bluuebunny/crossref_metadata_2025 huggingface dataset:
Informing Leadership Models
Authors: Toole Cheryl A. , DeGrazia Michele , Connor Jean Anne , Gauvreau Kimberlee , Kuzdeba Hillary Bishop , Hickey Patricia A.
Published: March 2018

Background

Neonatal intensive care units (NICUs) located in freestanding children’s hospitals may exhibit significant variation in nursing and organizational characteristics, which can serve as opportunities for collaboration to understand optimal staffing models and linkages to patient outcomes.

Objectives:

Adopting methods used by Hickey et al in pediatric cardiovascular critical care, the purpose of this study was to provide a foundational description of the nursing and organizational characteristics for NICUs located in freestanding children’s hospitals in the United States.

Methods

Clinical nurse leaders in NICUs located in freestanding children’s hospitals were invited to participate in an electronic cross-sectional survey. Descriptive analyses were used to summarize nursing and organizational characteristics.

Results

The response rate was 30% (13/43), with 69.2% of NICUs classified as level III/IV and 30.8% classified as level II/III. Licensed bed capacity varied significantly (range, 24-167), as did the proportion of full-time equivalent nurses (range, 71.78-252.3). Approximately three-quarters of staff nurses held baccalaureate degrees or higher. A quarter of nurses had 16 or more years (26.3%) of experience, and 36.9% of nurses had 11 or more years of nursing experience. Nearly one-third (29.2%) had 5 or less years of total nursing experience. Few nurses (10.6%) held neonatal specialty certification. All units had nurse educators, national and unit-based quality metrics, and procedural checklists.

Conclusion

This study identified (1) variation in staffing models signaling an opportunity for collaboration, (2) the need to establish ongoing processes for sites to participate in future collaborative efforts, and (3) survey modifications necessary to ensure a more comprehensive understanding of nursing and organizational characteristics in freestanding children’s hospital NICUs.
Effect of Valproate and Antidepressant Drugs on Clozapine Metabolism in Patients With Psychotic Mood Disorders
Authors: Marazziti Donatella , Palego Lionella , Betti Laura , Giannaccini Gino , Massimetti Enrico , Baroni Stefano , Ciapparelli Antonio , Lucacchini Antonio , Mucci Federico , Dell'Osso Liliana
Published: March 2018

Background:

The aim of the present study was to appraise retrospectively the influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma concentrations of clozapine (CLZ), the prototype of various second-generation antipsychotics, norclozapine (NCLZ, its main metabolite), and their ratio (NCLZ:CLZ).

Methods:

Sixty-seven psychotic patients with a prevalent diagnosis of bipolar disorder were studied. We then analyzed data altogether and subdivided them into 4 groups, according to pharmacological treatments: #1 CLZ (n = 21), #2 CLZ plus ADs (n = 13), #3 CLZ plus VPA (n = 16), and #4 CLZ plus ADs plus VPA (n = 17).

Results:

First, significant positive between CLZ and NCLZ plasma levels (in nanograms/milliliter) and the drug daily dosages (in milligrams/kilogram of body weight) (n = 67) were observed (Spearman: rCLZ = 0.49; rNCLZ = 0.61;P< 0.001). We then normalized by given doses CLZ and NCLZ plasma levels, natural log transformed them, and performed analysis of variance factor analyses followed by pairwise comparisons, performed on the 4 groups and the 3 CLZ parameters. We identified significant drug effects on (1) CLZ plasma levels, significantly higher in group #2 versus group #1, and (2) NCLZ:CLZ ratio, lower in group #2 versus groups #1 and #3. Significant drug × gender interactions were observed in group #3, showing higher NCLZ levels and NCLZ:CLZ ratios in men compared with women.

Conclusions:

Despite its inherent limitations, this observational study confirms the significant increase in plasma CLZ concentrations and reduction in NCLZ:CLZ ratio when this drug was coadministered with ADs (group #2), an effect apparently counteracted by VPA (group #4). The drug × gender interactions in patients taking both CLZ and VPA (group #3) warrant further prospective study.
The Association of Rehospitalization With Participation 5 Years After Traumatic Brain Injury
Authors: Erler Kimberly S. , Juengst Shannon B. , Whiteneck Gale G. , Locascio Joseph J. , Bogner Jennifer A. , Kaminski Jamie , Giacino Joseph T.
Published: March 2018

Objective:

To determine whether rehospitalization during the first 2 years after moderate to severe traumatic brain injury (TBI) is associated with poor participation at 5 years post-TBI, after controlling for demographic and severity factors.

Setting:

TBI Model Systems Program.

Participants:

Community-dwelling individuals with TBI, 16 years or older (n = 1940).

Design:

Retrospective data analysis of a multicenter prospective study.

Main Measures:

Participation Assessment with Recombined Tools-Objective (PART-O).

Results:

After controlling for demographic and severity factors, a general linear model indicated that rehospitalization status (ie, never rehospitalized during years 1 and 2, rehospitalized either during year 1 or 2, or rehospitalized during both years 1 and 2) predicted less participation at 5 years post-TBI (P = .0353). The PART-O scores were in the hypothesized direction, with the lowest covariate-adjusted mean participation score found for the group with rehospitalizations during both years and the highest covariate-adjusted mean participation score found in the group with no rehospitalizations. Examining total number of rehospitalizations during years 1 and 2, rather than rehospitalization status, yielded analogous results (P = .0148).

Conclusions:

This study suggests that rehospitalization in the first 2 years after TBI is negatively associated with participation at 5 years after injury. Since participation is considered a key indicator of successful TBI rehabilitation, minimizing the need for rehospitalizations and promoting health in the community setting should be a priority of postacute care for individuals with TBI.
Simplified Treatment of Possible Severe Bacterial Infection in Young Infants When Referral Is Not Feasible. What Happened There? What Are the Implications Here?
Authors: Hodgins Stephen
Published: March 2018

Severe bacterial infections remain one of the 3 leading causes of newborn death worldwide. Most such deaths could be prevented with timely and appropriate antibiotic treatment. However, in low-income countries, there are many such cases for which, practically speaking, it is not currently feasible to offer gold-standard, inpatient treatment with 7 days of parenteral antibiotics. Recent trial results, however, provide evidence for efficacy using simpler outpatient antibiotic regimens, equivalent to treatment with 7 days of procaine penicillin and gentamicin, given on an outpatient basis. Based on these findings, the World Health Organization has recently released guidelines endorsing such an approach for cases for which referral for inpatient treatment is not feasible. This brief report looks beyond the measured effect sizes in the published trials to other details on how they were implemented and what outcomes were observed for different groups of study participants. The report considers, further, the circumstances in country settings where such a strategy may be appropriate and offers issues for consideration by policy makers.
Campylobacter Concisus and Acute Gastroenteritis in Children
Authors: Tilmanne Anne , Martiny Delphine , Hallin Marie , Cornelius Angela , Wautier Magali , Quach Caroline , Lepage Philippe , Vandenberg Olivier
Published: March 2018

The role of Campylobacter concisus as a cause of acute gastroenteritis remains to be demonstrated. This prospective study includes 184 cases and 176 controls. It shows no evidence that C. concisus plays a role in acute gastroenteritis. Considering the very low prevalence in cases and controls, if there is an etiologic link, it would be moderate and difficult to demonstrate.
Safety, Effectiveness and Exposure-response of Micafungin in Infants
Authors: Rivera-Chaparro Nazario D. , Ericson Jessica , Wu Huali , Smith P. Brian , Clark Reese H. , Benjamin Daniel K. , Cohen-Wolkowiez Michael , Greenberg Rachel G.
Published: March 2018

Micafungin is used off-label in the United States to treat invasive candidiasis in neonates. We used an established pharmacokinetic model to determine micafungin exposures for 46 courses in 39 hospitalized infants. In this small cohort of infants, micafungin exposure was not associated with laboratory markers of liver toxicity, death or failure of microbiologic clearance.
Serum Levels of Syndecan-1 in Patients With Kawasaki Disease
Authors: Luo Li , Feng Siqi , Wu Yao , Su Ya , Jing Fengchuan , Yi Qijian
Published: March 2018

Background:

Kawasaki disease (KD) is an acute systemic vasculitis with coronary artery lesions (CALs) being the major concern. Syndecan-1 (SDC-1) is a major core protein expressed on the glycocalyx of endothelial cells. Shed SDC-1 in serum is regarded as a biomarker for endothelial activation or damage.

Methods:

In this study, we aimed to determine the serum levels of SDC-1 and evaluate the relationship between serum levels of SDC-1 and the CALs in the acute phase of KD. Serum SDC-1 levels were measured in 119 children with KD and in 43 healthy children as normal controls and in 40 children with febrile disease. All KD patients were administrated a single dose of intravenous immunoglobulin and aspirin per os within 10 days of KD onset.

Results:

Serum levels of SDC-1, in addition to albumin and hemoglobin, were significantly increased in patients with KD than in healthy controls and febrile controls. Furthermore, the serum levels of SDC-1, albumin and hemoglobin were significantly elevated in KD patients with CALs than those without CALs. Additionally, serum levels of SDC-1 were significantly correlated with levels of hemoglobin and serum albumin in patients with KD. After intravenous immunoglobulin therapy, serum levels of interleukin-6, soluble cell adhesion molecules-1 and resistin were reduced while serum levels of SDC-1 were significantly increased in KD patients.

Conclusions:

SDC-1 serum levels may mirror vascular endothelial damage and inflammation in KD. This might be utilized as a potential novel target for coronary artery protection in KD patients.
Longitudinal Association Between Human Parechovirus Central Nervous System Infection and Gross-Motor Neurodevelopment in Young Children
Authors: van Hinsbergh Ted M. T. , Elbers Roy G. , van Furth Marceline A. M. , Obihara Charlie C. C.
Published: March 2018

Background:

A paucity of studies investigated the association between human parechovirus (HPeV) central nervous system (CNS) infection and motor and neurocognitive development of children. This study describes the gross-motor function (GMF) in young children during 24 months after HPeV-CNS infection compared with children in whom no pathogen was detected.

Methods:

GMF of children was assessed with Alberta Infant Motor Scale, Bayley Scales of Infant and Toddler Development or Movement Assessment Battery for Children. We conducted multivariate analyses and adjusted for age at onset, maternal education and time from infection.

Results:

Of 91 included children, at onset <24 months of age, 11 had HPeV-CNS infection and in 47 no pathogen was detected. Nineteen children were excluded because of the presence of other infection, preterm birth or genetic disorder, and in 14 children, parents refused to consent for participation. We found no longitudinal association between HPeV-CNS infection and GMF (β = −0.53; 95% confidence interval: −1.18 to 0.07; P = 0.11). At 6 months, children with HPeV-CNS infection had suspect GMF delay compared with the nonpathogen group (mean difference = 1.12; 95% confidence interval: −1.96 to −0.30; P = 0.03). This difference disappeared during 24-month follow-up and, after adjustment for age at onset, both groups scored within the normal range for age. Maternal education and time from infection did not have any meaningful influence.

Conclusions:

We found no longitudinal association between HPeV-CNS infection and GMF during the first 24-month follow-up. Children with HPeV-CNS infection showed a suspect GMF delay at 6-month follow-up. This normalized during 24-month follow-up.
Heart Failure Self-care Within the Context of Patient and Informal Caregiver Dyadic Engagement
Authors: Buck Harleah G. , Hupcey Judith , Wang Hsiao-Lan , Fradley Michael , Donovan Kristine A. , Watach Alexa
Published: March 2018

Background:

Recent heart failure (HF) patient and informal caregiver (eg, dyadic) studies have either examined self-care from a qualitative or quantitative perspective. To date, the 2 types of data have not been integrated.

Objective:

The aim of this study was to understand HF self-care within the context of dyadic engagement.

Methods:

This was a cross-sectional, mixed methods (quantitative/qualitative) study. Heart failure self-care was measured with the Self-care of Heart Failure Index (v.6) dichotomized to adequate (≥70) or inadequate (<69). Dyadic symptom management type was assessed with the Dyadic Symptom Management Type scale. Interviews regarding self-care were conducted with both dyad members present. Content analytic techniques were used. Data were integrated using an information matrix and triangulated using Creswell and Plano Clark's methods.

Results:

Of the 27 dyads, HF participants were 56% men, with a mean age of 77 years. Caregivers were 74% women, with a mean age of 66 years, representing spouses (n = 14) and adult children (n = 7). Quantitatively, few dyads scored as adequate (≥70) in self-care; the qualitative data described the impact of adequacy on the dyads' behavior. Dyads who scored higher, individually or both, on self-care self-efficacy and self-care management were less likely to change from their life course pattern. Either the patient or dyad continued to handle all self-care as they always had, rather than trying new strategies or reaching out for help as the patient’s condition deteriorated.

Conclusions:

Our data suggest links that should be explored between dyadic adequacy and response to patients' symptoms. Future studies should assess dyadic adequacy longitudinally and examine its relationship to event-free survival and health services cost.
Quality of Life for Parents of Children With Congenital Heart Defect
Authors: Gregory Mary R. (Becky) , Prouhet Paula M. , Russell Cynthia L. , Pfannenstiel Brenda R.
Published: March 2018

Background:

As survival rates for infants born with severe forms of cardiac defects (congenital heart defect [CHD]) improve, attention is directed to evaluating factors that affect the child’s short- and long-term outcomes including parental quality of life (QOL).

Purpose:

The purpose of this review was to identify how parental QOL is affected when having a child with a CHD. Factors that influence parental QOL when having a child with a CHD will also be described.

Methods:

A systematic search of CINAHL, EMBASE, PsycINFO, and PubMed databases was performed. Thirty-three quantitative cross-sectional or cohort studies were selected for inclusion and analyzed for quality reporting using Strengthening the Reporting of Observational Studies in Epidemiology guidelines.

Results:

Heart defect severity, age of child, perceived support, and availability of economic resources were identified as factors affecting parental QOL. Parent gender was related to QOL and family functioning factors. Paternal outcomes were reported in 23 of the 33 studies (70%), with an average father participation rate of 40%.

Conclusions:

Having a child with CHD negatively affects parental QOL. Future research should include targeting fathers to improve understanding of their unique perceptions and needs. Longitudinal studies should also describe correlations of parental QOL with their child’s developmental outcomes. Efficacy studies testing supportive interventions on outcomes such as improved adjustment and QOL are needed.
User-centered Development of a Decision Aid for Patients Facing Implantable Cardioverter-Defibrillator Replacement
Authors: Lewis Krystina B. , Birnie David , Carroll Sandra L. , Clark Lorraine , Kelly Freya , Gibson Paul , Rockburn Lloyd , Rockburn Louise , Stacey Dawn
Published: March 2018

Background:

Because of battery depletion, an implantable cardioverter-defibrillator (ICD) generator requires surgical replacement every 5 to 7 years. Routine replacement is the norm without discussion with patients about whether or not to proceed.

Objective:

The aim of this study was to develop a patient decision aid (PDA) for patients facing ICD replacement and plan for its implementation.

Methods:

An embedded mixed-methods study was conducted using questionnaires and semistructured interviews focused on current ICD replacement practices; PDA acceptability, usability, and content; and PDA implementation. Transcripts were analyzed using constant comparative analysis.

Results:

Eighteen PDA end users in 16 interviews characterized the current ICD replacement approach as automatic without consideration for patient preferences. The PDA was positively received, and the content was iteratively revised 4 times during the interviews. Changes were related to missing and excess information, language, and wording. The PDA was identified as a means to support a shared decision-making (SDM) process, not to be used as a standalone instrument. To shift current practices to an SDM process, participants identified that an invitation to discuss the option of ICD replacement is required—whether initiated by the patient or the clinician.

Conclusion:

Currently, the option of ICD replacement is rarely offered, and patient preferences are seldom elicited. Participants believed the PDA to be a useful intervention that could help facilitate an SDM process for patients facing ICD replacement. Preparing for implementation during the development phase will allow us to strategize effectively to overcome perceived barriers and capitalize on perceived facilitators during actual implementation.
Clinical Trial of the Potassium Channel Activator Diazoxide for Major Depressive Disorder Halted Due to Intolerability
Authors: Kadriu Bashkim , Yuan Shiwen , Farmer Cristan , Nugent Allison C. , Lener Marc S. , Niciu Mark J. , Park Minkyung , Yazdian Aaron , Ballard Elizabeth D. , Henn Fritz A. , Henter Ioline D. , Park Lawrence T. , Zarate Carlos A.
Published: March 2018

Background

Some glutamatergic modulators have demonstrated rapid and relatively sustained antidepressant properties in patients with major depressive disorder. Because the potassium channel activator diazoxide increases glutamate uptake via potassium channel activation, we hypothesized that it might exert antidepressant effects by increasing the removal of glutamate from the synaptic cleft, thereby reducing excessive glutamate transmission.

Methods

This randomized, double-blind, placebo-controlled, crossover, single-site inpatient clinical study was conducted at the National Institute of Mental Health to assess the efficacy and safety of a 3-week course of diazoxide (200–400 mg daily, twice a day) versus a 3-week course of placebo in 6 participants with treatment-refractory major depressive disorder. The primary clinical outcome measure was change in Montgomery-Asberg Depression Rating Scale score from baseline to posttreatment. Quantitative insulin sensitivity check index, as well as concomitant imaging measures (electroencephalography, proton magnetic resonance spectroscopy, magnetoencephalography), were used as potential surrogate markers of target (KATP channel) engagement.

Results

The study was halted due to severe adverse effects. Given the small sample size, statistical evaluation of the effect of diazoxide on Montgomery-Asberg Depression Rating Scale scores or the imaging measures was not pursued. Visual inspection of the quantitative insulin sensitivity check index test revealed no evidence of target engagement.

Conclusions

Although the results are negative, they are an important addition to the literature in this rapidly changing field.
Risk Factors for Anal Dysplasia in Transgender Women: A Retrospective Chart Review
Authors: Fein Lydia A. , Rosa Cunha Isabella , Slomovitz Brian , Potter JoNell
Published: March 2018

Objective

The aim of the study was to assess risk factors for anal human papillomavirus (HPV) infection and anal dysplasia among a cohort of transgender women (TGW).

Methods

A retrospective chart review was conducted based on electronic medical records of TGW patients seen in the University of Miami Health System between 2010 and 2016. Outcome measures included risk factors of anal dysplasia, including HIV infection, receptive anal intercourse, and smoking history. Descriptive statistical analysis and χ2 testing were used.

Results

Sixty-nine TGW patients' charts were reviewed. Patients' ages ranged from 18 to 72 (mean = 38 [15]). Twenty-two (30%) were older than 50 years; 10 (15%) were black/African descent; 20 (29%) reported a smoking history; 6 (9%) were HIV positive, and 28 (72%) among those with known partner preference (n = 39) reported male partners. Male partner preference was significantly associated with being black/African descent (p = .009) and being single (p = .048). Older age was significantly associated with HIV-positive status (p = .023). The average number of risk factors per person was 2.10 (0.97). Sixty-one years or older had the highest average number of risk factors (2.90 [0.88]).

Conclusions

Because rates of HIV, dangerous sexual behaviors, and other risk factors for anal dysplasia continue to persist among TGW, this study reinforces the need to increase the focus on anal health in the care of TGW and the need for further research to guide patient care and anal dysplasia screening strategies among those individuals.
Esophageal pressure monitoring: why, when and how?
Authors: Yoshida Takeshi , Brochard Laurent
Published: March 2018

Purpose of review

Esophageal manometry has shown its usefulness to estimate transpulmonary pressure, that is lung stress, and the intensity of spontaneous effort in patients with acute respiratory distress syndrome. However, clinical uptake of esophageal manometry in ICU is still low. Thus, the purpose of review is to describe technical tips to adequately measure esophageal pressure at the bedside, and then update the most important clinical applications of esophageal manometry in ICU.

Recent findings

Each esophageal balloon has its own nonstressed volume and it should be calibrated properly to measure pleural pressure accurately: transpulmonary pressure calculated on absolute esophageal pressure reflects values in the lung regions adjacent to the esophageal balloon (i.e. dependent to middle lung). Inspiratory transpulmonary pressure calculated from airway plateau pressure and the chest wall to respiratory system elastance ratio reasonably reflects lung stress in the nondependent ‘baby’ lung, at highest risk of hyperinflation. Also esophageal pressure can be used to detect and minimize patient self-inflicted lung injury.

Esophageal manometry is not a complicated technique. There is a large potential to improve clinical outcome in patients with acute respiratory distress syndrome, acting as an early detector of risk of lung injury from mechanical ventilation and vigorous spontaneous effort.
Chapter 1. The Historical Roots of Paediatric Gastroenterology, Hepatology, and Nutrition
Authors: Weaver Lawrence T.
Published: March 2018

The last 50 years have seen the establishment of paediatric gastroenterology, hepatology, and nutrition (PGHAN) as a well‐recognised and thriving clinical specialty throughout most of Europe, and further afield. This has happened, in part, through the existence of the European Society for Paediatric Gastroenterology and Nutrition (ESPGHAN) as a forum for those interested in this branch of children's medicine. To illustrate the pan‐European roots of PGHAN, some key scientific and medical events, discoveries, and inventions relevant to 3 common clinical problems—diarrhoea, jaundice, and infant‐feeding—have been chosen to survey the historical development of the ways in which each was understood and treated within the changing thinking and practice of past times. Together they are used to trace the prehistory of ESPGHAN and provide a background against which to explain the genesis of the Society and how its spheres of clinical and scientific interest came to be defined.
Detection of Cytomegalovirus in Colonic Mucosa of Children With Inflammatory Bowel Disease
Authors: El‐Matary Wael , Stefanovici Camelia , Van Caeseele Paul , Deora Vini , McCurdy Jeff
Published: March 2018

Objectives:

Although it has been recommended to perform sigmoidoscopy to screen for cytomegalovirus (CMV) reactivation in acute severe colitis, the frequency of CMV reactivation in children with inflammatory bowel disease (IBD) is unknown. The aim of this study was to determine the frequency and management of CMV detection in colonic mucosa of children with IBD.

Methods:

In a retrospective study, consecutive IBD patients, <17 years old, with moderate to severe colitis who had sigmoid biopsy specimens evaluated for CMV by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and polymerase chain reaction (PCR) were included.

Results:

A total of 90 sigmoid biopsies were collected from 67 patient encounters from 58 patients with colitis: 61 patient encounters (91%) with UC/IBD‐U including biopsy samples from colectomy specimens of eight patients who had colectomy during the study period. Medication exposure included corticosteroids for 40 (69%) patients, and immunosuppressive agents for 31 (53.4%) patients. Four of 61 patient encounters (6.6%) with UC/IBD‐U, two with corticosteroid refractory disease, had positive biopsies for CMV by PCR but negative H&E and IHC. They responded to escalated medical therapy, without needing anti‐viral therapy, and none required colectomy over a median duration of follow up of 1.1 year (IQR 1–1.6).

Conclusions:

CMV presence is uncommon in colonic mucosa of children with IBD. Studies examining the underlying sero‐prevalence of CMV and its role of reactivation of colitis are required to determine if the current recommendation for routine sigmoidoscopy to exclude CMV infection in corticosteroid‐refractory acute severe colitis is justified.
The Membrane‐bound O‐Acyltransferase7 rs641738 Variant in Pediatric Nonalcoholic Fatty Liver Disease
Authors: Di Sessa Anna , Umano Giuseppina Rosaria , Cirillo Grazia , Del Prete Angela , Iacomino Roberta , Marzuillo Pierluigi , del Giudice Emanuele Miraglia
Published: March 2018

Background:

The rs641738 polymorphism in the membrane‐bound O‐acyltransferase domain containing protein 7 (MBOAT7) gene has been associated with increased risk of nonalcoholic fatty liver disease (NAFLD).

Objectives:

To investigate the association between the MBOAT7 rs641738 polymorphism and both hepatic steatosis and biochemical markers of liver damage and to evaluate the potential additive effect of this variant and the I148M patatin‐like phospholipase domain‐containing 3 (PNPLA3) and the rs58542926 transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms.

Methods:

One thousand and 2 obese children were genotyped for MBOAT7, PNPLA3, and TM6SF2 polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) and a genetic risk score from these polymorphisms were calculated.

Results:

Carriers of the MBOAT7 T allele showed both higher alanine transaminase (ALT) (P = 0.004) and PNFI values (P = 0.04) than noncarriers. These findings were confirmed also for the carriers of the MBOAT7 T allele polymorphism with hepatic steatosis compared with noncarriers. A higher genetic risk score was associated with higher ALT (P = 0.011) and with an odds ratio (OR) to show elevated ALT of 3.4 (95% CI 1.3–5.5, P = 0.003). Patients belonging to genetic risk score 3 group had an OR to present steatosis of 2.6 (95% CI 1.43–4.83, P = 0.0018) compared with those belonging to lower genetic risk score group.

Conclusions:

We first demonstrated in childhood obesity the role of the MBOAT7 rs641738 variant on serum ALT and the combined effect of the MBOAT7, PNPLA3, and TM6SF2 variants on NAFLD risk. We also provided the first pediatric association of the MBOAT7 polymorphism with indirect markers of liver fibrosis.
Gavage Feed Volume Determines the Gastric Emptying Rate in Preterm Infants
Authors: Ferreira Cristina H.F. , Martinez Francisco E. , Crott Gerson C. , Belik Jaques
Published: March 2018

Objective:

Feeding intolerance, manifesting as increased gastric residual, is a common finding in preterm neonates. Little is known about the regulation of gastric emptying early in life and the extent to which this plays a role in the preterm infants’ feeding tolerance. The goal of this study was to evaluate clinically stable 28‐ to 32‐week gestation neonates during the first 4 weeks of life and noninvasively determine their gastric emptying rate.

Study design:

Ultrasound measurements of gastric milk content volume were obtained from 25 neonates immediately after, 30 and/or 60 minutes following routine gavage feeds. The content emptying rate was calculated from the gastric volume data.

Results:

Gastric emptying rate was not postnatal age‐dependent, was significantly higher at 30 minutes, whenever compared with 60‐minute postfeed and directly proportional to the feed volume. At any postnatal age, the gastric emptying rate was at least 6‐fold greater, when comparing the lowest and highest average stomach content volumes.

Conclusions:

The gastric emptying rate of preterm infants is content volume‐dependent and unrelated to the postnatal age. Given the present findings, further investigation on the gastric residual of preterm infants receiving larger than currently administered feed volumes at the initiation of enteral nutrition, is warranted.
Thiopurine Optimization Through Combination With Allopurinol in Children With Inflammatory Bowel Diseases
Authors: Serpico Mark R. , Maltz Ross , Crandall Wallace , Bricker Josh , Dotson Jennifer L. , Kim Sandra C. , Boyle Brendan
Published: March 2018

Objectives:

Thiopurines are commonly used in the maintenance of remission for children with inflammatory bowel diseases (IBDs). Variation in drug metabolism may affect hepatotoxicity or therapeutic effect. We aimed to describe our center's experience with thiopurine optimization through the use of reduced thiopurine dosing in combination with allopurinol upon hepatotoxicity, drug metabolite levels, and clinical outcomes in children with IBD.

Methods:

Patients aged 2 to 21 years with IBD treated with the combination of thiopurines/allopurinol between 2008 and 2015 were retrospectively reviewed. Patients previously treated with antitumor necrosis factor therapy were excluded. Demographic data, transaminase levels (aspartate transaminase, alanine transaminase), drug metabolites levels (6‐thioguanine [6‐TG], 6‐methylmercaptopurine), physician global assessment, and corticosteroid use were recorded at baseline, 6, and 12 months.

Results:

Fifty‐two patients (29 girls, 56%) met inclusion criteria. Thirty‐two of 52 (62%) remained on the combination for 12 months. In those remaining on the thiopurine/allopurinol combination, median alanine transaminase and aspartate transaminase levels were reduced (P < 0.001) and median 6‐TG levels were increased (P < 0.001) at both 6 and 12 months. Corticosteroid use was decreased at both 6 (P < 0.001) and 12 months (P < 0.001) compared to use at baseline. Remission rates also improved at both 6 (P = 0.013) and 12 months (P = 0.003). Twenty of the 52 patients (38%) had discontinued the thiopurine/allopurinol combination within 12 months of initiation with 17 of 52 (33%) initiating antitumor necrosis factor therapy.

Conclusions:

Low‐dose thiopurines in combination with allopurinol improved hepatotoxicity and increased 6‐TG levels in children with IBD. Corticosteroid use was reduced and remission rates improved in those patients remaining on this combination for 1 year. However, approximately 40% of patients required a change in therapy within 12 months.
Brief Report: Differential Timing of Cholesterol Increase During Successful HCV Therapy: Impact of Type of Drug Combination
Authors: Rivero-Juarez Antonio , Camacho Angela , Brieva Teresa , Frias Mario , Lopez-Lopez Pedro , Risalde María A. , Machuca Isabel , Caston Juan J. , Martínez-Peinado Antonio , Rivero Antonio
Published: March 2018

Objective:

To evaluate factors associated with increased serum cholesterol levels during interferon-free hepatitis C virus (HCV) therapy.

Design:

Prospective longitudinal study.

Methods:

HIV-infected patients who started and successfully completed interferon-free therapy for chronic HCV infection were included. Patients were treated using 2 different regimens, based on the clinician's opinion: sofosbuvir and ledipasvir (SOF/LDV), or paritaprevir coadministered with ombitasvir and dasabuvir (PrOD). Both total cholesterol and low-density lipoprotein cholesterol were evaluated at baseline, weeks 1, 2, 4, 8, end of treatment (EOT), weeks SVR4, SVR12, and SVR24.

Results:

The study population therefore comprised 85 patients reaching sustained virological response, 42 (49.4%) of whom were treated with SOF/LDV, and 43 (50.6%) with PrOD. Patients using SOF/LDV was showed a higher increase on both total cholesterol and low-density lipoprotein cholesterol during treatment period than those receiving PrOD. Analyzing the overall increase from baseline to weeks 1, 2, 4, 8, and EOT, choice of HCV regimen was associated with differential increases in total cholesterol during therapy. After EOT, no differences were found between SOF/LDV and PrOD with respect to total cholesterol.

Conclusions:

Our study suggests that the differential timing of the restoration of cholesterol metabolism in HIV/HCV genotype 1 coinfected patients achieving sustained virological response is not mediated by HCV clearance but depends on the drug combination used.
Fast-Track Recovery Program After Major Liver Resection
Authors: Kapritsou Maria , Korkolis Dimitrios P. , Giannakopoulou Margarita , Kaklamanos Ioannis , Konstantinou Maria , Katsoulas Theodoros , Kiekkas Panagiotis , Konstantinou Evangelos A.
Published: March 2018

The objective of this study was to compare fast-track (FT) recovery protocol with the conventional one in patients treated with major liver resection by evaluating perioperative morbidity, length of hospitalization, and readmission rate. Sixty-two patients suffering from malignant liver tumors were surgically treated from May 2012 to April 2014. After randomization, they were prospectively divided into two groups: Group A patients (n = 32) followed FT recovery protocol and Group B patients (n = 30) were treated with the conventional (CON) protocol. Postoperative morbidity, readmission rate, and median hospital stay in the two groups were studied. Fast-track protocol was associated with a decreased complication (25%, p = .002), whereas the risk of postoperative morbidity was 2.4 times higher in patients treated with the CON protocol (60%, p = .002). Readmission rate was not significantly different between the two groups (6.25%, p = .35). Age (p = .382) and body mass index (p = .818) were not a suspending factor for following the FT protocol. Overall length of stay (postoperative days) in the FT group was (mean ± SD) 5.75 ± .5 and in the CON group was 13.5 ± 6.7 (p < .001). Fast-track recovery protocol seems to be safe and particularly efficient in patients undergoing major liver resections.
Normative Data for the Low Anterior Resection Syndrome Score (LARS Score)
Authors: Juul Therese , Elfeki Hossam , Christensen Peter , Laurberg Søren , Emmertsen Katrine J. , Bager Palle
Published: March 2018

Objective:

To provide normative data for the Low Anterior Resection Syndrome (LARS) score.

Background:

The LARS score is a validated and frequently used tool measuring bowel dysfunction after sphincter sparing surgery for rectal cancer. The interpretation of LARS score results has previously been limited by the lack of normative data.

Methods:

An age and sex-stratified random sample of 3440 citizens from the general population was drawn from the Danish civil registration system (age range 20–89 years, 50% females). A brief questionnaire including the LARS score and health-related items were distributed electronically or by post.

Results:

A total of 1875 (54.5%) responded, 54.0% were females. In the age group 50 to 79 years, relevant for most rectal cancer studies, the response rate was 70.5% (n = 807). In this specific age group, 18.8% of the females and 9.6% of the males had a LARS score ≥30, corresponding to the LARS score category “major LARS” (P = 0.001), and the median (interquartile range) LARS score was 16 (7–26) and 11 (4–22), respectively (P < 0.001). Responders with physical disease had a statistically significant higher risk of a LARS score ≥30, compared with responders without any physical disease (odds ratio 2.2, 95% confidence interval 1.6–2.9, P < 0.001).

Conclusions:

A LARS score ≥30 (major LARS) is common in the general population, especially in the age group 50 to 79 years. Normative data for the LARS score are now available and can be taken into account when interpreting LARS score results in scientific studies of bowel function after rectal cancer treatment.
High-throughput sequencing identification and characterization of potentially adhesion-related small RNAs in Streptococcus mutans
Authors: Zhu Wenhui , Liu Shanshan , Liu Jia , Zhou Yan , Lin Huancai
Published: March 2018

Purpose. Adherence capacity is one of the principal virulence factors of Streptococcus mutans, and adhesion virulence factors are controlled by small RNAs (sRNAs) at the post-transcriptional level in various bacteria. Here, we aimed to identify and decipher putative adhesion-related sRNAs in clinical strains of S. mutans.

Methodology. RNA deep-sequencing was performed to identify potential sRNAs under different adhesion conditions. The expression of sRNAs was analysed by quantitative real-time PCR (qRT-PCR), and bioinformatic methods were used to predict the functional characteristics of sRNAs.

Results. A total of 736 differentially expressed candidate sRNAs were predicted, and these included 352 sRNAs located on the antisense to mRNA (AM) and 384 sRNAs in intergenic regions (IGRs). The top 7 differentially expressed sRNAs were successfully validated by qRT-PCR in UA159, and 2 of these were further confirmed in 100 clinical isolates. Moreover, the sequences of two sRNAs were conserved in other Streptococcus species, indicating a conserved role in such closely related species. A good correlation between the expression of sRNAs and the adhesion of 100 clinical strains was observed, which, combined with GO and KEGG, provides a perspective for the comprehension of sRNA function annotation.

Conclusion. This study revealed a multitude of novel putative adhesion-related sRNAs in S. mutans and contributed to a better understanding of information concerning the transcriptional regulation of adhesion in S. mutans.
Discovery of directional chromatin-associated regulatory motifs affecting human gene transcription
Authors: Osato Naoki
Published: March 2018

Background

Chromatin interactions are essential in enhancer-promoter interactions (EPIs) and transcriptional regulation. CTCF and cohesin proteins located at chromatin interaction anchors and other DNA-binding proteins such as YY1, ZNF143, and SMARCA4 are involved in chromatin interactions. However, there is still no good overall understanding of proteins associated with chromatin interactions and insulator functions.

Results

Here, I describe a systematic and comprehensive approach for discovering DNA-binding motifs of transcription factors (TFs) that affect EPIs and gene expression. This analysis identified 96 biased orientations [64 forward-reverse (FR) and 52 reverse-forward (RF)] of motifs that significantly affected the expression level of putative transcriptional target genes in monocytes, T cells, HMEC, and NPC and included CTCF, cohesin (RAD21 and SMC3), YY1, and ZNF143; some TFs have more than one motif in databases; thus, the total number is smaller than the sum of FRs and RFs. KLF4, ERG, RFX, RFX2, HIF1, SP1, STAT3, and AP1 were associated with chromatin interactions. Many other TFs were also known to have chromatin-associated functions. The predicted biased orientations of motifs were compared with chromatin interaction data. Correlations in expression level of nearby genes separated by the motif sites were then examined among 53 tissues.

Conclusion

One hundred FR and RF orientations associated with chromatin interactions and functions were discovered. Most TFs showed weak directional biases at chromatin interaction anchors and were difficult to identify using enrichment analysis of motifs. These findings contribute to the understanding of chromatin-associated motifs involved in transcriptional regulation, chromatin interactions/regulation, and histone modifications.
Targeted Gene Bisulfite Sequencing Identifies Differential Methylation in p21
Authors: Kolli Ramya T. , Glenn Travis C. , Brown Bradley T. , Barnett Lillie M. , Lash Lawrence H. , Cummings Brian S.
Published: March 2018

Next-generation sequencing (NGS) methods are widely available to assess methylation of whole-genomes, reduced representation of genomes, and target capture of many loci, but simple, flexible, and low-cost methods are needed to leverage NGS for sequencing single-locus amplicons from large numbers of samples. We developed a two-stage PCR approach, targeted gene bisulfite sequencing (TGBS) which uses the Illumina MiSeq and Bismark bisulfite mapper, to assess site specific changes in methylation of the cyclin-dependent kinase inhibitor p21 (CDKN1a) after exposure to a DNA methyltransferase inhibitor, 5-aza-2’-deoxycytidine (5-Aza) and determine the differences between human and rat p21 methylation. TGBS analysis of human embryonic kidney cells (HEK293) and human proximal tubular cells (hPT) demonstrated variation at a known methylation sensitive site (SIE-1), but not in rat kidney cells. Treatment of cells with 5-Aza altered the methylation of this site in correlation with increased p21 protein expression. We also found that human and rat p21 promoter sequences differ considerably in the amount of basal DNA methylation. These data showed the utility of TGBS for rapid analysis of DNA methylation of specific loci. We provide links to a ready-to-run Virtualbox that includes the program and commands for methylation analysis of bisulfite datasets, including step-by-step directions.
1-Methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one
Authors: El Hafi Mohamed , Lahmidi Sanae , Boulhaoua Mohammed , Ramli Youssef , Essassi El Mokhtar , Mague Joel T.
Published: March 2018

The title molecule, C6H6N4O, is essentially planar [dihedral angle between the rings = 0.46 (9)°]. The crystal structure consists of sheets of molecules lying parallel to (-111) formed by a combination of N—H...O, C—H...O and C—H...H hydrogen bonds. The sheets are connected through π–π stacking interactions.
4-(1H-Indol-3-yl)-2,6-bis(pyrazin-2-yl)pyridine
Authors: Wang Jianwei , Yuan Caixia
Published: March 2018

In the title compound, C21H14N6, the pyridine ring and two pyrazine rings are nearly coplanar [dihedral angles = 2.03 (7) and 1.60 (7)°], while the dihedral angle between the indole ring system and the pyridine ring is 29.04 (6)°. In the crystal, molecules are linked by N—H...N hydrogen bonds, which generate [-110] chains. The packing is consolidated by C—H...N hydrogen bonds and aromatic π–π stacking, generating a three-dimensional network.
Does the use of honorific appellations in audit reports connote higher financial misstatement risk? Evidence from China
Authors: Chen Feng , Du Xingqiang , Lai Shaojuan , Ma Mary
Published: March 2018

Purpose

From the sociolinguistic perspective, the purpose of this paper is to examine whether the honorific and actual-name appellations that Chinese auditors use to address clients in audit reports connote differential financial misstatement risk. Specifically, the authors hypothesize that auditors’ use of honorifics signals their inferior social status relative to their clients, thereby leading to compromised auditor independence, lower audit quality, and higher financial misstatement risk.

Design/methodology/approach

The authors use a sample of manually coded appellation data from audit reports of Chinese public firms between 2003 and 2012 to conduct the research.

Findings

The authors find significantly greater financial misstatements, both in terms of likelihoods and magnitudes, for companies addressed by honorifics than for those addressed by actual names. Moreover, compared to auditors’ consistent honorific usage, discretionary honorific usage has a stronger positive association with misstatements. The authors further show that the positive association between honorific usage and client misstatement risk weakens when the audit firm is a Top 10 accounting firms in China, is an industry specialist, is formed as a partnership, or resides in a more concentrated audit market.

Originality/value

This study contributes to the sociolinguistics literature in accounting and provides evidence supporting the reform proposed by the International Auditing and Assurance Standards Board to enhance the usefulness of audit reporting.
The impact of pyramid ownership on earnings management
Authors: Mindzak Justin , Zeng Tao
Published: March 2018

Purpose

Unlike firms listed in the USA, many large firms in Canada belong to business groups organized as pyramids. A pyramidal structure refers to a business group that consists of a set of enterprises or other entities and displays a top-down chain of control. The purpose of this paper is to investigate the relationship between pyramid ownership and earnings management.

Design/methodology/approach

The paper is an empirical study using a sample of 165 Canadian listed firms from 2010 to 2015. The impact of pyramid ownership on both accrual-based and real earnings management is examined.

Findings

The findings show that pyramid-affiliated firms engage in less accrual-based and real earnings management than non-pyramid-affiliated firms. The results further show that the divergence between control rights and cash flow rights of the controlling shareholders in the pyramid-affiliated firms is positively related to real earnings management. Moreover, the results highlight that intra-group transactions (other than internal financing) among pyramid-affiliated firms lead to higher level of both accrual-based and real earnings management, but internal financing is negatively associated with real earnings management. Overall, this study provides the evidence which indicates that pyramid ownership structure and earnings management are related to each other.

Originality/value

The paper contributes to the earnings management literature by studying the impact of pyramid ownership structure on earnings management, especially real earnings management.