trainees generally spend the majority of their training in academic centers and may have minimal exposure to other practice models, it can be difficult to decide which is the best route to achieve satisfaction and success. Surgeons need to be aware of benefits and challenges associated with different practice models and with workplace factors in general that contribute to happiness at work. This article reviews common practice models and provide specific and practical advice for the female surgeon.
Female Cosmetic Genital Surgery
Authors: Hamori Christine A. , Stuzin James M.
Published: March 2018

Female cosmetic genital surgery is rapidly gaining popularity. Patient demand is increasing, and female cosmetic genital surgery is becoming a subspecialty of plastic surgery. Two predominant techniques exist in labia minora reduction: edge trim and wedge resection. Dr. Hamori prefers the wedge resection for most clinical situations. This video vignette clearly describes aesthetic analysis, marking, and technical execution for an extended wedge procedure. Patient safety and the management of patient expectations are emphasized.
Sientra AlloX2 Short-Term Case Study, Surgical Pearls, and Roundtable Discussion
Authors: Zeidler Kamakshi R. , Capizzi Peter J. , Pittman Troy A.
Published: March 2018

Background:

The AlloX2 Breast Tissue Expander (Sientra, Santa Barbara, Calif.) is a unique device that contains a second port to allow for transdermal communication with the pocket around the implant. The injection dome of this expander contains two ports; one is used for traditional saline injection, and a new second port facilitates fluid drainage from the periprosthetic space through an integral drain. The AlloX2 allows for the treatment of seromas and diagnostic fluid sampling to identify bacteria and hone antibiotic treatment in the setting of periprosthetic infection. This device has a significant advantage over traditional expanders, given that seromas and infections are the most common complications in implant-based breast reconstruction, with or without the use of soft-tissue support matrix.

Methods:

This article provides short-term case studies and surgical pearls from 3 surgeons who utilize the AlloX2 in primary breast reconstruction patients. Three surgeons implanted 40 primary reconstruction patients with AlloX2. Follow-up was approximately 6 months, per the standard of care. All patients implanted with AlloX2 underwent immediate reconstruction, with the exception of 1 delayed reconstruction.

Results:

The most common complications the patients experienced were seromas. In most cases, the surgeons successfully used the second port to drain periprosthetic fluid.

Conclusions:

The AlloX2 has been successful in treating seromas and should be considered a tool for noninvasive treatment of common complications of implant-based breast reconstruction. Three surgeons with varied backgrounds and techniques provide their surgical and postoperative management experiences and recommendations.
Characteristics of Volunteer Coaches in a Clinical Process Improvement Program
Authors: Morley Katharine E. , Barysauskas Constance M. , Carballo Victoria , Kalibatas Orinta , Rao Sandhya K. , Jacobson Joseph O. , Cummings Brian M.
Published: March 2018

Introduction:

The Partners Clinical Process Improvement Leadership Program provides quality improvement training for clinicians and administrators, utilizing graduates as volunteer peer coaches for mentorship. We sought to understand the factors associated with volunteer coach participation and gain insight into how to improve and sustain this program.

Methods:

Review of coach characteristics from course database and survey of frequent coaches.

Results:

Out of 516 Partners Clinical Process Improvement Leadership Program graduates from March 2010 to June 2015, 117 (23%) individuals volunteered as coaches. Sixty-one (52%) individuals coached once, 31 (27%) coached twice, and 25 (21%) coached 3 or more times. There were statistically significant associations between coaching and occupation (P = .005), Partners Clinical Process Improvement Leadership Program course taken (P = .001), and course location (P = .007). Administrators were more likely to coach than physicians (odds ratio: 1.75, P = .04). Reasons for volunteering as a coach included further development of skills, desire to stay involved with program, and enjoying mentoring. Reasons for repeated coaching included maintaining quality improvement skills, expanding skills to a wider variety of projects, and networking.

Conclusions:

A peer graduate volunteer coach model is a viable strategy for interprofessional quality improvement mentorship. Strategies that support repeat coaching and engage clinicians should be promoted to ensure an experienced and diversified group of coaches.
Out of Asia: the independent rise and global spread of fluoroquinolone-resistant Shigella
Authors: Chung The Hao , Baker Stephen
Published: March 2018

Shigella are ranked among the most prevalent aetiologies of diarrhoeal disease worldwide, disproportionately affecting young children in developing countries and high-risk communities in developed settings. Antimicrobial treatment, most commonly with fluoroquinolones, is currently recommended for Shigella infections to alleviate symptoms and control disease transmission. Resistance to fluoroquinolones has emerged in differing Shigella species (S. dysenteriae, flexneri and sonnei) since the turn of the 21st century, originating in endemic areas, and latterly spreading into non-endemic regions. Despite occurring independently, the emergence of fluoroquinolone resistance in these different Shigella species shares striking similarities regarding their epidemiology and resistance mechanisms. Here, we review and discuss the current epidemiology of fluoroquinolone-resistant Shigella species, particularly in the light of recent genomic insights.
National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB): Outline and Patient-Matching Technique
Authors: Shinichiro Kubo , Tatsuya Noda , Tomoya Myojin , Yuichi Nishioka , Tsuneyuki Higashino , Hiroki Matsui , Genta Kato , Tomoaki Imamura
Published: March 2018

Background

The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) is a comprehensive database of health insurance claims data under Japan’s National Health Insurance system. The NDB uses two types of personal identification variables (referred to in the database as “ID1” and “ID2”) to link the insurance claims of individual patients. However, the information entered against these ID variables is prone to change for several reasons, such as when claimants find or change employment, or due to variations in the spelling of their name. In the present study, we developed a new patient-matching technique that improves upon the existing system of using ID1 and ID2 variables. We also sought to validate a new personal ID variable (ID0) that we propose in order to enhance the efficiency of patient matching in the NDB database.

Methods

Our study targeted data from health insurance claims filed between April 2013 and March 2016 for hospitalization, combined diagnostic procedures, outpatient treatment, and dispensing of prescription medication. We developed a new patient-matching algorithm based on the ID1 and ID2 variables, as well as variables for treatment date and clinical outcome. We then attempted to validate our algorithm by comparing the number of patients identified by patient matching with the current ID1 variable and our proposed ID0 variable against the estimated patient population as of 1 October 2015.

Results

The numbers of patients in each sex and age group that were identified with the ID0 variable were lower than those identified using the ID1 variable. By using the ID0 variable, we were able to reduce the number of duplicate records for male and female patients by 5.8% and 6.4%, respectively. The numbers of children, adults older than 75 years, and women of reproductive age identified using the ID1 patient-matching variable were all higher than their corresponding estimates. Conversely, the numbers of these patients identified with the ID0 patient-matching variable were all within their corresponding estimates.

Conclusion

Our findings show that the proposed ID0 variable delivers more precise patient-matching results than the existing ID1 variable. The ID0 variable is currently the best available technique for patient matching in the NDB database. Future patient population estimates should therefore rely on the ID0 variable instead of the ID1 variable.
Herd Immunity to Ebolaviruses is not a Realistic Target for Current Vaccination Strategies
Authors: Masterson Stuart G. , Lobel Leslie , Carroll Miles W. , Wass Mark N. , Michaelis Martin
Published: March 2018

The recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R0, i.e. the number of secondary cases that result from an individual infection). Published R0 values were determined by a systematic literature research and ranged from 0.37 to 20. R0s ≥4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R0, the herd immunity threshold (Ic) was calculated using the equation Ic=1–(1/R0). The critical vaccination coverage (Vc) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation Vc=Ic/E. At an R0 of 4, the Ic is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/ logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health care workers, potentially in combination with ring vaccination approaches.
Characterizing Subpopulations with Better Response to Treatment Using Observational Data – an Epilepsy Case Study
Authors: Ozery-Flato Michal , El-Hay Tal , Aharonov Ranit , Parush-Shear-Yashuv Naama , Goldschmidt Yaara , Borghs Simon , Chan Jane , Haddad Nassim , Pierre-Louis Bosny , Kalilani Linda
Published: March 2018

Electronic health records and health insurance claims, providing observational data on millions of patients, offer great opportunities, and challenges, for population health studies. The objective of this study is identifying subpopulations that are likely to benefit from a given treatment using observational data. We refer to these subpopulations as “better responders” and focus on characterizing these using linear scores with a limited number of variables. Building upon well-established causal inference techniques for analyzing observational data, we propose two algorithms that generate such scores for identifying better responders, as well as methods for evaluating and comparing these scores. We applied our methodology to a large dataset of ~135,000 epilepsy patients derived from claims data. Out of this sample, 85,000 were used to characterize subpopulations with better response to next-generation (“Newer”) anti-epileptic drugs (AEDs), compared to an alternative treatment by first-generation (“Older”) AEDs. The remaining 50,000 epilepsy patients were then used to evaluate our scores. Our results demonstrate the ability of our scores to identify large subpopulations of epilepsy patients with significantly better response to newer AEDs.
RecurrentAIPL1c.487C>T truncating variant in Leber Congenital Amaurosis: Support of pathogenicity and regional implications
Authors: Abdallah Mohammed O.E. , Koko Mahmoud E. , Faisal Shima , Newport Melanie J. , Ibrahim Muntaser E.
Published: March 2018

Background

Leber Congenital Amaurosis (LCA) is a clinically and genetically heterogeneous inherited retinal dystrophy characterized by early onset visual impairment caused by mutations in not less than 17 genes.AIPL1mutations cause LCA type 4, comprising approximately 7% of LCA worldwide. The importance of establishing a genetic diagnosis lies in the promise of gene therapy demonstrated in mouse models.

Results

we genetically investigated a consanguineous Sudanese family with Leber Congenital Amaurosis. Eight members of the family were affected. Using whole exome sequencing in two siblings and their healthy mother, both inheritance-based and phenotype-based prioritization strategies converged to identify a truncating variant (rs62637009) inAIPL1, consistent with a diagnosis of LCA type 4.AIPL1c.487C>T is an ultra-rare cause of LCA4 that was seen previously in homozygous state in a single Palestinian family. This recurrent variant seems to have a regional importance with a likely founder effect.

Conclusions

This report adds evidence to the pathogenicity ofAIPL1c.487C>T meriting its conclusive annotation as a recurrent pathogenic variant. This variant is particularly relevant to the middle-eastern and northeast African regions.
Systematic genetic mapping of necroptosis identifies SLC39A7 as modulator of death receptor trafficking
Authors: Fauster Astrid , Rebsamen Manuele , Willmann Katharina L. , César-Razquin Adrian , Girardi Enrico , Bigenzahn Johannes W. , Schischlik Fiorella , Scorzoni Stefania , Bruckner Manuela , Konecka Justyna , Hörmann Katrin , Heinz Leonhard X. , Boztug Kaan , Superti-Furga Giulio
Published: March 2018

Regulation of cell and tissue homeostasis by programmed cell death is a fundamental process with wide physiological and pathological implications. The advent of scalable somatic cell genetic technologies creates the opportunity to functionally map these essential pathways, thereby identifying potential disease-relevant components. We investigated the genetic basis underlying necroptotic cell death by performing a complementary set of loss- and gain-of-function genetic screens. To this end, we establishedFADD-deficient haploid human KBM7 cells, which specifically and efficiently undergo necroptosis after a single treatment with either TNFα or the SMAC mimetic compound birinapant. A series of unbiased gene-trap screens identified key signaling mediators, such as TNFR1, RIPK1, RIPK3, and MLKL. Among the novel components, we focused on the zinc transporter SLC39A7, whose knock-out led to necroptosis resistance by affecting TNF receptor trafficking and ER homeostasis. Orthogonal, solute carrier (SLC)-focused CRISPR/Cas9-based genetic screens revealed the exquisite specificity of SLC39A7, among ~ 400 SLC genes, for TNFR1- and FAS-but not TRAIL-R1-mediated responses. The newly established cellular model also allowed genome-wide gain-of-function screening for genes conferring resistance to necroptosis via the CRISPR/Cas9synergistic activation mediator approach. Among these, we found cIAP1 and cIAP2, and characterized the role of TNIP1 (TNFAIP3-interacting protein 1), which prevented pathway activation in a ubiquitin-binding dependent manner. Altogether, the gain- and loss-of-function screens described here provide a global genetic chart of the molecular factors involved in necroptosis and death receptor signaling, prompting investigation of their individual contribution and potential role in pathological conditions.
Functional Deficits are Explained by Plantarflexor Remodeling Following Achilles Tendon Rupture Repair: Preliminary Findings
Authors: Baxter Josh R. , Hullfish Todd J. , Chao Wen
Published: March 2018

Achilles tendon ruptures are painful injuries that often lead to long-term functional deficits. Despite the prevalence of these injuries, the mechanism responsible for limited function has not yet been established. Therefore, the purpose of this study was to present preliminary findings that support a hypothesis that skeletal muscle remodeling is the driving factor of poor outcomes in some patients. Biomechanical and ultrasonography assessments were performed on a patient that presented with poor functional outcomes 2.5 years after a surgically-repaired acute Achilles tendon rupture. Single-leg heel raise function was decreased by 70% in the affected limb while walking mechanics showed no deficits. Ultrasonography revealed that the affected limb had shorter, more pennated, and less thick medial gastrocnemius muscles compared to the unaffected limb. A simple computational model of a maximal-effort plantarflexion contraction was employed to test the implications of muscle remodeling on single-leg heel raise function. Subject-specific fascicle length and pennation measurements explained deficits in ankle work and power that strongly agreed with experimentally measured values using motion capture. These preliminary findings support the hypothesis that skeletal muscle goes extensively remodels in response to a ruptured tendon, which reduces the amount of work and power the joint can generate. This multidisciplinary framework of biomechanical, imaging, and computational modeling provides a unique platform for studying the complex interactions between structure and function in patients recovering from Achilles tendon injuries.
IL-33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization
Authors: He Zhengxiang , Chen Lili , Furtado Glaucia C. , Lira Sergio A.
Published: March 2018

IL-33 is a cytokine found in the extracellular space (mature IL-33) or in the cell nucleus (full-length IL-33). Nuclear accumulation of IL-33 has been reported in intestinal epithelial cells (IEC) during intestinal inflammation and cancer, but a functional role for this nuclear form remains unclear. To study the role of nuclear IL-33inIEC, we generated transgenic mice expressing full-length IL-33inthe intestinal epithelium (Vfl33mice). Expression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33. Over-expression of full-length IL-33 by IEC did not promote gut inflammation, but induced expression of genes in the IEC and lamina propria lymphocytes (LPL) that correlated negatively with genes expressed in inflammatory bowel diseases (IBD). Because the IL-33 receptor ST2 is expressed by IEC, there was the potential that both the mature and full-length forms could mediate this effect. To specifically interrogate the transcriptional role of nuclear IL-33,weintercrossed theVfl33mice with ST2-deficient mice. ST2 deficiency completely abrogated the transcriptional effects elicited by IL-33 expression, suggesting that the transcriptional effects of IL-33 on IEC are mediated by its mature, not its nuclear form.

Highlights

Expression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33.

Full-length IL-33 induced differential gene expression in IEC and LPL that was negatively associated with intestinal inflammatory diseases

IL-33 regulated gene expression in IEC via its extracellular (mature) form not via its nuclearform.
Multi ‘omics comparison reveals metabolome biochemistry, not microbiome composition or gene expression, corresponds to elevated biogeochemical function in the hyporheic zone
Authors: Graham Emily B. , Crump Alex R. , Kennedy David W. , Arntzen Evan , Fansler Sarah , Purvine Samuel O. , Nicora Carrie D. , Nelson William , Tfaily Malak M. , Stegen James C.
Published: March 2018

Biogeochemical hotspots are pervasive at terrestrial-aquatic interfaces, particularly within groundwater-surface water mixing zones (hyporheic zones), and they are critical to understanding spatiotemporal variation in biogeochemical cycling. Here, we use multi ‘omic comparisons of hotspots to low-activity sediments to gain mechanistic insight into hyporheic zone organic matter processing. We hypothesized that microbiome structure and function, as described by metagenomics and metaproteomics, would distinguish hotspots from low-activity sediments through a shift towards carbohydrate-utilizing metabolic pathways and elucidate discrete mechanisms governing organic matter processing in each location. We also expected these differences to be reflected in the metabolome, whereby hotspot carbon (C) pools and metabolite transformations therein would be enriched in sugar-associated compounds. In contrast to expectations, we found pronounced phenotypic plasticity in the hyporheic zone microbiome that was denoted by similar microbiome structure, functional potential, and expression across sediments with dissimilar metabolic rates. Instead, diverse nitrogenous metabolites and biochemical transformations characterized hotspots. Metabolomes also corresponded more strongly to aerobic metabolism than bulk C content only (explaining 67% vs. 42% of variation), and bulk C did not improve statistical models based on metabolome composition alone. These results point to organic nitrogen as a significant regulatory factor influencing hyporheic zone organic matter processing. Based on our findings, we propose incorporating knowledge of metabolic pathways associated with different chemical fractions of C pools into ecosystem models will enhance prediction accuracy.