bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atorvastatin, but not pravastatin, inhibits cardiac Akt/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes
Authors: Godoy Joseph C. , Niesman Ingrid R. , Busija Anna R. , Kassan Adam , Schilling Jan M. , Schwarz Anna , Alvarez Erika A. , Dalton Nancy D. , Drummond John C. , Roth David M. , Kararigas Georgios , Patel Hemal H. , Zemljic-Harpf Alice E. 
Published: August 2018

ABSTRACTStatins, which reduce LDL‐cholesterol by inhibition of 3‐hydroxy‐3‐methylglutaryl–coenzyme A reductase, are among the most widely prescribed drugs. Skeletal myopathy is a known statin‐induced adverse effect associated with mitochondrial changes. We hypothesized that similar effects would occur in cardiac myocytes in a lipophilicity‐dependent manner between 2 common statins: atorvastatin (lipophilic) and pravastatin (hydrophilic). Neonatal cardiac ventricular myocytes were treated with atorvastatin and pravastatin for 48 h. Both statins induced endoplasmic reticular (ER) stress, but only atorvastatin inhibited ERK1/2T202/Y204, AktSer473, and mammalian target of rapamycin signaling; reduced protein abundance of caveolin‐1, dystrophin, epidermal growth factor receptor, and insulin receptor‐β; decreased Ras homolog gene family member A activation; and induced apoptosis. In cardiomyocyte‐equivalent HL‐1 cells, atorvastatin, but not pravastatin, reduced mitochondrial oxygen consumption. When male mice underwent atorvastatin and pravastatin administration per os for up to 7 mo, only long‐term atorvastatin, but not pravastatin, induced elevated serum creatine kinase; swollen, misaligned, size‐variable, and disconnected cardiac mitochondria; alteration of ER structure; repression of mitochondria‐ and endoplasmic reticulum–related genes; and a 21% increase in mortality in cardiac‐specific vinculin‐knockout mice during the first 2 months of administration. To our knowledge, we are the first to demonstrate in vivo that long‐term atorvastatin administration alters cardiac ultrastructure, a finding with important clinical implications.——Godoy, J. C., Niesman, I. R., Busija, A.R., Kassan, A., Schilling, J. M., Schwarz, A., Alvarez, E. A., Dalton, N. D., Drummond, J. C., Roth, D.M., Kararigas, G., Patel, H. H., Zemljic‐Harpf, A. E. Atorvastatin, but not pravastatin, inhibits cardiac Akt/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes. FASEB J. 33, 1209–1225 (2019). www.fasebj.org
Complicated appendicitis and considerations for interval appendectomy
Authors: Perez Kelly Sue , Allen Steven R. 
Published: August 2018

ABSTRACT
Acute appendicitis is one of the most common surgical emergencies. Of the 300,000 appendectomies performed each year, 25% are due to complicated appendicitis. This article reviews the incidence and pathophysiology of acute appendicitis, the nonoperative management of complicated appendicitis, and the rationales for and against interval appendectomy.
Burnout, job satisfaction, and stress levels of PAs
Authors: Coplan Bettie , McCall Timothy C. , Smith Noël , Gellert Vivienne L. , Essary Alison C. 
Published: August 2018

ABSTRACT

Objective:
The main goal of this study was to assess burnout, job satisfaction, and stress to gain insight into the work lives of female and male PAs.

Methods:
Data were obtained from the 2016 American Academy of PAs salary survey. Descriptive statistics were used to assess questions related to burnout, happiness, and stress and to compare responses by sex.

Results:
Analysis revealed that, in general, PAs experience modest levels of burnout but are happy at work. More than half (55.6%) rated spending too many hours at work as an important contributor to stress. A higher percentage of female PAs than male PAs (32.2% versus 25.6%) have quit a job due to stress.

Conclusions:
Overall, PAs rate aspects of work life favorably. Further research on factors that contribute to the PA work experience may help inform interventions aimed at improving job satisfaction among healthcare professionals.
Attending Follow-up Appointments After Pediatric Traumatic Brain Injury: Caregiver-Perceived Barriers and Facilitators
Authors: Lever Kimberly , Peng Jin , Lundine Jennifer P. , Caupp Sarah , Wheeler Krista K. , Sribnick Eric A. , Xiang Henry 
Published: August 2018

Objective:
To examine barriers and facilitators for follow-up care of children with traumatic brain injury (TBI).

Setting:
Urban children's hospital.

Participants:
Caregivers of children (aged 2-18 years) discharged from an inpatient unit with a TBI diagnosis in 2014-2015.

Design:
Survey of caregivers.

Main Measures:
Caregiver-reported barriers and facilitators to follow-up appointment attendance.

Results:
The sample included 159 caregivers who completed the survey. The top 3 barriers were “no need” (38.5%), “schedule conflicts” (14.1%), and “lack of resources” (10.3%). The top 5 identified facilitators were “good hospital experience” (68.6%), “need” (37.8%), “sufficient resources” (35.8%), “well-coordinated appointments” (31.1%), and “provision of counseling and support” (27.6%). Caregivers with higher income were more likely to report “no need” as a barrier; females were less likely to do so. Nonwhite caregivers and those without private insurance were more likely to report “lack of resources” as a barrier. Females were more likely to report “good hospital experience” and “provision of counseling and support” as a facilitator. Nonwhite caregivers were more likely to report “need” but less likely to report “sufficient resources” as facilitators.

Conclusions:
Care coordination, assistance with resources, and improvements in communication and the hospital experience are ways that adherence might be enhanced.
Cognitive Rehabilitation With Mobile Technology and Social Support for Veterans With TBI and PTSD: A Randomized Clinical Trial
Authors: Elbogen Eric B. , Dennis Paul A. , Van Voorhees Elizabeth E. , Blakey Shannon M. , Johnson Jacqueline L. , Johnson Sally C. , Wagner H. Ryan , Hamer Robert M. , Beckham Jean C. , Manly Tom , Belger Aysenil 
Published: August 2018

Objective:
To investigate effects of cognitive rehabilitation with mobile technology and social support on veterans with traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD).

Participants:
There were 112 dyads, comprised by a veteran and a family member or friend (224 participants in total).

Design:
Dyads were randomized to the following: (1) a novel intervention, Cognitive Applications for Life Management (CALM), involving goal management training plus mobile devices for cueing and training attentional control; or (2) Brain Health Training, involving psychoeducation plus mobile devices to train visual memory.

Main Measures:
Executive dysfunction (disinhibition, impulsivity) and emotional dysregulation (anger, maladaptive interpersonal behaviors) collected prior to randomization and following intervention completion at 6 months.

Results:
The clinical trial yielded negative findings regarding executive dysfunction but positive findings on measures of emotion dysregulation. Veterans randomized to CALM reported a 25% decrease in anger over 6 months compared with 8% reduction in the control (B = −5.27, P = .008). Family/friends reported that veterans randomized to CALM engaged in 26% fewer maladaptive interpersonal behaviors (eg, aggression) over 6 months compared with 6% reduction in the control (B = −2.08, P = .016). An unanticipated result was clinically meaningful change in reduced PTSD symptoms among veterans randomized to CALM (P < .001).

Conclusion:
This preliminary study demonstrated effectiveness of CALM for reducing emotional dysregulation in veterans with TBI and PTSD.
Correlation of Demarcation Line Depth With Medium-Term Efficacy of Different Corneal Collagen Cross-Linking Protocols in Keratoconus
Authors: Mesen Ali , Bozkurt Banu , Kamis Umit , Okudan Suleyman 
Published: August 2018

Purpose:
To compare demarcation line depth (DD) and topographic changes among different corneal collagen cross-linking (CXL) protocols and to evaluate the relation of DD with medium-term efficacy of CXL in halting progression of keratoconus.

Methods:
The study included 124 patients (mean age 19 ± 4.8 years) with progressive keratoconus who underwent conventional (3 mW/cm2/30 min), accelerated (18 mW/cm2/5 min), or transepithelial (TE) CXL (3 mW/cm2/30 min) and followed up for at least 2 years. Baseline and final corneal topographic parameters and DD determined with anterior segment optical coherence tomography 1 month after CXL were compared among the protocols and the correlation between DD and topographic changes at the end of 24 months was analyzed. P < 0.05 was considered as statistically significant.

Results:
Mean DD was significantly higher in the conventional and accelerated groups (335.19 ± 71.13 μm and 304.97 ± 94.45 μm, respectively) compared with the TE group (239.92 ± 71.37 μm) (P < 0.001). After conventional and TE CXL, keratometric parameters improved remarkably, whereas accelerated CXL only lowered K1 and Kmax (P < 0.05). No correlation was found between DD and topographic changes (P > 0.05). Progression was detected in 3 eyes in the conventional group (4.1%), 3 in the accelerated group (7.7%), and none in the TE group. The use of either riboflavin D or M made no differences in terms of DD and topographic parameters (P > 0.05).

Conclusions:
In conventional and accelerated protocols, corneal stromal demarcation line is deeper compared with TE CXL; however, the DD has no correlation with topographic changes, which means that DD is not a direct measure for the efficacy of CXL.
Cefoxitin Prophylaxis During Pediatric Cardiac Surgery: Retrospective Exploration of Postoperative Trough Levels
Authors: Ricci Zaccaria , Benegni Simona , Cies Jeffrey J. , Marinari Eleonora , Haiberger Roberta , Garisto Cristiana , Cairoli Sara , Di Chiara Luca , Goffredo Bianca 
Published: August 2018

Background:
This study aimed to explore inter-individual variability of cefoxitin trough levels, predictors of serum cefoxitin concentration and the probability of target attainment of drug levels above 4 mg/L after pediatric cardiac surgery.

Methods:
Retrospective study on children scheduled for elective cardiac surgery and having cefoxitin trough levels available up to 24 hours postsurgery.

Results:
Overall, 68 children (9 neonates, 34 infants, 15 children below or equal to 10 years old and 10 patients above this age) were included. Of these, 16 surgeries were performed off cardiopulmonary bypass and 52 were performed on cardiopulmonary bypass. The free cefoxitin concentrations showed a median (interquartile range) concentration of 1.7 (0.6–4.2) mg/L. The range of cefoxitin concentrations showed a 150-fold and 340-fold variability at cardiac intensive care unit admission and after 24 hours, respectively. The pharmacodynamics (PD) targets of free cefoxitin at 100% of the dosing interval, considering Eucast breakpoints for Methicillin Sensitive Staphylococcus Aureus (4 mg/L) and E.Coli (8 mg/L), were obtained in 28% and 16% of patients, respectively. Patient weight (odds ratio, 0.7; 95% confidence interval, 0.62–0.92; P = 0.006) and serum creatinine concentrations (odds ratio, 25; 95% confidence interval, 18–36; P = 0.004) showed a significant relationship with the PD targets.

Conclusions:
Cefoxitin trough concentrations vary significantly in the first 24 hours after pediatric cardiac surgery. Both serum creatinine and body weight showed independent associations with cefoxitin concentration. The PD target was not obtained in the vast majority of the explored population, regardless of the target bacteria.
Minimum Duration of Antibiotic Treatment Based on Blood Culture in Rule Out Neonatal Sepsis
Authors: Ur Rehman Durrani Naveed , Rochow Niels , Alghamdi Jameel , Pelc Anna , Fusch Christoph , Dutta Sourabh 
Published: August 2018

Background:
Neonatologists usually wait 48 hours for blood culture results before deciding to discontinue antibiotics. The objective of the study was to analyze time to positive blood culture in rule out sepsis and estimate the minimum duration of antibiotics.

Methods:
Retrospective analysis of blood culture at the Neonatal Intensive Care Unit, McMaster Children’s Hospital (January 2004 to December 2013) using BacT/Alert® 3D microbial system was conducted. We calculated average time taken for blood culture samples to emit a positive signal and compared it between Gram-positive and Gram-negative organisms. Kaplan-Meier curves for time to detect positive culture were generated. A Cox proportional hazard regression model with the outcome variable “time to detect positive blood culture” and predictor variables “early-onset sepsis (EOS) versus late-onset sepsis (LOS)”, “Gram-positive versus Gram-negative” and “definite versus possible pathogen versus contaminant” was generated.

Results:
Of 7,480 blood cultures performed in 9,254 neonates, 885 samples grew microorganisms. 845 culture reports from 627 neonates were analyzed. Definite or opportunistic pathogens caused 815 (96%) infections (54 EOS and 791 LOS) and the rest were contaminants. Gram-negative organisms grew significantly faster than Gram-positive (P < 0.001). Cultures from EOS were positive significantly earlier than LOS (P = 0.032). Gram-negative status was an independent predictor of early detection of a positive culture (hazard ratio 3.5 [95% CI, 2.7–4.5] P < 0.001).

Conclusion:
The probability of positive blood culture beyond 24 hours for a Gram-negative organism is small. Empiric antimicrobial treatment can be reduced after 24 hours to target only Gram-positive organisms in LOS and can be stopped in EOS unless clinical or laboratory parameters strongly suggest sepsis.
A cross-sectional study investigating frequency and features of definitely diagnosed diabetic painful polyneuropathy
Authors: Truini Andrea , Spallone Vincenza , Morganti Roberto , Tamburin Stefano , Zanette Giampietro , Schenone Angelo , De Michelis Chiara , Tugnoli Valeria , Simioni Valentina , Manganelli Fiore , Dubbioso Raffaele , Lauria Giuseppe , Lombardi Raffaella , Jann Stefano , De Toni Franceschini Luisa , Tesfaye Solomon , Fiorelli Marco , Spagnoli Alessandra , Cruccu Giorgio ,   On behalf of the Neuropathic Pain Special Interest Group of the Italian Society of Neurology
Published: August 2018

Abstract
This cross-sectional multicentre study aimed at investigating frequency and features of painful diabetic polyneuropathy. We consecutively enrolled 816 patients attending hospital diabetic outpatient clinics. We first definitely diagnosed diabetic polyneuropathy and pure small-fibre polyneuropathy using clinical examination, nerve conduction study, and skin biopsy or quantitative sensory testing. Adhering to widely agreed criteria, we then identified neuropathic pain and diagnosed painful polyneuropathy using a combined approach of clinical examination and diagnostic tests. Of the 816 patients, 36% had a diabetic polyneuropathy associated with male sex, age, and diabetes severity; 2.5% of patients had a pure small-fibre polyneuropathy, unrelated to demographic variables and diabetes severity. Of the 816 patients, 115 (13%) suffered from a painful polyneuropathy, with female sex as the only risk factor for suffering from painful polyneuropathy. In this large study, providing a definite diagnosis of diabetic polyneuropathy and pure small-fibre polyneuropathy, we show the frequency of painful polyneuropathy and demonstrate that this difficult-to-treat complication is more common in women than in men.
Ocular Syphilis and Human Immunodeficiency Virus Coinfection Among Syphilis Patients in North Carolina, 2014–2016
Authors: Cope Anna B. , Mobley Victoria L. , Oliver Sara E. , Larson Mara , Dzialowy Nicole , Maxwell Jason , Rinsky Jessica L. , Peterman Thomas A. , Fleischauer Aaron , Samoff Erika 
Published: August 2018

Background
Ocular syphilis (OS) has been associated with human immunodeficiency virus (HIV) coinfection previously. We compared demographic and clinical characteristics of syphilis patients with and without HIV to identify risk factors for developing OS.

Methods
We reviewed all syphilis cases (early and late) reported to the North Carolina Division of Public Health during 2014 to 2016 and categorized HIV status (positive, negative, unknown) and OS status based on report of ocular symptoms with no other defined etiology. We estimated prevalence ratios (PR) and 95% confidence intervals (CI) for OS by HIV status. Among syphilis patients with HIV, we compared viral loads and CD4 cell counts by OS status. We compared symptom resolution by HIV status for a subset of OS patients.

Results
Among 7123 confirmed syphilis cases, 2846 (39.9%) were living with HIV, 109 (1.5%) had OS, and 59 (0.8%) had both. Ocular syphilis was more prevalent in syphilis patients with HIV compared to HIV-negative/unknown-status patients (PR, 1.8; 95% CI, 1.2–2.6). Compared with other patients with HIV, the prevalence of OS was higher in patients with viral loads greater than 200 copies/mL (1.7; 1.0–2.8) and in patients with a CD4 count of 200 cells/mL or less (PR, 2.3; 95% CI, 1.3–4.2). Among 11 patients with severe OS, 9 (81.8%) were HIV-positive. Among 39 interviewed OS patients, OS symptom resolution was similar for HIV-positive (70.0%) and HIV-negative/unknown-status (68.4%) patients.

Conclusions
Syphilis patients with HIV were nearly twice as likely to report OS symptoms as were patients without documented HIV. Human immunodeficiency virus–related immunodeficiency possibly increases the risk of OS development in co-infected patients.
Utilization and Abandonment of Low Vision Devices Prescribed on a Mobile Clinic
Authors: Gobeille Micaela R. , Malkin Alexis G. , Jamara Richard , Ross Nicole C. 
Published: August 2018

SIGNIFICANCE
Device utilization and abandonment for patients seen on a mobile clinic are explored. Findings are informative for resource allocation in a novel low vision rehabilitation (LVR) delivery model. This study also explores the relationships between device abandonment and LVR patient-reported functional outcomes.

PURPOSE
This prospective cohort study investigated low vision device utilization and abandonment in a novel mobile clinic delivery model.

METHODS
A device abandonment questionnaire was administered by telephone 3 months and 1 year after mobile clinic LVR. Participants (n = 65) had previously met the U.S. definition of legal blindness and were prescribed a total of 154 devices at their low vision consultative visits. Trends in device utilization and correlations with clinical and demographic participant characteristics, as well as functional outcomes as assessed by Massof Activity Inventory, are explored.

RESULTS
An average of 2.6 device recommendations were made per participant. Digital magnification, optical magnifiers, and filters were most frequently recommended. At 3 months, 29% of participants abandoned at least one device, although only 17% of received devices were abandoned. There was no significant difference in the number of devices used, abandoned, or not received at 3 months versus 1 year after LVR. Devices prescribed for reading goals were most frequently used and least often abandoned, whereas glare control and distance magnification devices were more frequently abandoned. Neither patient characteristics nor Massof Activity Inventory change score was predictive of device abandonment. There was no significant difference in the odds of device abandonment in comparison with a previous study that assessed academic outpatient LVR clinics using the same questionnaire.

CONCLUSIONS
Although more device recommendations are given per patient on the mobile clinic, there is no significant difference in device abandonment for patients seen on the mobile clinic versus other outpatient LVR delivery models.
Fittle: A Novel Braille Toy
Authors: Jain Tania , Christy Beula , Das Anthony Vipin , Bhaumik Debanshu , Satgunam PremNandhini 
Published: August 2018

SIGNIFICANCE
Toys for children with visual impairment and blindness are very limited. We have developed a three-dimensional (3D)–printed Braille puzzle with a potential for educational use.

PURPOSE
This article describes the development of a novel Braille toy using 3D printing technology that potentially could be used for teaching Braille for children with blindness and/or profound visual impairment.

METHODS
Fittle is a 3D-printed puzzle with embossed Braille letters. Upon correct fitting of the puzzle, one not only can spell the Braille word but also would be able to feel the contour of the representative object that the word denotes. A smartphone application (Sound of Fittle) was developed to be used in conjunction with Fittle. A pilot testing was done on participants with vision impairment. Time taken to solve the puzzle and/or identify the Braille letters was calculated. Three Fittle puzzles were tested. Instructions to solve the puzzle were given only after the first attempt.

RESULTS
Seven participants (one adult and six children) were recruited. The mean time taken for the first attempt was longer (4.5 minutes), and upon instructions, the time taken to solve the puzzle was reduced on an average by a factor of 2.5. All the subjects were able to fit and read the embossed Braille in the Fittle.

CONCLUSIONS
Fittle is a novel Braille toy made using 3D printing technology. Fittle can potentially be used as an educational toy. The Sound of Fittle application gives the experiential sound for the associated word. The designs for the Fittle and the application are made available as open source on the Internet. Anyone with an access to a 3D printer can print, produce, and use the Fittle for free. With instructions, an individual can quickly learn to solve and play with the puzzle.
Epistemological Trends in the Literature on Mobile Devices, Mobile Learning, and Learners with Visual Impairments
Authors: Hayhoe Simon 
Published: August 2018

ABSTRACT
This study is significant because learning with mobile devices is increasing as a method of educating and training learners with visual impairments, but evaluation of its method is rare. In addition, the epistemological model used in this study is designed to improve future research designs. This article reviews the literature on the use of mobile devices by learners with visual impairments in a variety of learning environments. The study's three objectives are to pursue avenues of research in m-learning and visual impairment, stimulate debate on the nature and role of mobile technologies in the education of learners with visual impairments, and develop a debate on the best use of technologies in m-learning. The study uses an epistemological model of visual impairment as an instrument to critically analyze different ontologies and paradigms of research. The epistemological model is also analyzed as an analytical instrument. The study identifies three academic paradigms in this field: (1) conceptual, (2) design and user testing, (3) m-learning in situ. The study also finds these three paradigms ontologize visual impairment in different ways, meaning that there is little cohesion in research and practice. The study finds that research on the development and use of technologies by learners with visual impairments is restricted by a lack of cohesion in theory and practice. This lack of cohesion is thought to be largely due to the immature nature of this topic as a field of study.