bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dexamethasone Does Not Inhibit Treadmill Training–Induced Angiogenesis in Myocardium: Role of MicroRNA-126 Pathway
Authors: Herrera Naiara A. , Duchatsch Francine , Tardelli Lidieli P. , Dionísio Thiago J. , Santos Carlos F. , Amaral Sandra L. 
Published: October 2020

Abstract:
Dexamethasone (DEX) has important anti-inflammatory activities; however, it induces hypertension and skeletal muscle microcirculation rarefaction. Nevertheless, nothing is known about DEX outcomes on cardiac microcirculation. By contrast, exercise training prevents skeletal and cardiac microvessel loss because of microRNA expression and a better balance between their related angiogenic and apoptotic proteins in spontaneously hypertensive rats. The purpose of this study was to investigate whether DEX and/or exercise training could induce microRNA alterations leading to cardiac angiogenesis or microvascular rarefaction. Animals performed 8 weeks of exercise training and were treated with DEX (50 μg/kg per day, subcutaneously) for 14 days. Cardiovascular parameters were measured, and the left ventricle muscle was collected for analyses. DEX treatment increased arterial pressure and did not cause cardiac microcirculation rarefaction. Treadmill training prevented the DEX-induced increase in arterial pressure. In addition, training, regardless of DEX treatment, increased microRNA-126 expression, phospho-protein kinase B/protein kinase B, and endothelial nitric oxide synthase levels associated with cardiac angiogenesis. In conclusion, this study suggests, for the first time, that treadmill training induces myocardial angiogenesis because of angiogenic pathway improvement associated with an increase in microRNA-126. Furthermore, DEX, per se, did not cause capillary density alterations and did not attenuate cardiac angiogenesis induced by training.
The Use of Voltage Sensitive Dye di-4-ANEPPS and Video-Based Contractility Measurements to Assess Drug Effects on Excitation–Contraction Coupling in Human-Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: Hortigon-Vinagre Maria Pura , Zamora Victor , Burton Francis L. , Smith Godfrey L. 
Published: October 2020

Abstract:
Because cardiotoxicity is one of the leading causes of drug failure and attrition, the design of new protocols and technologies to assess proarrhythmic risks on cardiac cells is in continuous development by different laboratories. Current methodologies use electrical, intracellular Ca2+, or contractility assays to evaluate cardiotoxicity. Increasingly, the human-induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) are the in vitro tissue model used in commercial assays because it is believed to recapitulate many aspects of human cardiac physiology. In this work, we demonstrate that the combination of a contractility and voltage measurements, using video-based imaging and fluorescence microscopy, on hiPSC-CMs allows the investigation of mechanistic links between electrical and mechanical effects in an assay design that can address medium throughput scales necessary for drug screening, offering a view of the mechanisms underlying drug toxicity. To assess the accuracy of this novel technique, 10 commercially available inotropic drugs were tested (5 positive and 5 negative). Included were drugs with simple and specific mechanisms, such as nifedipine, Bay K8644, and blebbistatin, and others with a more complex action such as isoproterenol, pimobendan, digoxin, and amrinone, among others. In addition, the results provide a mechanism for the toxicity of itraconazole in a human model, a drug with reported side effects on the heart. The data demonstrate a strong negative inotropic effect because of the blockade of L-type Ca2+ channels and additional action on the cardiac myofilaments. We can conclude that the combination of contractility and action potential measurements can provide wider mechanistic knowledge of drug cardiotoxicity for preclinical assays.
Impact of the Potential Antitumor Agent 2-(4-Hydroxyphenyl) Amino-1,4-Naphthoquinone (Q7) on Vasomotion Is Mediated by the Vascular Endothelium, But Not Vascular Smooth Muscle Cell Metabolism
Authors: Palacios Javier , Benites Julio , Owen Gareth I. , Morales Pablo , Chiong Mario , Nwokocha Chukwuemeka R. , Paredes Adrián , Cifuentes Fredi 
Published: October 2020

Abstract:
Vasomotion is defined as rhythmic oscillations in arterial diameter that regulate the blood flow and blood pressure. Because antitumor treatment may impair vascular functions and increase the blood pressure, we sought to evaluate whether a new naphthoquinone derivative, postulated as an antitumor agent, manifests adverse effects on vascular function. In this article, we evaluated the toxicity of 2-(4-hydroxyphenyl) amino-1,4-naphthoquinone (Q7) and its effects on vascular vasomotion in 3 models of vascular structure: endothelial cells, aortic ring, and smooth muscle cells. Although showing nontoxic effects, Q7 inhibited the formation of capillary-like structures of the EA.hy926 endothelial cell line grown on Matrigel. In exvivo experiments with aortic rings precontracted with phenylephrine (PE, 10−6 M), Q7 (10−5 M) significantly (P < 0.05) reduced vascular rhythmic contractions induced by the acetylcholine (ACh; 10−7-10−5 M), whereas sodium nitroprusside (a nitric oxide donor; 10−8 M) recovered the vasomotion. Furthermore, Q7 (10−5 M) did not decrease KCl-induced vascular rhythmic contractions in the aortic rings precontracted with BaCl2 (a nonselective K+ channel blocker; 10−3 M). Vascular smooth muscle cells (A7r5) preincubated with Q7 (10−5 M) for 3 hours also demonstrated a reduced glucose uptake. However, the Adenosine Triphosphate content was unaffected, suggesting that the rapid reduction in vasomotion observed in vascular reactivity experiments did not involve cellular metabolism but may be due to faster mechanisms involving endothelial nitric oxide and K+ channels leading to oscillations in intracellular Ca2+. In summary, the naphthoquinone derivative Q7 presents low cytotoxicity yet may alter the endothelial cell response and vasomotion in the absence of changes in smooth muscle cell metabolism.
Evaluating the Benefits of Exercise Training in HFrEF or COPD Patients
Authors: Gudjonsdottir Marta , Thoroddsen Egill , Karlsdottir Arna E. , Kristjansdottir Asdis , Jonasson Magnus R. , Asgeirsdottir Magdalena , Sigurdsson Stefan B. , Kristjansson Karl 
Published: October 2020

Background:
Heart failure with reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD) are relatively common conditions with similar symptoms of exercise intolerance and dyspnea. The aim of this study was to compare exercise capacity, ventilatory response, and breathing pattern in patient groups with either advanced HFrEF or COPD before and after exercise training.

Methods:
An observational study was conducted with parallel groups of 25 HFrEF and 25 COPD patients who took part in 6 wk of inpatient rehabilitation with exercise training. All patients underwent cardiopulmonary exercise tests at the start and end of the training, with resting arterial blood gas measurements.

Results:
The average peak oxygen uptake (V˙o2) was low at the start of the study but increased significantly after training in both groups, or by 2.2 ± 2.1 mL/kg/min in HFrEF patients and 1.2 ± 2.2 mL/kg/min in COPD patients. At ISO-V˙o2 (ie, same level of V˙o2 in pre- and post-exercise tests), carbon dioxide production (V˙co2) decreased after exercise training in both groups. Similarly, at ISO-V˙E (ie, same level of ventilation), breathing frequency (f) decreased and tidal volume (VT) increased, resulting in an improved breathing pattern (lower f/VT ratio) after training.

Conclusion:
The findings of this study show that exercise training in severely affected patient groups with HFrEF or COPD led to an increase in maximal exercise capacity, a more favorable breathing pattern, and a diminished V˙co2 during exercise. Therefore, comparisons of V˙co2 and breathing pattern at ISO-levels of V˙o2 or V˙E before and after training are valuable and underutilized outcome measures in treatment studies.
Identification of Optimal Measures of Human Abuse Potential
Authors: Shram Megan J. , Levy-Cooperman Naama , Ratcliffe Sian , Mills Catherine , Bartlett Cynthia , Chen Nancy , Setnik Beatrice , Sellers Edward M. , Schoedel Kerri A. 
Published: October 2020

Abstract

Background
Human abuse potential studies include multiple measures to assess the subjective effects of central nervous system–active drugs. In this retrospective analysis, measurement properties of commonly used measures were assessed, and factor analysis was conducted to identify a core battery of measures.

Methods
Measures of positive, negative and other effects, for example, bipolar “at-the-moment” Drug Liking visual analog scale (VAS), were derived for active controls and placebo from 19 studies in recreational drug users (N = 570). Distribution, placebo response, variability, convergent/discriminant validity, parameter effect sizes (eg, maximum effect [E
max], time-averaged area under the effect curve), and predictive validity were evaluated. A factor analysis was conducted with 9 studies.

Results
Most parameters were not normally distributed. Bipolar VAS exhibited the lowest variability. Drug Liking VAS E
max was very sensitive, showed large effect sizes (>1.0), and was moderately to strongly correlated with E
max of other positive effects measures (r > 0.5), but weaker with less specific scales (eg, high, Any Effects VAS); time-averaged area under the effect curve showed higher variability and lower effect sizes. Maximum effect at any dose (E
maxD) was significantly correlated with E
max across all selected measures and showed higher effect sizes. In the overall factor analysis, factors could be categorized into positive effects/euphoria (77% of variance), negative effects (17.9%), and pharmacologic effects (5%). For predictive validity, effect sizes for Drug Liking VAS E
max/E
maxD were moderately correlated with postmarket adverse events related to abuse (R
2 = 0.52).

Conclusions
A core battery of 7 subjective measures was proposed, with additional measures added based on pharmacologic effects.
Sunscreen and Tanning Bed Use in High-Risk College-Aged Students
Authors: Graham Emily M. , Merrill Katreena C. 
Published: October 2020

ABSTRACT
Skin cancer is the most prevalent cancer in the United States. Contributing factors include phenotypic exposure to ultraviolet radiation, lack of protective measures, and using high-risk behaviors. Protective measures (sunblock/protective clothing) are not popular with college-aged individuals, whereas tanning bed use is highly prevalent. The purpose of this study was to describe phenotypic risk factors for skin cancer, application of sunscreen, and tanning bed use in college students. A convenience sample of 673 students (55% male) completed a descriptive survey during winter, spring, and summer months. Researchers collected information about phenotypic risk factors using the Fitzpatrick Skin Scale, use of sunscreen, previous tanning bed use, and gender. Furthermore, 9.5% of college-aged individuals reported using sunscreen. Sunscreen use varied by season (p = .009) but not by skin type. Women reported higher sunscreen use (p = .0001). In addition, 12.6% disclosed a history of tanning bed use (M = 1.2). Male participants were more likely to use tanning beds during winter months (p = .015). Skin type did not influence tanning bed use. College-aged individuals are not sufficiently protecting themselves from the sun. More attention is needed to help melano-compromised individuals, especially men, understand how risk factors influence the development of skin cancer.
Update on Dermatoporosis
Authors: Vanzi Valentina , Toma Elena 
Published: October 2020

ABSTRACT
Skin fragility caused by structural and functional deterioration is ubiquitous especially in older people, and it determines a significant impact on quality of life. Dermatoporosis is a relatively new term used to describe the chronic skin insufficiency and fragility syndrome marked by morphological and functional manifestations. It is much more than a merely cosmetic problem. Dermatoporosis' manifestations may determine an increased risk of morbidity and mortality. Severe stages of dermatoporosis may determine skin lacerations, deep dissecting hematomas, and skin necrosis. Most patients affected by dermatoporosis are between 70 and 90 years old, but first clinical signs may start at around 40–60 years. Nurses have a key role in preventing dermatoporosis and managing its complications, promoting patients' safety and skin integrity.
Assessment of High Flow Nasal Cannula Oxygenation in Endobronchial Ultrasound Bronchoscopy
Authors: Irfan Mujammil , Ahmed Mohammed , Breen David 
Published: October 2020

Background:
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely implemented in evaluating mediastinal disease. EBUS-TBNA is performed with low flow oxygen systems or general anesthesia. Little data exist on use of high flow nasal cannula (HFNC) in EBUS-TBNA.

Methods:
This was a single center parallel group randomized controlled trial comparing oxygenation through HFNC (Optiflow) against nasal prongs during EBUS. The primary end-point was the drop in oxygen saturations from procedure commencement, recorded by pulse oximetry, to the lowest level during EBUS-TBNA. Secondary end-points included changes in venous blood carbon dioxide, lowest oxygen saturation, changes in end-tidal CO2 during the procedure, intubation within 8 hours of the procedure and patient experience reported on a visual analog scale.

Results:
We randomized 20 patients to each study arm. The primary outcome of oxygen desaturation during the procedure was statistically significant with a difference of 7.7 percentage points (95% confidence interval, 4.91-10.49, P<0.001). The secondary outcome measure of lowest oxygen saturation was also statistically significant with a difference of −9.2 (95% confidence interval, −11.96 to −6.44, P<0.001). There was no difference in safety outcomes, visual analog scale score or in their willingness to return for repeat procedure.

Conclusion:
This single institution study in a university, tertiary referral center confirms that EBUS-TBNA performed with HFNC is associated with a statistically significant lower drop in oxygen saturation. Additional studies are needed to assess if this translates into improved clinical outcomes postprocedure.
Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation
Authors: Heller Debra S. , Day Tania , Allbritton Jill I. , Scurry James , Radici Gianluigi , Welch Kathryn , Preti Mario ,   for the ISSVD Difficult Pathologic Diagnoses Committee
Published: October 2020

Objective
The aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM).

Materials and Methods
The International Society of the Study of Vulvovaginal Diseases tasked the difficult pathologic diagnoses committee to develop consensus recommendations for clinicopathologic diagnosis of vulvar lichen planus, lichen sclerosus, and dVIN. The dVIN subgroup reviewed the literature and formulated diagnostic criteria that were reviewed by the committee and then approved by the International Society of the Study of Vulvovaginal Diseases membership.

Results
Differentiated vulvar intraepithelial neoplasia is the immediate precursor of human papillomavirus (HPV)–independent vulvar squamous cell carcinoma and shows a spectrum of clinical and microscopic appearances, some overlapping with HPV-related neoplasia. The histopathologic definition of dVIN is basal atypia combined with negative or nonblock-positive p16 and basal overexpressed, aberrant negative, or wild-type p53. The most common pattern of dVIN is keratinizing with acanthosis, aberrant rete ridge pattern, and premature maturation. The morphologic spectrum of keratinizing dVIN includes hypertrophic, atrophic, acantholytic, and subtle forms. A few dVIN cases are nonkeratinizing, with basaloid cells replacing more than 60% of epithelium. Vulvar aberrant maturation is an umbrella term for lesions with aberrant maturation that arise out of lichenoid dermatitis and lack the basal atypia required for dVIN.

Conclusions
Evaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders. Close surveillance of women with lichen sclerosus and use of these recommendations may assist in prevention of HPV-independent squamous cell carcinoma through detection and treatment of dVIN and VAM.
Migration and Psychosis
Authors: di Giacomo Ester , Giampieri Emanuela D. , Pellicioli Cristian , Rabboni Massimo , Clerici Massimo 
Published: October 2020

Abstract
In the last years, there has been a huge migratory flow to Italy. Migration is a risk factor for the development of psychopathology, especially psychosis and posttraumatic stress disorder. We aimed at investigating the burden and characteristics of psychotic features among immigrants in Lombardy, one of the most involved regions. A total of 7819 patients had at least one psychiatric appointment in 2013, 10.3% of them where immigrants. Patients from Africa showed a significant higher rate of psychosis, psychiatric onset, compulsory admissions, and number of professional appointments. Our result can confirm a cultural specificity of psychotic manifestations and their burden on the mental health system.
The Problem of Aggregating Validators for Psychiatric Disorders
Authors: Solomon Miriam , Kendler Kenneth S. 
Published: October 2020

Abstract
Since the time of the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, evidence for the validity of psychiatric disorders has been expressed in the form of validators, which are instances of particular kinds of evidence. There has never been an explicit discussion of how the validators should be aggregated to come to an overall conclusion about the strength of the evidence for a psychiatric category. We include both the challenges of aggregating validators of the same type and the challenges of aggregating different types of validators. We consider five different alternatives: informal aggregation, weighted informal aggregation (simple evidence hierarchy), formal aggregation, underdetermination, and inclusion of values. Each of the alternatives has different implications. We suggest that, going forward, aggregation of validators should be more explicit, maximizing rigor and reproducibility.
Handlebar Hernia
Authors: García Sánchez Paula , Bote Gascón Patricia , González Bertolín Isabel , Bueno Barriocanal Marta , López López Rosario , de Ceano-Vivas la Calle María 
Published: October 2020

Abstract
Handlebar hernia is a type of traumatic abdominal wall hernia caused by the impact of a bicycle handlebar against the abdominal wall. A good anamnesis and physical examination are important for the correct diagnosis, and ultrasonography is an accessible tool in the emergency department for imaging confirmation. We describe a case of an 11-year-old girl who presented to the emergency department after an abdominal trauma caused by a handlebar. Ultrasonography revealed an abdominal wall defect with herniation of omentum and bowel loops. Conservative management was initially established, followed by surgical treatment due to persistent symptoms.
Does Postmortem Imaging Provide Additional Findings After Unexpected Deaths in Infants and Children?
Authors: Yurkovich Chelsey , Nazer Dena , Farooqi Ahmad , Kannikeswaran Nirupama 
Published: October 2020

Objectives
The yield of postmortem imaging (PMI) after sudden unexpected deaths in children has not been well studied. Findings consistent with physical abuse detected on PMI may alert the physician to this diagnosis before the autopsy results. Our objectives are to describe the PMI performed and their diagnostic yield after unexpected deaths in children and to adherence to the American Academy of Pediatrics guidelines regarding performance of skeletal survey and autopsy in infants at our institution.

Methods
We performed a retrospective study of unexpected deaths in children 2 years or younger between 2008 and 2018. Children with known traumatic deaths and those transferred after a cardiopulmonary arrest at an outside institution were excluded. We collected patient demographics, physical examination findings, and type of PMI performed along with their results.

Results
We analyzed 150 deaths with majority (128; 85.3%) being infants. No PMI was performed in 20 children (13.3%). An autopsy was not performed in 22 children (14.6%). A skeletal survey and an autopsy were performed only in 72.6% (93/128) infants. PMI provided additional findings in 51 infants (34%) and 13 children (59.1%) aged 13 to 24 months. PMI identified abuse in 11 children with a negative physical examination result, 3 of whom had a negative autopsy.

Conclusions
The American Academy of Pediatrics recommendations of performance of a skeletal survey and an autopsy were not adhered to after all infant deaths. PMI is useful in identification of additional findings in children 2 years or younger, especially those concerning for physical abuse in infants with a negative physical examination.
Determining Intentionality of Pediatric Firearm Injuries by International Classification of Disease Code
Authors: Donnelly Katie A. , Badolato Gia M. , Goyal Monika K. 
Published: October 2020

Objective
Firearm injuries are a leading cause of serious injury and death in childhood. The accuracy of International Classification of Disease (ICD) codes to assign intent is unclear. The objective of this study was to assess the validity of documented ICD codes for firearm injury intent compared with chart review.

Methods
We performed a retrospective cohort study of children (<= 18 years) presenting to a tertiary care level 1 pediatric trauma center with firearm injuries between 2006 and 2017. We compared agreement between ICD codes and intent of injury determined by medical record review using Cohen κ. Intent for medical record review was assigned via the injury spectrum of intentionality (suicide attempt, accidental firing, mistaken target, firearm assault and unknown). For comparison with ICD codes, all medical record review cases marked as mistaken target were classified as accidental. A sensitivity analysis was then performed, coding all mistaken targets as assault.

Results
There were 122 cases identified over the study period. The most common intent by ICD code was assault (n = 80, 65.6%). Medical record review categorized most injuries as mistaken targets. When mistaken target was categorized as accidental, most firearm injuries were coded as accidental (n = 89, 72.9%) Similar results were seen when mistaken target was categorized as assault, most injuries were categorized as assault (n = 79, 79.5%) Cohen κ was 0.15 when mistaken targets were categorized as accident and 0.30 when categorized as assault.

Conclusions
The ICD codes do not fully describe the intent of firearm injury. Revising ICD codes to account for mistaken targets could help to improve the validity of ICD codes for intent.