bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension
Authors: Egnatchik Robert A. , Brittain Evan L. , Shah Amy T. , Fares Wassim H. , Ford H. James , Monahan Ken , Kang Christie J. , Kocurek Emily G. , Zhu Shijun , Luong Thong , Nguyen Thuy T. , Hysinger Erik , Austin Eric D. , Skala Melissa C. , Young Jamey D. , Roberts L. Jackson , Hemnes Anna R. , West James , Fessel Joshua P. 
Published: November 2016

Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disease driven by alteration in the normal functioning of multiple metabolic pathways affecting all of the major carbon substrates, including amino acids. We found that human pulmonary hypertension patients (WHO Group I, PAH) exhibit systemic and pulmonary‐specific alterations in glutamine metabolism, with the diseased pulmonary vasculature taking up significantly more glutamine than that of controls. Using cell culture models and transgenic mice expressing PAH‐causing BMPR2 mutations, we found that the pulmonary endothelium in PAH shunts significantly more glutamine carbon into the tricarboxylic acid (TCA) cycle than wild‐type endothelium. Increased glutamine metabolism through the TCA cycle is required by the endothelium in PAH to survive, to sustain normal energetics, and to manifest the hyperproliferative phenotype characteristic of disease. The strict requirement for glutamine is driven by loss of sirtuin‐3 (SIRT3) activity through covalent modification by reactive products of lipid peroxidation. Using 2‐hydroxybenzylamine, a scavenger of reactive lipid peroxidation products, we were able to preserve SIRT3 function, to normalize glutamine metabolism, and to prevent the development of PAH in BMPR2 mutant mice. In PAH, targeting glutamine metabolism and the mechanisms that underlie glutamine‐driven metabolic reprogramming represent a viable novel avenue for the development of potentially disease‐modifying therapeutics that could be rapidly translated to human studies.
HIV & AIDS: A Very Short Introduction
Authors: Whiteside Alan 
Published: November 2016

Abstract
HIV/AIDS: A Very Short Introduction provides an introduction to AIDS—the most serious human epidemic in centuries—tackling the science, politics, demographics, and devastating consequences of the disease. The first case was identified in 1981; by 2004 approximately forty million people were living with the disease, and about twenty million had died. The outlook today is a little brighter. Although HIV/AIDS continues to be a pressing public health issue, the epidemic has stabilized. The worst affected regions are Southern and Eastern Africa. Elsewhere, HIV is found in specific, often marginalized populations. Although there remains no cure for HIV, there have been unprecedented breakthroughs in understanding the disease and developing drugs.
Adverse Obstetric Outcomes After Local Treatment for Cervical Preinvasive and Early Invasive Disease According to Cone Depth: Systematic Review and Meta-analysis
Authors: Kyrgiou Maria , Athanasiou Antonios , Paraskevaidi Maria , Mitra Anita , Kalliala Ilkka , Martin-Hirsch Pierre , Arbyn Marc , Bennett Phillip , Paraskevaidis Evangelos 
Published: November 2016

(Abstracted from BMJ 2016;354:i3633)
Local cervical treatment for preinvasive cervical disease such as cervical intraepithelial neoplasia (CIN) has been associated with an increased risk of preterm birth, perinatal morbidity, and mortality in a later pregnancy. This meta-analysis aimed to investigate the impact of treatment for cervical preinvasive and early invasive disease on obstetric outcomes and to see how this risk could be modified by the cone depth and comparison group.
Health Care Utilization and Cost in Children and Adolescents With Chronic Pain
Authors: Ruhe Ann-Kristin , Frosch Michael , Wager Julia , Linder Roland , Pfenning Ingo , Sauerland Dirk , Zernikow Boris 
Published: November 2016

Objectives:
The aim of this study was to analyze changes in health care utilization and cost among a sample of highly impaired children and adolescents who sought a 3-week intensive interdisciplinary pain treatment (IIPT).

Materials and Methods:
Claims data from 7 statutory health insurance companies were analyzed for 65 children and adolescents who sought IIPT at the German Paediatric Pain Centre. The annual health care utilization and cost were determined for the following 4 areas: outpatient care, inpatient care, medications, and remedies and aids. We analyzed the changes in resource utilization in the year before (pre_1 y) IIPT and in the subsequent year (post_1 y).

Results:
Within the first year after IIPT, overall health care costs did not decrease significantly. However, the pattern of health care utilization changed. First, significantly more children and adolescents started outpatient psychotherapy (P=0.001). Second, the number of hospitalized children decreased significantly from 1-year pre to 1-year post (P=0.001). Accordingly, there were significantly fewer hospitalizations for primary chronic pain disorders at 1-year post (P<0.001). The prescription of nonopioids, co-analgesics and opioids was significantly reduced from 1-year pre to 1-year post (all P<0.013).

Discussion:
The present results indicate that the health care costs of children and adolescents with severe chronic pain disorders do not significantly decrease 1 year after IIPT; however, the treatment becomes more goal-focused. Differential diagnosis measures and nonindicated therapeutic interventions decreased, and more indicated interventions, such as psychotherapy, were used. Future research is needed to investigate the economic long-term changes after IIPT.
Transient Receptor Potential Vanilloid 4 and Serum Glucocorticoid–regulated Kinase 1 Are Critical Mediators of Lung Injury in Overventilated Mice In Vivo
Authors: Michalick Laura , Erfinanda Lasti , Weichelt Ulrike , van der Giet Markus , Liedtke Wolfgang , Kuebler Wolfgang M. 
Published: November 2016

Abstract

Background
Mechanical ventilation can cause lung endothelial barrier failure and inflammation cumulating in ventilator-induced lung injury. Yet, underlying mechanotransduction mechanisms remain unclear. Here, the authors tested the hypothesis that activation of the mechanosensitive Ca2+ channel transient receptor potential vanilloid (TRPV4) by serum glucocorticoid–regulated kinase (SGK) 1 may drive the development of ventilator-induced lung injury.

Methods
Mice (total n = 54) were ventilated for 2 h with low (7 ml/kg) or high (20 ml/kg) tidal volumes and assessed for signs of ventilator-induced lung injury. Isolated-perfused lungs were inflated with continuous positive airway pressures of 5 or 15 cm H2O (n = 7 each), and endothelial calcium concentration was quantified by real-time imaging.

Results
Genetic deficiency or pharmacologic inhibition of TRPV4 or SGK1 protected mice from overventilation-induced vascular leakage (reduction in alveolar protein concentration from 0.84 ± 0.18 [mean ± SD] to 0.46 ± 0.16 mg/ml by TRPV4 antagonization), reduced lung inflammation (macrophage inflammatory protein 2 levels of 193 ± 163 in Trpv4
−/−
vs. 544 ± 358 pmol/ml in wild-type mice), and attenuated endothelial calcium responses to lung overdistension. Functional coupling of TRPV4 and SGK1 in lung endothelial mechanotransduction was confirmed by proximity ligation assay demonstrating enhanced TRPV4 phosphorylation at serine 824 at 18% as compared to 5% cyclic stretch, which was prevented by SGK1 inhibition.

Conclusions
Lung overventilation promotes endothelial calcium influx and barrier failure through a mechanism that involves activation of TRPV4, presumably due to phosphorylation at its serine 824 residue by SGK1. TRPV4 and SGK1 may present promising new targets for prevention or treatment of ventilator-induced lung injury.
Comparison of Percutaneous Reduction and Pin Fixation in Acute and Chronic Pediatric Mallet Fractures
Authors: Reddy Manoj , Ho Christine A. 
Published: November 2016

Background:
Although pediatric mallet fractures are more common than adult fractures, no techniques have focused on surgical fixation of pediatric mallet fractures. This study aims to describe the technique and results of percutaneous reduction and fixation in acute and chronic pediatric mallet fractures.

Methods:
This is a retrospective review of 51 pediatric mallet fractures treated with percutaneous wire fixation from 2007 to 2014; 38 were acute fractures and 13 were chronic (>4 wk from injury). Surgical technique was identical for all fractures: (1) levering the dorsal fragment into its anatomical bed with a percutaneous towel clip; (2) percutanously transfixing the distal interphalangeal joint in slight hyperextension; (3) placing 2 percutaneous kirschner wires, 1 radial and 1 ulnar, from the dorsal epiphyseal fragment to the volar metaphyseal cortex. Outcomes were defined by the Crawford classification.

Results:
Average age was 14.6 years (range, 11 to 18 y). Mean time from injury to surgery was 16.2 days in the acute group and 50.8 days in the chronic group. Mean joint surface involvement was 50.8% of the articular base with a mean of 2.0 mm of articular gap (acute fractures 1.9 mm, chronic fractures 2.5 mm, P=0.017). Average preoperative extensor lag was 24.6 degrees. Average operative time was 31 minutes for acute fractures and 40 minutes for chronic fractures. Mean length of follow-up was 78.5 days. At final follow-up, all patients healed with an articular gap of 0.2 mm in the acute group and 0.6 mm in the chronic group (P=0.037) with no nonunions or volar subluxations. All patients but 8 (5 acute, 3 chronic) achieved full extension with an average extensor lag of 1.1 degree for the entire cohort. No patient had >10-degree extensor lag at final follow-up. All patients achieved full active flexion of 90 degrees at final follow-up. In the acute group, the Crawford classification was excellent in 87% (33/38), good in 13% (5/38). In the chronic group, results were excellent in 77% (10/13), good in 23% (3/13) (P>0.05). There were no fair or poor outcomes in either group. A clinical dorsal bump was noted in 18% of patients (22% in the acute group, 15% in the chronic group, P>0.05). There were no infections, wire breakages, nail deformities, or unplanned returns to surgery.

Conclusions:
This percutaneous surgical technique to treat pediatric mallet fractures achieves favorable clinical and radiographic results with minimal complications, even in chronic fractures. Results are better than reported for adult mallet fractures.

Level of Evidence:
Level II.
Cryopreserved, Xeno-Free Human Umbilical Cord Mesenchymal Stromal Cells Reduce Lung Injury Severity and Bacterial Burden in Rodent Escherichia coli–Induced Acute Respiratory Distress Syndrome
Authors: Curley Gerard F. , Jerkic Mirjana , Dixon Steve , Hogan Grace , Masterson Claire , O’Toole Daniel , Devaney James , Laffey John G. 
Published: November 2016

Objective:
Although mesenchymal stem/stromal cells represent a promising therapeutic strategy for acute respiratory distress syndrome, clinical translation faces challenges, including scarcity of bone marrow donors, and reliance on bovine serum during mesenchymal stem/stromal cell proliferation. We wished to compare mesenchymal stem/stromal cells from human umbilical cord, grown in xeno-free conditions, with mesenchymal stem/stromal cells from human bone marrow, in a rat model of Escherichia coli pneumonia. In addition, we wished to determine the potential for umbilical cord-mesenchymal stem/stromal cells to reduce E. coli–induced oxidant injury.

Design:
Randomized animal study.

Setting:
University research laboratory.

Subjects:
Male Sprague-Dawley rats.

Interventions:
Acute respiratory distress syndrome was induced in rats by intratracheal instillation of E. coli (1.5–2 × 109 CFU/kg). “Series 1” compared the effects of freshly thawed cryopreserved umbilical cord-mesenchymal stem/stromal cells with bone marrow-mesenchymal stem/stromal cells on physiologic indices of lung injury, cellular infiltration, and E. coli colony counts in bronchoalveolar lavage. “Series 2” examined the effects of cryopreserved umbilical cord-mesenchymal stem/stromal cells on survival, as well as measures of injury, inflammation and oxidant stress, including production of reactive oxidative species, reactive oxidative species scavenging by superoxide dismutase-1 and superoxide dismutase-2.

Measurements and Main Results:
In “Series 1,” animals subjected to E. coli pneumonia who received umbilical cord-mesenchymal stem/stromal cells had improvements in oxygenation, respiratory static compliance, and wet-to-dry ratios comparable to bone marrow-mesenchymal stem/stromal cell treatment. E. coli colony-forming units in bronchoalveolar lavage were reduced in both cell therapy groups, despite a reduction in bronchoalveolar lavage neutrophils. In series 2, umbilical cord-mesenchymal stem/stromal cells enhanced animal survival and decreased alveolar protein and proinflammatory cytokine concentrations, whereas increasing interleukin-10 concentrations. Umbilical cord-mesenchymal stem/stromal cell therapy decreased nicotinamide adenine dinucleotide phosphate-oxidase 2 and inducible nitric oxide synthase and enhanced lung concentrations of superoxide dismutase-2, thereby reducing lung tissue reactive oxidative species concentrations.

Conclusions:
Our results demonstrate that freshly thawed cryopreserved xeno-free human umbilical cord-mesenchymal stem/stromal cells reduce the severity of rodent E. coli–induced acute respiratory distress syndrome. Umbilical cord-mesenchymal stem/stromal cells, therefore, represent an attractive option for future clinical trials in acute respiratory distress syndrome.
Neuralgic Amyotrophy Associated With Hepatitis E Virus Infection: First Case in the United States
Authors: Avila Jose D. , Lacomis David , Lam Erek M. 
Published: November 2016

Abstract
Hepatitis E is an emerging viral infection in developed countries. It can present with multiple extra-hepatic manifestations, including neuralgic amyotrophy. We report a 52-year-old man who presented with neck and shoulder pain followed by orthopnea and left arm weakness. Electrodiagnostic testing showed left phrenic neuropathy and denervation in bilateral C5 and C6 myotomes. He also had elevated liver enzymes, which led to the diagnosis of acute hepatitis E. This is the first case of neuralgic amyotrophy associated with hepatitis E in the United States. Hepatitis E should be considered in patients with neuralgic amyotrophy, particularly men with bilateral symptoms, and if there is unexplained elevation of transaminases. The role of antiviral therapy remains unclear.
Cutaneous Malignant Melanoma With Rhabdoid Morphology and Smooth Muscle Differentiation: A Challenging Histopathologic Diagnosis
Authors: Prieto-Torres Lucía , Alegría-Landa Victoria , Llanos Concepción , Córdoba Alicia , Kutzner Heinz , Requena Luis 
Published: November 2016

Abstract:Divergent differentiation or metaplastic change is a rare feature exhibited occasionally in malignant melanoma (MM), which is characterized by the development of morphologically, immunochemically, and/or ultrastructurally nonmelanocytic cells within the tumor. Smooth muscle differentiation in MM is an exceedingly rare phenomenon reported only in a few cases in the literature. We report the case of a 69-year-old woman who presented with a pure dermal amelanotic MM with smooth muscle cell differentiation and an area of rhabdoid morphology, which made the accurate histopathologic diagnostic of MM challenging.
Is Trough Concentration of Vancomycin Predictive of the Area Under the Curve? A Clinical Study in Elderly Patients
Authors: Bel Kamel Anis , Bourguignon Laurent , Marcos Micaela , Ducher Michel , Goutelle Sylvain 
Published: November 2016

Background:Current guidelines suggest that vancomycin trough concentrations (Cmin) between 15 and 20 mg/L should be achieved to optimize vancomycin exposure and effect. The objective of this study was to analyze the correlation between vancomycin Cmin and the area under the concentration–time curve (AUC) and assess the ability to predict an AUC target of 400 mg·h/L based on Cmin.Methods:A retrospective analysis of vancomycin therapeutic drug monitoring data collected in 95 elderly patients treated with intermittent intravenous vancomycin was performed. For each patient, individual pharmacokinetic parameters of vancomycin and AUC24were estimated from concentration measurements using a Bayesian approach. The relationship between vancomycin Cmin and AUC was studied using global and local correlation analysis as well as logistic regression with Receiver Operating Characteristic curve analysis.Results:The overall correlation between AUC24and Cmin was significant but moderate (R2= 0.51). When vancomycin Cmin was greater than 15 mg/L, the corresponding AUC24was >400 mg·h/L in 95% of cases. However, AUC24values >400 mg·h/L were obtained with Cmin < 15 mg/L in more than 30% of the cases. The logistic regression analysis identified a Cmin value of 10.8 mg/L as the optimal predictor of AUC24> 400 mg·h/L.Conclusions:The results of this study indicate that the recommended target range of 15–20 mg/L for vancomycin Cmin seems acceptable for controlling vancomycin exposure, although a value of approximately 11 mg/L appears to be optimal and may be safer.
BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION ASSOCIATED WITH RENAL CANCER: THE IMPORTANCE OF INDOCYANINE GREEN ANGIOGRAPHY AND EARLY DIAGNOSIS
Authors: Kniggendorf Vinicius F. , Neto Elmar T. , Maia Elizabeth M. , Grando Joao P. S. , Bardal Anne M. C. , Beato Patrícia M. M. , Torres Caroline C. , Maia Mauricio 
Published: November 2016

Purpose:
To report a case of bilateral diffuse uveal melanocytic proliferation associated with renal carcinoma and to illustrate the importance of ancillary examinations to early diagnosis and treatment.

Design:
Clinical case report.

Methods:
A 56-year-old man reported a 3-day history of visual impairment and scotoma in the right eye. An ophthalmoscopic examination, visual field test, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and systemic evaluation were performed.

Results:
Fundus examination showed multiple nevus-like uveal pigmented lesions bilaterally. Optical coherence tomography showed a subfoveal serous retinal detachment and focal loss of the retinal pigment epithelium with adjacent areas of retinal pigment epithelial thickening in the right eye, explaining the scotoma on the visual field examination. Indocyanine green angiography showed multiple round areas of hypofluorescence corresponding to the nevus-like pigmented tumors seen on funduscopy, and retinal pigment epithelium damage corresponding to hypoautofluorescence on fundus autofluorescence imaging and window defects points seen on fluorescein angiography bilaterally. After bilateral diffuse uveal melanocytic proliferation diagnosis, a systemic workup showed clear cell carcinoma in the left kidney. Owing to the tumoral size, chemotherapy was administered.

Conclusion:
Renal carcinoma associated with bilateral diffuse uveal melanocytic proliferation is rare, and the patterns observed in the ancillary examinations, including indocyanine green angiography, are useful for early-stage diagnosis and immediate referral for systemic investigation and treatment.
Effect of Trabeculotomy on Corneal Endothelial Cell Loss in Cases of After Penetrating-Keratoplasty Glaucoma
Authors: Kusakabe Ayaka , Okumura Naoki , Wakimasu Koichi , Kayukawa Kanae , Kondo Masami , Koizumi Noriko , Sotozono Chie , Kinoshita Shigeru , Mori Kazuhiko 
Published: November 2016

Purpose:
The aim of this study was to evaluate the effect of trabeculotomy (TLO) on glaucoma and endothelial cell loss after penetrating keratoplasty (PK).

Methods:
A retrospective study was conducted on consecutive patients who underwent PK and in whom more than 24 months of follow-up was available. Patients were categorized into the PK+TLO group [ie, TLO for post-PK glaucoma (n = 10)] and the PK group [PK alone (n = 73)]. Intraocular pressure (IOP) was evaluated during each follow-up examination. Central corneal endothelium images were obtained and analyzed to determine corneal endothelial cell (CEC) density.

Results:
The mean duration period from original PK to TLO for secondary glaucoma was 25.5 ± 34.9 months in the PK+TLO group. Mean preoperative IOP in the PK+TLO group was 35.8 mm Hg, and decreased to 17.5 mm Hg at 24 months postoperative (P < 0.01). CEC density decreased in the same manner in both groups. In the PK+TLO group, mean CEC density was 1838 cells per square millimeter before TLO and decreased to 1195 cells per square millimeter at 24 months after TLO. In the PK group, mean CEC density decreased from 1870 to 1209 cells per square millimeter at each corresponding time point.

Conclusions:
TLO for post-PK glaucoma appeared to safely lower IOP, although repeated surgeries were required in some patients, and did not accelerate CEC loss.
Porous Versus Nonporous Orbital Implants After Enucleation for Uveal Melanoma: A Randomized Study
Authors: Ho Vivian W. M. , Hussain Rumana N. , Czanner Gabriela , Sen Julia , Heimann Heinrich , Damato Bertil E. 
Published: November 2016

Purpose:
To compare hydroxyapatite with acrylic implants after enucleation for uveal melanoma with respect to eyelid position, ocular motility, implant complications, and patient satisfaction.

Methods:
Patients undergoing primary enucleation for uveal melanoma between May 2005 and November 2012 at the Liverpool Ocular Oncology Centre, United Kingdom, were randomized between hydroxyapatite and acrylic implants. Questionnaires were sent to patients and ocularists to comment on the main outcomes.

Results:
A total of 416 patients were recruited in the study, of whom 281 were included, with 49.5% (139/281) and 50.5% (142/281) receiving a hydroxyapatite (HA) or acrylic (AC) implant. Mailed questionnaires completed at ≥18 months by patients showed no significant differences between the groups in eyelid position, prosthetic motility, socket complications, and patient satisfaction. Complications included implant extrusion (1% vs 4%), enophthalmos (26% vs 26%), and superior sulcus deformity (24% vs 24%) with HA and AC implants, respectively, (Fisher exact test p > 0.0125 in all, Bonferroni correction). Questionnaires completed by ocularists indicated no significant differences in eyelid opening, prosthetic motility, and other complications at 6 months (Fisher exact test, p > 0.05 in all); there was a higher prevalence of ptosis with AC than HA implants (46% vs 25%, p = 0.03) and a greater need for ocularists’ treatment with HA than AC (50% vs 28%, p = 0.03).

Conclusions:
Patient-reported outcomes after enucleation for uveal melanoma indicate no major differences between hydroxyapatite and acrylic implants in surgical outcomes and patient satisfaction. There was a higher prevalence of ptosis with AC and a greater need of ocularists’ visits with HA at around 6 months observed by ocularists.