bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison study of solving diffusion equations with different algorithm methods
Authors: Huang Houbing , Wang Xueyun , Ma Xingqiao
Published: December 2016

A comparison study for solving diffusion equations with different algorithm methods is studied to understand the oxygen vacancy defect transport under the electric field. We compare computational efficiency and numerical accuracy with different algorithm methods, including finite difference, finite element (COMSOL), and Fourier-Chebysev spectral methods. All the results of oxygen vacancy distribution under an electric field from different algorithm methods are compared with the analytical solution results. Two kinds of boundary conditions are used in solving diffusion equations and the absolute error of different methods are discussed. The main purpose of these results is to provide guidance for studying the role of point defect transport in the degradation and breakdown of devices.
Evaluation of root porosity and radial oxygen loss of disomic addition lines of Hordeum marinum in wheat
Authors: Konnerup Dennis , Malik A. l. Imran , Islam A. K. M. R. , Colmer Timothy David
Published: December 2016

Hordeum marinum Huds. is a waterlogging-tolerant wild relative of wheat (Triticum aestivum L.). Greater root porosity (gas volume per root volume) and formation of a barrier to reduce root radial O2 loss (ROL) contribute to the waterlogging tolerance of H. marinum and these traits are evident in some H. marinum–wheat amphiploids. We evaluated root porosity, ROL patterns and tolerance to hypoxic stagnant conditions for 10 various H. marinum (two accessions) disomic chromosome addition (DA) lines in wheat (two varieties), produced from two H. marinum–wheat amphiploids and their recurrent wheat parents. None of the DA lines had a barrier to ROL or higher root porosity than the wheat parents. Lack of a root ROL barrier in the six DA lines for H. marinum accession H21 in Chinese Spring (CS) wheat indicates that the gene(s) for this trait do not reside on one of these six chromosomes; unfortunately, chromosome 3 of H. marinum has not been isolated in CS. Unlike the H21–CS amphiploid, which formed a partial ROL barrier in roots, the H90–Westonia amphiploid and the four derived DA lines available did not. The unaltered root aeration traits in the available DA lines challenge the strategy of using H. marinum as a donor of these traits to wheat.
Common and heritable components of white matter microstructure predict cognitive function at 1 and 2 y
Authors: Lee Seung Jae , Steiner Rachel J. , Yu Yang , Short Sarah J. , Neale Michael C. , Styner Martin Andreas , Zhu Hongtu , Gilmore John H.
Published: December 2016

Significance

The integrity or microstructure of white matter as determined by diffusion tensor imaging (DTI) is related to cognitive function. Most studies focus on individual tracts, even though the microstructure of white matter tracts throughout the brain is highly correlated. In older adults, a common property of white matter predicts cognitive function, though it is not known if common factors are present in early childhood development or how they relate to cognitive function. Here, we found that DTI-based common underlying factors that emerge at this age are significantly related to cognitive abilities from birth to age 2 y. These findings indicate that the functional specialization of cognition and the anatomical differentiation of fibers cooccur in the neonatal and infant brain.
One Health approach to cost-effective rabies control in India
Authors: Fitzpatrick Meagan C. , Shah Hiral A. , Pandey Abhishek , Bilinski Alyssa M. , Kakkar Manish , Clark Andrew D. , Townsend Jeffrey P. , Abbas Syed Shahid , Galvani Alison P.
Published: December 2016

Over 20,000 rabies deaths occur annually in India, representing one-third of global human rabies. The Indian state of Tamil Nadu has pioneered a “One Health” committee to address the challenge of rabies in dogs and humans. Currently, rabies control in Tamil Nadu involves postexposure vaccination of humans after dog bites, whereas potential supplemental approaches include canine vaccination and sterilization. We developed a data-driven rabies transmission model fit to human rabies autopsy data and human rabies surveillance data from Tamil Nadu. Integrating local estimates for canine demography and costs, we predicted the impact of canine vaccination and sterilization on human health outcomes and evaluated cost-effectiveness according to the WHO criteria for India, which correspond to thresholds of $1,582 and $4,746 per disability-adjusted life-years (DALYs) for very cost-effective and cost-effective strategies, respectively. We found that highly feasible strategies focused on stray dogs, vaccinating as few as 7% of dogs annually, could very cost-effectively reduce human rabies deaths by 70% within 5 y, and a modest expansion to vaccinating 13% of stray dogs could cost-effectively reduce human rabies by almost 90%. Through integration over parameter uncertainty, we find that, for a cost-effectiveness threshold above $1,400 per DALY, canine interventions are at least 95% likely to be optimal. If owners are willing to bring dogs to central point campaigns at double the rate that campaign teams can capture strays, expanded annual targets become cost-effective. This case study of cost-effective canine interventions in Tamil Nadu may have applicability to other settings in India and beyond.
Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues
Authors: Rapuano Kristina M. , Zieselman Amanda L. , Kelley William M. , Sargent James D. , Heatherton Todd F. , Gilbert-Diamond Diane
Published: December 2016

Significance

Genetic predisposition and sensitivity to environmental cues jointly give rise to maladaptive human behaviors, such as unhealthy eating. Despite the dramatic rise in obesity rates, the relationship between these factors is not well understood. Here we show that children genetically at risk for obesity exhibit stronger reward-related responses to real-world food cues (i.e., food advertisements) in the nucleus accumbens, a brain area canonically associated with reward processing. Additionally, this structure is larger in children at a higher risk for obesity. Taken together, these findings offer one explanation for how genetic risk for obesity may predispose individuals to engage in unhealthy eating behaviors and may inform strategies targeting early intervention.
Hierarchy stability moderates the effect of status on stress and performance in humans
Authors: Knight Erik L. , Mehta Pranjal H.
Published: December 2016

Significance

High-status leadership roles are theorized to reduce stress compared with subordinate roles, but higher rank is not always stress-free. Here we demonstrate that high status inhibits stress responses and improves performance during a mock interview in a stable hierarchy, but high status boosts stress responses and carries no performance advantage in an unstable hierarchy. Feeling in control was an asset for interview performance, but increased testosterone reactivity was a liability. These findings have applications for improving outcomes in stressful evaluative settings, such as job interviews, and may hold translational implications for the influence of status on health.
Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity
Authors: Li Minshu , Li Zhiguo , Yao Yang , Jin Wei-Na , Wood Kristofer , Liu Qiang , Shi Fu-Dong , Hao Junwei
Published: December 2016

Significance

Ischemic stroke is a leading cause of death and disability worldwide. Evidence indicates the detrimental effects of lymphocyte infiltration into the ischemic brain. However, a knowledge gap exists relating to the brain-specific cellular constituents and environmental factors that dictate the phenotype and function of infiltrating lymphocytes. Astrocytes bridge interactions between ischemic neurons and lymphocytes. We show that brain ischemia induces robust up-regulation of astrocytic interleukin-15 (IL-15). The present study was directed toward understanding the role of astrocyte-derived factors such as IL-15 in stroke. We discovered that astrocytic IL-15 is necessary and sufficient to amplify cell-mediated immune responses that promote ischemic brain injury. These results provide definitive evidence on the role of astrocyte-derived IL-15 in ischemic brain injury.
Automatic design of fiber-reinforced soft actuators for trajectory matching
Authors: Connolly Fionnuala , Walsh Conor J. , Bertoldi Katia
Published: December 2016

Significance

Fluid-powered elastomeric soft robots have been shown to be able to generate complex output motion using a simple control input such as pressurization of a working fluid. This capability, which mimics similar functions often found in biology, results from variations in mechanical properties of the soft robotic body that cause it to strain to different degrees when stress is applied with the fluid. In this work, we outline a mechanics- and optimization-based approach that enables the automatic selection of mechanical properties of a fiber-reinforced soft actuator to match the kinematic trajectory of the fingers or thumb during a grasping operation. This methodology can be readily extended to other applications that require mimicking or assisting biological motions.
Ownership of an artificial limb induced by electrical brain stimulation
Authors: Collins Kelly L. , Guterstam Arvid , Cronin Jeneva , Olson Jared D. , Ehrsson H. Henrik , Ojemann Jeffrey G.
Published: December 2016

Significance

Creating a prosthetic device that feels like one’s own limb is a major challenge in applied neuroscience. We show that ownership of an artificial hand can be induced via electrical stimulation of the hand somatosensory cortex in synchrony with touches applied to a prosthetic hand in full view. These findings suggest that the human brain can integrate “natural” visual input and direct cortical-somatosensory stimulation to create the multisensory perception that an artificial limb belongs to one’s own body.
Triazoles inhibit cholesterol export from lysosomes by binding to NPC1
Authors: Trinh Michael N. , Lu Feiran , Li Xiaochun , Das Akash , Liang Qiren , De Brabander Jef K. , Brown Michael S. , Goldstein Joseph L.
Published: December 2016

Significance

In animal cells, cholesterol is essential for the assembly of membranes and production of steroid hormones and bile acids. Cells obtain cholesterol through receptor-mediated endocytosis of LDL into lysosomes. After lysosomal degradation, LDL-derived cholesterol must cross the lysosomal membrane to execute its functions. Lysosomal export is mediated by Niemann–Pick C1 (NPC1), a membrane protein. Here we show that the triazole drugs posaconazole and itraconazole inhibit lysosomal cholesterol export. A photoactivatable derivative of posaconazole cross-links to NPC1 in intact cells and to purified NPC1 in lipid nanodiscs. A point mutation in the membrane domain of NPC1 prevents lysosomal export of cholesterol and blocks posaconazole cross-linking.
Growth and Maturation of Acadian Redfish in the Gulf of Maine
Authors: Sullivan Kevin M. , Duclos Kristin L. , Parker Steven J. , Berlinsky David L.
Published: December 2016

Acadian Redfish Sebastes fasciatus were captured by otter trawl from inshore and offshore sites in the Gulf of Maine. Fish weights and lengths were recorded, sagittal annuli were counted for age determination, and ovarian histology was conducted to develop ogives for length and age at maturity for females. Maximum observed ages of males and females were 25 and 37 years, respectively, but very few males greater than 21 years and females greater than 25 years of age were observed. Growth functions were significantly different between males and females, and similar growth rates (k) but higher maximum length (L∞) and lower t0 values were observed in females. Mature female Acadian Redfish ranged in length and age from 17 to 39 cm and from 4 to 37 years, respectively, attaining 100% maturity at ~26 cm and ~10 years. Median length at maturity (L50) was 21.7 cm and median age at maturity (A50) was 6.6 years. Smaller, immature fish were primarily sampled from inshore locations. The results of this study were very similar to previous data from a depleted Acadian Redfish population in the Gulf of Maine from 1975 to 1980, suggesting that these population parameters have not changed despite population recovery.

Received March 16, 2016; accepted September 12, 2016Published online December 20, 2016
Progress in ciliary ion channel physiology
Authors: Pablo Juan Lorenzo , DeCaen Paul G. , Clapham David E.
Published: December 2016

Mammalian cilia are ubiquitous appendages found on the apical surface of cells. Primary and motile cilia are distinct in both morphology and function. Most cells have a solitary primary cilium (9+0), which lacks the central microtubule doublet characteristic of motile cilia (9+2). The immotile primary cilia house unique signaling components and sequester several important transcription factors. In contrast, motile cilia commonly extend into the lumen of respiratory airways, fallopian tubes, and brain ventricles to move their contents and/or produce gradients. In this review, we focus on the composition of putative ion channels found in both types of cilia and in the periciliary membrane and discuss their proposed functions. Our discussion does not cover specialized cilia in photoreceptor or olfactory cells, which express many more ion channels.
Arterial Destiffening in Previously Untreated Mild Hypertensives After 1 Year of Routine Clinical Management
Authors: Rodilla Enrique , Millasseau Sandrine , Costa Jose Antonio , Pascual Jose Maria
Published: December 2016

BACKGROUND

Arterial stiffness, measured with pulse wave velocity (PWV), is now classified as a marker of target organ damage (TOD) alongside left ventricular hypertrophy and moderately increased albuminuria. Interventional studies on treated hypertensive patients have shown that PWV could be improved. Our aim was to assess changes in arterial stiffness after 1 year of routine clinical practice in never-treated hypertensive patients.

PATIENTS AND METHODS

We studied 356 never-treated patients with suspected hypertension. After standard clinical assessment during which presence of TOD was evaluated, hypertension diagnosis was confirmed in 231 subjects who subsequently received standard routine care. Both hypertensive and the 125 controls came back for a follow-up visit after 1 year.

RESULTS

Hypertensive patients were slightly older (46 ± 12 vs. 50 ± 12 years, P < 0.001), with higher mean arterial pressure (MAP)-adjusted PWV compared to controls (8.6 ± 2.0 vs. 8.0 ± 1.7 m/s, P < 0.001) and 47% of them presented 1 or more TOD. After 1 year of treatment, MAP was similar in both groups (94.9 vs. 96.2 mm Hg; P = ns), but adjusted PWV remained significantly higher in the hypertensive patients (7.8 ± 1.4 vs. 8.3 ± 1.7 m/s, P = 0.004). The prevalence of elevated PWV was reduced from 20% to 12%. All antihypertensive drugs achieved the same blood pressure (BP) and PWV reduction with the exception of vasodilating beta-blockers which gave slightly better results probably due to heart rate reduction.

CONCLUSION

BP reduction in newly diagnosed hypertensive patients improves arterial stiffness within a year of real-life clinical practice. Patients with the highest PWV and the largest reduction of BP “destiffened” the most whatever antihypertensive class was used.
Lineage-specific mutational clustering in protein structures predicts evolutionary shifts in function
Authors: Adams Jeremy , Mansfield Michael J , Richard Daniel J , Doxey Andrew C
Published: December 2016

Motivation

Spatially clustered mutations within specific regions of protein structure are thought to result from strong positive selection for altered protein functions and are a common feature of oncoproteins in cancer. Although previous studies have used spatial substitution clustering to identify positive selection between pairs of proteins, the ability of this approach to identify functional shifts in protein phylogenies has not been explored.

Results

We implemented a previous measure of spatial substitution clustering (the P3D statistic) and extended it to detect spatially clustered substitutions at specific branches of phylogenetic trees. We then applied the analysis to 423 690 phylogenetic branches from 9261 vertebrate protein families, and examined its ability to detect historical shifts in protein function. Our analysis identified 19 607 lineages from 5362 protein families in which substitutions were spatially clustered on protein structures at P3D < 0.01. Spatially clustered substitutions were overrepresented among ligand-binding residues and were significantly enriched among particular protein families and functions including C2H2 transcription factors and protein kinases. A small but significant proportion of branches with spatially clustered substitution also were under positive selection according to the branch-site test. Lastly, exploration of the top-scoring candidates revealed historical substitution events in vertebrate protein families that have generated new functions and protein interactions, including ancient adaptations in SLC7A2, PTEN, and SNAP25. Ultimately, our work shows that lineage-specific, spatially clustered substitutions are a useful feature for identifying functional shifts in protein families, and reveal new candidates for future experimental study.

Availability and Implementation

Source code and predictions for analyses performed in this study are available at: https://github.com/doxeylab/evoclust3d

Supplementary information

Supplementary data are available at Bioinformatics online.
LncRNA/DNA binding analysis reveals losses and gains and lineage specificity of genomic imprinting in mammals
Authors: Liu Haihua , Shang Xiaoxiao , Zhu Hao
Published: December 2016

Motivation

Genomic imprinting is regulated by lncRNAs and is important for embryogenesis, physiology and behaviour in mammals. Aberrant imprinting causes diseases and disorders. Experimental studies have examined genomic imprinting primarily in humans and mice, thus leaving some fundamental issues poorly addressed. The cost of experimentally examining imprinted genes in many tissues in diverse species makes computational analysis of lncRNAs’ DNA binding sites valuable.

Results

We performed lncRNA/DNA binding analysis in imprinting clusters from multiple mammalian clades and discovered the following: (i) lncRNAs and imprinting sites show significant losses and gains and distinct lineage-specificity; (ii) binding of lncRNAs to promoters of imprinted genes may occur widely throughout the genome; (iii) a considerable number of imprinting sites occur in only evolutionarily more derived species; and (iv) multiple lncRNAs may bind to the same imprinting sites, and some lncRNAs have multiple DNA binding motifs. These results suggest that the occurrence of abundant lncRNAs in mammalian genomes makes genomic imprinting a mechanism of adaptive evolution at the epigenome level.

Availability and Implementation

The data and program are available at the database LongMan at lncRNA.smu.edu.cn.

Supplementary information

Supplementary data are available at Bioinformatics online.
ProQ3D: improved model quality assessments using deep learning
Authors: Uziela Karolis , Menéndez Hurtado David , Shu Nanjiang , Wallner Björn , Elofsson Arne
Published: December 2016

Protein quality assessment is a long-standing problem in bioinformatics. For more than a decade we have developed state-of-art predictors by carefully selecting and optimising inputs to a machine learning method. The correlation has increased from 0.60 in ProQ to 0.81 in ProQ2 and 0.85 in ProQ3 mainly by adding a large set of carefully tuned descriptions of a protein. Here, we show that a substantial improvement can be obtained using exactly the same inputs as in ProQ2 or ProQ3 but replacing the support vector machine by a deep neural network. This improves the Pearson correlation to 0.90 (0.85 using ProQ2 input features).

Availability and Implementation

ProQ3D is freely available both as a webserver and a stand-alone program at http://proq3.bioinfo.se/

Supplementary information

Supplementary data are available at Bioinformatics online.
Image-Based Quantification of Plant Immunity and Disease
Authors: Laflamme Bradley , Middleton Maggie , Lo Timothy , Desveaux Darrell , Guttman David S.
Published: December 2016

Measuring the extent and severity of disease is a critical component of plant pathology research and crop breeding. Unfortunately, existing visual scoring systems are qualitative, subjective, and the results are difficult to transfer between research groups, while existing quantitative methods can be quite laborious. Here, we present plant immunity and disease image-based quantification (PIDIQ), a quantitative, semi-automated system to rapidly and objectively measure disease symptoms in a biologically relevant context. PIDIQ applies an ImageJ-based macro to plant photos in order to distinguish healthy tissue from tissue that has yellowed due to disease. It can process a directory of images in an automated manner and report the relative ratios of healthy to diseased leaf area, thereby providing a quantitative measure of plant health that can be statistically compared with appropriate controls. We used the Arabidopsis thaliana–Pseudomonas syringae model system to show that PIDIQ is able to identify both enhanced plant health associated with effector-triggered immunity as well as elevated disease symptoms associated with effector-triggered susceptibility. Finally, we show that the quantitative results provided by PIDIQ correspond to those obtained via traditional in planta pathogen growth assays. PIDIQ provides a simple and effective means to nondestructively quantify disease from whole plants and we believe it will be equally effective for monitoring disease on excised leaves and stems.
Postoperative Analgesia by a Transversus Abdominis Plane Block Using Different Concentrations of Ropivacaine for Abdominal Surgery
Authors: Sun Ni , Wang Shouyong , Ma Pengpeng , Liu Shuting , Shao Aijie , Xiong Ling
Published: December 2016

Background:

Transversus abdominis plane block (TAPB) has been proven to be an effective means of postoperative anesthesia, but the optimum effective concentration of ropivacaine warrants further research.

Objective:

This study aimed to identify the optimal ropivacaine concentration of TAPB using a meta-analysis.

Materials and Methods:

This study consisted of a meta-analysis of randomized controlled trials (RCTs). We searched online databases, including PubMed, Embase, the Cochrane Database of Systematic Reviews, and Web of Science. RCTs investigating the 24-hour postoperative opioid consumption and the rest and dynamic pain scores 2, 12, and 24 hours after surgery were included in this analysis. We also assessed opioid-related side-effects and patient satisfaction 24 hours after surgery.

Results:

Nineteen RCTs (1217 patients) were included in this meta-analysis, which showed that only TAPB with 0.375% and 0.5% ropivacaine was able to reduce opioid consumption 24 hours after surgery by weighted mean differences of −6.55 and −4.44 mg (morphine IV equivalents), respectively (P<0.05). A meta-regression analysis did not reveal an association between the local anesthetic dose (in mg), surgery, anesthesia, block timing, and the TAPB effect on opioid consumption. Ropivacaine concentrations of 0.375% and 0.5% reduced the 2-hour postoperative pain score and reduced the incidence of nausea and vomiting, but this analgesic effect disappeared at 12 and 24 hours. Only TAPB with 0.375% ropivacaine improved the degree of satisfaction 24 hours after surgery (weighted mean difference of 0.87 [0.08-1.66], P=0.03).

Conclusion:

In terms of efficacy and safety, the use of 0.375% ropivacaine for TAPB is preferred in the clinical work.
Children With Cochlear Implants and Their Parents: Relations Between Parenting Style and Children’s Social-Emotional Functioning
Authors: Ketelaar Lizet , Wiefferink Carin H. , Frijns Johan H. M. , Rieffe Carolien
Published: December 2016

Objectives:

Parenting a child who has a severe or profound hearing loss can be challenging and at times stressful, and might cause parents to use more adverse parenting styles compared with parents of hearing children. Parenting styles are known to impact children’s social-emotional development. Children with a severe to profound hearing loss may be more reliant on their parents in terms of their social-emotional development when compared with their hearing peers who typically have greater opportunities to interact with and learn from others outside their family environment. Identifying the impact which parenting styles pertain on the social-emotional development of children who have cochlear implants (CIs) could help advance these children’s well-being. Therefore, the authors compared parenting styles of parents with hearing children and of parents with children who have a CI, and examined the relations between parenting styles and two key aspects of children’s social-emotional functioning: emotion regulation and empathy.

Design:

Ninety-two hearing parents and their children (aged 1 to 5 years old), who were either hearing (n = 46) or had a CI (n = 46), participated in this cross-sectional study. Parents completed questionnaires concerning their parenting styles (i.e., positive, negative and uninvolved), and regarding the extent to which their children expressed negative emotions (i.e., anger and sadness) and empathy. Furthermore, an emotion-regulation task measuring negative emotionality was administered to the children.

Results:

No differences in reported parenting styles were observed between parents of hearing children and parents of children with a CI. In addition, negative and uninvolved parenting styles were related to higher levels of negative emotionality in both groups of children. No relation was found between positive parenting and children’s social-emotional functioning. Hearing status did not moderate these relationships. Language mediated the relationship between parenting styles and children’s social-emotional functioning.

Conclusions:

Children’s hearing status did not impact parenting styles. This may be a result of the support that parents of children with a CI receive during their enrollment in the rehabilitation program preceding and after implantation. Rehabilitation programs should dedicate more attention to informing parents about the impact of parenting behaviors on children’s social-emotional functioning. Offering parenting courses as part of the program could promote children’s well-being. Future longitudinal research should address the directionality of the relations between parenting styles and children’s social-emotional functioning.
Correctional Nursing
Authors: Holwick Angela
Published: December 2016

The purpose of this article is to give insights into challenges faced by inmates, many of whom may be struggling with substance abuse, while almost all deal with physical and emotional problems—and offer a Christian nursing response. Resources for exploring correctional nursing are provided.
Updates on the role of receptor activator of nuclear factor κB/receptor activator of nuclear factor κB ligand/osteoprotegerin pathway in breast cancer risk and treatment
Authors: Bayer Christian M. , Beckmann Matthias W. , Fasching Peter A.
Published: December 2016

Purpose of review

Treatment with bisphosphonates and denosumab is the standard of care in bone metastatic disease. In addition, the adjuvant therapy of denosumab or bisphosphonates is very effective to prevent loss of bone mineral density, for example in osteoporosis. However, it is still unclear if this therapy has an influence on preventing cancer.

Recent findings

Since the identification of novel genes in the 1980s, it took about 30 years until denosumab, as a fully human mAb against receptor activator of nuclear factor (NF)-κB ligand (RANKL), could be introduced to clinical practice. The discovery of the receptor activator of NF-κB/RANKL/osteoprotegerin pathway in the 1990s is an example of how modern databases of genes were utilized to discover new pathways relevant to a variety of diseases. The essential role of this pathway for the function, differentiation and survival of osteoclasts, and the influence on the bone microenvironment helped to understand the vicious circle of bone resorption and destruction in many skeletal diseases.

In the following review, we discuss the important role of rational targeting concerning receptor activator of NF-κB/RANKL/osteoprotegerin and the bisphosphonate therapy and provide an update for the related treatment of patients suffering from breast cancer and further implications for clinical practice and research using denosumab as a potential chemoprevention in BRCA1-related breast cancer.
TX-004HR vaginal estradiol has negligible to very low systemic absorption of estradiol
Authors: Archer David F. , Constantine Ginger D. , Simon James A. , Kushner Harvey , Mayer Philip , Bernick Brian , Graham Shelli , Mirkin Sebastian
Published: December 2016

Objective:

To evaluate the pharmacokinetics of TX-004HR vaginal estradiol softgel capsules when used for treating moderate-to-severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy.

Methods:

A substudy of the REJOICE trial (multicenter, double-blind, placebo-controlled, phase 3) evaluated the pharmacokinetics of 4, 10, and 25-μg TX-004HR doses once/d for 2 weeks, followed by twice/wk for 10 weeks. Serum samples obtained at 2, 4, 6, 10, and 24 hours postdose on days 1 and 14, and once on day 84, were analyzed for area under the serum concentration-time curve, t
max, C
min, C
avg, and C
max for estradiol, estrone, and estrone conjugates.

Results:

Seventy-two women (mean 59 y) participated. TX-004HR 4 μg showed no statistical differences from placebo in estradiol pharmacokinetic (PK) parameters. At 10 μg, estradiol C
max was statistically higher than placebo on day 1, but was not different from placebo on day 14. With 25 μg, estradiol PK parameters were statistically higher than placebo. Estradiol C
avg values for 25 μg were 9.1 pg/mL on day 1 and 7.1 pg/mL on day 14. Estrone and estrone conjugate PK parameters with TX-004HR were lower than or similar to placebo across all doses. No drug accumulation was observed.

Conclusions:

Vaginal TX-004HR resulted in negligible to very low systemic absorption of estradiol. No statistical differences in estradiol PK parameters were observed on day 14 with 4 and 10 μg, and only minor increases were observed with 25 μg (within the normal postmenopausal range). This PK substudy, in conjunction with the primary efficacy results, demonstrated that TX-004HR provided local benefits of estradiol with limited systemic exposure.
CRYSTALLINE RETINOPATHY AND RETINAL VASCULOPATHY IN CALCIFIC UREMIC ARTERIOLOPATHY (CALCIPHYLAXIS)
Authors: Naysan Jonathan , Dansingani Kunal K. , Balaratnasingam Chandrakumar , Mrejen Sarah , Levasseur Steven , Merkur Andrew , Yannuzzi Lawrence A.
Published: December 2016

Purpose:

To report the posterior segment and retinal vascular manifestations of calcific uremic arteriolopathy (calciphylaxis). Clinical findings are correlated with multimodal imaging results.

Methods:

Observational case report.

Results:

A 65-year-old white woman on hemodialysis was referred for assessment of poor vision bilaterally. Clinical examination demonstrated a crystalline retinopathy with stigma of previous retinal arterial occlusion. Fluorescein angiography revealed delayed retinal arterial filling bilaterally, sheathing of vessels, and peripheral nonperfusion. The crystals were hyperautofluorescent. Spectral domain and enhanced depth imaging optical coherence tomography localized the crystals within the retina with a predilection for the retinal arterial vasculature. The choriocapillaris was not involved. Two years prior, the patient developed necrotic skin lesions which were biopsied and confirmed the diagnosis of calciphylaxis.

Conclusion:

Calcific uremic arteriolopathy is an extremely rare cause of thrombogenic microangiopathy in end-stage renal disease patients. Retinal arterial occlusion appears to be a rare but significant cause of visual loss in this disease and is likely to be consequent to crystalline deposition in the retinal vasculature.
NEW OBSERVATIONS REGARDING THE RETINOPATHY OF GENETICALLY CONFIRMED KEARNS–SAYRE SYNDROME
Authors: Kozak Igor , Oystreck Darren T. , Abu-Amero Khaled K. , Nowilaty Sawsan R. , Alkhalidi Hisham , Elkhamary Sahar M. , Mohamed Sarar , Hamad Muddathir H. A. , Salih Mustafa A. , Blakely Emma L. , Taylor Robert W. , Bosley Thomas M.
Published: December 2016

Purpose:

To report novel retinal findings in Kearns–Sayre syndrome and correlate degree of retinopathy with other clinical findings.

Methods:

Observational case series of patients from Saudi Arabia with retinal and neuroophthalmologic examinations, medical chart review, and mitochondrial genetic evaluation.

Results:

The three unrelated patients had progressive external ophthalmoplegia and pigmentary retinopathy bilaterally. Muscle biopsy in two of the cases revealed mitochondrial myopathy. All three had abnormal findings on neuroimaging and modestly reduced visual acuity in both eyes with a variable pigmentary retinopathy. One of the patients had bilateral subretinal fibrosis with a full-thickness macular hole in the right eye. All three patients had single, large-scale mitochondrial DNA (mtDNA) deletions (5.0–7.6 kb in size) with blood mtDNA heteroplasmy levels ranging from below 20% to 57%. Severity of pigmentary retinopathy did not correlate with severity of progressive external ophthalmoplegia, but did correspond grossly with electroretinographic abnormalities, just as the degree of ocular motility restriction and ptosis in each patient correlated with the size of their extraocular muscles on neuroimaging. In addition, the size of the single, large-scale mtDNA deletion and level of mtDNA heteroplasmy corresponded with degree of ocular motility restriction but not with severity of retinopathy.

Conclusion:

Subretinal fibrosis and macular hole are novel retinal observations which expand clinical profile in Kearns–Sayre syndrome. Genetic testing for mtDNA deletions and heteroplasmy in blood, muscle biopsy, careful ocular and retinal examination including electroretinography, and imaging are indispensable tests for this condition.
Is There a Role for Inflammation in Contact Lens Discomfort?
Authors: Willcox Mark D. P.
Published: December 2016

Purpose:

The aim of this study was to examine the literature with respect to inflammation of the ocular surface and the presence of inflammatory mediators in the tear film during contact lens wear.

Methods:

The literature on contact lens discomfort that relates to signs of inflammation was searched. Reference was paid to the cardinal signs of inflammation (pain, heat, redness, and swelling) as well as the appearance of inflammatory mediators in the tear film during contact lens wear.

Results:

Contact lens wear does induce discomfort, which is a mild form of pain, and wearing of lenses can induce increases in limbal and conjunctival redness. However, there is little evidence for a direct relationship between limbal or conjunctival redness and contact lens discomfort. Contact lenses may increase the temperature of the ocular surface by a small amount (≤2.1°C). Corneal or conjunctival swelling has not been associated with contact lens discomfort. Complement or kinin breakdown products or histamine in tears are not associated with contact lens discomfort. Cytokines are generally not related to discomfort, although nerve growth factor levels were increased in tears of symptomatics in one report. The presence of degraded lipids, leukotriene B4and peroxidation products, and the enzyme secretory phospholipase A2 in tears has been associated with contact lens discomfort, and this area is worthy of further research.

Conclusions:

There have been only a few studies that have investigated a role for inflammation in contact lens–induced discomfort, and the strongest associations have been found with lipid degradation processes.
Long-term Outcomes and Complications of Pars Plana Baerveldt Implantation in Children
Authors: Vinod Kateki , Panarelli Joseph F. , Gentile Ronald C. , Sidoti Paul A.
Published: December 2016

Purpose of the Study:

The purpose of the study was to report long-term outcomes and complications of Baerveldt glaucoma implant (BGI) surgery with pars plana tube insertion in children.

Materials and Methods:

The medical records of consecutive aphakic and pseudophakic children (<16 y of age) who underwent BGI surgery with pars plana tube insertion between 1990 and 2013 were retrospectively reviewed. Main outcome measures were intraocular pressure and number of glaucoma medications. Postoperative complications were recorded. Failure was defined as an intraocular pressure <5 or ≥21 mm Hg (with or without glaucoma medications), loss of light perception, or need for additional glaucoma surgery.

Results:

Thirty-seven children were identified with a mean age of 6.0±4.7 years (range, 4 mo to 14.5 y). Mean follow-up after pars plana BGI surgery was 6.5±3.4 years (range, 9 mo to 12.8 y) for patients who met success criteria. Mean intraocular pressure and mean number of glaucoma medications at most recent follow-up for patients with successful intraocular pressure control were 13.8±4.1 and 2.3±1.9 mm Hg, respectively. The Kaplan-Meier survival analysis revealed 1-, 3-, 5-, and 7-year success rates of 94.5%, 74.6%, 65.0%, and 45.8%, respectively. Complications included tube exposure in 1 patient (2.7%), tube obstruction in 8 patients (21.6%), and retinal detachment in 9 patients (24.3%). Seventeen patients (45.9%) failed due to inadequate intraocular pressure control, of whom 9 (24.3%) required additional glaucoma surgery.

Conclusions:

Although pars plana BGI surgery is a reasonable option for managing refractory glaucoma in aphakic and pseudophakic children, surgeons must be aware of the potential need for additional glaucoma surgery and/or posterior segment complications with extended follow-up.
Sekundo’s Applanator: 5 Years of Experience With Transconjunctival Suturing
Authors: Elbaz Hisham , Sekundo Walter , Schröder Frank-Michael , Schulze Stephan
Published: December 2016

Sekundo’s Applanator is a new surgical instrument used mainly in transconjunctival scleral flap suturing in cases of postoperative hypotony after trabeculectomy. In contrast to Hoskins lens, it offers better visualization of the border of the scleral flap with good intraoperative stabilization of the globe; thus, it increases the effectiveness and decreases the time of the surgical procedure. Sekundo’s Applanator was also found to be useful in reducing the size of an oversized bleb after trabeculectomy and in the closure of leaking sutureless sclerotomies after vitrectomies. In this report, we present and discuss the properties, uses, and advantages of this new instrument to the ophthalmic community.
Topography of itch: evidence of distinct coding for pruriception in the trigeminal nerve
Authors: Andersen Hjalte H. , Elberling Jesper , Lo Vecchio Silvia , Arendt-Nielsen Lars
Published: December 2016

Introduction:

Little is known about the topographical distribution of pruriception (in particular for nonhistaminergic itch), although conditions with chronic itch frequently occur in distinct anatomic and often bilateral patterns. This study aimed to investigate regional differences in the sensitivity to itch stimuli by assessing the intensity of itch, pain, and cutaneous neurogenic flare evoked by histamine and cowhage in different anatomic regions in 20 healthy volunteers.

Methods:

Itch was induced by 1% histamine applied with a prick lancet or by insertion of 25±5 cowhage spicules in 4 regions: volar/dorsal forearm, lower back, and chin. The duration and intensity of itch and pain following each pruritic stimulus were measured by a continuous visual analogue scale (VAS0-100). Sensitivity to touch-evoked itch was assessed by von Frey filaments and cutaneous flare was quantified by full-field laser perfusion imaging.

Results:

Peak itch intensity was lower at the chin (19.4±3.6) compared with other areas (mean of 3 locations; 41.3±4.4), independently of whether histamine or cowhage was applied (P<0.01). Baseline sensitivity to touch-evoked itch was higher on the chin (P<0.01), but here hyperknesis did not develop in contrast to other areas (P<0.05). Cutaneous flare was more intense but had a smaller dispersion at the chin, compared with other areas (P<0.01).

Discussion:

In conclusion, sensitivity to histaminergic and non-histaminergic itch diverges considerably between body regions. Lower density of pruriceptive CMH and CMI-neurons or distinct neuronal substrates for itch in the mandibular part of the trigeminal area may explain the observed reduced itch and vasomotor responses.
The Effectiveness of Health Education on Maternal Anxiety, Circumcision Knowledge, and Nursing Hours: A Quasi-Experimental Study
Authors: Chang Shu-Fang , Hung Chich-Hsiu , Hsu Yu-Yun , Liu Yi , Wang Tsu-Nai
Published: December 2016

Background:

Many studies have shown that providing health education before surgery may significantly increase health knowledge and decrease anxiety in both patients and their family members. However, few studies have compared the effects on pediatric outpatient surgery outcomes of different health education instruction modes.

Purpose:

This study compares the effects of two health education delivery modes on maternal knowledge and anxiety, the number of unexpected early hospital follow-up visits, and the time spent by nurses on health education.

Method:

A quasi-experimental design with pretest and posttest was used to compare the effect on the outcomes of pediatric circumcision of a multimedia compact disc (CD) and a printed material.

Seventy mothers of children who underwent Plastibell circumcision participated in this study.

Results:

Both the printed material and the multimedia CD significantly increased the knowledge and reduced the anxiety levels of the participants. However, no significant differences in unscheduled early hospital follow-up visits postsurgery were found between the two modes of instruction. Furthermore, we found that significantly fewer hours were spent by nurses on health education for the multimedia CD group in comparison with the printed material group.

Conclusions/Implications for Practice:

In the current clinical environment of common staffing shortages, information tools may be used to cost-effectively assist and simplify nursing work. The findings of this study may provide a reference to medical centers that are working to reduce the time spent by nurses on health education for outpatient surgery patients. Furthermore, audiovisual health education tools are recommended to increase nursing effectiveness and save nursing time.
Care, Autonomy, and Gender in Nursing Practice: A Historical Study of Nurses’ Experiences
Authors: Galbany-Estragués Paola , Comas-d’Argemir Dolors
Published: December 2016

Background:

Care is the essence of the nursing role and is closely related to the concept of professional autonomy. Autonomy is implicated in power relations between doctors and nurses and between men and women. These relationships are closely linked to care practices and the inequality of nursing and medicine.

Purpose:

The aim of this study was to analyze nursing discourse regarding the concept of care and its relationship to the concept of autonomy and gender.

Methods:

This is a historical study based on oral interviews that took place between November 2008 and February 2011. We interviewed 19 nursing professionals who currently worked at the Hospital of the Holy Spirit (near Barcelona) or had worked there between 1961 and 2010. Semistructured interviews were recorded, transcribed, and analyzed.

Results:

We highlight four main themes: “a real nurse”; “more technology, less care”; “the fragility of autonomy”; and “the invisibility of nursing work.” These themes show the contradictions in the nursing profession that are based on the concept of care. However, in daily practice, the concept of care varies. Time pressure distances the nursing practice from its theoretical context. Changes in the concept of care are related to transformations in the health system and nursing work.

Conclusions/Implications for Practice:

Changes related to the autonomy of nursing are related to changes in the concept of care. In practice, care has a biomedical orientation. Care has become technologized and bureaucratized, which reduces the time that is spent with the patient. In a context in which medical authority predominates, nursing’s struggle for autonomy is based on the recognition of the value of care. When care becomes invisible, the autonomy of nursing as a profession is threatened. This conclusion allows reflections about shifts in the concept of care and how they affect clinical practice and the autonomy of the nursing profession.
Hemodynamic response to primary prophylactic therapy with nonselective β-blockers is related to a reduction of first variceal bleeding risk in liver cirrhosis: a meta-analysis
Authors: Kerbert Annarein J.C. , Chiang Fang W.T. , van der Werf Mark , Stijnen Theo , Slingerland Hilde , Verspaget Hein W. , van Hoek Bart , Coenraad Minneke J.
Published: December 2016

The current primary prophylaxis for esophageal variceal bleeding in cirrhotic patients consists of nonselective β-blocker (NSBB) therapy. However, only approximately half of the patients achieve a sufficient hemodynamic response to NSBB therapy. Clinical application of hemodynamic response monitoring is still under debate. The aim of this meta-analysis is to assess the potential clinical value of monitoring the hemodynamic response to NSBB therapy using hepatic venous pressure gradient (HVPG) measurements in the primary prophylaxis for variceal bleeding. A systematic literature search was performed in PubMed, Embase, Web of Science, and the COCHRANE Library. Randomized-controlled trials and case series that included cirrhotic patients receiving primary prophylaxis for variceal bleeding with NSBBs and hemodynamic response monitoring using HVPG measurements were included for analysis. The primary outcome measure was variceal bleeding. A fixed-effect analysis was carried out using the Mantel–Haenszel method for relative risks. Six of the 1172 papers found were selected on the basis of stringent selection criteria. Hemodynamic response (HVPG ≤12 mmHg and/or a reduction of ≥20%, or ≥10% in one study, from baseline) to β-blocker therapy was associated significantly with a lower risk of variceal bleeding (relative risk=0.13, 95% confidence interval=0.06–0.29) compared with a nonresponse. Patients achieving a hemodynamic response to NSBB therapy have a lower risk of variceal bleeding than hemodynamic nonresponders. Hemodynamic monitoring in primary prophylaxis is of potential clinical value and requires further assessment in large cohort randomized-controlled trials.