bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal porogen platforms for calcium phosphate cement degradation
Authors: Lodoso‐Torrecilla Irene , Grosfeld Eline‐Claire , Marra Abe , Smith Brandon T , Mikos Antonios G , Ulrich Dietmar JO , Jansen John A , van den Beucken Jeroen JJP
Published: March 2019

Calcium phosphate cements (CPCs) represent excellent bone substitute materials due to their biocompatibility and injectability. However, their poor degradability and lack of macroporosity limits bone regeneration. The addition of poly(d,l‐lactic‐co‐glycolic acid) (PLGA) particles improves macroporosity and therefore late stage material degradation. CPC degradation and hence, bone formation at an early stage remains challenging, due to the delayed onset of PLGA degradation (i.e., after 2–3 weeks). Consequently, we here explored multimodal porogen platforms based on sucrose porogens (for early pore formation) and PLGA porogens (for late pore formation) to enhance CPC degradation and analyzed mechanical properties, dynamic in vitro degradation and in vivo performance in a rat femoral bone defect model. Porogen addition to CPC showed to decrease compressive strength of all CPC formulations; transition of the crystal phase upon in vitro incubation increased compressive strength. Although dynamic in vitro degradation showed rapid sucrose dissolution within 1 week, no additional effects on CPC degradation or bone formation were observed upon in vivo implantation. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1713–1722, 2019.
Mechanical Competence and Bone Quality Develop During Skeletal Growth
Authors: Zimmermann Elizabeth A , Riedel Christoph , Schmidt Felix N , Stockhausen Kilian E , Chushkin Yuriy , Schaible Eric , Gludovatz Bernd , Vettorazzi Eik , Zontone Federico , Püschel Klaus , Amling Michael , Ritchie Robert O , Busse Björn
Published: March 2019

Bone fracture risk is influenced by bone quality, which encompasses bone's composition as well as its multiscale organization and architecture. Aging and disease deteriorate bone quality, leading to reduced mechanical properties and higher fracture incidence. Largely unexplored is how bone quality and mechanical competence progress during longitudinal bone growth. Human femoral cortical bone was acquired from fetal (n = 1), infantile (n = 3), and 2- to 14-year-old cases (n = 4) at the mid-diaphysis. Bone quality was assessed in terms of bone structure, osteocyte characteristics, mineralization, and collagen orientation. The mechanical properties were investigated by measuring tensile deformation at multiple length scales via synchrotron X-ray diffraction. We find dramatic differences in mechanical resistance with age. Specifically, cortical bone in 2- to 14-year-old cases exhibits a 160% greater stiffness and 83% higher strength than fetal/infantile cases. The higher mechanical resistance of the 2- to 14-year-old cases is associated with advantageous bone quality, specifically higher bone volume fraction, better micronscale organization (woven versus lamellar), and higher mean mineralization compared with fetal/infantile cases. Our study reveals that bone quality is superior after remodeling/modeling processes convert the primary woven bone structure to lamellar bone. In this cohort of female children, the microstructural differences at the femoral diaphysis were apparent between the 1- to 2-year-old cases. Indeed, the lamellar bone in 2- to 14-year-old cases had a superior structural organization (collagen and osteocyte characteristics) and composition for resisting deformation and fracture than fetal/infantile bone. Mechanistically, the changes in bone quality during longitudinal bone growth lead to higher fracture resistance because collagen fibrils are better aligned to resist tensile forces, while elevated mean mineralization reinforces the collagen scaffold. Thus, our results reveal inherent weaknesses of the fetal/infantile skeleton signifying its inferior bone quality. These results have implications for pediatric fracture risk, as bone produced at ossification centers during children's longitudinal bone growth could display similarly weak points. © 2019 American Society for Bone and Mineral Research.
Caveolin‐1 regulates human trabecular meshwork cell adhesion, endocytosis, and autophagy
Authors: Wu Zhenggen , Huang Chukai , Xu Ciyan , Xie Lijing , Liang Jia‐Jian , Liu Lifang , Pang Chi Pui , Ng Tsz Kin , Zhang Mingzhi
Published: March 2019

Impaired trabecular meshwork (TM) outflow is implicated in the pathogenesis of primary open‐angle glaucoma (POAG). We previously identified the association of a caveolin‐1 (CAV1) variant with POAG by genome‐wide association study. Here we report a study of
CAV1 knockout (KO) effect on human TM cell properties. We generated human
CAV1‐KO TM cells by CRISPR/Cas9 technology, and we found that the
CAV1‐KO TM cells less adhered to the surface coating than the wildtype TM cells by 69.34% (
P < 0.05), but showed no difference in apoptosis. Higher endocytosis ability of dextran and transferrin was also observed in the
CAV1‐KO TM cells (4.37 and 1.89‐fold respectively,
P < 0.001), compared to the wildtype TM cells. Moreover, the
CAV1‐KO TM cells had higher expression of extracellular matrix‐degrading enzyme genes (
ADMTS13 and
MMP14) as well as autophagy‐related genes (
ATG7 and
BECN1) and protein (LC3B‐II) than the wildtype TM cells. In summary, results from this study showed that the
CAV1‐KO TM cells have reduced adhesion with higher extracellular matrix‐degrading enzyme expression, but increased endocytosis and autophagy activities, indicating that
CAV1 could be involved in the regulation of adhesion, endocytosis, and autophagy in human TM cells.
Ceding and Succeeding: How the Altruistic Can Benefit from the Selfish in Joint Decisions
Authors: Lowe Michael , Nikolova Hristina , Miller Chadwick J. , Dommer Sara Loughran
Published: March 2019

We examine how the interplay of two partners’ interpersonal orientations (selfish vs. altruistic) in a decision‐making dyad impacts the extent to which the joint decision matches each partners’ individual a priori preferences. Two experiments, in which we manipulate and measure interpersonal orientations, as well as examine real consumption decisions, demonstrate the benefit of mismatching interpersonal orientations (selfish‐altruistic) in dyadic decisions. Specifically, altruistic and selfish consumers reach joint decisions that better reflect their individual preferences when working with a partner who has the opposite interpersonal orientation (heterogeneous dyad) versus a matching one (homogeneous dyad). Initial evidence suggests that this effect occurs because homogeneous dyads are more prone to engage in negotiation (communication that involves departure from one's initial position to a mutually serving position) than heterogeneous dyads. This leads homogeneous dyads to focus more on equally preferred options than on their own most preferred options, which pushes them further down both partners’ preferences lists. This research contributes to the literature on joint decision making and has important implications for consumer well‐being.
GLIM criteria for the diagnosis of malnutrition – A consensus report from the global clinical nutrition community
Authors: Cederholm T. , Jensen G.L. , Correia M.I.T.D. , Gonzalez M.C. , Fukushima R. , Higashiguchi T. , Baptista G. , Barazzoni R. , Blaauw R. , Coats A.J.S. , Crivelli A.N. , Evans D.C. , Gramlich L. , Fuchs‐Tarlovsky V. , Keller H. , Llido L. , Malone A. , Mogensen K.M. , Morley J.E. , Muscaritoli M. , Nyulasi I. , Pirlich M. , Pisprasert V. , de van der Schueren M.A.E. , Siltharm S. , Singer P. , Tappenden K. , Velasco N. , Waitzberg D. , Yamwong P. , Yu J. , Van Gossum A. , Compher C. ,   GLIM Core Leadership Committee, GLIM Working Group
Published: March 2019

Rationale

This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings.

Methods

In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face‐to‐face meetings, telephone conferences, and e‐mail communications.

Results

A two‐step approach for the malnutrition diagnosis was selected, i.e., first screening to identify “at risk” status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology‐related diagnosis categories.

Conclusion

A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re‐considered every 3–5 years.
Symptomatic severe hypophosphatemia after intravenous ferric carboxymaltose
Authors: Fang Wendy , McMahon Lawrence P , Bloom Stephen , Garg Mayur
Published: March 2019

Intravenous iron is commonly prescribed for treatment of iron deficiency, with modern formulations demonstrating an acceptable safety profile in the majority of patients. We report the case of a patient who was hospitalised with muscle pain, deteriorating mobility and multiple fractures following repeated ferric carboxymaltose infusions. Investigations revealed severe hypophosphatemia with serum phosphate of 0.27 mmol/L, 25‐hydroxyvitamin D (25OHD) level of 32 nmol/L and insufficiency fractures of the sacrum and L5 transverse process. The patient's hypophosphatemia was corrected with several infusions of intravenous phosphate, as well as oral phosphate and calcitriol, with subsequent resolution of her muscle aches, back pain and immobility.

The risk of persistent hypophosphatemia and osteomalacia may be higher with iron carboxymaltose than other iron formulations and a transient increase in intact fibroblast growth factor‐23 with reduced renal tubular phosphate absorption has been postulated as the key mechanism. This risk appears increased by repeated iron infusions, underlying malnutrition, hypophosphatemia at baseline, vitamin D deficiency, hyperparathyroidism or anti‐resorptive medication use. The true risk and incidence of hypophosphatemia need to be clarified so that appropriate monitoring, prevention and treatment strategies can be developed.
Effects of duration of initial treatment on postoperative complications in pancreatic cancer
Authors: Yamada Suguru , Takami Hideki , Sonohara Fuminori , Hayashi Masamichi , Fujii Tsutomu , Kodera Yasuhiro
Published: March 2019

Background

We analyzed the clinical impact of chemotherapy or chemoradiotherapy as initial treatment (IT), focusing on treatment duration, on morbidity and mortality in patients with resected pancreatic ductal adenocarcinoma.

Methods

We enrolled 509 consecutive patients, with 417 in the upfront surgery group and 92 in the IT group. The IT group was subdivided into 72 patients treated for <8 months and 20 treated ≥8 months. We compared rates of postoperative Clavien–Dindo grade ≥III complications between the groups. Multivariate logistic regression analysis was used to find independent predictors of complications.

Results

The upfront surgery and IT groups did not significantly differ in overall postsurgical complications. In contrast, rates of overall complications significantly differed between the <8 months and ≥8 months IT groups, although their background clinical factors did not differ. In multivariate analysis, operative procedure (distal pancreatectomy and distal pancreatectomy with celiac axis resection) (odds ratio [OR] 6.950, P = 0.0416) and IT ≥8 months (OR 4.508, P = 0.0156) were independent predictive factors for postoperative complications.

Conclusions

Postoperative complications were significantly higher in the ≥8 months IT group, and multivariate analysis demonstrated that operative procedure and ≥8 months IT were independent predictive factors.
Monoexponential, Biexponential, and stretched‐exponential models using diffusion‐weighted imaging: A quantitative differentiation of breast lesions at 3.0T
Authors: Jin Ya‐Nan , Zhang Yan , Cheng Jing‐Liang , Zheng Dan‐Dan , Hu Ying
Published: March 2019

Background

Diffusion‐weighted imaging (DWI) plays an important role in the differentiation of malignant and benign breast lesions.

Purpose

To investigate the utility of various diffusion parameters obtained from monoexponential, biexponential, and stretched‐exponential DWI models in the differential diagnosis of breast lesions.

Study Type

Prospective.

Population

Sixty‐one patients (age range: 25–68 years old; mean age: 46 years old) with 31 malignant lesions, 42 benign lesions, and 28 normal breast tissues diagnosed initially by clinical palpation, ultrasonography, or conventional mammography were enrolled in the study from January to September 2016.

Field Strength

3.0T MR scanner, T1WI, T2WI, DWI (conventional and multi‐b values), dynamic contrast‐enhanced.

Assessment

The apparent diffusion coefficient (ADC) was calculated by monoexponential analysis. The diffusion coefficient (ADCslow), pseudodiffusion coefficient (ADCfast), and perfusion fraction (f) were calculated using the biexponential model. The distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α) were obtained using a stretched‐exponential model. All parameters were compared for malignant tumors, benign tumors, and normal breast tissues. A receiver operating characteristic curve was used to compare the ability of these parameters, in order to differentiate benign and malignant breast lesions.

Statistical Tests

All statistical analyses were performed using statistical software (SPSS).

Results

ADC, ADCslow, f, DDC, and α values were significantly lower in malignant tumors when compared with normal breast tissues and benign tumors (P < 0.05). However, ADC and f had higher area under the receiver operating characteristic curve (AUC) values (0.889 and 0.919, respectively).

Data Conclusion

The parameters derived from the biexponential and stretched‐exponential DWI could provide additional information for differentiating between benign and malignant breast tumors when compared with conventional diffusion parameters.

Level of Evidence: 4

Technical Efficacy: Stage 4

J. Magn. Reson. Imaging 2019;50:1461–1467.
Neuroepigenetics of arousal: Gamma oscillations in the pedunculopontine nucleus
Authors: Garcia‐Rill Edgar
Published: March 2019

Four major discoveries on the function of the pedunculopontine nucleus (PPN) have significantly advanced our understanding of the role of arousal in neurodegenerative disorders. The first was the finding that stimulation of the PPN‐induced controlled locomotion on a treadmill in decerebrate animals, the second was the revelation of electrical coupling in the PPN and other arousal and sleep–wake control regions, the third was the determination of intrinsic gamma band oscillations in PPN neurons, and the last was the discovery of gene transcription resulting from the manifestation of gamma activity in the PPN. These discoveries have led to novel therapies such as PPN deep brain stimulation (DBS) for Parkinson’s disease (PD), identified the mechanism of action of the stimulant modafinil, determined the presence of separate mechanisms underlying gamma activity during waking versus REM sleep, and revealed the presence of gene transcription during the manifestation of gamma band oscillations. These discoveries set the stage for additional major advances in the treatment of a number of disorders.
Responses of wheat to zinc sulfate fertilizer and plant growth‐promoting rhizobacteria under cadmium stress in soil
Authors: Safari Marzieh , Alishah Farzaneh Nahari , Dolatabad Hossein Kari , Ndu Udonna , Schulthess Cristian P. , Sorooshzadeh Ali
Published: March 2019

Cadmium (Cd) is a major pollutant in soils as a result of extensive use of fertilizers, mining and industrial discharges. Zinc (Zn) and certain bacterial species have been known to alleviate Cd toxicity in plants. In this study, the individual and combined effects of the application of Zn and Pseudomonas species with the aim of reducing Cd stress in wheat cultivars were investigated. Plants (durum wheat and bread wheat) were exposed to different concentrations of Cd and Zn, and either P. putida or P. fluorescens in a growth chamber. Concentrations of Zn, Cd, chlorophyll (Chl), carotenoid, hydrogen peroxide (H2O2), and malondialdehyde (MDA), as well as antioxidant enzyme activities were assayed. The addition of Zn in soils reduced the toxicity of Cd in durum wheat more than in bread wheat even though there was more uptake of Zn in bread wheat. Analysis of variance showed that by using Zn fertilizer and Pseudomonas species the amounts of peroxidase (POD), polyphenoloxidase (PPO), MDA, and H2O2 were reduced at three growth stages. Surprisingly, with increasing Zn concentration, Cd concentration in plant tissue was slightly increased, which suggests that adding Zn to soil could facilitate Cd desorption from soil particles. Application of Pseudomonas and Zn could be a promising solution to reduce detrimental effects of Cd, especially in durum wheat.
Spatially tracking carbon through the root–rhizosphere–soil system using laser ablation‐IRMS
Authors: Denis Elizabeth H. , Ilhardt Peter D. , Tucker Abigail E. , Huggett Nicholas L. , Rosnow Joshua J. , Moran James J.
Published: March 2019

The intimate relationships between plant roots, rhizosphere, and soil are fostered by the release of organic compounds from the plant into soil through various forms of rhizodeposition and the simultaneous harvesting of nutrients from the soil to the plant. Here we present a method to spatially track and map the migration of plant‐derived carbon (C) through roots into the rhizosphere and surrounding soil using laser ablation‐isotope ratio mass spectrometry (LA‐IRMS). We used switchgrass microcosms containing soil from field plots at the Kellogg Biological Station (Hickory Corners, Michigan, USA) which have been cropped with switchgrass since 2008. We used a 13CO2 tracer to isotopically label switchgrass plants for two diel cycles and tracked subsequent movement of labeled C using the spatially specific (< 100 µm resolution) δ13C analysis enabled by LA‐IRMS. This approach permitted assessment of variable C flow through different roots and enabled mapping of spatial variability of C allocation to the rhizosphere. Highly 13C‐enriched C (consistent with production during the 13CO2 application period) extended ≈ 0.5–1 mm from the root into the soil, suggesting that the majority of recent plant‐derived C was within this distance of the root after 48 h. Tracking the physical extent of root exudation into the rhizosphere can help evaluate the localization of plant‐microbe interactions in highly variable subsurface environments, and the use of the isotopic label can differentiate freshly fixed C (presumably from root exudates) from other types of subsurface C (e.g., plant necromass and microbial turnover). The LA‐IRMS technique may also serve as a valuable screening technique to identify areas of high activity for additional microbial or geochemical assays.
Modified normalization method in in vivo stratum corneum analysis using confocal Raman microscopy to compensate nonhomogeneous distribution of keratin
Authors: Choe Chunsik , Choe Sehyok , Schleusener Johannes , Lademann Jürgen , Darvin Maxim E.
Published: March 2019

The quantitative determination of substance concentration in the stratum corneum (SC) is important for profiling of the skin barrier function‐related parameters and for investigating drug delivery through the SC. Hereby, confocal Raman microscopy (CRM) is a widely used method, which can be applied noninvasively and in vivo. Most analysis methods are based on the assumption that keratin is distributed homogeneously throughout the SC. In this study, the depth profiles of keratin‐related Raman peaks (1,003, 1,450, 1,650, and 2,935 cm−1) are investigated in detail. It was shown that each of these Raman peaks can be used for the precise determination of the skin surface position, which is important in case of overlapping of these with Raman bands associated to a formulation for treated skin. For correction of the depth‐dependent signal attenuation, that is, normalization, the 1,450, 1,650, and 2,935 cm−1 peaks can be used, whereas the 1,003 cm−1 peak cannot. Further analysis shows that the keratin concentration is nonhomogeneous throughout the SC and decreases towards its bottom due to water increase. Thus, the concentration of certain substances in the SC, such as urea, lipids, water, or natural moisturizing factor, determined using normalization on the keratin peak intensity, is overestimated in the deep SC layers starting from 30% SC depth. The correction coefficients were calculated for all four Raman peaks and for all SC depths with 10% increments. It was determined that at the bottom of the SC, the values obtained using keratin normalization should be multiplied by 0.88 (for 1,003 or 1,450 cm−1), 0.94 (for 1,650 cm−1), and 0.92 (for 2,935 cm−1) in order to compensate nonhomogeneous distribution of keratin in the SC. Thus, original values are overestimated at the SC bottom by 6–12%. The presented correction mechanism is proposed to be used for further correction.
A comparison of the chemical composition and antioxidant activity of several new early‐ to mid‐season apple cultivars for a warmer climate with traditional cultivars
Authors: Kim Inhwan , Ku Kyung‐Hyung , Jeong Moon‐Cheol , Kim Sang Seop , Mitchell Alyson E , Lee Jihyun
Published: March 2019

Background

New early‐ to mid‐season apple cultivars are being developed to help address warmer growing seasons due to climate change. Free sugars, organic acids, total phenolic content, total flavonoid content, antioxidant activity and phenolic composition were determined in the pulp and peel of six new and six traditional apple cultivars. In addition, the phenolic profiles of apple peels were characterized using high‐resolution mass spectrometry. Forty‐eight polyphenol compounds were identified, by accurate mass, in apple peel.

Results

Compared to Fuji apples, a new apple cultivar, Decobell, contained 2.6‐ and 1.4‐fold higher levels of the sum of individual polyphenol levels in the peel and the pulp, respectively. Decobell apples showed similar sugar‐to‐acid ratio (0.27) to Fuji apples (0.25).

Conclusions

The results indicate that the Decobell cultivar could have the best quality characteristics in terms of sugar‐to‐acid ratios and health‐promoting activities due to the phenolic profiles. © 2019 Society of Chemical Industry
Variant hepatic arterial anatomy encountered during pancreatoduodenectomy does not influence postoperative outcomes or resection margin status: A matched pair analysis of 105 patients
Authors: Alexakis Nicholas , Bramis Konstandinos , Toutouzas Konstandinos , Zografos George , Konstadoulakis Manoussos
Published: March 2019

Background/Aim

Anatomic vascular abnormalities of the hepatic arteries are frequent. The aim of the study was to analyze the influence of hepatic arterial variations on postoperative morbidity and resection margin status after pancreatoduodenectomy (PD).

Materials/Methods

Patients who underwent PD over a 7‐year period (2010‐2017) were included in the study. Patients with variant hepatic arterial anatomy were matched 1:2 for age, sex, ASA score, and histology.

Results

A total of 232 patients underwent PD. Variant hepatic arterial anatomy was found in 35 (15.1% of the total patient population). The most common variation was an accessory right hepatic artery (8.19%) and a replaced right hepatic artery (5.60%) arising from the superior mesenteric artery. These 35 patients were compared with 70 patients with no hepatic artery variations. Postoperative surgical complications occurred in 12.1% and 26.5% (P = 0.08) and in‐hospital mortality was 6% and 5.4% (
P = 0.99) between patients with and without variant hepatic arteries. There was no difference in positive resection margins (R1) (18.2% vs 20.5%,
P = 0.99) between the two groups.

Conclusions

An aberrant hepatic artery does not increase morbidity or R1 resection in patients undergoing PD.
Evaluating novel silica hydride‐based stationary phases for the analysis of phytocannabinoids and other psychoactive drugs
Authors: Watanabe Seiichiro , Santos Theresa Q. , Matyska‐Pesek Maria T. , Pesek Joseph J.
Published: March 2019

Three silica hydride based novel chromatographic phases chemically‐bonded with allyloxy‐DL‐alpha‐tocopherol, allylpentafluorophenyl, and 1‐eicosene moieties were evaluated as separation media for selected phytocannabinoids and other substances of abuse. In order to assess column selectivity, a series of reference standards was analyzed and detected by using liquid chromatography with mass spectrometry. Further, quantitative detections of cannabidiol and tetrahydrocannabinol were attempted for the extracts of cannabis plants and cannabidiol gummy formulation. For potential bioanalytical applications, the columns were evaluated for substance screening in a human urine matrix. In summary, the newly developed columns are functional and effective for the analysis of phytocannabinoids and various psychoactive drugs with or without the presence of biological matrices.
Correlation between Hypervascularization of the First Annular Pulley on Color Doppler Imaging of Trigger Finger and Patients’ Backgrounds
Authors: Sato Junko , Ishii Yoshinori , Noguchi Hideo
Published: March 2019

Objectives

The aim of this study was to investigate the correlation between hypervascularization of the first annular (A1) pulley on color Doppler imaging of trigger finger and patients’ backgrounds.

Methods

A total of 148 trigger digits from 144 patients were studied with ultrasound at the time of initial diagnosis. We observed the A1 pulley at the level of the metacarpophalangeal joint in a transverse image and noted the presence or absence of a signal in the A1 pulley on color Doppler imaging. Patients’ ages, sexes, clinical grades, symptom durations, prevalence of interphalangeal joint contracture, and visual analog scale pain scores were compared between the groups with positive and negative Doppler findings.

Results

The 144 patients included 45 men and 99 women. Sixty‐one of 148 digits (41%) showed positive Doppler findings in the A1 pulley. Patients’ ages and visual analog scale scores in the Doppler‐positive group were slightly greater than those in the Doppler‐negative group (P = .03; P < .01, respectively). The digit with positive Doppler findings tended to be categorized into a severer grade and into the group with a shorter symptom duration (P < .01 for both).

Conclusions

Hypervascularization of the A1 pulley tended to appear in an earlier period after the patients had become aware of symptoms, as frequently as their symptoms became severe, in conjunction with higher pain scores. Doppler imaging of the A1 pulley might help in better understanding patients’ conditions.
Demonstrating the benefits of a multidisciplinary aerodigestive program
Authors: Ruiz Amanda G. , Bhatt Jay M. , DeBoer Emily M. , Friedlander Joel , Janosy Norah , Peterson Melissa Brooks , Wine Todd , Deterding Robin , Prager Jeremy D.
Published: March 2019

Objectives/Hypothesis

The Aerodigestive Program (the Aero Program) at Children's Hospital Colorado is a multidisciplinary program focused on airway, digestive, and lung disorders in complex children, involving collaboration between gastroenterology, pulmonology, anesthesiology, and otolaryngology in clinic and operating room. These programs have proliferated as institutions focus on providing greater care coordination and family satisfaction. However, few cost, charge, and satisfaction data exist to support these resource‐intensive programs. The goal of this study was to investigate the value of combined triple endoscopy delivered by the Aero Program through analysis of institutional charges, direct costs, operating room efficiency metrics, and parent satisfaction.

Study Design

Program evaluation.

Methods

Finance, satisfaction, efficiency, and quality‐of‐care metrics were evaluated within and outside of the Aero Program through retrospective queries of electronic health records, administrative databases, and parent surveys at our institution.

Results

Mean anesthesia time in the Aero Program was 54 minutes (49–60; 95% confidence interval), which was significantly less (P < .0001) than the estimated 89 minutes of having the three procedures done separately. Average charges and average direct costs for triple endoscopy were 38.8% and 41.9% less than the sum of the averages for separate procedures, respectively. Parent satisfaction was high for the Aero Program care.

Conclusions

As organizations move toward greater coordination of care for complex patients, multidisciplinary programs must demonstrate their value by delivering cost‐effective care. Aerodigestive programs have the potential to provide satisfying care that is less costly to the organization, insurer, and family. These programs represent a step in the evolution toward higher value care and value‐based payment methodology.

Level of Evidence

4 Laryngoscope, 130:521–525, 2020
Pattern of cochlear obliteration after vestibular Schwannoma resection according to surgical approach
Authors: Feng Yening , Lane John I. , Lohse Christine M. , Carlson Matthew L.
Published: March 2019

Objectives/Hypothesis

To investigate the prevalence and course of cochlear obliteration according to microsurgical approach to inform clinical decision making regarding optimal timing of cochlear implantation.

Study Design

Retrospective radiologic review and chart review.

Methods

Patients who underwent microsurgical resection of vestibular schwannoma (VS) with a minimum of two available postoperative magnetic resonance imaging (MRI) scans were analyzed. The prevalence and timing of cochlear and labyrinthine obliteration was classified using relevant MRI sequences.

Results

MRI studies in 60 patients were analyzed: 20 translabyrinthine (TL), 20 retrosigmoid, and 20 middle fossa (MF) cases. The first and last postoperative MRI was obtained a median of 3.4 months (interquartile range (IQR), 3.0–3.7 months) and 35 months (IQR, 27–83 months) after surgery, respectively. At the time of the first postoperative MRI, 21 (35%) patients had partial basal turn obliteration, and none of the patients had complete basal turn obliteration. At the time of the last postoperative MRI, six (10%) patients had partial basal turn obliteration and 17 (28%) patients had complete basal turn obliteration. The pattern of partial or complete basal turn obliteration differed significantly among all three surgical approaches (P < .001). Specifically, the risk of partial or complete obliteration of the basal turn was highest in the TL cohort and lowest in the MF cohort.

Conclusions

The prevalence and timing of cochlear obliteration after VS microsurgery varies significantly according to surgical approach. The risk of early and complete obliteration is highest in the TL group and lowest in the MF cohort. These data may inform clinical decision making regarding optimal timing of cochlear implantation in patients with advanced hearing loss after microsurgical resection.

Level of Evidence

4 Laryngoscope, 130:474–481, 2020
Prediction of Alcohol Relapse Among Liver Transplant Candidates With Less Than 6 Months of Abstinence Using the High‐Risk Alcoholism Relapse Score
Authors: Lombardo‐Quezada Julissa , Colmenero Jordi , López‐Pelayo Hugo , Gavotti Carolina , Lopez Ana , Crespo Gonzalo , Lopez Eva , Gual Antoni , Lligoña Anna , Navasa Miquel
Published: March 2019

The selection of liver transplantation (LT) candidates with alcohol‐use disorder (AUD) is influenced by the risk of alcohol relapse (AR) after LT. We aimed to investigate the risk factors of AR after LT and its impact on graft and recipient outcomes. A retrospective study was conducted that included all consecutive patients with AUD undergoing LT from January 2004 to April 2016 (n = 309), excluding patients with alcoholic hepatitis. Odds ratios (ORs) and 95% confidence intervals (CIs) for AR were analyzed by multinomial logistic regression. Cox regression with time‐dependent covariates was used to analyze patient survival and graft cirrhosis. There were 70 (23%) patients who presented AR (median follow‐up, 68 months), most of them (n = 44, 63%) presenting heavy AR. The probability of heavy AR was 2.3%, 7.5%, 12%, and 29% at 1, 3, 5, and 10 years after LT, respectively. The independent risk factors for heavy AR included a High‐Risk Alcoholism Relapse (HRAR) score ≥3 (OR, 2.39; 95% CI, 1.02‐5.56; P = 0.04) and the duration of abstinence (months) before LT (OR, 0.81; 95% CI, 0.66‐0.98; P = 0.03). In recipients with <6 months of abstinence before LT, the probability of heavy AR after LT was higher in patients with an HRAR score ≥3 than in those with an HRAR score <3 (20%, 36.7%, and 47% versus 6.8%, 12.4%, and 27% at 1, 3, and 5 years, respectively; log‐rank 0.013). The risk of graft cirrhosis was increased in patients with heavy AR (hazard ratio, 3.44; 95% CI, 1.58‐7.57; P = 0.002) compared with nonrelapsers, with no differences in patient survival. In conclusion, the HRAR score is helpful in identifying the risk of harmful AR after LT in candidates with <6 months of alcohol abstinence without alcoholic hepatitis. These patients could benefit from a longterm integrative patient‐centered approach after LT until lifestyle changes are implemented.
Engineering Lignocellulose Fibers with Higher Thermal Stability through Natural Fiber Welding
Authors: Durkin David P. , Frank Benjamin P. , Haverhals Luke M. , Howard Fairbrother D. , De Long Hugh C. , Trulove Paul C.
Published: March 2019

This study reveals how natural fiber welding (NFW) can be used to engineer biopolymer materials with improved thermal stability. First, it is shown how NFW without binders improves lignocellulose yarn thermal stability by ≈17 °C, primarily by condensing microfibril structure. Next, silanized‐cellulose nanofibrils (Si‐CNFs) are developed as NFW binders; this silanization process alters CNF physical and thermal properties. During pyrolysis, SixOynetworks form, which delay CNF decomposition (up to 37 °C), slow cellulose mass loss rates (up to 89%), and can enhance char yield more than twofold. When used as NFW binders, Si‐CNFs increase lignocellulose yarn thermal stability (up to 17 °C) proportional to siloxane amount, and can reduce cellulose mass loss rates (≈25% compared to welding without binder). These exciting results highlight the potential of NFW as a green‐engineering process to transform natural fibers into more thermally stable, biocomposite textile yarns.
The role of mass spectrometry and related techniques in the analysis of extractable and leachable chemicals
Authors: Sica Vincent P. , Krivos Kady L. , Kiehl Douglas E. , Pulliam Christopher J. , Henry Ian D. , Baker Timothy R.
Published: March 2019

In addition to degradation products, impurities, and exogenous contaminants, industries such as pharmaceutical, food, and others must concern themselves with leachables. These chemicals can derive from containers and closures or migrate from labels or secondary containers and packaging to make their way into products. Identification and quantification of extractables (potential leachables) and leachables, typically trace level analytes, is a regulatory expectation intended to ensure consumer safety and product fidelity. Mass spectrometry and related techniques have played a significant role in the analysis of extractables and leachables (E&L). This review provides an overview of how mass spectrometry is used for E&L studies, primarily in the context of the pharmaceutical industry. This review includes work flows, examples of how identification and quantification is done, and the importance of orthogonal data from several different detectors. E&L analyses are driven by the need for consumer safety. These studies are expected to expand in existing areas (e.g., food, textiles, toys, etc.) and into new, currently unregulated product areas. Thus, this topic is of interest to audiences beyond just the pharmaceutical and health care industries. Finally, the potential of universal detector approaches used in other areas is suggested as an opportunity to drive E&L research progress in this arguably understudied, under‐published realm.
Prodromal Parkinson's Disease: The Decade Past, the Decade to Come
Authors: Postuma Ronald B. , Berg Daniela
Published: March 2019

The past decade has seen a dramatic expansion of the field of prodromal PD. Ten years ago, there were only six known prodromal markers of disease, none of which had more than two studies documenting diagnostic value. We now have at least 16 markers, with as many as 10 prospective studies for a single marker. This review summarizes the major advances over the last decade and speculates about the advances we will see in the decade to come. The most notable advances over the last decade came through the study of high‐risk cohorts (REM sleep behavior disorder and later genetic and autonomic cohorts), the generation of more representative population‐based cohorts for studying prodromal PD, major advances in neuroimaging of early disease stages, the emerging likelihood that tissue biopsy will be able to diagnose prodromal PD, and the coalescence of prodromal markers into discrete criteria. As the next decade dawns, we await increasing precision of sensitivity and specificity estimates of known markers, the discovery of new biomarkers of prodromal disease, improvements in diagnosis using combined methods/criteria (with increasing recognition of prodromal PD as one stage of the full PD spectrum), and ultimately the development of neuroprotective therapy that can be provided at the earliest stages of disease. © 2019 International Parkinson and Movement Disorder Society
Mutations in the mitochondrial tryptophanyl‐tRNA synthetase cause growth retardation and progressive leukoencephalopathy
Authors: Maffezzini Camilla , Laine Isabelle , Dallabona Cristina , Clemente Paula , Calvo‐Garrido Javier , Wibom Rolf , Naess Karin , Barbaro Michela , Falk Anna , Donnini Claudia , Freyer Christoph , Wredenberg Anna , Wedell Anna
Published: March 2019

Background

Mutations in mitochondrial aminoacyl tRNA synthetases form a subgroup of mitochondrial disorders often only perturbing brain function by affecting mitochondrial translation. Here we report two siblings with mitochondrial disease, due to compound heterozygous mutations in the mitochondrial tryptophanyl‐tRNA synthetase (WARS2) gene, presenting with severe neurological symptoms but normal mitochondrial function in skeletal muscle biopsies and cultured skin fibroblasts.

Methods

Whole exome sequencing on genomic DNA samples from both subjects and their parents identified two compound heterozygous variants c.833T>G (p.Val278Gly) and c.938A>T (p.Lys313Met) in the WARS2 gene as potential disease‐causing variants. We generated patient‐derived neuroepithelial stem cells and modeled the disease in yeast and Drosophila melanogaster to confirm pathogenicity.

Results

Biochemical analysis of patient‐derived neuroepithelial stem cells revealed a mild combined complex I and IV defect, while modeling the disease in yeast demonstrated that the reported aminoacylation defect severely affects respiration and viability. Furthermore, silencing of wild type WARS2 in Drosophila melanogaster showed that a partial defect in aminoacylation is enough to cause lethality.

Conclusions

Our results establish the identified WARS2 variants as disease‐causing and highlight the benefit of including human neuronal models, when investigating mutations specifically affecting the nervous system.
Co‐occurrence of ATXN3 and ATXN2 repeat expansions in Chinese ataxia patients with slow saccades
Authors: Wu Chao , Cai Qiong , You Huajing , Zhou Xiangxue , Chen Dingbang , Mo Guiling , Li Xunhua
Published: March 2019

Background

The presence of more than one polyQ‐related gene within a single individual is a rare incidence, which may provide the potential opportunity to study the combined effects of these spinocerebellar ataxia (SCA) genes.

Methods

We retrospectively analyzed genetic data from 112 SCA3 probands and found Patient 1 harbored expanded ATXN2 allele (33 repeats) and intermediate TBP allele (41 repeats), and Patient 2 with intermediate ATXN2 allele (32 repeats). Detailed clinical and oculomotor performances were investigated. The age at onset and oculomotor parameters of both patients were compared with matched pure SCA3 groups controlling either disease severity or CAG repeats.

Results

Most of the clinical phenotypes and oculomotor characteristics of these two patients were common to typical SCA3 patients. Compared to pure SCA3 groups controlling disease severity, mild reduced horizontal saccade velocity could be detected in both patients. However, mild expansions of the ATXN2 allele seemed to have no influence on the age at onset of Patient 1 but might have a mild impact on Patient 2.

Conclusion

Our study provides supporting evidence that mild expansions of ATXN2 may have modifying effects on SCA3 phenotype. Larger control series and longitudinal data are warranted to confirm our results.
Discontinuous finite volume method for compressible miscible displacement problems in porous media
Authors: Wang Ping , Jiang Ziwen , Yin Zhe , Xu Qiang
Published: March 2019

The compressible miscible displacement problem in porous media is modeled by a coupled system of two nonlinear partial differential equations: the pressure equation and the concentration equation are parabolic equation. In this article, we present discontinuous finite volume method for the concentration equation and the pressure equation. The optimal order error estimates for pressure and concentration are obtained in a mesh dependent norm.
Dietary Palmitoleic Acid Attenuates Atherosclerosis Progression and Hyperlipidemia in Low‐Density Lipoprotein Receptor‐Deficient Mice
Authors: Yang Zhi‐Hong , Pryor Milton , Noguchi Audrey , Sampson Maureen , Johnson Brittany , Pryor Matthew , Donkor Kwame , Amar Marcelo , Remaley Alan T.
Published: March 2019

Scope

Palmitoleic acid (palmitoleate; C16:1 n‐7), an omega‐7 monounsaturated fatty acid (MUFA) found in plants and marine sources, has been shown to favorably modulate lipid and glucose metabolism. However, its impact on atherosclerosis has not been examined in detail.

Methods and Results

LDL receptor knock out (LDLR‐KO) mice are fed a Western diet supplemented with 5% (w/w) palmitoleate concentrate, oleic‐rich olive oil, or none (control) for 12 weeks. Dietary palmitoleate increases hepatic C16:1 levels, improves plasma and hepatic lipid/lipoprotein profiles (≈40% decrease in triglycerides), and reduces the atherosclerotic plaque area by ≈45% compared with control or olive oil group (p < 0.05). These favorable changes are accompanied by the downregulation of key genes, such as Srebp1c, Scd1, Il‐1β, and Tnfα. ApoB‐depleted plasma from mice fed palmitoleate has increased cholesterol efflux capacity by 20% from ABCA1‐expressing cells (p < 0.05). A beneficial effect of palmitoleate on glucose metabolism (54% decreased in HOMA‐IR, p < 0.05) is also observed.

Conclusions

Dietary‐supplemented palmitoleate reduces atherosclerosis development in LDLR‐KO mice, and is associated with improvement of lipid and glucose metabolism and favorable changes in regulatory genes involved in lipogenesis and inflammation. These findings imply the potential role of dietary palmitoleate in the prevention of cardiovascular disease and diet‐induced metabolic disorders.
Technical Note: Anti‐phase microwave illumination‐based thermoacoustic tomography of in vivo human finger joints
Authors: Chi Zihui , Huang Lin , Ge Shaoli , Jiang Huabei
Published: March 2019

Purpose

Thermoacoustic tomography (TAT) has been studied to image joints. While several joint tissues could be thermoacoustically imaged, tendons and bone could not be recovered completely or clearly. The purpose of this study was to overcome this limitation.

Methods

We developed a novel TAT system based on anti‐phase microwave illumination method to image the proximal interphalangeal joint and middle phalanx of a right middle finger from a healthy volunteer. The performance of this new system for imaging joints and tendons was compared with that by in‐phase microwave illumination and a conventional pyramidal horn antenna.

Results

Anti‐phase microwave illumination can produce relatively homogeneous electric (E)‐Field distributions inside the joint tissues. The homogeneous E‐Field distributions can enhance the detectability of flexor tendon and extensor tendon. Anti‐phase microwave illumination could image the flexor tendon, and extensor tendon and bone, which were not clearly imaged by the in‐phase microwave illumination or by the horn antenna. The images generated by the in‐phase microwave illumination and pyramidal horn antenna were almost identical in terms of the tissue types they imaged.

Conclusions

Anti‐phase illumination can overcome the limitation associated with the conventional TAT by adding the ability of completely delineating tendons and bone in the joints. This study paves the way for us to continue the study and to validate its utility in detection of joint diseases.
Growth Disparity in Sympatric Kokanee Breeding Groups
Authors: Klein Zachary B , Quist Michael C , Dux Andrew M , Corsi Matthew P
Published: March 2019

Growth is arguably the most important dynamic rate function due to its interaction with survival and recruitment. As such, understanding the mechanisms underlying growth is a primary focus of fisheries research. Kokanee Oncorhynchus nerka in Lake Pend Oreille, Idaho, provide an interesting case study for investigating the factors that influence growth. Early-run and late-run kokanee occur in Lake Pend Oreille, but early-run fish generally grow faster than late-run fish. The observed growth disparity between early- and late-run fish could be due to genetic differences between the two groups. Conversely, a common hatchery practice of slowing growth by reducing feed has been hypothesized to elicit a compensatory growth response in early-run fish and to explain the size difference between breeding groups. Using two different experiments, we tested the hypotheses that (1) early-run kokanee are genetically disposed to grow faster than late-run kokanee at identical water temperatures; and (2) feed restriction elicits a compensatory growth response in early-run kokanee that explains the observed size difference between breeding groups. Estimates of mean FL, weight, Fulton's condition factor (K), and specific growth rate (SGR) were not significantly different (P ≥ 0.05) between early-run and late-run fish in the first experiment. However, water temperature was positively related to mean FL, weight, K, and SGR for both breeding groups. Fish that were subjected to food deprivation exhibited an increased growth rate and obtained weights similar to those of control fish. Overall, our results suggest that early- and late-run fish have similar growth potential, but certain hatchery practices likely provide early-run fish with an initial advantage in growth, size, or both.