bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between green space and depressive symptoms in pregnant women: moderating roles of socioeconomic status and physical activity
Authors: McEachan R R C , Prady S L , Smith G , Fairley L , Cabieses B , Gidlow C , Wright J , Dadvand P , van Gent D , Nieuwenhuijsen M J
Published: November 2015

Background

The current study explored the association between green space and depression in a deprived, multiethnic sample of pregnant women, and examined moderating and mediating variables.

Method

7547 women recruited to the ‘Born in Bradford’ cohort completed a questionnaire during pregnancy. A binary measure of depressive symptoms was calculated using a validated survey. Two green space measures were used: quintiles of residential greenness calculated using the normalised difference vegetation index for three neighbourhood sizes (100, 300 and 500 m buffer zones around participant addresses); access to major green spaces estimated as straight line distance between participant address and nearest green space (>0.5 hectares). Logistic regression analyses examined relationships between green space and depressive symptoms, controlling for ethnicity, demographics, socioeconomic status (SES) and health behaviours. Multiplicative interactions explored variations by ethnic group, SES or activity levels. Mediation analysis assessed indirect effects via physical activity.

Results

Pregnant women in the greener quintiles were 18–23% less likely to report depressive symptoms than those in the least green quintile (for within 100 m of green space buffer zone). The green space-depressive symptoms association was significant for women with lower education or who were active. Physical activity partially mediated the association of green space, but explained only a small portion of the direct effect.

Conclusions

Higher residential greenness was associated with a reduced likelihood of depressive symptoms. Associations may be stronger for more disadvantaged groups and for those who are already physically active. Improving green space is a promising intervention to reduce risk of depression in disadvantaged groups.
Haemorrhoids: modern diagnosis and treatment
Authors: Hollingshead J R F , Phillips R K S
Published: November 2015

Haemorrhoids present often to primary and secondary care, and haemorrhoidal procedures are among the most common carried out. They may co-exist with more serious pathology, and correct evaluation is important. In most cases a one-off colonoscopy in patients aged 50 or above with flexible sigmoidoscopy in younger patients is reasonable. Many people with haemorrhoids do not require treatment. Topical remedies provide no more than symptomatic relief—and even evidence for this is poor. Bulk laxatives alone may improve symptoms of both bleeding and prolapse and seem as effective as injection sclerotherapy. Rubber band ligation is effective in 75% of patients in the short term, but does not treat prolapsed haemorrhoids or those with a significant external component. Conventional haemorrhoidectomy remains the most effective treatment in the long term, the main limitation being post-operative pain. Metronidazole, topical sphincter relaxants and operative technique have all been shown to reduce pain. Stapled haemorrhoidectomy and haemorrhoidal artery ligation techniques are probably less effective but less painful. Long-term data are poor for all procedures, with many studies reporting only 1–3 years of follow-up data. Haemorrhoids are common in pregnancy, occurring in 40% of women. They can usually be treated conservatively during pregnancy, with any treatment delayed until after delivery. Acutely strangulated haemorrhoids may be treated either conservatively or operatively. There is an increased risk of anal stenosis after acute surgery, but the risks of sepsis and sphincter damage are less significant than previously thought. The majority of patients who are treated conservatively will still require definitive treatment at a later date.
The acute effect of maximal exercise on central and peripheral arterial stiffness indices and hemodynamics in children and adults
Authors: Melo Xavier , Fernhall Bo , Santos Diana A. , Pinto Rita , Pimenta Nuno M. , Sardinha Luís B. , Santa-Clara Helena
Published: November 2015

This study compared the effects of a bout of maximal running exercise on arterial stiffness in children and adults. Right carotid blood pressure and artery stiffness indices measured by pulse wave velocity (PWV), compliance and distensibility coefficients, stiffness index α and β (echo-tracking), contralateral carotid blood pressure, and upper and lower limb and central/aortic PWV (applanation tonometry) were taken at rest and 10 min after a bout of maximal treadmill running in 34 children (7.38 ± 0.38 years) and 45 young adults (25.22 ± 0.91 years) having similar aerobic potential. Two-by-two repeated measures analysis of variance and analysis of covariance were used to detect differences with exercise between groups. Carotid pulse pressure (PP; η2 = 0.394) increased more in adults after exercise (p < 0.05). Compliance (η2 = 0.385) decreased in particular in adults and in those with high changes in distending pressure, similarly to stiffness index α and β. Carotid PWV increased more in adults and was related to local changes in PP but not mean arterial pressure (MAP). Stiffness in the lower limbs decreased (η2 = 0.115) but apparently only in those with small MAP changes (η2 = 0.111). No significant exercise or group interaction effects were found when variables were adjusted to height. An acute bout of maximal exercise can alter arterial stiffness and hemodynamics in the carotid artery and within the active muscle beds. Arterial stiffness and hemodynamic response to metabolic demands during exercise in children simply reflect their smaller body size and may not indicate a particular physiological difference compared with adults.
Correlations between structure, microstructure, density and dielectric properties of the lead-free ferroelectrics Bi0.5(Na,K)0.5TiO3
Authors: Anjali K. , Ajithkumar T. G. , Joy P. A.
Published: November 2015

Solid solutions of the lead-free ferroelectric oxides Bi[Formula: see text]Na[Formula: see text]TiO3 (BNT) and Bi[Formula: see text]K[Formula: see text]TiO3 (BKT), represented as ([Formula: see text])BNT–xBKT, are studied for very close compositions in the range [Formula: see text] to understand the correlation between the structure and the properties. Compositions are varied in steps of [Formula: see text] in the range [Formula: see text] and [Formula: see text] and [Formula: see text] in the range [Formula: see text], to precisely locate the structural transition as well as the morphotropic phase boundary (MPB) region and the compositional region of best performance. Rietveld refinement analysis of the powder X-ray diffraction patterns showed monoclinic phase up to x = 0.17 and a mixture of monoclinic and tetragonal phases for [Formula: see text]. Similarly, the density and the dielectric constant showed linear variation up to [Formula: see text] and a large increase above this composition, showing maximum values in the compositional range [Formula: see text], corresponding to the MPB region. Microstructural features also showed corresponding changes, indicating close relationship between the structure, microstructure and properties of the different compositions.
Glacial history of Mt Chelmos, Peloponnesus, Greece
Authors: Pope R. J. , Hughes P. D. , Skourtsos E.
Published: November 2015

Mt Chelmos in the Peloponnesus was glaciated by a plateau ice field during the most extensive Pleistocene glaciation. Valley glaciers radiated out from an ice field over the central plateau of the massif. The largest glaciations are likely to be Middle Pleistocene in age. Smaller valley and cirque glaciers formed later and boulders on the moraines of these glacial phases have been dated using
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Cl terrestrial cosmogenic nuclide exposure dating. These ages indicate a Late Pleistocene age with glacier advance/stabilization at 40–30 ka, glacier retreat at 23–21 ka and advance/stabilization at 13–10 ka. This indicates that the glacial maximum of the last cold stage occurred during Marine Isotope Stage 3, several thousand years before the global Last Glacial Maximum (Marine Isotope Stage 2). The last phase of moraine-building occurred at the end of the Pleistocene, possibly during the Younger Dryas.
Remodeling of the rat distal colon in diabetes: function and ultrastructure
Authors: Siegman Marion J. , Eto Masumi , Butler Thomas M.
Published: November 2015

This study seeks to define and explain remodeling of the distal colon in the streptozotocin (STZ)-treated rat model of diabetes through analysis of resting and active length dependence of force production, chemical composition, and ultrastructure. Compared with untreated controls, the passive stiffness on extension of the diabetic muscle is high, and active force produced at short muscle lengths is amplified but is limited by an internal resistance to shortening. The latter are accounted for by a significant increase in collagen type 1, with no changes in types 3 and 4. In the diabetic colon, ultrastructural studies show unique, conspicuous pockets of collagen among muscle cells, in addition to a thickened basement membrane and an extracellular space filled with collagen fibers and various fibrils. Measurements of DNA and total protein content revealed that the diabetic colon underwent hypertrophy, along with a proportional increase in actin and myosin contents, with no change in the actin-to-myosin ratio. Active force production per cross-sectional area was not different in the diabetic and normal muscles, consistent with the proportionality of changes in contractile proteins. The stiffness and the limit to shortening of the diabetic colon were significantly reduced by treatment with the glycation breaker alagebrium chloride (ALT-711), with no change in collagen contents. Functionally, this study shows that, in diabetes, the production of collagen type 1 and glycation increase stiffness, which limits distensibility on filling and limits shortening and expulsion of contents, both of which can be alleviated by treatment with ALT-711.
Hypoxia-inducible factor 3 biology: complexities and emerging themes
Authors: Duan Cunming
Published: November 2015

The hypoxia-inducible factor (HIF) family has three distinct members in most vertebrates. All three HIFs consist of a unique and oxygen-labile α-subunit and a common and stable β-subunit. While HIF-1 and HIF-2 function as master regulators of the transcriptional response to hypoxia, much less is known about HIF-3. The HIF-3α gene gives rise to multiple HIF-3α variants due to the utilization of different promoters, different transcription initiation sites, and alternative splicing. These HIF-3α variants are expressed in different tissues, at different developmental stages, and are differentially regulated by hypoxia and other factors. Recent studies suggest that different HIF-3α variants have different and even opposite functions. There is strong evidence that full-length HIF-3α protein functions as an oxygen-regulated transcription activator and that it activates a unique transcriptional program in response to hypoxia. Many HIF-3α target genes have been identified. While some short HIF-3α variants act as dominant-negative regulators of HIF-1/2α actions, other HIF-3α variants can inhibit HIF-1/2α actions by competing for the common HIF-β. There are also a number of HIF-3α variants yet to be explored. Future studies of these naturally occurring HIF-3α variants will provide new and important insights into HIF biology and may lead to the development of new therapeutic strategies.
Iron overload results in hepatic oxidative stress, immune cell activation, and hepatocellular ballooning injury, leading to nonalcoholic steatohepatitis in genetically obese mice
Authors: Handa Priya , Morgan-Stevenson Vicki , Maliken Bryan D. , Nelson James E. , Washington Shenna , Westerman Mark , Yeh Matthew M. , Kowdley Kris V.
Published: November 2015

The aim of this study was to determine the effect of iron overload in the development of nonalcoholic steatohepatitis (NASH) in a genetically obese mouse model (Lepr db/db). Leptin receptor-deficient mice were fed a normal or an iron-supplemented chow for 8 wk and switched to normal chow for 8 wk. All dietary iron (DI)-fed mice developed hepatic iron overload predominantly in the reticuloendothelial system. Hepatocellular ballooning injury was observed in the livers of 85% of DI mice, relative to 20% of chow-fed Lepr db/db. Hepatic malonyldialdehyde levels and mRNA levels of antioxidant genes ( Nrf2, Gpx1, and Hmox1) were significantly increased in the DI mice. Hepatic mRNA levels of mitochondrial biogenesis regulators Pgc1α, Tfam, Cox4, and Nrf1 were diminished in the DI mice. In addition, gene expression levels of cytokines ( Il6, Tnfα) and several innate and adaptive immune cell markers such as Tlr4, Inos, CD11c, CD4, CD8, and Ifnγ were significantly increased in livers of the DI group. Strikingly, Nlrp3, a component of the inflammasome and Il18, a cytokine elicited by inflammasome activation, were significantly upregulated in the livers of DI mice. In addition, RAW 264.7 macrophages loaded with exogenous iron showed significantly higher levels of inflammatory markers ( Inos, Tnfα, Mcp1, Tlr4). Thus dietary iron excess leads to hepatic oxidative stress, inflammasome activation, induction of inflammatory and immune mediators, hepatocellular ballooning injury, and therefore NASH in this model. Taken together, these studies indicate a multifactorial role for iron overload in the pathogenesis of NASH in the setting of obesity and metabolic syndrome.
Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver
Authors: Eckert Christoph , Kim Yong Ook , Julich Henrike , Heier Eva-Carina , Klein Niklas , Krause Elmar , Tschernig Thomas , Kornek Miroslaw , Lammert Frank , Schuppan Detlef , Lukacs-Kornek Veronika
Published: November 2015

Podoplanin/gp38+ stromal cells present in lymphoid organs play a central role in the formation and reorganization of the extracellular matrix and in the functional regulation of immune responses. Gp38+ cells are present during embryogenesis and in human livers of primary biliary cirrhosis. Since little is known about their function, we studied gp38+ cells during chronic liver inflammation in models of biliary and parenchymal liver fibrosis and steatohepatitis. Gp38+ cells were analyzed using flow cytometry and confocal microscopy, and the expression of their steady state and inflammation-associated genes was evaluated from healthy and inflamed livers. Gp38+ cells significantly expanded in all three models of liver injury and returned to baseline levels during regression of inflammation. Based on CD133 and gp38 expression in the CD45−CD31−Asgpr1− liver cell fraction, numerous subsets could be identified that were negative for CD133 (gp38hiCD133−, gp38lowCD133−, and gp38−CD133−). Moreover, among the CD133+ cells, previously identified as progenitor population in injured liver, two subpopulations could be distinguished based on their gp38 expression (gp38−CD133+ and CD133+gp38+). Importantly, the distribution of the identified subsets in inflammation illustrated injury-specific changes. Moreover, the gp38+CD133+ cells exhibited liver progenitor cell characteristics similar to the gp38−CD133+ population, thus representing a novel subset within the classical progenitor cell niche. Additionally, these cells expressed distinct sets of inflammatory genes during liver injury. Our study illuminates a novel classification of the stromal/progenitor cell compartment in the liver and pinpoints a hitherto unrecognized injury-related alteration in progenitor subset composition in chronic liver inflammation and fibrosis.
Hyperthermia, dehydration, and osmotic stress: unconventional sources of exercise-induced reactive oxygen species
Authors: King Michelle A. , Clanton Thomas L. , Laitano Orlando
Published: November 2015

Evidence of increased reactive oxygen species (ROS) production is observed in the circulation during exercise in humans. This is exacerbated at elevated body temperatures and attenuated when normal exercise-induced body temperature elevations are suppressed. Why ROS production during exercise is temperature dependent is entirely unknown. This review covers the human exercise studies to date that provide evidence that oxidant and antioxidant changes observed in the blood during exercise are dependent on temperature and fluid balance. We then address possible mechanisms linking exercise with these variables that include shear stress, effects of hemoconcentration, and signaling pathways involving muscle osmoregulation. Since pathways of muscle osmoregulation are rarely discussed in this context, we provide a brief review of what is currently known and unknown about muscle osmoregulation and how it may be linked to oxidant production in exercise and hyperthermia. Both the circulation and the exercising muscle fibers become concentrated with osmolytes during exercise in the heat, resulting in a competition for available water across the muscle sarcolemma and other tissues. We conclude that though multiple mechanisms may be responsible for the changes in oxidant/antioxidant balance in the blood during exercise, a strong case can be made that a significant component of ROS produced during some forms of exercise reflect requirements of adapting to osmotic challenges, hyperthermia challenges, and loss of circulating fluid volume.
Constructing quasi-linear V̇o2 responses from nonlinear parameters
Authors: Wilcox Samuel L. , Broxterman Ryan M. , Barstow Thomas J.
Published: November 2015

Oxygen uptake (V̇o2) kinetics have been shown to be governed by a nonlinear control system across a range of work rates. However, the linearity of the V̇o2 response to ramp incremental exercise would appear to be the result of a linear control system. This apparent contradiction could represent a balancing of changing V̇o2 kinetics parameter values across a range of work rates. To test this, six healthy men completed bouts of ramp incremental exercise at 15, 30, and 60 W/min (15R, 30R, 60R, respectively) and four bouts of an extended-step incremental exercise. V̇o2 parameter values were derived from the step exercise using two monoexponential models: one starting at time zero and encompassing the entire stage (MONO), and the other truncated to the first 5 min and allowing a time delay (5TD). The resulting parameter values were applied to an integrative model to estimate the ramp responses. As work rate increased, gain values increased ( P < 0.001 for MONO and 5TD), as did mean response time (or time constant) values (MONO: P < 0.001; 5TD: P = 0.003). Up to maximal V̇o2 (V̇o2 max), the gains of the estimated ramp responses from both models were not different from the gains of the actual observed V̇o2 responses for 15R and 30R (15R: 11.3 ± 1.2, 11.7 ± 0.7, 10.9 ± 0.3; 30R: 10.5 ± 0.8, 11.0 ± 0.5, 10.7 ± 0.3 ml O2·min−1·W−1, for actual, MONO, 5TD, respectively) but were significantly greater for 60R (8.7 ± 1.0, 9.9 ± 0.4, 10.3 ± 0.3 ml O2·min−1·W−1 for actual, MONO, 5TD, respectively). Up to 80%V̇o2 max gain values were not significantly different for any ramp rate ( P > 0.05 for all). We conclude that the apparent linearity of the V̇o2 response to ramp incremental exercise is consequent to a balancing of increasing time constant and gain parameter values.
Primary motor cortex LTP/LTD-like plasticity in probable corticobasal syndrome
Authors: Suppa Antonio , Di Stasio Flavio , Marsili Luca , Upadhyay Neeraj , Belvisi Daniele , Conte Antonella , Modugno Nicola , Colosimo Carlo , Berardelli Alfredo
Published: November 2015

Whether the primary motor cortex (M1) contributes to the pathophysiology of corticobasal syndrome (CBS) remains unclear. In this study in patients with probable CBS, we tested whether M1 plasticity contributes to the pathophysiology of symptoms in the contralateral “less affected” limb, manifesting only parkinsonism, and in the contralateral “more affected” limb, manifesting parkinsonism plus other motor and nonmotor symptoms. In Experiment 1, we applied intermittent/continuous theta-burst stimulation (iTBS/cTBS) over the M1 contralateral to the less affected limb in 17 patients. In Experiment 2, we applied iTBS/cTBS over the M1 contralateral to the more affected limb in 14 of the 17 patients. We measured iTBS/cTBS-induced plasticity as reflected by motor-evoked potential (MEP) changes. Data were compared with those obtained in 17 healthy subjects (HS). In Experiment 1, TBS over the M1 contralateral to the less affected limb disclosed reduced plasticity in patients than in HS. In Experiment 2, in 5 of 14 patients we recorded abnormally low-amplitude MEPs, preventing the evaluation of plasticity in the M1 contralateral to the more affected limb. In the remaining nine patients, TBS disclosed abnormal plasticity characterized by high intersubject variability. In these nine patients, the response to TBS correlated with specific patients' clinical features. In the present study in patients with probable CBS, we have demonstrated heterogeneous abnormalities of M1 that contribute to the pathophysiology of this condition.
Na+ current in presynaptic terminals of the crayfish opener cannot initiate action potentials
Authors: Lin Jen-Wei
Published: November 2015

Action potential (AP) propagation in presynaptic axons of the crayfish opener neuromuscular junction (NMJ) was investigated by simultaneously recording from a terminal varicosity and a proximal branch. Although orthodromically conducting APs could be recorded in terminals with amplitudes up to 70 mV, depolarizing steps in terminals to −20 mV or higher failed to fire APs. Patch-clamp recordings did detect Na+ current ( INa) in most terminals. The INa exhibited a high threshold and fast activation rate. Local perfusion of Na+-free saline showed that terminal INa contributed to AP waveform by slightly accelerating the rising phase and increasing the peak amplitude. These findings suggest that terminal INa functions to “touch up” but not to generate APs.
Hamiltonian Dynamics and Adiabatic Invariants for Time-Dependent Superconducting Qubit-Oscillators and Resonators in Quantum Computing Systems
Authors: Choi Jeong Ryeol
Published: November 2015

An adiabatic invariant, which is a conserved quantity, is useful for studying quantum and classical properties of dynamical systems. Adiabatic invariants for time-dependent superconducting qubit-oscillator systems and resonators are investigated using the Liouville-von Neumann equation. At first, we derive an invariant for a simple superconducting qubit-oscillator through the introduction of its reduced Hamiltonian. Afterwards, an adiabatic invariant for a nanomechanical resonator linearly interfaced with a superconducting circuit, via a coupling with a time-dependent strength, is evaluated using the technique of unitary transformation. The accuracy of conservation for such invariant quantities is represented in detail. Based on the results of our developments in this paper, perturbation theory is applicable to the research of quantum characteristics of more complicated qubit systems that are described by a time-dependent Hamiltonian involving nonlinear terms.
Identification of Proximal and Distal 22q11.2 Microduplications among Patients with Cleft Lip and/or Palate: A Novel Inherited Atypical 0.6 Mb Duplication
Authors: Sedghi Maryam , Abdali Hossein , Memarzadeh Mehrdad , Salehi Mansoor , Nouri Narges , Hosseinzadeh Majid , Nouri Nayereh
Published: November 2015

Misalignments of low-copy repeats (LCRs) located in chromosome 22, particularly band 22q11.2, predispose to rearrangements. A variety of phenotypic features are associated with 22q11.2 microduplication syndrome which makes it challenging for the genetic counselors to recommend appropriate genetic assessment and counseling for the patients. In this study, multiplex ligation probe dependent amplification (MLPA) analysis was performed on 378 patients with cleft lip and/or palate to characterize rearrangements in patients suspected of 22q11.2 microduplication and microdeletion syndromes. Of 378 cases, 15 were diagnosed with a microdeletion with various sizes and 3 with duplications. For the first time in this study an atypical 0.6 Mb duplication is reported. Illustration of the phenotypes associated with the microduplications increases the knowledge of phenotypes reported in the literature.
A Reconstruction Algorithm for Blade Surface Based on Less Measured Points
Authors: Liu Jia , Zhao Ji , Yang Xu , Liu Jiming , Qu Xingtian , Wang Xin
Published: November 2015

A reconstruction algorithm for blade surface from less measured points of section curves is given based on B-spline surface interpolation. The less measured points are divided into different segments by the key geometric points and throat points which are defined according to design concepts. The segmentations are performed by different fitting algorithms with consideration of curvature continuity as their boundary condition to avoid flow disturbance. Finally, a high-quality reconstruction surface model is obtained by using the B-spline curve meshes constructed by paired points. The advantage of this algorithm is the simplicity and effectivity reconstruction of blade surface to ensure the aerodynamic performance. Moreover, the obtained paired points can be regarded as measured points to measure and reconstruct the blade surface directly. Experimental results show that the reconstruction blade surface is suitable for precisely representing blade, evaluating machining accuracy, and analyzing machining allowance.
Maxillary Swelling as the First Evidence of Multiple Myeloma
Authors: Kasamatsu Atsushi , Kimura Yasushi , Tsujimura Hideki , Kanazawa Harusachi , Koide Nao , Miyamoto Isao , Endo-Sakamoto Yosuke , Shiiba Masashi , Tanzawa Hideki , Uzawa Katsuhiro
Published: November 2015

Multiple myeloma is a malignant neoplasm of plasma cells characterized by proliferation of a single clone of abnormal immunoglobulin-secreting plasma cells. Since the amount of hemopoietic bone marrow is decreased in the maxilla, oral manifestations of multiple myeloma are less common in the maxilla than in the mandible. We report the case of 33-year-old Japanese man who presented with a mass in the right maxillary alveolar region. Computed tomography and magnetic resonance images showed a soft tissue mass in the right maxilla eroding the anterior and lateral walls of the maxillary sinus and extending into the buccal space. The biopsy results, imaging, and laboratory investigations led to the diagnosis of multiple myeloma. This case report suggests that oral surgeons and dentists should properly address oral manifestations as first indications of multiple myeloma.
A Review of the Literature on Primary Leiomyosarcoma of the Prostate Gland
Authors: Venyo Anthony Kodzo-Grey
Published: November 2015

Primary leiomyosarcoma of the prostate (PLSOP) is rare, with less than 200 cases reported so far. PLSOPs present with lower urinary tract symptoms, haematuria, and perineal pain; may or may not be associated with a history of previous treatment for adenocarcinoma of prostate by means of radiotherapy and or hormonal treatment; may afflict children and adult male. Examination may reveal benign enlarged prostate and hard enlarged mass. PLSOPs may be diagnosed by histological examination findings of spindle-shaped carcinoma cells in prostate specimens. Immunohistochemical staining tends to be positive for vimentin, CD44, smooth muscle actin, and calponin, focally positive for desmin, and at times positive for keratin. They stain negatively for PSA, S-100, CD34, CD117, and cytokeratin. Cytogenetic study on primary leiomyosarcoma of the prostate gland may show clonal chromosomal rearrangement involving Chromosomes 2, 3, 9, 11, and 19. On the whole the prognosis is poor. Surgery with or without chemotherapy would appear to be the mainstay of treatment for PLSOPs that are operable, but generally there is no consensus opinion on the best therapeutic approach. Most cases of PLSOPs are diagnosed in an advanced stage of the disease. A global multicenter trial is required to find therapies that would improve the prognosis.
The Spectral Radius for a Class of Double-Star-Like Tree Systems with Maximal Degree 4
Authors: Mao Yufeng , Xu Meijin , Chen Xiaodong , Liu Yan-Jun , Li Kai
Published: November 2015

We mainly study the properties of the 4-double-star-like tree, which is the generalization of star-like trees. Firstly we use graft transformation method to obtain the maximal and minimum extremal graphs of 4-double-star-like trees. Secondly, by the relations between the degree and second degree of vertices in maximal extremal graphs of 4-double-star-like trees we get the upper bounds of spectral radius of 4-double-star-like trees.
The Influence of a Continuing Medical Education Campaign on New Strategies to Improve Appropriate Use of Antibiotics
Authors: Bucklin Brenda A. , Gibbs Ronald S. , Wieber Carolyn , Myers Leslie
Published: November 2015

Introduction. Widespread use of antibiotics has led to drug-resistant bacteria and reports of drug-resistant infections. A continuing medical education (CME) campaign was used to improve antibiotic use among primary care providers. Methods. The Office of CME and Professional Development at the University of Colorado School of Medicine produces a semiannual, week-long course for primary care providers. A 2-year multifaceted CME campaign consisted of course content on antibiotic use, a practice audit, and two surveys to measure perceptions of the problem of antibiotic overuse, potential barriers to achieving appropriate use, and strategies to overcome barriers. Results. The overall response rate in the 2nd part of the campaign was 68.4%. Sixty-six percent of respondents had implemented at least one strategy to reduce antibiotic overuse. The rate was significantly higher among those who had attended previous reviews (81.0%) compared with those who had attended neither (54%, p=0.0002). However, there was no “dose effect” on the rate of implementing a new strategy. Conclusions. Overuse of antibiotic therapy has important public health implications. Results suggest that mixed interactive and didactic CME program was effective in increasing awareness of antibiotic overuse and strategies for reducing antibiotic administration.
Outcomes of Cryoballoon Ablation in High- and Low-Volume Atrial Fibrillation Ablation Centres: A Russian Pilot Survey
Authors: Mikhaylov Evgeny N. , Lebedev Dmitry S. , Pokushalov Evgeny A. , Davtyan Karapet V. , Ivanitskii Eduard A. , Nechepurenko Anatoly A. , Kosonogov Alexey Ya. , Kolunin Grigory V. , Morozov Igor A. , Termosesov Sergey A. , Maykov Evgeny B. , Khomutinin Dmitry N. , Eremin Sergey A. , Mayorov Igor M. , Romanov Alexander B. , Shabanov Vitaliy V. , Shatakhtsyan Victoria , Tsivkovskii Viktor , Revishvili Amiran Sh. , Shlyakhto Evgeny V.
Published: November 2015

Purpose. The results of cryoballoon ablation (CBA) procedure have been mainly derived from studies conducted in experienced atrial fibrillation (AF) ablation centres. Here, we report on CBA efficacy and complications resulting from real practice of this procedure at both high- and low-volume centres.Methods. Among 62 Russian centres performing AF ablation, 15 (24%) used CBA technology for pulmonary vein isolation. The centres were asked to provide a detailed description of all CBA procedures performed and complications, if encountered.Results. Thirteen sites completed interviews on all CBAs in their centres (>95% of CBAs in Russia). Six sites were high-volume AF ablation (>100 AF cases/year) centres, and 7 were low-volume AF ablation. There was no statistical difference in arrhythmia-free rates between high- and low-volume centres (64.6 versus 60.8% at 6 months). Major complications developed in 1.5% of patients and were equally distributed between high- and low-volume centres. Minor procedure-related events were encountered in 8% of patients and were more prevalent in high-volume centres. Total event and vascular access site event rates were higher in women than in men.Conclusions. CBA has an acceptable efficacy profile in real practice. In less experienced AF ablation centres, the major complication rate is equal to that in high-volume centres.
Biocompatibility and Bioimaging Application of Carbon Nanoparticles Synthesized by Phosphorus Pentoxide Combustion Method
Authors: Roy Shibsekhar , Korzeniowska Barbara , Dixit Chandra K. , Manickam Gowri , Daniels Stephen , McDonagh Colette
Published: November 2015

Carbon nanoforms have emerged as a versatile bioimaging tool. In this work, we have synthesized four different carbon nanoparticles of different dimensions (10–100 nm) and variable fluorescence quantum efficiency (0.007 to 0.37) from four different carbon sources by phosphorus pentoxide‐mediated combustion. The fluorescence quantum efficiency of the resulting self‐passivated nanoparticles has been empirically correlated to the molecular weight and viscosity of the respective carbon source used in the synthesis. The carbon nanoparticles have been found to be significantly biocompatible as observed in the MTS assay. We have applied these biocompatible luminescent carbon nanoparticles as high brightness fluorescent probes for staining human blood platelets with very high target specificity.
Bolus Residue Scale: An Easy-to-Use and Reliable Videofluoroscopic Analysis Tool to Score Bolus Residue in Patients with Dysphagia
Authors: Rommel Nathalie , Borgers Charlotte , Van Beckevoort Dirk , Goeleven Ann , Dejaeger Eddy , Omari Taher I.
Published: November 2015

Background. We aimed to validate an easy-to-use videofluoroscopic analysis tool, the bolus residue scale (BRS), for detection and classification of pharyngeal retention in the valleculae, piriform sinuses, and/or the posterior pharyngeal wall.Methods. 50 randomly selected videofluoroscopic images of 10 mL swallows (recorded in 18 dysphagia patients and 8 controls) were analyzed by 4 experts and 6 nonexpert observers. A score from 1 to 6 was assigned according to the number of structures affected by residue. Inter- and intrarater reliabilities were assessed by calculation of intraclass correlation coefficients (ICCs) for expert and nonexpert observers. Sensitivity, specificity, and interrater agreement were analyzed for different BRS levels.Results. Intrarater reproducibility was almost perfect for experts (mean ICC 0.972) and ranged from substantial to almost perfect for nonexperts (mean ICC 0.835). Interjudge agreement of the experts ranged from substantial to almost perfect (mean ICC 0.780), but interrater reliability of nonexperts ranged from substantial to good (mean 0.719). BRS shows for experts a high specificity and sensitivity and for nonexperts a low sensitivity and high specificity.Conclusions. The BRS is a simple, easy-to-carry-out, and accessible rating scale to locate pharyngeal retention on videofluoroscopic images with a good specificity and reproducibility for observers of different expertise levels.
Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study
Authors: Di Lauro Salvatore , Castrejón Melissa , Fernández Itziar , Rojas Jimena , Coco Rosa M. , Sanabria María R. , Rodríguez de la Rua Enrique , Pastor J. Carlos
Published: November 2015

Purpose. To quantify the frequency of visual loss after successful retinal detachment (RD) surgery in macula-on patients in a multicentric, prospective series of RD.Methods. Clinical variables from consecutive macula-on RD patients were collected in a prospective multicentric study. Visual loss was defined as at least a reduction in one line in best corrected visual acuity (VA) with Snellen chart. The series were divided into 4 subgroups: (1) all macula-on eyes (n=357); (2) macula-on patients with visual loss at the third month of follow-up (n=53) which were further subdivided in (3) phakic eyes (n=39); and (4) pseudophakic eyes (n=14).Results. Fifty-three eyes (14.9%) had visual loss three months after surgery (n=39phakic eyes;n=14pseudophakic eyes). There were no statistically significant differences between them regarding their clinical characteristics. Pars plana vitrectomy (PPV) was used in 67.2% of cases, scleral buckle in 57.7%, and scleral explant in 11.9% (36.1% were combined procedures).Conclusions. Around 15% of macula-on RD eyes lose VA after successful surgery. Development of cataracts may be one cause in phakic eyes, but vision loss in pseudophakic eyes could have other explanations such as the effect of released factors produced by retinal ischemia on the macula area. Further investigations are necessary to elucidate this hypothesis.
Techniques and Methods for Testing the Postural Function in Healthy and Pathological Subjects
Authors: Paillard Thierry , Noé Frédéric
Published: November 2015

The different techniques and methods employed as well as the different quantitative and qualitative variables measured in order to objectify postural control are often chosen without taking into account the population studied, the objective of the postural test, and the environmental conditions. For these reasons, the aim of this review was to present and justify the different testing techniques and methods with their different quantitative and qualitative variables to make it possible to precisely evaluate each sensory, central, and motor component of the postural function according to the experiment protocol under consideration. The main practical and technological methods and techniques used in evaluating postural control were explained and justified according to the experimental protocol defined. The main postural conditions (postural stance, visual condition, balance condition, and test duration) were also analyzed. Moreover, the mechanistic exploration of the postural function often requires implementing disturbing postural conditions by using motor disturbance (mechanical disturbance), sensory stimulation (sensory manipulation), and/or cognitive disturbance (cognitive task associated with maintaining postural balance) protocols. Each type of disturbance was tackled in order to facilitate understanding of subtle postural control mechanisms and the means to explore them.
Stereotypes of Aging: Their Effects on the Health of Older Adults
Authors: Dionigi Rylee A.
Published: November 2015

The purpose of this review is to present findings on the effects of stereotypes of aging on health outcomes related to older adults, such as physical and mental functioning (specifically) and overall well-being and perceived quality of life (more broadly). This review shows that both positive and negative stereotypes of aging can have enabling and constraining effects on the actions, performance, decisions, attitudes, and, consequently, holistic health of an older adult. This review further highlights a variety of limitations in stereotype research in aging contexts, including a lack of qualitative studies focusing on older adult perspectives and the fluctuating definition of what constitutes “good health” during older age.
Neuropilin-2 Regulates Endosome Maturation and EGFR Trafficking to Support Cancer Cell Pathobiology
Authors: Dutta Samikshan , Roy Sohini , Polavaram Navatha S. , Stanton Marissa J. , Zhang Heyu , Bhola Tanvi , Hönscheid Pia , Donohue Terrence M. , Band Hamid , Batra Surinder K. , Muders Michael H. , Datta Kaustubh
Published: November 2015

Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies, where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells and is often associated with increased metastatic potential and drug resistance. We found that NRP2 depletion in human prostate and pancreatic cancer cells resulted in the accumulation of EEA1/Rab5-positive early endosomes concomitant with a decrease in Rab7-positive late endosomes, suggesting a delay in early-to-late endosome maturation. NRP2 depletion also impaired the endocytic transport of cell surface EGFR, arresting functionally active EGFR in endocytic vesicles that consequently led to aberrant ERK activation and cell death. Mechanistic investigations revealed that WD-repeat– and FYVE-domain–containing protein 1 (WDFY1) functioned downstream of NRP2 to promote endosome maturation, thereby influencing the endosomal trafficking of EGFR and the formation of autolysosomes responsible for the degradation of internalized cargo. Overall, our results indicate that the NRP2/WDFY1 axis is required for maintaining endocytic activity in cancer cells, which supports their oncogenic activities and confers drug resistance. Therefore, therapeutically targeting endocytosis may represent an attractive strategy to selectively target cancer cells in multiple malignancies. Cancer Res; 76(2); 418–28. ©2015 AACR.
Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting
Authors: Werner Simone , Krause Friedemann , Rolny Vinzent , Strobl Matthias , Morgenstern David , Datz Christian , Chen Hongda , Brenner Hermann
Published: November 2015

Purpose: In initial studies that included colorectal cancer patients undergoing diagnostic colonoscopy, we had identified a serum marker combination able to detect colorectal cancer with similar diagnostic performance as fecal immunochemical test (FIT). In this study, we aimed to validate the results in participants of a large colorectal cancer screening study conducted in the average-risk, asymptomatic screening population.

Experimental Design: We tested serum samples from 1,200 controls, 420 advanced adenoma patients, 4 carcinoma in situ patients, and 36 colorectal cancer patients with a 5-marker blood test [carcinoembryonic antigen (CEA)+anti-p53+osteopontin+seprase+ferritin]. The diagnostic performance of individual markers and marker combinations was assessed and compared with stool test results.

Results: AUCs for the detection of colorectal cancer and advanced adenomas with the 5-marker blood test were 0.78 [95% confidence interval (CI), 0.68–0.87] and 0.56 (95% CI, 0.53–0.59), respectively, which now is comparable with guaiac-based fecal occult blood test (gFOBT) but inferior to FIT. With cutoffs yielding specificities of 80%, 90%, and 95%, the sensitivities for the detection of colorectal cancer were 64%, 50%, and 42%, and early-stage cancers were detected as well as late-stage cancers. For osteopontin, seprase, and ferritin, the diagnostic performance in the screening setting was reduced compared with previous studies in diagnostic settings while CEA and anti-p53 showed similar diagnostic performance in both settings.

Conclusions: Performance of the 5-marker blood test under screening conditions is inferior to FIT even though it is still comparable with the performance of gFOBT. CEA and anti-p53 could contribute to the development of a multiple marker blood-based test for early detection of colorectal cancer. Clin Cancer Res; 22(7); 1725–33. ©2015 AACR.
Arterial Decellularized Scaffolds Produced Using an Innovative Automatic System
Authors: Pellegata Alessandro F. , Dominioni Tommaso , Ballo Filippo , Maestroni Silvia , Asnaghi M. Adelaide , Zerbini Gianpaolo , Zonta Sandro , Mantero Sara
Published: November 2015

There is still an unmet clinical need for small-caliber artery substitution. Decellularized scaffolds in tissue engineering represent a promising solution. We have developed an innovative system for the automatic decellularization of blood vessels, used to process pig arteries. The system is able to automatically drive a decellularization process in a safe and reliable environment, with complex time patterns, using up to three different decellularization solutions, and providing at the same time a physical stress to improve the decellularization. The decellularization of pig arteries was evaluated by means of histology, DNA quantification and mechanical testing. Outcomes showed scaffolds with no cellular or nuclear remnants and a well-preserved tissue structure, corroborated by mechanical properties similar to native tissue. Decellularized scaffolds were seeded on the inner layer with human endothelial cells and implanted as iliac artery replacement in 4 pharmacologically immune-compromised pigs. This chimeric model was performed as a very preliminary evaluation to investigate the performances of these scaffolds in vivo, and to investigate the fate of seeded cells. Recipients were sacrificed on day 14 and day 70 after surgery, and vessels were found to be patent and with no evidence of thrombi formation. The inner layer was covered by endothelial cells, and the migration of cells positive for α-smooth-muscle actin was observed from the outer layer towards the tunica media. Intriguingly, the endothelial cells on explanted vessels were entirely derived from the host while the seeded cells were lost. In conclusion, this work presents a novel tool for a safe and controlled production of arterial scaffolds, with good decellularization outcomes and a good performance in a short-term, large-animal implantation.
Lang anhaltendes Ansprechen auf die Behandlung mit Ipilimumab: Ein Argument gegen die Erhaltungstherapie?
Authors: Dick Julika , Enk Alexander , Hassel Jessica Cecile
Published: November 2015

Ipilimumab, ein monoklonaler CTLA-4-Antikörper, ist das erste Medikament, das das Gesamtüberleben bei metastasiertem Melanom verbessert hat. Allerdings sind noch Fragen zum Therapieregime offen, z.B. ob eine Erhaltungstherapie notwendig ist, um ein langfristiges Ansprechen zu erzielen. Wir stellen 3 Patienten mit metastasiertem Melanom vor, die nach Progression unter Chemotherapie mit Ipilimumab behandelt wurden. Bei all diesen Patienten führte Ipilimumab zu einer langfristigen Tumorkontrolle über mindestens 32 Monate. Bemerkenswert ist, dass bei allen Patienten eine schwere Autoimmuntoxizität auftrat und die Ipilimumab-Therapie nach 1 bzw. 2 Zyklen abgesetzt wurde. Die hier geschilderten Fälle belegen, dass ein langfristiges Ansprechen auf Ipilimumab ohne Erhaltungstherapie möglich ist.
Zielgerichtetes Vorgehen gegen onkogene Faktoren
Authors: Zhao Yujie , Adjei Alex A.
Published: November 2015

Krebs ist eine genetische Erkrankung, die durch eine Reihe von somatischen und/oder Keimbahn-Mutationen verursacht wird. Die Rollen der Onkogene und Tumorsuppressor-Gene im Krebsgeschehen auf molekularer Ebene sind umfassend erforscht. Das zielgerichtete therapeutische Vorgehen gegen Onkogenprodukte hat sich als attraktiver Ansatz mit großem klinischem Erfolg etabliert; Tumorsuppressoren hingegen gelten als nicht mit Wirkstoffen erreichbar, da es nach heutigem Stand der Technologie nicht möglich ist, die Tumorsuppressor-Funktion bei metastasierter Erkrankung wiederherzustellen. Zwar stehen inzwischen systematische Methoden zur Verfügung, um genetische Veränderungen beim individuellen Patienten nachzuweisen, doch die Unterscheidung zwischen Driver- und Passenger-Mutationen sowie die Erkennung und Validierung von Wirkstoff-Targets stellen weiterhin Herausforderungen dar. Protein-Tyrosinkinasen spielen zentrale Rollen in praktisch allen zellulären Prozessen, und sie besitzen strukturelle Merkmale, durch die sie mit Wirkstoffen erreichbar sind. Monoklonale Antikörper und niedermolekulare Inhibitoren sind die beiden Hauptklassen der zielgerichteten Therapeutika, von denen jede ihre Stärken und Schwächen hat. Erste Erfolge sind zwar bereits erzielt worden, doch die Targeted-Therapie steht noch vor vielen Hürden und Herausforderungen, die es zu überwinden gilt.