bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Retrospective Study on Mycophenolic Acid Drug Interactions: Effect of Prednisone, Sirolimus, and Tacrolimus With MPA
Authors: Alvarez-Elías Ana C. , Yoo Elisa C. , Todorova Ekaterina K. , Singh Ram N. , Filler Guido 
Published: April 2017

Abstract:
Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), is widely used as an antirejection drug after renal transplantation. There is growing evidence supporting the notion that there is substantial variability in the intra- and interpatient exposure to MPA. Drug interactions involving MPA with tacrolimus, steroids, and sirolimus have been understudied. The objective of this study was to determine the relationship between MPA, steroids, tacrolimus, and sirolimus. MPA trough concentrations from 37 pediatric renal transplant recipients (mean age 7.6 years at transplant) followed for a median follow-up of 7.8 years were analyzed retrospectively and 2131 dose-normalized MPA trough concentrations were evaluated against all known covariates including all concomitant immunosuppressant drug doses and exposure, age, albumin, hematocrit, and estimated glomerular filtration rate (eGFR). Age, hematocrit, and estimated glomerular filtration rate affected the dose-normalized MPA trough concentrations. The authors used appropriate linear regression univariate models and created 5 different multivariate models to examine individual drug–drug interactions (DDIs). Although the authors' findings support the notion that there is a DDI between MMF and both sirolimus and steroids, the sample size was small, and these findings should be confirmed in future studies. The authors found no DDIs between tacrolimus and MMF, the prodrug of MPA. These findings are important because there is a tendency to under-dose MMF early and to overdose late after transplantation. The DDI between sirolimus and MMF has not been described. Although therapeutic drug monitoring of MMF therapy is often not performed, the data presented here indicate a necessity for therapeutic drug monitoring. This is especially true when converting from tacrolimus to sirolimus, as a way to avoid MPA underexposure and organ rejection.
Superficial Circumflex Iliac Artery Perforator Flap for Dorsalis Pedis Reconstruction
Authors: Tashiro Kensuke , Yamashita Shuji 
Published: April 2017

Summary:
Reconstruction of dorsalis pedis with soft tissue is challenging because it needs to preserve thin structure to ensure that the patient will be able to wear shoes. Here, we report the use of a thin superficial circumflex iliac artery perforator (SCIP) flap in dorsalis pedis reconstruction. A 67-year-old man presented with a third-degree burn, which exposed his extensor tendons. A thin SCIP flap from the left inguinal region measuring 15 × 4 cm was transferred to the dorsalis pedis region. Postoperatively, no major cosmetic or functional problems were observed. Because the invasiveness of the donor site is nearly same between SCIP flap and skin graft from inguinal region, SCIP flap is better solution in point of textural qualities for dorsalis pedis reconstruction.
Mammary Malignant Ulcer after Radiotherapy: Unpleasant Surprise
Authors: Vindigni Vincenzo , Kohlscheen Eva , Kraljic Tajna , Bassetto Franco , Pavan Chiara 
Published: April 2017

Summary:
We present a case of a woman, 79 years old, followed by Psychiatry for depressive episodes after breast cancer removal. She was operated on for ductal breast carcinoma in 1983. Afterward she was submitted to adjuvant radiotherapy. She came to our attention for a chronic skin ulcer that developed into the radio-treated area about 4 years ago. We performed a skin biopsy and programed adipose tissue grafts to promote wound healing. The result of the biopsy was unexpected: dermal localization of not differentiated breast carcinoma. She is currently under systemic chemotherapy treatment. The key message is to always perform a skin biopsy of a chronic skin ulcer developed after breast cancer removal before planning surgical reconstruction.
Inferior Limb Salvage by Combined Free-tissue Transfer and the Crane Principle Revisited
Authors: Thione Alessandro , Cavadas Pedro C. 
Published: April 2017

Summary:
Aggressive treatment of ischemia of the lower extremities has decreased the number of amputations in both diabetic and nondiabetic patients; combined vascular reconstruction and microvascular free-flap transfer has been used to improve distal perfusion and cover large tissue defects caused by the critical limb ischemia during the past 30 years. We present our experience with a 71-year-old diabetic patient who underwent revascularization with a vascular bypass and a simultaneous microvascular flap reconstruction for limb salvage after domestic trauma. An extension of the “crane” principle was used to solve bypass exposure due to wound late complication. After 1-year follow-up, the patient was able to walk without pain. Combining 3 well-established methods of arterial revascularization and free-flap transfer and the old “crane principle,” we achieved limb salvage, offering an alternative to below-knee amputation.
Immunogenicity of the Inactivated Japanese Encephalitis Virus Vaccine IXIARO in Children From a Japanese Encephalitis Virus-endemic Region
Authors: Dubischar Katrin L. , Kadlecek Vera , Sablan Benjamin , Borja-Tabora Charissa Fay , Gatchalian Salvacion , Eder-Lingelbach Susanne , Kiermayr Sigrid , Spruth Martin , Westritschnig Kerstin 
Published: April 2017

Background:
Japanese encephalitis (JE) is a major public health concern in Asia and poses a small but potentially fatal threat to travelers from nonendemic countries, including children. No JE vaccine for pediatric use has been available in Europe and the United States.

Methods:
Age-stratified cohorts of children between 2 months and 17 years received 2 doses of Vero cell-derived inactivated JE virus vaccine (IXIARO; Valneva Austria GmbH, Vienna, Austria) administered 28 days apart [<3 years, 0.25 mL (half adult dose); ≥3 years, 0.5 mL (full adult dose)]. Immunogenicity endpoints were seroconversion rate, 4-fold increase in JE neutralizing antibody titer and geometric mean titer assessed 56 days and 7 months after the first vaccination in 496 subjects of the intent-to-treat population. The immune response to JE virus at both time points was also analyzed according to prevaccination JE virus and dengue virus serostatus.

Results:
At day 56, seroconversion was attained in ≥99.2% of subjects with age-appropriate dosing, 4-fold increases in titer were reported for 77.4%–100% in various age groups, and geometric mean titers ranged from 176 to 687, with younger children having the strongest immune response. At month 7, seroconversion was maintained in 85.5%–100% of subjects. Pre-existing JE virus immunity did not impact on immune response at day 56; however, it led to a better persistence of protective antibody titers at month 7.

Conclusions:
IXIARO is highly immunogenic at both doses tested in the pediatric population, leading to protective antibody titers at day 56 in >99% of subjects who received the age-appropriate dose.
Elevated Immune Response Among Children 4 Years of Age With Pronounced Local Adverse Events After the Fifth Diphtheria, Tetanus, Acellular Pertussis Vaccination
Authors: van der Lee Saskia , Kemmeren Jeanet M. , de Rond Lia G. H. , Öztürk Kemal , Westerhof Anneke , de Melker Hester E. , Sanders Elisabeth A. M. , Berbers Guy A. M. , van der Maas Nicoline A. T. , Rümke Hans C. , Buisman Anne-Marie 
Published: April 2017

Background:
In the Netherlands, acellular pertussis vaccines replaced the more reactogenic whole-cell pertussis vaccines. This replacement in the primary immunization schedule of infants coincided with a significant increase in pronounced local adverse events (AEs) in 4 years old children shortly after the administration of a fifth diphtheria, tetanus, acellular pertussis and inactivated polio (DTaP-IPV) vaccine. The objective of this study was to investigate possible differences in vaccine antigen-specific immune responses between children with and without a pronounced local AE after the fifth DTaP-IPV vaccination.

Methods:
Blood was sampled in 2 groups of 4-year-olds: a case group reporting pronounced local swelling and/or erythema up to extensive limb swelling at the injection site (n = 30) and a control group (n = 30). Peripheral blood mononuclear cells were stimulated with individual vaccine antigens. Plasma antigen-specific IgG, IgG subclass and total IgE concentrations and T-cell cytokine [interferon-gamma, interleukin (IL)-13, IL-17 and IL-10] production by stimulated peripheral blood mononuclear cells were determined by multiplex bead-based fluorescent multiplex immunoassays.

Results:
In children with AEs, significantly higher total IgE and vaccine antigen-specific IgG and IgG4 responses as well as levels of the T-helper 2 (Th2) cytokine IL-13 were found after pertussis, tetanus and diphtheria stimulation compared with controls.

Conclusions:
Children with pronounced local reactions show higher humoral and cellular immune responses. Acellular vaccines are known to skew toward more Th2 responses. The pronounced local AEs may be associated with more Th2 skewing after the fifth DTaP-IPV vaccination, but other biologic factors may also impact the occurrence of these pronounced local reactions.
Differentiating Delirium From Sedative/Hypnotic-Related Iatrogenic Withdrawal Syndrome: Lack of Specificity in Pediatric Critical Care Assessment Tools*
Authors: Madden Kate , Burns Michele M. , Tasker Robert C. 
Published: April 2017

Objectives:
To identify available assessment tools for sedative/hypnotic iatrogenic withdrawal syndrome and delirium in PICU patients, the evidence supporting their use, and describe areas of overlap between the components of these tools and the symptoms of anticholinergic burden in children.

Data Sources:
Studies were identified using PubMed and EMBASE from the earliest available date until July 3, 2016, using a combination of MeSH terms “delirium,” “substance withdrawal syndrome,” and key words “opioids,” “benzodiazepines,” “critical illness,” “ICU,” and “intensive care.” Review article references were also searched.

Study Selection:
Human studies reporting assessment of delirium or iatrogenic withdrawal syndrome in children 0–18 years undergoing critical care. Non-English language, exclusively adult, and neonatal intensive care studies were excluded.

Data Extraction:
References cataloged by study type, population, and screening process.

Data Synthesis:
Iatrogenic withdrawal syndrome and delirium are both prevalent in the PICU population. Commonly used scales for delirium and iatrogenic withdrawal syndrome assess signs and symptoms in the motor, behavior, and state domains, and exhibit considerable overlap. In addition, signs and symptoms of an anticholinergic toxidrome (a risk associated with some common PICU medications) overlap with components of these scales, specifically in motor, cardiovascular, and psychiatric domains.

Conclusions:
Although important studies have demonstrated apparent high prevalence of iatrogenic withdrawal syndrome and delirium in the PICU population, the overlap in these scoring systems presents potential difficulty in distinguishing syndromes, both clinically and for research purposes.
Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy
Authors: Granovsky Yelena , Nahman-Averbuch Hadas , Khamaisi Mogher , Granot Michal 
Published: April 2017

Abstract

Introduction:
Alleviation of pain, by either medical or surgical therapy, is accompanied by transition from less efficient, or pro-nociceptive, to efficient conditioned pain modulation (CPM). Spontaneous decrease or resolution of pain with disease progression is reported for some patients with painful diabetic neuropathy (PDN).

Objectives:
To explore whether CPM changes similarly in parallel to spontaneous resolution of pain in PDN patients.

Methods:
In this cross-sectional study, thirty-three patients with PDN underwent psychophysical assessment of pain modulation on the forearm, remote from the clinical pain.

Results:
Pain duration was not correlated with neuropathic pain intensity, yet, it correlated with CPM efficiency; patients with longer pain duration had same pain level, but more efficient CPM than those with short-pain duration (ρ = −0.417; P = 0.025, Spearman correlation). Patients with pain more than 2 years (median split) expressed efficient CPM that was not different from that of healthy controls. These patients also had lower temporal summation of pain than the short-pain duration patients group (P < 0.05). The 2 patient groups did not differ in clinical pain characteristics or use of analgesics.

Conclusion:
Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to “normalize” with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.
Women report higher pain intensity at a lower level of inflammation after knee surgery compared with men
Authors: Solheim Nina , Östlund Simon , Gordh Torsten , Rosseland Leiv Arne 
Published: April 2017

AbstractIntroduction and Objectives:We previously found that women report more pain after knee arthroscopic procedures than men. It remains unclear whether this is due to different biochemical responses or nociceptive mechanisms.Methods:We analyzed acute pain-related inflammatory markers in a clinical model of patient self-reported pain immediately after knee surgery. To simultaneously measure 92 inflammatory biomarkers, we used the proximity extension assay with the Proseek Multiplex Inflammation I panel (Olink Bioscience, Uppsala, Sweden). Knee surgery was performed under general anesthesia with propofol and remifentanil. Analgesic drugs were only administered on patient request.Results:Women were 4.9 times more likely to report moderate or severe pain than men (95% confidence interval, 1.2–19.6,P= 0.024). Patient age, preoperative pain, and surgery duration were not significant factors. We analyzed synovial fluids from 44 patients (23 women, 21 men). After false discovery rate correction, MMP-10 was the only biomarker that was higher among men (P= 0.01). Linear discriminant analysis showed that 3 proteins (IL-8, CCL-4, and MCP-2) were expressed at higher levels in men, with differences of >1 normalized protein expression. No proteins were overexpressed by >1 normalized protein expression in women.Conclusion:Acute pain after knee arthroscopy was more intense in women, but pro-inflammatory biomarkers and MMP-10 were higher in men. Further knowledge of cytokine function is required before concluding that the disparities in biomarker expression are clinically unimportant. The similar biochemical signaling between sexes suggests that central mechanisms are of greater importance in sex-specific joint pain perception.
Ultrasound Molecular Imaging of Inflammation in Mouse Abdominal Aorta
Authors: Wang Shiying , Unnikrishnan Sunil , Herbst Elizabeth B. , Klibanov Alexander L. , Mauldin Frank William , Hossack John A. 
Published: April 2017

Objectives
The aim of this study was to demonstrate a new clinically translatable ultrasound molecular imaging approach, modulated acoustic radiation force-based imaging, which is capable of rapid and reliable detection of inflammation as validated in mouse abdominal aorta.

Materials and Methods
Animal studies were approved by the Institutional Animal Care and Use Committee at the University of Virginia. C57BL/6 mice stimulated with tumor necrosis factor α, or fed with a high-fat diet, were used as inflammation (MInflammation) and diet-induced obesity (DIO) (MDIO) models, respectively. C57BL/6 mice, not exposed to tumor necrosis factor α or DIO, were used as controls (MNormal). P-selectin–targeted (MBP-selectin), vascular cell adhesion molecule (VCAM)-1–targeted (MBVCAM-1), and isotype control (MBControl) microbubbles were synthesized by conjugating anti–P-selectin, anti–VCAM-1, and isotype control antibodies to microbubbles, respectively. The abdominal aortas were imaged for 180 seconds during a constant infusion of microbubbles. A parameter, residual-to-saturation ratio (RSR), was used to assess P-selectin and VCAM-1. Statistical analysis was performed with the Student t test.

Results
For the inflammation model, RSR of the MInflammation + MBP-selectin group was significantly higher (40.9%, P < 0.0005) than other groups. For the DIO model, RSR of the MDIO + MBVCAM-1 group was significantly higher (60.0%, P < 0.0005) than other groups. Immunohistochemistry staining of the abdominal aorta confirmed the expression of P-selectin and VCAM-1.

Conclusions
A statistically significant assessment of P-selectin and VCAM-1 in mouse abdominal aorta was achieved. This technique yields progress toward rapid targeted molecular imaging in large blood vessels and thus has the potential for early diagnosis, treatment selection, and risk stratification of atherosclerosis.
Computed Tomography of the Head and Neck Region for Tumor Staging—Comparison of Dual-Source, Dual-Energy and Low-Kilovolt, Single-Energy Acquisitions
Authors: May Matthias Stefan , Bruegel Joscha , Brand Michael , Wiesmueller Marco , Krauss Bernhard , Allmendinger Thomas , Uder Michael , Wuest Wolfgang 
Published: April 2017

Purpose
The aim of this study was to intra-individually compare the image quality obtained by dual-source, dual-energy (DSDE) computed tomography (CT) examinations and different virtual monoenergetic reconstructions to a low single-energy (SE) scan.

Materials and Methods
Third-generation DSDE-CT was performed in 49 patients with histologically proven malignant disease of the head and neck region. Weighted average images (WAIs) and virtual monoenergetic images (VMIs) for low (40 and 60 keV) and high (120 and 190 keV) energies were reconstructed. A second scan aligned to the jaw, covering the oral cavity, was performed for every patient to reduce artifacts caused by dental hardware using a SE-CT protocol with 70-kV tube voltages and matching radiation dose settings. Objective image quality was evaluated by calculating contrast-to-noise ratios. Subjective image quality was evaluated by experienced radiologists.

Results
Highest contrast-to-noise ratios for vessel and tumor attenuation were obtained in 40-keV VMI (all P < 0.05). Comparable objective results were found in 60-keV VMI, WAI, and the 70-kV SE examinations. Overall subjective image quality was also highest for 40-keV, but differences to 60-keV VMI, WAI, and 70-kV SE were nonsignificant (all P > 0.05). High kiloelectron volt VMIs reduce metal artifacts with only limited diagnostic impact because of insufficiency in case of severe dental hardware. CTDIvol did not differ significantly between both examination protocols (DSDE: 18.6 mGy; 70-kV SE: 19.4 mGy; P = 0.10).

Conclusions
High overall image quality for tumor delineation in head and neck imaging were obtained with 40-keV VMI. However, 70-kV SE examinations are an alternative and modified projections aligned to the jaw are recommended in case of severe artifacts caused by dental hardware.
Impact of Distance to Treatment Center on Care Seeking for Pelvic Floor Disorders
Authors: English Emily , Rogo-Gupta Lisa 
Published: April 2017

Objective
The aim of this study was to evaluate the impact of distance from residence to treatment center on access to care for female pelvic floor disorders at an academic institution.

Methods
A retrospective cross-sectional study was conducted of women seen for pelvic floor disorders at an academic institution from 2008 to 2014. Patient characteristics were extracted from charts. Geographical and US census data was obtained from public records and used to calculate distance from patient residence to physician office. Statistical analysis was performed using R Software (Version 0.98.1102) and Microsoft Excel (Version 14.4.7). Statistical significance was defined as a 2-sided P value of less than 0.05, and the χ2 test was used to determine associations of categorical variables.

Results
A total of 3015 patients were included in the analysis. The mean distance traveled was 93 miles. Thirty percent of patients traveled more than 50 miles. Many patients (43%) reported having the symptoms for more than 2 years. Patients who traveled farther were significantly more likely to be white, English-speaking, and with pelvic organ prolapse as primary complaint. These patients were more likely to plan surgery at the first visit than patients who traveled less far (29% vs 14%). Patients who traveled farther were also more likely to live in counties with a low percentage of persons older than 65 years and low percentage of female inhabitants.

Conclusions
Women who travel the farthest for treatment of pelvic floor disorders have experienced the symptoms for longer duration and are more willing to plan surgery at presentation. These women also come from counties with fewer elderly women, suggesting future outreach care should focus on similar geographic areas.
The effect of common inversion polymorphismsIn(2L)t and In(3R)Moon patterns of transcriptional variation inDrosophila melanogaster
Authors: Lavington Erik , Kern Andrew D. 
Published: April 2017

AbstractChromosomal inversions are an ubiquitous feature of genetic variation. Theoretical models describe several mechanisms by which inversions can drive adaptation and be maintained as polymorphisms. While inversions have been shown previously to be under selection, or contain genetic variation under selection, the specific phenotypic consequences of inversions leading to their maintenance remain unclear. Here we use genomic sequence and expression data from the Drosophila Genetic Reference Panel to explore the effects of two cosmopolitan inversions,In(2L)tandIn(3R)Mo, on patterns of transcriptional variation. We demonstrate that each inversion has a significant effect on transcript abundance for hundreds of genes across the genome. Inversion affected loci (IAL) appear both within inversions as well as on unlinked chromosomes. Importantly, IAL do not appear to be influenced by the previously reported genome-wide expression correlation structure. We found that five genes involved with sterol uptake, four of which are Niemann-Pick Type 2 orthologs, are upregulated in flies withIn(3R)Mobut do not have SNPs in LD with the inversion. We speculate that this upregulation is driven by genetic variation inmod(mdg4)that is in LD withIn(3R)Mo. We find that there is little evidence for regional or position effect of inversions on gene expression at the chromosomal level but do find evidence for the distal breakpoint ofIn(3R)Mointerrupting one gene and possibly disassociating the two flanking genes from regulatory elements.
Light GuidedIn-vivoActivation of Innate Immune Cells with Photocaged TLR 2/6 Agonist
Authors: Ah Ryu Keun , McGonnigal Bethany , Moore Troy , Mancini Rock J. , Esser-Kahn Aaron P. 
Published: April 2017

AbstractThe complexity of the immune system creates challenges in exploring its importance and robustness. To date, there have been few techniques developed to manipulate individual components of the immune system in an in vivo environment. Here we show a light-based dendritic cell (DC) activation allowing spatial and temporal control of immune activation in vivo. Additionally, we show time dependent changes in RNA profiles of the draining lymph node, suggesting a change in cell profile following DC migration and indicating that the cells migrating have been activated towards antigen presentation.