bluuebunny/crossref_metadata_2025 huggingface dataset:
Scene coherence can affect the local response to natural images in human V1
Authors: Mannion Damien J. , Kersten Daniel J. , Olman Cheryl A.
Published: September 2015

Neurons in primary visual cortex (V1) can be indirectly affected by visual stimulation positioned outside their receptive fields. Although this contextual modulation has been intensely studied, we have little notion of how it manifests with naturalistic stimulation. Here, we investigated how the V1 response to a natural image fragment is affected by spatial context that is consistent or inconsistent with the scene from which it was extracted. Using functional magnetic resonance imaging at 7 T, we measured the blood oxygen level‐dependent signal in human V1 (n = 8) while participants viewed an array of apertures. Most apertures showed fragments from a single scene, yielding a dominant perceptual interpretation which participants were asked to categorize, and the remaining apertures each showed fragments drawn from a set of 20 scenes. We find that the V1 response was significantly increased for apertures showing image structure that was coherent with the dominant scene relative to the response to the same image structure when it was non‐coherent. Additional analyses suggest that this effect was mostly evident for apertures in the periphery of the visual field, that it peaked towards the centre of the aperture, and that it peaked in the middle to superficial regions of the cortical grey matter. These findings suggest that knowledge of typical spatial relationships is embedded in the circuitry of contextual modulation. Such mechanisms, possibly augmented by contributions from attentional factors, serve to increase the local V1 activity under conditions of contextual consistency.
Localization and expression of GABA transporters in the suprachiasmatic nucleus
Authors: Moldavan Michael , Cravetchi Olga , Williams Melissa , Irwin Robert P. , Aicher Sue A. , Allen Charles N.
Published: September 2015

GABA is a principal neurotransmitter in the suprachiasmatic hypothalamic nucleus (SCN), the master circadian clock. Despite the importance of GABA and GABA uptake for functioning of the circadian pacemaker, the localization and expression of GABA transporters (GATs) in the SCN has not been investigated. The present studies used Western blot analysis, immunohistochemistry and electron microscopy to demonstrate the presence of GABA transporter 1 (GAT1) and GAT3 in the SCN. By using light microscopy, GAT1 and GAT3 were co‐localized throughout the SCN, but were not expressed in the perikarya of arginine vasopressin‐ or vasoactive intestinal peptide‐immunoreactive (‐ir) neurons of adult rats, nor in the neuronal processes labelled with the neurofilament heavy chain. Using electron microscopy, GAT1‐ and GAT3‐ir was found in glial processes surrounding unlabelled neuronal perikarya, axons, dendrites, and enveloped symmetric and asymmetric axo‐dendritic synapses. Glial fibrillary acidic protein‐ir astrocytes grown in cell culture were immunopositive for GAT1 and GAT3 and both GATs could be observed in the same glial cell. These data demonstrate that synapses in the SCN function as ‘tripartite’ synapses consisting of presynaptic axon terminals, postsynaptic membranes and astrocytes that contain GABA transporters. This model suggests that astrocytes expressing both GATs may regulate the extracellular GABA, and thereby modulate the activity of neuronal networks in the SCN.
Ionotropic glutamate receptor GluA4 and T‐type calcium channel Cav3.1 subunits control key aspects of synaptic transmission at the mouse L5B‐POm giant synapse
Authors: Seol Min , Kuner Thomas
Published: September 2015

The properties and molecular determinants of synaptic transmission at giant synapses connecting layer 5B (L5B) neurons of the somatosensory cortex (S1) with relay neurons of the posteriomedial nucleus (POm) of the thalamus have not been investigated in mice. We addressed this by using direct electrical stimulation of fluorescently labelled single corticothalamic terminals combined with molecular perturbations and whole‐cell recordings from POm relay neurons. Consistent with their function as drivers, we found large‐amplitude excitatory postsynaptic currents (EPSCs) and multiple postsynaptic action potentials triggered by a single presynaptic action potential. To study the molecular basis of these two features, ionotropic glutamate receptors and low voltage‐gated T‐type calcium channels were probed by virus‐mediated genetic perturbation. Loss of GluA4 almost abolished the EPSC amplitude, strongly delaying the onset of action potential generation, but maintaining the number of action potentials generated per presynaptic action potential. In contrast, knockdown of the Cav3.1 subunit abrogated the driver function of the synapse at a typical resting membrane potential of −70 mV. However, when depolarizing the membrane potential to −60 mV, the synapse relayed single action potentials. Hence, GluA4 subunits are required to produce an EPSC sufficiently large to trigger postsynaptic action potentials within a defined time window after the presynaptic action potential, while Cav3.1 expression is essential to establish the driver function of L5B‐POm synapses at hyperpolarized membrane potentials.
Connectomics and graph theory analyses: Novel insights into network abnormalities in epilepsy
Authors: Gleichgerrcht Ezequiel , Kocher Madison , Bonilha Leonardo
Published: September 2015

The assessment of neural networks in epilepsy has become increasingly relevant in the context of translational research, given that localized forms of epilepsy are more likely to be related to abnormal function within specific brain networks, as opposed to isolated focal brain pathology. It is notable that variability in clinical outcomes from epilepsy treatment may be a reflection of individual patterns of network abnormalities. As such, network endophenotypes may be important biomarkers for the diagnosis and treatment of epilepsy. Despite its exceptional potential, measuring abnormal networks in translational research has been thus far constrained by methodologic limitations. Fortunately, recent advancements in neuroscience, particularly in the field of connectomics, permit a detailed assessment of network organization, dynamics, and function at an individual level. Data from the personal connectome can be assessed using principled forms of network analyses based on graph theory, which may disclose patterns of organization that are prone to abnormal dynamics and epileptogenesis. Although the field of connectomics is relatively new, there is already a rapidly growing body of evidence to suggest that it can elucidate several important and fundamental aspects of abnormal networks to epilepsy. In this article, we provide a review of the emerging evidence from connectomics research regarding neural network architecture, dynamics, and function related to epilepsy. We discuss how connectomics may bring together pathophysiologic hypotheses from conceptual and basic models of epilepsy and in vivo biomarkers for clinical translational research. By providing neural network information unique to each individual, the field of connectomics may help to elucidate variability in clinical outcomes and open opportunities for personalized medicine approaches to epilepsy. Connectomics involves complex and rich data from each subject, thus collaborative efforts to enable the systematic and rigorous evaluation of this form of “big data” are paramount to leverage the full potential of this new approach.
Human activities cause distinct dissolved organic matter composition across freshwater ecosystems
Authors: Williams Clayton J. , Frost Paul C. , Morales‐Williams Ana M. , Larson James H. , Richardson William B. , Chiandet Aisha S. , Xenopoulos Marguerite A.
Published: September 2015

Dissolved organic matter (DOM) composition in freshwater ecosystems is influenced by the interactions among physical, chemical, and biological processes that are controlled, at one level, by watershed landscape, hydrology, and their connections. Against this environmental template, humans may strongly influence DOM composition. Yet, we lack a comprehensive understanding of DOM composition variation across freshwater ecosystems differentially affected by human activity. Using optical properties, we described DOM variation across five ecosystem groups of the Laurentian Great Lakes region: large lakes, Kawartha Lakes, Experimental Lakes Area, urban stormwater ponds, and rivers (n = 184 sites). We determined how between ecosystem variation in DOM composition related to watershed size, land use and cover, water quality measures (conductivity, dissolved organic carbon (DOC), nutrient concentration, chlorophyll a), and human population density. The five freshwater ecosystem groups had distinctive DOM composition from each other. These significant differences were not explained completely through differences in watershed size nor spatial autocorrelation. Instead, multivariate partial least squares regression showed that DOM composition was related to differences in human impact across freshwater ecosystems. In particular, urban/developed watersheds with higher human population densities had a unique DOM composition with a clear anthropogenic influence that was distinct from DOM composition in natural land cover and/or agricultural watersheds. This nonagricultural, human developed impact on aquatic DOM was most evident through increased levels of a microbial, humic‐like parallel factor analysis component (C6). Lotic and lentic ecosystems with low human population densities had DOM compositions more typical of clear water to humic‐rich freshwater ecosystems but C6 was only present at trace to background levels. Consequently, humans are strongly altering the quality of DOM in waters nearby or flowing through highly populated areas, which may alter carbon cycles in anthropogenically disturbed ecosystems at broad scales.
A dynamic leaf gas‐exchange strategy is conserved in woody plants under changing ambient CO2: evidence from carbon isotope discrimination in paleo and CO2 enrichment studies
Authors: Voelker Steven L. , Brooks J. Renée , Meinzer Frederick C. , Anderson Rebecca , Bader Martin K.‐F. , Battipaglia Giovanna , Becklin Katie M. , Beerling David , Bert Didier , Betancourt Julio L. , Dawson Todd E. , Domec Jean‐Christophe , Guyette Richard P. , Körner Christian , Leavitt Steven W. , Linder Sune , Marshall John D. , Mildner Manuel , Ogée Jérôme , Panyushkina Irina , Plumpton Heather J. , Pregitzer Kurt S. , Saurer Matthias , Smith Andrew R. , Siegwolf Rolf T. W. , Stambaugh Michael C. , Talhelm Alan F. , Tardif Jacques C. , Van de Water Peter K. , Ward Joy K. , Wingate Lisa
Published: September 2015

Rising atmospheric [CO2], ca, is expected to affect stomatal regulation of leaf gas‐exchange of woody plants, thus influencing energy fluxes as well as carbon (C), water, and nutrient cycling of forests. Researchers have proposed various strategies for stomatal regulation of leaf gas‐exchange that include maintaining a constant leaf internal [CO2], ci, a constant drawdown in CO2 (ca − ci), and a constant ci/ca. These strategies can result in drastically different consequences for leaf gas‐exchange. The accuracy of Earth systems models depends in part on assumptions about generalizable patterns in leaf gas‐exchange responses to varying ca. The concept of optimal stomatal behavior, exemplified by woody plants shifting along a continuum of these strategies, provides a unifying framework for understanding leaf gas‐exchange responses to ca. To assess leaf gas‐exchange regulation strategies, we analyzed patterns in ci inferred from studies reporting C stable isotope ratios (δ13C) or photosynthetic discrimination (∆) in woody angiosperms and gymnosperms that grew across a range of ca spanning at least 100 ppm. Our results suggest that much of the ca‐induced changes in ci/ca occurred across ca spanning 200 to 400 ppm. These patterns imply that ca − ci will eventually approach a constant level at high ca because assimilation rates will reach a maximum and stomatal conductance of each species should be constrained to some minimum level. These analyses are not consistent with canalization toward any single strategy, particularly maintaining a constant ci. Rather, the results are consistent with the existence of a broadly conserved pattern of stomatal optimization in woody angiosperms and gymnosperms. This results in trees being profligate water users at low ca, when additional water loss is small for each unit of C gain, and increasingly water‐conservative at high ca, when photosystems are saturated and water loss is large for each unit C gain.
Nursing staff and their team: Impact on intention to leave
Authors: Trybou J. , Malfait S. , Gemmel P. , Clays E.
Published: September 2015

Aim

The aim was to examine the relationship between the quality of team–member exchange experienced by nursing staff and their intention to leave. Job satisfaction and affective organizational commitment are considered as mediators.

Background

While the shortage of nurses is a management and policy priority, few studies have studied the relationships between nursing staff and their team, key organizational attitudes, and intentions to leave the organization.

Method

A questionnaire was administered to 217 registered nurses and nurse assistants in Belgium. Data were collected in 2012. To analyse the data, descriptive statistics, correlation, regression and path analyses were conducted.

Findings

Team–member exchange has a positive impact on nursing staff satisfaction and affective commitment. Job satisfaction and affective organizational commitment fully mediated the impact of team–member exchange on nursing staff's intention to leave.

Conclusion and implications for nursing and health policy

This study illustrates the potential benefits of the positive influence of team–member exchange on key organizational attitudes of nursing staff, and the negative influence on intention to leave through affective commitment and job satisfaction.
Endoplasmic reticulum stress of Kupffer cells involved in the conversion of natural regulatory T cells to Th17 cells in liver ischemia‐reperfusion injury
Authors: Gao Jialin , Jiang Zhonghua , Wang Shuai , Zhou Yuan , Shi Xiaolei , Feng Min
Published: September 2015

Background and Aim:

Our previous studies have shown that regulatory T cells (Tregs) are reduced and Th17 cells are elevated in liver insults. Recent studies have indicated the critical role of endoplasmic reticulum (ER) stress of Kupffer cells (KCs) in evoking liver inflammation following reperfusion. The objective of this study was to investigate the role of ER stress of KCs in the conversion of Tregs to Th17 cells and the effect on liver ischemia‐reperfusion injury.

Methods:

The partial warm liver ischemia‐reperfusion injury mouse model was adopted. ER stress of KCs and the frequency of Tregs and Th17 cells following reperfusion were analyzed. Apart from depletion and adoptive transfer of KCs, KCs were isolated from ischemic lobes and co‐cultured with Tregs to study the effect of KCs on Tregs and Th17 cells.

Results:

It was found that KCs induced ER stress, decreased natural Tregs (nTregs), and increased Th17 cells after reperfusion. Depletion of KCs modulated the reduction of nTregs and elevation of Th17 cells. Co‐culture with stressed KCs led to the reduction in nTregs and elevation of Th17 cells. This effect was suppressed by anti‐interleukin‐6. Adoptive transfer of these stressed KCs resulted in the reduction in nTregs and elevation of Th17 cells and caused liver injury.

Conclusion:

Endoplasmic reticulum stress of KCs contributed to the conversion of nTregs to Th17 cells due to interleukin‐6, resulting in the worsening of liver insult.
Akt2 and p‐Akt overexpression in oral cancer cells is due to a reduced rate of protein degradation
Authors: Archewa Prakasit , Pata Supansa , Chotjumlong Pareena , Supanchart Chayarop , Krisanaprakornkit Suttichai , Iamaroon Anak
Published: September 2015

Objective

To quantitatively measure the increased expression of Akt2 and its phosphorylated form (p‐Akt) in oral cancer cell lines and investigate the post‐translational mechanism for Akt2 and p‐Akt overexpression.

Methods

Three oral cancer cell lines and three cell lines of primary human oral keratinocytes (HOKs) were cultured and the degrees of Akt2 and p‐Akt expression was evaluated by immunoblot analysis and flow cytometry. Each cell line was incubated with cycloheximide, an inhibitor of new protein synthesis, for various times to quantitatively determine the remaining expression levels of Akt2 and p‐Akt by flow cytometry. The localization of Akt2 and p‐Akt was assessed by immunofluorescence.

Results

The levels of Akt2 and p‐Akt proteins were significantly higher in cancer cell lines than those in HOKs (P < 0.05). When the new protein synthesis was blocked by cycloheximide treatment, the degradation rate of Akt2 and p‐Akt in oral cancer cells was significantly lower than that in HOKs (P < 0.05). Both Akt2 and p‐Akt were more intensely stained in the cytoplasm of cancer cells, whereas HOKs expressed Akt2 and p‐Akt only minimally.

Conclusion

Both Akt2 and p‐Akt were overexpressed in oral cancer cells, which may be partly explained by a reduced rate of protein degradation in order to maintain high cytosolic levels.
Cognitive dysfunctions in occipital lobe epilepsy compared to temporal lobe epilepsy
Authors: Santangelo Gabriella , Trojano Luigi , Vitale Carmine , Improta Ilaria , Alineri Irma , Meo Roberta , Bilo Leonilda
Published: September 2015

Objective

To compare cognitive profiles of occipital lobe epilepsy (OLE) and temporal lobe epilepsy (TLE) and to investigate whether impairment of visuospatial functions is a specific deficit of OLE.

Method

Eighteen patients with OLE, 18 patients with TLE, and 18 controls underwent a neuropsychological battery assessing memory, visuospatial functions, and frontal/executive functions.

Results

Multivariate analysis evidenced poorer performance of patients with TLE and patients with OLE relative to controls on tasks assessing verbal and non‐verbal long‐term memory, frontal functions, and visuospatial functions. Patients with OLE had poorer performance than patients with TLE on visuospatial tasks, whereas patients with TLE performed worse than patients with OLE on verbal long‐term memory test. Discriminant analysis identified two canonical discriminant functions: The first explained 53.3% of the variance, and the second explained 46.7% of the variance. The first function included verbal and non‐verbal memory tests distinguishing controls from both OLE and TLE, whereas the second factor including a visuoconstructional test distinguished OLE from TLE and controls.

Conclusions

The results demonstrate that visuoconstructional dysfunction is related to OLE and support the idea that alterations of occipito‐parietal stream may be specific to patients with OLE.
Bony orbital maldevelopment after enucleation
Authors: Ji Yongrong , Ye Fuxiang , Zhou Huifang , Xie Qing , Ge Shengfang , Fan Xianqun
Published: September 2015

One common belief in ophthalmology is that enucleation at an early age will result in bony orbital maldevelopment and facial asymmetry. However, the age range in which enucleation is associated with risk of orbital maldevelopment and the extent of asymmetry remains controversial. In this study, patients who had undergone unilateral enucleation at different ages without orbital implantation were analysed to investigate bony orbital development after enucleation. A total of 87 Chinese adult patients were included. Their bony orbital volume and orbital aditus area were measured using three‐dimensional reconstructive models based on patients' computer tomography scans. The ratio of the parameter values of the affected orbit to the unaffected orbit was calculated and described as the orbital symmetry index. The results showed that the bony orbit grew until approximately 18 years old. Enucleation after that age did not affect the orbit, whereas enucleation before that age led to significant orbital maldevelopment. The relative reduction ranged up to 20% in orbital volume and 17% in the orbital aditus area. The extent of orbital maldevelopment was correlated to the age of enucleation. The symmetry index of orbital volume = −0.0003x2 + 0.0159x + 0.8112 (x = the age of enucleation). The symmetry index of the orbital aditus area = −0.0002x2 + 0.0119x + 0.8504 (x = the age of enucleation). The regression formulae were used to predict the severity of orbital asymmetry after unilateral enucleation, and evaluate the necessity and efficacy of interventions following enucleation.
Complete Genome Sequence of a Novel Wild tomato mosaic virus Isolate Infecting Nicotiana tabacum in China
Authors: Sun Hangjun , Liu Wei , Yang Jinguang , Wang Fenglong , Shen Lili , Li Ying , Sun Dongmei , Qian Yumei
Published: September 2015

Virus particles of approximately 740–760 nm in length and 13 nm in diameter were observed from a diseased Nicotiana tabacum (tobacco) plant in Sichuan Province, China. The complete genomic sequence of the virus isolate XC1 was determined to contain 9659 nucleotides without 3′ terminal poly(A) tail. XC1 has a genome typical of members of the genus Potyvirus, encoding a large polyprotein of 3075 amino acids. Putative proteolytic cleavage sites and a number of well characterized functional motifs were identified by sequence comparisons with those of known potyviruses. Sequence comparison revealed that XC1 shared the highest level of nucleotide sequence identity (76.5%) with Wild tomato mosaic virus (WTMV). Phylogenetic analysis showed that XC1 was closely related to the WTMV Guangdong isolate with an identity of 94.3% between CP gene sequence of the two viruses. We thus named XC1 WTMV‐XC‐1 as a novel isolate of WTMV. The full sequence of WTMV‐XC‐1 may serve as a basis for future investigations on the gene diversity of WTMV.
Feral cat home‐range size varies predictably with landscape productivity and population density
Authors: Bengsen A. J. , Algar D. , Ballard G. , Buckmaster T. , Comer S. , Fleming P. J. S. , Friend J. A. , Johnston M. , McGregor H. , Moseby K. , Zewe F.
Published: September 2015

An understanding of the factors that drive inter‐population variability in home‐range size is essential for managing the impacts of invasive species with broad global distributions, such as the feral domestic cat (Felis catus). The assumption that home‐range sizes scale negatively with landscape productivity is fundamental to many spatial behaviour models, and inter‐site variation in landscape productivity has often been invoked to explain the vast differences in feral cat home‐range sizes among different regions. However, the validity of this explanation has not been tested or described. We used regression models to examine the ability of remotely sensed landscape productivity data, average body weight and population density to explain differences in the size of feral cat home ranges estimated across a diverse collection of sites across the globe. As expected for a solitary polygynous carnivore, female cats occupied smaller home ranges in highly productive sites, and range sizes of male cats scaled positively with those of females. However, the relationship between range size and productivity broke down at highly seasonal sites. Home‐range size also scaled negatively with population density, but there was no clear relationship with average body weight. The relationships we describe should be useful for predicting home‐range sizes and for designing effective feral cat control and monitoring programmes in many situations. More generally, these results confirm the importance of landscape productivity in shaping the spatial distribution of solitary carnivores, but the nature of the relationship is more complicated than is often appreciated.
Long‐term outcomes of end‐stage kidney disease for patients with IgA nephropathy: A multi‐centre registry study
Authors: Zhang Lei , Liu Xusheng , Pascoe Elaine M , Badve Sunil V , Boudville Neil C , Clayton Philip A , De Zoysa Janak , Hawley Carmel M , Kanellis John , McDonald Stephen P , Peh Chen Au , Polkinghorne Kevan R , Johnson David W
Published: September 2015

Background

Clinical outcomes of patients with end‐stage kidney disease (ESKD) receiving renal replacement therapy (RRT) secondary to IgA nephropathy (IgAN) have not been well described.

Aim

To investigate the characteristics, treatments and outcomes of ESKD because of kidney‐limited IgAN and Henoch‐Schönlein purpura nephritis (HSPN) in the Australian and New Zealand RRT populations.

Methods

All ESKD patients who commenced RRT in Australia and New Zealand between 1971 and 2012 were included. Dialysis and transplant outcomes were evaluated in both a contemporary cohort (1998–2012) and the entire cohort (1971–2012).

Results

Of 63 297 ESKD patients, 3721 had kidney‐limited IgAN, and 131 had HSPN. For the contemporary cohort of IgAN patients on dialysis (n = 2194), 10‐year patient survival was 65%. Of 1368 contemporary IgAN patients who received their first renal allograft, 10‐year patient, overall renal allograft and death‐censored renal allograft survival were 93%, 82% and 88%, respectively. Using multivariable Cox regression analysis, patients with IgAN had favourable dialysis patient survival (adjusted hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.57–0.69), overall renal allograft survival (HR 0.67, 95% CI 0.57–0.79) and renal transplant patient survival (HR 0.58, 95% CI 0.45–0.74) compared with ESKD controls. Similar results were found in the entire cohort and when using competing‐risks models. Compared with kidney‐limited IgAN patients, those with HSPN had worse dialysis patient survival (HR 1.94, 95% CI 1.02–3.69), overall renal allograft survival (HR 3.40, 95% CI 1.00–11.55) and renal transplant patient survival (HR 3.50, 95% CI 1.03–11.92).

Conclusion

IgAN ESKD was associated with better dialysis and renal transplant outcomes compared with other forms of ESKD. The survival outcomes of ESKD patients with HSPN were worse than kidney‐limited IgAN.
What is Presentism?
Authors: Deasy Daniel
Published: September 2015

Different versions of theA‐theory of time(according to which some instant of time is absolutely, objectively present) are traditionally defined in terms of whether everything is present, or whether there are also past and future things. In this paper I argue that the traditional way of defining A‐theories should be abandoned. I focus on the traditional definition ofpresentism, according to whichalways, everything is present(§2). First, I argue that there are good reasons to reject all the most plausible interpretations of the predicate ‘is present’ as it appears in the traditional definition of presentism (§3). It follows that there are also good reasons to reject the most plausible interpretations of the traditional definitions of the other A‐theories. I then argue that there is a better way of defining the A‐theories, in terms of the question of whether existence has a beginning and an end (§4). Finally, I argue that what goes for the traditional definition of presentism goes for the traditional definition of its modal analogueactualism, according to whichnecessarily, everything is actual(§5): there are good reasons to reject the traditional definition of actualism in favour of a definition in terms of contingent existence.
Perspectives on Intravenous Oxycodone for Control of Postoperative Pain
Authors: Pergolizzi Joseph V. , Seow‐Choen Francis , Wexner Steven D. , Zampogna Gianpietro , Raffa Robert B. , Taylor Robert
Published: September 2015

Intravenous (IV) analgesia has particular advantages in the immediate postoperative period. For example, IV administration results in a faster onset of pain relief and results in more predictable pharmacokinetics than does administration by other routes. It also allows for convenient dosing before or during surgery, permitting the initiation of effective analgesia in the early phase of the postoperative period. In addition, when patients are able to tolerate oral intake, they can be switched from IV to oral dosing based on maintaining the predictable analgesia established by the IV route. IV morphine is widely used for the control of postoperative pain, but there is a trend toward the use of oxycodone. Oxycodone (which may be mediated partly through kappa‐ as well as mu‐opioid receptors) offers several potential advantages. Published studies comparing IV oxycodone to other IV opioids for postsurgical pain report that oxycodone is a safe and effective analgesic. Some studies show that IV oxycodone may be associated with greater pain control, fewer or less severe adverse events, and faster onset of action, although the results are not consistent across all studies. Oxycodone has been reported to be safe in the geriatric and other special populations when adequate clinical adjustments are made. Thus, the clinical reports and oxycodone's pharmacologic profile make intravenous oxycodone a potentially important “new” old drug for postoperative pain control.
Blood Pressure Monitoring During the Induction and Maintenance Period of Propranolol Therapy for Complicated Infantile Hemangiomas: A Prospective Study of 109 Infants
Authors: Hengst Meike , Oelert Monika , Hoeger Peter H.
Published: September 2015

Background

Propranolol has become the first‐line treatment for complicated infantile hemangiomas (CIHs) worldwide. Recommendations for monitoring infants undergoing propranolol therapy vary. Data on long‐term blood pressure (BP) monitoring have not been reported before.

Objective

The objective of the current study was to monitor BP in full‐term infants during the induction and maintenance phase of propranolol therapy.

Methods

BP was monitored prospectively in 109 infants (mean age 2.8 mos, range 1–5 mos) with CIHs during the induction (3–4 days in the hospital during up‐dosing from 0.5 to 2.0 mg/kg/day) and maintenance (6 mos) phases of oral propranolol therapy.

Results

Four children were excluded from the study because of sinus bradycardia (n = 2 [1.8%]) or lethargy (n = 2 [1.8%]). Mean systolic BP (SBP) decreased by 5 mmHg with the increase in propranolol dosage. Low (<5th percentile) SBP or diastolic BP (DBP) was observed in 2 of 105 children (1.9%) each. During the maintenance phase, 2 of 105 children (1.9%) had occasional SBP readings of less than 70 mmHg. No hypotension was observed after the third month of therapy. Low DBP (<36 mmHg) was recorded in 16 (15.2%) children after the first month, in 8.6% after the second, and in 2.9% during the third and fourth months of therapy. No patients exhibited clinical hypotension, bradycardia, or other known side effects of propranolol. Clinical response to therapy was excellent.

Limitations

Reference BP values were derived from published tables, not from an untreated control group.

Conclusions

In healthy full‐term infants, propranolol (2 mg/kg/day divided in three doses) is well tolerated. No clinically significant hypotension was observed. We conclude that for otherwise healthy infants, BP monitoring during long‐term propranolol therapy for CIHs is not necessary.
Retrospective Study on Autoimmune Blistering Disease in Paediatric Patients
Authors: Kong Yan Ling , Lim Yen Loo , Chandran Nisha Suyien
Published: September 2015

Background

Autoimmune blistering diseases (AIBDs) are rare in children and their prevalence in Singapore is unclear. We aimed to investigate the clinical and immunopathologic characteristics of children diagnosed with AIBDs in Singapore.

Materials and Methods

The clinical and histology databases at the National Skin Centre in Singapore were searched to identify patients younger than 18 years old diagnosed with an AIBD from January 1, 1998, through December 31, 2012. Patient demographic characteristics, presentation, triggers, investigations, treatments, and disease course were analyzed.

Results

Twelve patients with AIBDs were identified; five (41.7%) had linear immunoglobulin A disease (LAD); two (16.7%) each had pemphigus vulgaris (PV), bullous pemphigoid, and bullous systemic lupus erythematosus; and one (8.3%) had pemphigus foliaceus. Four (33.3%) were female and eight (66.7%) male. The mean age of onset was 8.7 years (range 2–17 years). Most patients were treated with steroids and adjuvant immunosuppressants. Intravenous rituximab was used effectively in a patient with recalcitrant PV. The mean follow‐up was 2.35 years (range 0.17–7.33 years). As of the last follow‐up, four (33.3%) patients were in complete remission off therapy, two (16.7%) were in complete remission on therapy, four (33.3%) were in partial remission on therapy, and two (16.7%) were lost to follow‐up.

Conclusion

Consistent with the existing literature, our study shows that LAD is the most common cause of AIBDs in children. Although common in the West, dermatitis herpetiformis was not identified in the current study. Intravenous rituximab may be considered in recalcitrant childhood PV, but vigilant monitoring for side effects is crucial. Immunohistopathologic evaluation is important and repeat biopsies may be of value in patients with atypical disease courses.
Gödel's and Other Paradoxes
Authors: Slater Hartley
Published: September 2015

Francesco Berto has recently written “The Gödel Paradox and Wittgenstein's Reasons,” about a paradox first formulated by Graham Priest in 1971. The major reason for disagreeing with Berto's conclusions concerns his elucidation of Wittgenstein's understanding of Gödel's theorems. Seemingly, Wittgenstein was some kind of proto‐paraconsistentist. Priest himself has also, though in a different way, tried to tar Wittgenstein with the same brush. But the resolution of other paradoxes is intimately linked with the resolution of the Gödel Paradox, and with understanding Wittgenstein's views of Gödel's theorems. So this paper discusses some other paradoxes before looking at Wittgenstein's relevant views.
Oxygen uptake is more efficient in idiopathic pulmonary arterial hypertension than in chronic thromboembolic pulmonary hypertension
Authors: Shi Xiaofang , Guo Jian , Gong Sugang , Sapkota Rikesh , Yang Wenlan , Liu Hui , Xiang Wenjing , Wang Lan , Sun Xingguo , Liu Jinming
Published: September 2015

Background and objective

The responses of oxygen uptake efficiency (OUE) during cardiopulmonary exercise training (CPET) have not been reported in patients with pulmonary hypertension. We aimed to investigate the differences in OUE between patients with idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Methods

Forty‐four patients with IPAH and 29 patients with CTEPH were retrospectively enrolled into our study. All patients underwent right‐heart catheterization, pulmonary function test and performed the 6‐min walk test and CPET.

Results

We found that oxygen uptake efficiency plateau (OUEP) and oxygen uptake efficiency at anaerobic threshold (OUE@AT) was significantly higher in IPAH than that in CTEPH (both P = 0.002). However, patients with CTEPH had lower mean pulmonary artery pressure, pulmonary vascular resistance and transpulmonary gradient (all P < 0.05). The correlation between OUEP and heart rate at anaerobic threshold (HR_AT) was significant (r = 0.376, P < 0.05); however, no statistically significant correlation was found with ventilation at anaerobic threshold (VE_AT) (r = −0.074, P > 0.05) in patients with IPAH. In patients with CTEPH, both anaerobic threshold (r = 0.307, P > 0.05) and VE_AT (r = −0.709, P < 0.0001) were reduced. OUEP were higher in WHO functional class I/II patients than in WHO functional class III/IV patients (all P < 0.05).

Conclusions

OUEP and OUE@AT are higher in IPAH than that in CTEPH not in proportion to haemodynamics, probably due to differences in cardiac function and pulmonary vascular occlusion. OUEP correlates well with the exercise capacity and the severity of the disease.
Functional Partial Linear Single‐index Model
Authors: Wang Guochang , Feng Xiang‐Nan , Chen Min
Published: September 2015

This paper deals with the problem of predicting the real‐valued response variable using explanatory variables containing both multivariate random variable and random curve. The proposed functional partial linear single‐index model treats the multivariate random variable as linear part and the random curve as functional single‐index part, respectively. To estimate the non‐parametric link function, the functional single‐index and the parameters in the linear part, a two‐stage estimation procedure is proposed. Compared with existing semi‐parametric methods, the proposed approach requires no initial estimation and iteration. Asymptotical properties are established for both the parameters in the linear part and the functional single‐index. The convergence rate for the non‐parametric link function is also given. In addition, asymptotical normality of the error variance is obtained that facilitates the construction of confidence region and hypothesis testing for the unknown parameter. Numerical experiments including simulation studies and a real‐data analysis are conducted to evaluate the empirical performance of the proposed method.
Ageing, metabolism and cardiovascular disease
Authors: Costantino Sarah , Paneni Francesco , Cosentino Francesco
Published: September 2015

Age is one of the major risk factors associated with cardiovascular disease (CVD). About one‐fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66Shc, JunD and NF‐kB. This overview will provide the background for attractive molecular targets to prevent age‐driven pathology in the vasculature and the heart.

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Dichotomous roles for externalized cardiolipin in extracellular signaling: Promotion of phagocytosis and attenuation of innate immunity
Authors: Balasubramanian Krishnakumar , Maeda Akihiro , Lee Janet S. , Mohammadyani Dariush , Dar Haider Hussain , Jiang Jian Fei , St. Croix Claudette M. , Watkins Simon , Tyurin Vladimir A. , Tyurina Yulia Y. , Klöditz Katharina , Polimova Anastassia , Kapralova Valentyna I. , Xiong Zeyu , Ray Prabir , Klein-Seetharaman Judith , Mallampalli Rama K. , Bayir Hülya , Fadeel Bengt , Kagan Valerian E.
Published: September 2015

A phospholipid common to mitochondria and bacteria promotes phagocytosis and inhibits cytokine production by macrophages.
Rapid multiplex analysis of lipid raft components with single-cell resolution
Authors: Schatzlmaier Philipp , Supper Verena , Göschl Lisa , Zwirzitz Alexander , Eckerstorfer Paul , Ellmeier Wilfried , Huppa Johannes B. , Stockinger Hannes
Published: September 2015

The association of lipid rafts with nuclei during partial cell lysis enables their analysis by flow cytometry.
Epigenetic resolution of inflammation
Authors: Ferrarelli Leslie K.
Published: September 2015

A DNA demethylase recruits a histone deacetylase to turn off the expression of a cytokine in immune cells and prevent chronic inflammation.
Adapting to the nucleus
Authors: Foley John F.
Published: September 2015

In addition to mediating T cell receptor signaling at the plasma membrane, the adaptor protein SLP-76 is required for optimal nuclear entry of transcription factors.
Reduction of Toxoplasma gondii Development Due to Inhibition of Parasite Antioxidant Enzymes by a Dinuclear Iron(III) Compound
Authors: Portes J. A. , Souza T. G. , dos Santos T. A. T. , da Silva L. L. R. , Ribeiro T. P. , Pereira M. D. , Horn A. , Fernandes C. , DaMatta R. A. , de Souza W. , Seabra S. H.
Published: September 2015

Toxoplasma gondii
, the causative agent of toxoplasmosis, is an obligate intracellular protozoan that can infect a wide range of vertebrate cells. Here, we describe the cytotoxic effects of the dinuclear iron compound [Fe(HPCINOL)(SO
4
)]
2
-μ-oxo, in which HPCINOL is the ligand 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol, on
T. gondii
infecting LLC-MK2 host cells. This compound was not toxic to LLC-MK2 cells at concentrations of up to 200 μM but was very active against the parasite, with a 50% inhibitory concentration (IC
50
) of 3.6 μM after 48 h of treatment. Cyst formation was observed after treatment, as indicated by the appearance of a cyst wall,
Dolichos biflorus
lectin staining, and scanning and transmission electron microscopy characteristics. Ultrastructural changes were also seen in
T. gondii
, including membrane blebs and clefts in the cytoplasm, with inclusions similar to amylopectin granules, which are typically found in bradyzoites. An analysis of the cell death pathways in the parasite revealed that the compound caused a combination of apoptosis and autophagy. Fluorescence assays demonstrated that the redox environment in the LLC-MK2 cells becomes oxidant in the presence of the iron compound. Furthermore, a reduction in superoxide dismutase and catalase activities in the treated parasites and the presence of reactive oxygen species within the parasitophorous vacuoles were observed, indicating an impaired protozoan response against these radicals. These findings suggest that this compound disturbs the redox equilibrium of
T. gondii
, inducing cystogenesis and parasite death.
Confirmed Plasmodium vivax Resistance to Chloroquine in Central Vietnam
Authors: Thanh Pham Vinh , Hong Nguyen Van , Van Nguyen Van , Louisa Melva , Baird Kevin , Xa Nguyen Xuan , Peeters Grietens Koen , Hung Le Xuan , Duong Tran Thanh , Rosanas-Urgell Anna , Speybroeck Niko , D'Alessandro Umberto , Erhart Annette
Published: September 2015

Plasmodium vivax
resistance to chloroquine (CQ) is currently reported in almost all countries where
P. vivax
is endemic. In Vietnam, despite a first report on
P. vivax
resistance to chloroquine published in the early 2000s,
P. vivax
was still considered sensitive to CQ. Between May 2009 and December 2011, a 2-year cohort study was conducted in central Vietnam to assess the recommended radical cure regimen based on a 10-day course of primaquine (0.5 mg/kg/day) together with 3 days of CQ (25 mg/kg). Here we report the results of the first 28-day follow-up estimating the cumulative risk of
P. vivax
recurrences together with the corresponding CQ blood concentrations, among other endpoints. Out of 260 recruited
P. vivax
patients, 240 completed treatment and were followed up to day 28 according to the WHO guidelines. Eight patients (3.45%) had a recurrent
P. vivax
infection, at day 14 (
n
= 2), day 21 (
n
= 1), and day 28 (
n
= 5). Chloroquine blood concentrations, available for 3/8 recurrent infections (days 14, 21, and 28), were above the MIC (>100 ng/ml whole blood) in all of these cases. Fever and parasitemia (both sexual and asexual stages) were cleared by day 3. Anemia was common at day 0 (35.8%), especially in children under 10 years (50%), and hemoglobin (Hb) recovery at day 28 was substantial among anemic patients (median change from day 0 to 28, +1.7 g/dl; interquartile range [IQR], +0.7 to +3.2). This report, based on CQ blood levels measured at the time of recurrences, confirms for the first time
P. vivax
CQ resistance in central Vietnam and calls for further studies using standardized protocols for accurately monitoring the extent and evolution of
P. vivax
resistance to chloroquine in Vietnam. These results, together with the mounting evidence of artemisinin resistance in central Vietnam, further highlight the increasing threat of antimalarial drug resistance to malaria elimination in Vietnam.
Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy
Authors: Parikh Sunil , Fehintola Fatai , Huang Liusheng , Olson Alexander , Adedeji Waheed A. , Darin Kristin M. , Morse Gene D. , Murphy Robert L. , Taiwo Babafemi O. , Akinyinka Olusegun O. , Adewole Isaac F. , Aweeka Francesca T. , Scarsi Kimberly K.
Published: September 2015

Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration.
Genetic Contexts of
bla
NDM-1
in Patients Carrying Multiple NDM-Producing Strains
Authors: Wailan Alexander M. , Sartor Anna L. , Zowawi Hosam M. , Perry John D. , Paterson David L. , Sidjabat Hanna E.
Published: September 2015

The carbapenem resistance determinant
bla
NDM-1
has been found in various Gram-negative bacteria and upon different plasmid replicon types (Inc). Here, we present four patients within two hospitals in Pakistan harboring between two and four NDM-1-producing Gram-negative bacilli of different species coresident in their stool samples. We characterize the
bla
NDM-1
genetic contexts of these 11 NDM-1-producing Gram-negative bacilli in addition to other antimicrobial resistance mechanisms, plasmid replicon profiles, and sequence types (STs) in order to understand the underlying acquisition mechanisms of carbapenem resistance within these bacteria. Two common plasmid types (IncN2 and IncA/C) were identified to carry
bla
NDM-1
among the six different bacterial species isolated from the four patients. Two of these strains were novel
Citrobacter freundii
ST 20 and ST 21. The same IncN2-type
bla
NDM-1
genetic context was found in all four patients and within four different species. The IncA/C-type
bla
NDM-1
genetic context was found in two different species and in two of the four patients. Combining genetic context characterization with other molecular epidemiology methods, we were able to establish the molecular epidemiological links between genetically unrelated bacterial species by linking their acquisition of an IncN2 or IncA/C plasmid carrying
bla
NDM-1
for carbapenem resistance. By combining plasmid characterization and in-depth genetic context assessment, this analysis highlights the importance of plasmids in antimicrobial resistance. It also provides a novel approach for investigating the underlying mechanisms of
bla
NDM-1
-related spread between bacterial species and genera via plasmids.