bluuebunny/crossref_metadata_2025 huggingface dataset:
Topological organisation of the phosphatidylinositol 4,5-bisphosphate–phospholipase C resynthesis cycle: PITPs bridge the ER–PM gap
Authors: Cockcroft Shamshad , Raghu Padinjat
Published: November 2016

Phospholipase C (PLC) is a receptor-regulated enzyme that hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the plasma membrane (PM) triggering three biochemical consequences, the generation of soluble inositol 1,4,5-trisphosphate (IP3), membrane-associated diacylglycerol (DG) and the consumption of PM PI(4,5)P2. Each of these three signals triggers multiple molecular processes impacting key cellular properties. The activation of PLC also triggers a sequence of biochemical reactions, collectively referred to as the PI(4,5)P2 cycle that culminates in the resynthesis of this lipid. The biochemical intermediates of this cycle and the enzymes that mediate these reactions are topologically distributed across two membrane compartments, the PM and the endoplasmic reticulum (ER). At the PM, the DG formed during PLC activation is rapidly converted into phosphatidic acid (PA) that needs to be transported to the ER where the machinery for its conversion into PI is localised. Conversely, PI from the ER needs to be rapidly transferred to the PM where it can be phosphorylated by lipid kinases to regenerate PI(4,5)P2. Thus, two lipid transport steps between membrane compartments through the cytosol are required for the replenishment of PI(4,5)P2 at the PM. Here, we review the topological constraints in the PI(4,5)P2 cycle and current understanding how these constraints are overcome during PLC signalling. In particular, we discuss the role of lipid transfer proteins in this process. Recent findings on the biochemical properties of a membrane-associated lipid transfer protein of the PITP family, PITPNM proteins (alternative name RdgBα/Nir proteins) that localise to membrane contact sites are discussed. Studies in both Drosophila and mammalian cells converge to provide a resolution to the conundrum of reciprocal transfer of PA and PI during PLC signalling.
The increasing diversity of functions attributed to the SAFB family of RNA-/DNA-binding proteins
Authors: Norman Michael , Rivers Caroline , Lee Youn-Bok , Idris Jalilah , Uney James
Published: November 2016

RNA-binding proteins play a central role in cellular metabolism by orchestrating the complex interactions of coding, structural and regulatory RNA species. The SAFB (scaffold attachment factor B) proteins (SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM), which are highly conserved evolutionarily, were first identified on the basis of their ability to bind scaffold attachment region DNA elements, but attention has subsequently shifted to their RNA-binding and protein–protein interactions. Initial studies identified the involvement of these proteins in the cellular stress response and other aspects of gene regulation. More recently, the multifunctional capabilities of SAFB proteins have shown that they play crucial roles in DNA repair, processing of mRNA and regulatory RNA, as well as in interaction with chromatin-modifying complexes. With the advent of new techniques for identifying RNA-binding sites, enumeration of individual RNA targets has now begun. This review aims to summarise what is currently known about the functions of SAFB proteins.
Oestrogen receptor negativity in breast cancer: a cause or consequence?
Authors: Gajulapalli Vijaya Narasihma Reddy , Malisetty Vijaya Lakshmi , Chitta Suresh Kumar , Manavathi Bramanandam
Published: November 2016

Endocrine resistance, which occurs either by de novo or acquired route, is posing a major challenge in treating hormone-dependent breast cancers by endocrine therapies. The loss of oestrogen receptor α (ERα) expression is the vital cause of establishing endocrine resistance in this subtype. Understanding the mechanisms that determine the causes of this phenomenon are therefore essential to reduce the disease efficacy. But how we negate oestrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable. To answer that, two important approaches are considered: (1) understanding the cellular origin of heterogeneity and ER negativity in breast cancers and (2) characterization of molecular regulators of endocrine resistance. Breast tumours are heterogeneous in nature, having distinct molecular, cellular, histological and clinical behaviour. Recent advancements in perception of the heterogeneity of breast cancer revealed that the origin of a particular mammary tumour phenotype depends on the interactions between the cell of origin and driver genetic hits. On the other hand, histone deacetylases (HDACs), DNA methyltransferases (DNMTs), miRNAs and ubiquitin ligases emerged as vital molecular regulators of ER negativity in breast cancers. Restoring response to endocrine therapy through re-expression of ERα by modulating the expression of these molecular regulators is therefore considered as a relevant concept that can be implemented in treating ER-negative breast cancers. In this review, we will thoroughly discuss the underlying mechanisms for the loss of ERα expression and provide the future prospects for implementing the strategies to negate ER negativity in breast cancers.
Enhanced protective responses to a serotype-independent pneumococcal vaccine when combined with an inactivated influenza vaccine
Authors: Babb Rachelle , Chen Austen , Ogunniyi Abiodun D. , Hirst Timothy R. , Kara Ervin E. , McColl Shaun R. , Alsharifi Mohammed , Paton James C.
Published: November 2016

Streptococcus pneumoniae and influenza are the world's foremost bacterial and viral respiratory pathogens. We have previously described a γ-irradiated influenza A virus (γ-FLU) vaccine that provides cross-protective immunity against heterosubtypic infections. More recently, we reported a novel non-adjuvanted γ-irradiated S. pneumoniae (γ-PN) vaccine that elicits serotype-independent protection. Considering the clinical synergism of both pathogens, combination of a serotype-independent pneumococcal vaccine with a broad-spectrum influenza vaccine to protect against both infections would have a considerable clinical impact. In the present study, we co-immunized C57BL/6 mice intranasally (IN) with a mixture of γ-PN (whole inactivated cells) and γ-FLU (whole inactivated virions) and examined protective efficacy. Co-immunization enhanced γ-PN vaccine efficacy against virulent pneumococcal challenge, which was dependent on CD4+ T-cell responses. In contrast, vaccination with γ-PN alone, co-immunization enhanced pneumococcal-specific effector T-helper 17 cell (Th17) and Th1 memory cell, promoted development of CD4+ tissue-resident memory (TRM) cells and enhanced Pneumococcus-specific antibody responses. Furthermore, co-immunization elicited significant protection against lethal influenza challenge, as well as against co-infection with both influenza and S. pneumoniae. This is the first report showing the synergistic effect of combining whole cell and whole virion vaccines to both S. pneumoniae and influenza as a single vaccine to protect against individual and co-infection, without compromising pathogen-specific immunity.
SoC control for improved battery life and throughput performance under VST‐TDMA
Authors: Torres Boris , Quintero Vanessa , Estevez Claudio , Orchard Marcos , Azurdia César
Published: November 2016

Energy independence is a wireless device quality that demands the utmost exigency. Energy harvesting devices (EHD) alleviate the energy constraints demanded by these nodes and with the use of protocols, such as variable slot time‐time division multiple access (VST‐TDMA) energy self‐sustainability can be attained at the cost of throughput. To allow high throughput levels and self‐sustainability the system can allow the power consumption to be greater than the energy harvesting rate while a state‐of‐charge (SoC) of 30% or greater is maintained. To achieve this the system must accurately estimate the SoC, which is not a trivial task. In this work, a battery model is incorporated into the VST‐TDMA protocol to estimate the battery model parameters, including the SoC, which successfully allows it to maintain appropriate SoC levels.
Real‐time calibration of space zoom cameras based on fixed stars
Authors: Xia Qi , Qi Naiming , Ye Dong , Guo Yubo , Wang Tianye
Published: November 2016

Compared with fixed focus cameras, zoom cameras can be used to provide more precise measurements in space tasks. However, the calibration of zoom cameras in this case is a difficulty, as it is not convenient to set up a calibration device on the spacecraft. To solve this problem, the authors present a real‐time zoom camera calibration algorithm based on fixed stars. With the star images captured by the zoom camera, they firstly use a star identification method to recognise the identity of stars. By means a series of coordinate transformation, they are able to build the one‐to‐one mapping between the pixel coordinates and epoch celestial coordinates of the stars. Finally, the internal and external parameters of the zoom camera are obtained based on the thick lens zoom camera model. Simulation and experiment results show that the internal parameters of zoom cameras are rarely affected by the noise of latitude, longitude and time. Furthermore, the calibration precision and robustness of focal length reaches a satisfactory level.
Improved use of WT kinetic energy for system frequency support
Authors: Xu Guoyi , Xu Lie
Published: November 2016

To ensure security operation of power systems with high wind penetration, wind turbines (WTs) are required to participate system frequency control. The amount of WT kinetic energy used for system frequency control is discussed and minimum rotor speeds according to different WT operation states are defined to avoid large drop of mechanical power during WT frequency control. The effect of different power shapes of releasing the kinetic energy on system frequency support is investigated and two methods are proposed. The first one is aimed at reducing the rate of change of frequency (ROCOF), whereas the second one aimed to reduce both the ROCOF and frequency nadir. The proposed strategies not only make full use of the available kinetic energy but also lead to a smooth transition when the rotor re‐accelerates. The performance of the proposed strategies is validated by simulations using MATLAB/Simulink. The results indicate significant improvement on system frequency control.
Research on wind power ramp events prediction based on strongly convective weather classification
Authors: Xiong Yi , Zha Xiaoming , Qin Liang , Ouyang Tinghui , Xia Tian
Published: November 2016

In this study a forecasting model for wind power ramps based on strongly convective weather classification is presented. First, the dynamics and thermodynamic behaviours of strongly convective weather are characterised by the predictors in the selected region. Then the support vector domain description for ramps scenario classification is introduced to establish an initialised extremum model, and the parameter templates method is used to identify the ramps weather in strongly convective weather library. Meanwhile, the original wind speed data is modified to obtain more accurate wind speed, and a new wind power ramps definition is proposed based on the ramp character itself and its impact on the power grid. Thus the catastrophe detection method (Bernaola Galvan algorithm) used for strongly convective weather forecasting. Finally, the wind power ramps forecasting method based on the discrimination of convective weather is developed. Comparing with the existing wind power ramps forecasting algorithms, the proposed prediction method here gets into meteorologic essence of triggering great fluctuation of wind speed.
Distributed finite‐time cooperative control of droop‐controlled microgrids under switching topology
Authors: Wang Xinsheng , Zhang Huaqiang , Li Changxi
Published: November 2016

As a small‐scale power system, microgrid (MG) will lose support from the main grid if it switches to islanded mode because of the pre‐planned scheduling or unplanned disturbances. To synchronise the frequency and voltage to their reference values, a secondary frequency and voltage cooperative control is proposed in this study. The proposed secondary control can synchronise the frequency and voltage to their reference values in finite time and achieve the active power sharing simultaneously. Moreover, it is suitable for switching communication architecture. The MG is considered as multi‐agent systems and the system stability is proved by multi‐agent theory and finite‐time stability theory. A simulation system is established in Matlab/Simulink environment, and the results show the effectiveness of the proposed controller.
Design of broadband high‐efficient PA based on hybrid continuous modes
Authors: Ni Chun , Chen Mingsheng , Zhang Zhongxiang , Zhang Liang , Wu Xianliang
Published: November 2016

An ultra‐wide band high‐efficient power amplifier (PA) which employs both series of continuous modes and series of inverse continuous modes is presented for the first time. Consequently, the solutions space of fundamental impedance is expanded greatly. The operation frequency range of this mode can achieve more than two‐octave bandwidth. Multistage transmission‐line low‐pass filter matching network has been utilised for matching fundamental impedance and suppressing of high‐order harmonic. To verify this method, a high‐efficient PA, which operates across 0.3–2.7 GHz (160% bandwidth) is designed. Simulation and experimental results show that the drain efficiency of this PA achieves 61.4–81.9%, and 8.3–16.6 W output power in the target band.
Does the ‘extinct’ eastern quoll (Dasyurus viverrinus) persist in Barrington Tops, New South Wales?
Authors: Frankham Greta J. , Thompson Sean , Ingleby Sandy , Soderquist Todd , Eldridge Mark D. B.
Published: November 2016

The eastern quoll (Dasyurus viverrinus) is believed to be extinct on the Australian mainland, with the last confirmed record in 1963. Recently an eastern quoll specimen was located that had been found in northern Barrington Tops National Park (200 km north of Sydney) in 1989. Partial sequences (~200 bp) of the mitochondrial DNA gene Cytochrome b were obtained from the Barrington Tops specimen and compared with sequences from known mainland and Tasmanian eastern quolls. The genetic data, while limited, are most consistent with the Barrington Tops specimen being derived from the ‘extinct’ mainland eastern quoll population. This suggests that eastern quolls survived for decades longer on the Australian mainland than previously thought and raises the possibility that they may still persist in remote areas such as Barrington Tops.
How old are the eucalypts? A review of the microfossil and phylogenetic evidence
Authors: Macphail Mike , Thornhill Andrew H.
Published: November 2016

Molecular age estimates for the Eucalypteae (family Myrtaceae) suggest that the eucalypts, possibly associated with fire, have been present for ~65 million years. In contrast, macrofossils and fossil pollen attributable to three important eucalypt genera (Angophora, Corymbia and Eucalyptus) in the Eucalypteae date to ~51–53 million years ago (mid-Early Eocene) in Patagonia, eastern Antarctica and south-eastern Australia. At present, there is no fossil evidence to show that eucalypts had evolved before this epoch, i.e. when Australia was part of eastern Gondwana, although this seems probable on the basis of molecular-dated phylogenetic analyses. The primary reason is the absence of macrofossils, whereas the earliest fossil eucalypt-type pollen recorded (Myrtaceidites tenuis) is attributed to Angophora and Corymbia, not Eucalyptus. This pollen type is recorded in Australia and Antarctica but not in New Zealand or South America. The only Myrtaceidites morphospecies found in Upper Cretaceous and Paleocene deposits in Australia is M. parvus, whose affinity lies with multiple extant Myrtaceae groups other than the Eucalypteae. In the present paper, we review current phylogenetic and microfossil databases for the eucalypts and assess this evidence to develop a ‘consensus’ position on the origin and evolution of the eucalypts in the Australian region.
Molecular Insights into the Interaction Between the SPRY Domain-Containing SOCS Box Protein SPSB2 and Peptides Based on the Binding Motif from iNOS
Authors: Leung Eleanor W. W. , Mulcair Mark D. , Yap Beow Keat , Nicholson Sandra E. , Scanlon Martin J. , Norton Raymond S.
Published: November 2016

SPRY domain-containing SOCS box proteins SPSB1, 2, and 4 mediate the proteasomal degradation of inducible nitric oxide synthase (iNOS) and thereby modulate the amount of NO available for combating infectious organisms. A highly conserved Asp-Ile-Asn-Asn-Asn (DINNN) motif found at the N-terminus of iNOS binds to SPSB2 with nanomolar affinity. The design of specific and potent inhibitors of iNOS–SPSB interactions will be aided by a better understanding of the interactions of this DINNN sequence with SPSB2. Although crystal structures of SPSB complexes with DINNN peptides are available, aspects of the interaction between peptide and protein are still not fully understood. Here, our results from surface plasmon resonance and NMR spectroscopy indicate that residues flanking the DINNN motif, which make no direct contact with SPSB2 in the available crystal structures, nonetheless play an important role in enhancing the binding affinity to SPSB2, by up to 80-fold. Mutational analysis of the DINNN sequence showed that mutation of the Asp or the first Asn residue to Ala reduced the binding affinity by 200- or 600-fold respectively, whereas mutation of the third Asn made binding undetectable. Ala substitution of the second Asn residue caused a 30-fold drop in binding affinity. Substitution of the Ile had very little effect on the binding affinity and substitutions with bulky residues were tolerated. This provides an opportunity for further modification for therapeutic applications. These results highlight the complex interplay of peptide sequence and protein binding and inform efforts to design peptide therapeutics to disrupt the iNOS–SPSB interaction.
Dehydrogenative Coupling of Hydrosilanes and Alcohols by Alkali Metal Catalysts for Facile Synthesis of Silyl Ethers
Authors: Harinath Adimulam , Bhattacharjee Jayeeta , Anga Srinivas , Panda Tarun K.
Published: November 2016

Cross-dehydrogenative coupling (CDC) of hydrosilanes with hydroxyl groups, using alkali metal hexamethyldisilazide as a single-component catalyst for the formation of Si–O bonds under mild condition, is reported. The potassium salt [KN(SiMe3)2] is highly efficient and chemoselective for a wide range of functionalized alcohols (99 % conversion) under solvent-free conditions. The CDC reaction of alcohols with silanes exhibits first-order kinetics with respect to both catalyst and substrate concentrations. The most plausible mechanism for this reaction suggests that the initial step most likely involves the formation of an alkoxide followed by the formation of metal hydride as active species.
Phenotypic screening meets natural products in drug discovery†
Authors: Futamura Yushi , Yamamoto Kai , Osada Hiroyuki
Published: November 2016

The Nobel Prize in Physiology or Medicine 2015 was awarded for discoveries related to the control of parasitic diseases using natural products of microbial and plant origin. In current drug discovery programs, synthesized compounds are widely used as a screening source; however, this award reminds us of the importance of natural products. Here, we introduce our phenotypic screening methods based on changes in cell morphology and discuss their effectiveness and impact for natural products in drug discovery.
Natural products discovery from micro-organisms in the post-genome era†
Authors: Ikeda Haruo
Published: November 2016

With the decision to award the Nobel Prize in Physiology or Medicine to Drs. S. Ōmura, W.C. Campbell, and Y. Tu, the importance and usefulness of natural drug discovery and development have been revalidated. Since the end of the twentieth century, many genome analyses of organisms have been conducted, and accordingly, numerous microbial genomes have been decoded. In particular, genomic studies of actinomycetes, micro-organisms that readily produce natural products, led to the discovery of biosynthetic gene clusters responsible for producing natural products. New explorations for natural products through a comprehensive approach combining genomic information with conventional methods show great promise for the discovery of new natural products and even systematic generation of unnaturally occurring compounds.
Continuing fascination of exploration in natural substances from microorganisms†
Authors: Takahashi Yoko
Published: November 2016

In the search for novel organic compounds, I think it is of paramount importance not to overlook the pursuit of microorganism diversity and the abilities those microorganisms hold as a resource. In commemoration of Professor Satoshi Ōmura’s Nobel Prize in Physiology or Medicine, I will briefly describe the microorganism that produces avermectin and then discuss how innovating isolation methods and pioneering isolation sources have opened the door to numerous new microorganism resources. Furthermore, as exploratory research of substances views the world from many different angles—from biological activity to a compound’s physiochemical properties—it is possible to discover a novel compound from a well-known microorganism. Based on this, I will discuss the future prospects of exploratory research.
The quest for industrial enzymes from microorganisms†
Authors: Yamaguchi Shotaro
Published: November 2016

Satoshi Ōmura, Professor Emeritus at Kitasato University, was awarded the Nobel Prize for his discovery of a substance of tremendous value to mankind from a microorganism. As a researcher who regularly deals with enzymes produced by microorganisms and a person engaged in microorganism-based business, Professor Ōmura’s Nobel Prize fills me with great pride and joy. It is perhaps not surprising that this Nobel Prize-winning research would emerge from Asia, specifically Japan, where people live in harmony with nature rather than try to conquer it. At Amano Enzyme Inc., we devote ourselves to searching for novel enzymes from microorganisms. While incorporating my own experiences, I will recount the stories of a few discoveries of valuable enzyme-producing microbes in soil and bacterial strain libraries. I will also briefly introduce microbial strain library construction as a tool for facilitating the identification of the desired producing bacteria.
Influence of hard inclusions on microstructural characteristics and textural components during dissimilar friction-stir welding of an PM Al–Al2O3–SiC hybrid nanocomposite with AA1050 alloy
Authors: Khodabakhshi F. , Simchi A. , Kokabi A. H. , Gerlich A. P. , Nosko M. , Švec P.
Published: November 2016

Owing to the advantages of nanocomposites for structural applications, we present microstructural evolutions and texture development during dissimilar friction stir welding (DFSW) of an Al-matrix hybrid nanocomposite (Al-2 vol.-% Al2O3-2 vol.-% SiC) with AA1050. It is shown that DFSW can successfully be performed at a rotating speed of 1200 rev min−1 and a transverse speed of 50 mm min−1 while locating the nanocomposite at retreating side. Formation of macro-, micro-, and nano-mechanical interlocks between dissimilar base materials (BMs) as a result of FSW tool stirring action possessed an impact influence on the mechanical performance of dissimilar welds. Electron microscopy revealed formation of a three-modal grain structure from microscale (>1 µm) to nanoscale (<100 nm) range in the stir zone of the joint materials. Texture components included a mixture of [Formula: see text] shear elements and ideal [Formula: see text] random orientations, as compared to the completely random and Cu-P preferred textures for the aluminum and composite BMs.
No ATG8s, no problem? How LC3/GABARAP proteins contribute to autophagy
Authors: Martens Sascha
Published: November 2016

The ATG8 family LC3/GABARAP proteins are attached to the membrane of nascent autophagosomes, but their functions during autophagy are unclear. In this issue, Nguyen et al. (2016. J. Cell Biol. https://doi.org/10.1083/jcb.201607039) show that LC3/GABARAP proteins are not essential for autophagosome formation but are critical for autophagosome–lysosome fusion.
GTSE1 leads cancer cells into CIN
Authors: Short Ben
Published: November 2016

Study reveals that protein regulates spindle microtubule dynamics by inhibiting microtubule depolymerase MCAK.
On multiplicatively dependent vectors of algebraic numbers
Authors: Pappalardi Francesco , Sha Min , Shparlinski Igor , Stewart Cameron
Published: November 2016

In this paper, we give several asymptotic formulas for the number of multiplicatively dependent vectors of algebraic numbers of fixed degree, or within a fixed number field, and bounded height.
On the irreducibility of global descents for even unitary groups and its applications
Authors: Morimoto Kazuki
Published: November 2016

In this paper, we prove the irreducibility of global descents for even unitary groups. More generally, through Fourier-Jacobi coefficients of automorphic forms, we give a bijection between a certain set of irreducible cuspidal automorphic representations of

U

(
n
,
n
)
(

A

)

\mathrm {U}(n,n)(\mathbb {A})

and a certain set of irreducible square-integrable automorphic representations of

U

(
2
n
,
2
n
)
(

A

)

\mathrm {U}(2n, 2n)(\mathbb {A})

. We also give three applications of the irreducibility of global descents. As a global application, we prove a rigidity theorem for irreducible generic cuspidal automorphic representations of

U

(
n
,
n
)

\mathrm {U}(n,n)

. Moreover, as a local application, we prove the irreducibility of explicit local descents for a couple of supercuspidal representations and a local converse theorem for generic representations in the case of

U

(
n
,
n
)

\mathrm {U}(n,n)

.
The Painful Truth
Authors: Webster Lynn
Published: November 2016

The Painful Truth describes the personal and social implications of living with chronic pain and paints a picture of how society can do a better job of helping people who are in pain. In Part 1, the author-a former president of the American Academy of Pain Medicine-tells in-depth stories about some of his patients, using each story to focus on a key issue that frequently surfaces in the lives of people who have pain. The value of a positive attitude, the way that pain combines with other things going on in a person’s life, the reality of prejudice, the risk of becoming addicted to opioids, the power of love, the possibility of leveraging faith for healing, the burden and necessity of caregiving, and the need to be active in managing and making decisions for one’s own life-these are issues that come out in the stories. In Part 2, Webster talks about the issue of pain on a societal level. He faces head-on the thorny decisions involved in the use of opioids to treat chronic pain. Finally he argues that we need a cultural transformation to increase the acceptance of people who are in pain and to mobilize society’s resources to find cures for pain and make them available to all who need them. The Painful Truth, while intended for laypeople, is also helpful to medical professionals and policymakers.
Tracing the Hercules stream with Gaia and LAMOST: new evidence for a fast bar in the Milky Way
Authors: Monari Giacomo , Kawata Daisuke , Hunt Jason A. S. , Famaey Benoit
Published: November 2016

The length and pattern speed of the Milky Way bar are still controversial. Photometric and spectroscopic surveys of the inner Galaxy, as well as gas kinematics, favour a long and slowly rotating bar, with corotation around a Galactocentric radius of 6 kpc. On the other hand, the existence of the Hercules stream in local velocity space favours a short and fast bar with corotation around 4 kpc. This follows from the fact that the Hercules stream looks like a typical signature of the outer Lindblad resonance of the bar. As we showed recently, reconciling this local stream with a slow bar would need to find a yet unknown alternative explanation, based, for instance, on the effect of spiral arms. Here, by combining the TGAS catalogue of the Gaia DR1 with LAMOST radial velocities, we show that the position of Hercules in velocity space as a function of radius in the outer Galaxy indeed varies exactly as predicted by fast bar models with a pattern speed no less than 1.8 times the circular frequency at the Sun's position.
Distinctive Trajectories of Opioid Use Over an Extended Follow-up of Patients in a Multisite Trial on Buprenorphine + Naloxone and Methadone
Authors: Hser Yih-Ing , Huang David , Saxon Andrew J. , Woody George , Moskowitz Andrew L. , Matthews Abigail G. , Ling Walter
Published: November 2016

Objectives:

Uncovering heterogeneities in longitudinal patterns (trajectories) of opioid use among individuals with opioid use disorder can increase our understanding of disease progression and treatment responses to improve care. The present study aims to identify distinctive opioid use trajectories and factors associated with these patterns among participants randomized to treatment with methadone (MET) or buprenorphine + naloxone (BUP).

Methods:

Growth mixture modeling was applied to identify distinctive opioid use trajectories among 795 opioid users after their enrollment in a multisite trial during 2006 to 2009, with follow-up interviews conducted during 2011 to 2014.

Results:

Four distinctive trajectories were identified based on opioid use over the follow-up period: low use (42.0%), high use (22.3%), increasing use (17.1%), and decreasing use (18.6%). Greater odds of being in the high use group (relative to low use) was associated with Hispanics (relative to African American, odds ratio [OR] 3.21), injection drug use (OR 2.12), higher mental health functioning at baseline (OR 1.23), location on the West Coast (vs East Coast, OR 2.15), and randomization to BUP (relative to MET, OR 1.53). High use and increasing use groups had greater severity in problems related to drug, employment, legal, and social/family relationships, and worsened mental health functioning at follow-up. Participation in treatment significantly accounted for both within and between-group differences in opioid use.

Conclusions:

Continued treatment is necessary to reduce risk for opioid use and related adverse consequences, particularly among individuals (eg, injecting drug) at risk for consistently high level of opioid use.
Intention to Drive After Drinking Among Medical Students: Contributions of the Protection Motivation Theory
Authors: Amaral Ricardo Abrantes , Malbergier André , Lima Danielle Ruiz , Santos Verena Castellani Vitor , Gorenstein Clarice , Andrade Arthur Guerra de
Published: November 2016

Objective:

The aim of this study was to investigate whether cognitive variables proposed by the protection motivation theory (PMT) were predictive of occasional and frequent intention to drive after drinking in medical students.

Methods:

One hundred fifty-five students attending preclinical years at a Medical School in São Paulo, Brazil, participated in the study. They were asked about their last month substance use, history of drinking and driving, including driving after binge drinking, and risk perceptions based on a self-report questionnaire with statements about protection motivation, threat, and coping appraisals from the PMT model.

Results:

Fifty-two students (33%) had previous experience of driving after drinking during the last year, and 54 students (35%) reported intention to drive after drinking within the next year. Regression analysis showed that higher scores in perception of personal vulnerability to risks were associated with occasional and frequent intention to continue pursuing this particular behavior. Poorer evaluations about short-term consequences of alcohol consumption and cognitions regarding external rewards were significantly associated with reported intention to continue driving after drinking.

Conclusions:

Considering the social and health impact of alcohol-impaired behaviors, our findings suggest the need of interventional efforts focused in increasing students’ awareness about the negative consequences of drinking and driving aiming to enhance their motivation towards more adaptive behaviors.
COMT and BDNF Gene Variants Help to Predict Alcohol Consumption in Alcohol-dependent Patients
Authors: Klimkiewicz Anna , Mach Anna , Jakubczyk Andrzej , Klimkiewicz Jakub , Wnorowska Anna , Kopera Maciej , Fudalej Sylwia , Burmeister Margit , Brower Kirk , Wojnar Marcin
Published: November 2016

Background:

The neurobiology of alcohol dependence (AD) involves alterations in neurotransmitters and the stress response. We hypothesized that an interaction between functional variants of dopaminergic and neurotrophic genes may influence drinking in AD.

Methods:

The relationship between alcohol consumption and single-nucleotide polymorphisms, Val66Met in the brain-derived neurotrophic factor (BDNF), and Val158Met in the catechol-O-methyltransferase (COMT), was analyzed among 281 alcohol-dependent individuals.

Results:

Individuals carrying both the COMT Met158Met genotype and the BDNF Val66Val genotype drank more than those with other variants of these genes (P = 0.039). Those who had a family history of AD also drank more than those without a family history (P = 0.048). Patients with both Met/Met genotype in the COMT Val158Met polymorphism and Val/Val genotype in the BDNF Val66Met polymorphism suffered from more health problems than those carrying other variants (P = 0.030) and had lower motivation to change drinking patterns (P = 0.031).

Conclusions:

Patients carrying both the BDNF Val66Val and COMT Met158Met variants had higher alcohol consumption. These effects may be influenced by the effects of BDNF and COMT on dopamine responses to alcohol. Motivation-enhancing strategies might benefit the group of patients identified by genotyping in this study, and also treatment aimed at reducing alcohol consumption.
Cold Pain Threshold Identifies a Subgroup of Individuals With Knee Osteoarthritis That Present With Multimodality Hyperalgesia and Elevated Pain Levels
Authors: Wright Anthony , Benson Heather A.E. , Will Rob , Moss Penny
Published: November 2016

Objectives:

Cold hyperalgesia has been established as an important marker of pain severity in a number of conditions. This study aimed to establish the extent to which patients with knee osteoarthritis (OA) demonstrate widespread cold, heat, and pressure hyperalgesia. OA participants with widespread cold hyperalgesia were compared with the remaining OA cohort to determine whether they could be distinguished in terms of hyperalgesia, pain report, pain quality, and physical function.

Methods:

A total of 80 participants with knee OA and 40 matched healthy, pain-free controls participated. OA participants completed a washout of their usual medication. Quantitative sensory testing was completed at 3 sites using standard methods. Cold pain threshold (CPT) and heat pain thresholds (HPT) were tested using a Peltier thermode and pressure pain thresholds (PPT) using a digital algometer. All participants completed the short-form health survey questionnaire and OA participants completed the PainDETECT, Western Ontario and McMaster Universities Osteoarthritis Index of the Knee (WOMAC), and pain quality assessment scale questionnaires.

Results:

OA participants demonstrated widespread cold hyperalgesia (P<0.0001), had lower PPT at the index knee (P<0.0001) compared with controls and reported decreased physical health on the SF-36 (P=0.01). The OA subcohort with high global CPT (≥12.25°C) exhibited multimodality sensitization compared with the remaining OA cohort (PPT P<0.0001; CPT P<0.0001; HPT P=0.021 index knee). This group also reported increased pain, decreased function, and more features of neuropathic pain.

Discussion:

This study identified a specific subgroup of patients with knee OA who exhibited widespread, multimodality hyperalgesia, more pain, more features of neuropathic pain, and greater functional impairment. Identification of patients with this pain phenotype may permit more targeted and effective pain management.
Treatment of Palmar Hyperhidrosis With Needle Injection Versus Low-Pressure Needle-Free Jet Injection of OnabotulinumtoxinA: An Open-Label Prospective Study
Authors: Vadeboncoeur Sophie , Richer Vincent , Nantel-Battista Mélissa , Benohanian Antranik
Published: November 2016

BACKGROUND

OnabotulinumtoxinA (OnabotA) injections are effective to treat palmar hyperhidrosis (HH) but are quite painful.

OBJECTIVE

To evaluate efficacy and pain of OnabotA injection using a needle-free jet apparatus compared with the traditional needle injection to treat palmar HH.

METHODS

Twenty patients were recruited for a prospective open-label study. Their right hand was injected with 1% lidocaine with a jet injector, after which OnabotA was injected with a needle. The left hand was injected with OnabotA directly using the jet injector. Pain scores were recorded for both techniques. At 0, 1, 3, and 6 months, severity of palmar HH was evaluated with the Hyperhidrosis Disease Severity Scale (HDSS).

RESULTS

One point reduction in the HDSS score at 1 month showed no statistical difference between both hands (p = .451). However, the HDSS score at 1 month from baseline dropped by 1.6 for the hand treated with traditional needle injection of OnabotA compared with 1.25 for the hand treated with jet injections (p = .031). There was no statistical difference in the pain on injection with both techniques (p = .1925).

CONCLUSION

This study demonstrates effective and relatively painless use of a low-pressure jet injector for OnabotA in palmar HH.
Subcutaneous Implant-based Breast Reconstruction with Acellular Dermal Matrix/Mesh: A Systematic Review
Authors: Salibian Ara A. , Frey Jordan D. , Choi Mihye , Karp Nolan S.
Published: November 2016

Background:

The availability of acellular dermal matrix (ADM) and synthetic mesh products has prompted plastic surgeons to revisit subcutaneous implant-based breast reconstruction. The literature is limited, however, with regards to evidence on patient selection, techniques, and outcomes.

Methods:

A systematic review of the Medline and Cochrane databases was performed for original studies reporting breast reconstruction with ADM or mesh, and subcutaneous implant placement. Studies were analyzed for level of evidence, inclusion/exclusion criteria for subcutaneous reconstruction, reconstruction characteristics, and outcomes.

Results:

Six studies (186 reconstructions) were identified for review. The majority of studies (66.7%) were level IV evidence case series. Eighty percent of studies had contraindications for subcutaneous reconstruction, most commonly preoperative radiation, high body mass index, and active smoking. Forty percent of studies commenting on patient selection assessed mastectomy flap perfusion for subcutaneous reconstruction. Forty-five percent of reconstructions were direct-to-implant, 33.3% 2-stage, and 21.5% single-stage adjustable implant, with ADM utilized in 60.2% of reconstructions versus mesh. Pooled complication rates included: major infection 1.2%, seroma 2.9%, hematoma 2.3%, full nipple-areola complex necrosis 1.1%, partial nipple-areola complex necrosis 4.5%, major flap necrosis 1.8%, wound healing complication 2.3%, explantation 4.1%, and grade III/IV capsular contracture 1.2%.

Conclusions:

Pooled short-term complication rates in subcutaneous alloplastic breast reconstruction with ADM or mesh are low in preliminary studies with selective patient populations, though techniques and outcomes are variable across studies. Larger comparative studies and better-defined selection criteria and outcomes reporting are needed to develop appropriate indications for performing subcutaneous implant-based reconstruction.
CHOROIDAL CHANGES ASSOCIATED WITH SEROUS MACULAR DETACHMENT IN EYES WITH STAPHYLOMA, DOME-SHAPED MACULA OR TILTED DISK SYNDROME
Authors: Tan Anna C. S. , Yzer Suzanne , Freund K. Bailey , Dansingani Kunal K. , Phasukkijwatana Nopasak , Sarraf David
Published: November 2016

Purpose:

To study the relationship of choroidal abnormalities with serous retinal detachment (SRD) in eyes with staphyloma, dome-shaped macula, or tilted disk syndrome.

Methods:

Group 1, 28 eyes of 20 patients with staphyloma/dome-shaped macula/tilted disk syndrome associated with SRD was compared with Group 2, 30 eyes of 20 patients, with staphyloma/dome-shaped macula/tilted disk syndrome but without SRD. Radial and en-face optical coherence tomography and choroidal analysis were performed.

Results:

Group 1 had a thicker mean subfoveal choroidal thickness (161 μm vs. 92 μm, P < 0.05) and a greater variation in choroidal thickness (112 μm vs. 76 μm, P > 0.05) compared with eyes of Group 2. Focal abrupt changes in choroidal thickness were more commonly seen in Group 1 versus eyes in Group 2 (90% vs. 30%, P < 0.05) and this area of abrupt change was located within or at the edge of the SRD in 64% of eyes. Large choroidal vessels (pachyvessels) (82% located within the area of SRD) were always associated with the presence of SRD.

Conclusion:

An abrupt transition in choroidal thickness may be involved in the pathogenesis of SRD. In some cases, a radial scan pattern may better demonstrate mild SRD, choroidal contours and the focal choroidal variations than horizontal or vertical raster scan patterns.
Which Prosthetic Foot to Prescribe?: Biomechanical Differences Found during a Single-Session Comparison of Different Foot Types Hold True 1 Year Later
Authors: De Asha Alan Richard , Barnett Cleveland T. , Struchkov Vasily , Buckley John G.
Published: November 2016

Introduction

Clinicians typically use findings from cohort studies to objectively inform judgments regarding the potential (dis)advantages of prescribing a new prosthetic device. However, before finalizing prescription, a clinician will typically ask a patient to “try out” a change of prosthetic device while the patient is at the clinic. Observed differences in gait when using the new device should be the result of the device's mechanical function but could also conceivably be a result of patient-related factors, which can change from day to day and can thus make device comparisons unreliable. To determine whether a device's mechanical function consistently has a more meaningful impact on gait than patient-related factors, the present study undertook quantitative gait analyses of an individual with a transtibial amputation walking using two different foot-ankle devices on two occasions over a year apart. If the observed differences present between devices, established using quantitative gait analysis, were in the same direction and of similar magnitude on each of the two occasions, this would indicate that device-related factors were more important than patient-related factors.

Materials and Methods

One adult man with a unilateral transtibial amputation completed repeated walking trials using two different prosthetic foot devices on two separate occasions, 14 months apart. Walking speed and sagittal plane joint kinematics and kinetics for both limbs were assessed on each occasion. Clinically meaningful differences in these biomechanical outcome variables were defined as those with an effect size difference (d) between prosthetic conditions of at least 0.4 (i.e., medium effect size).

Results

Eight variables, namely, walking speed, prosthetic ankle peak plantarflexion and dorsiflexion, and peak positive power and residual knee loading response flexion, peak stance-phase extension and flexion moments, and peak negative power, displayed clinically meaningful differences (d > 0.4) between foot devices during the first session. All eight of these showed similar effect size differences during the second session despite the participant being heavier and older.

Conclusions

Findings suggest that a prosthetic device's mechanical function consistently has a more meaningful impact on gait than patient-related factors do. These findings support the current clinical practice of making decisions regarding prosthetic prescription for an individual based on a single-session evaluation of his/her gait using two different devices. However, to confirm this conclusion, a case series using the same approach as the present study could be undertaken.
Effects of Intratympanic Dexamethasone on High-Dose Radiation Ototoxicity In Vivo
Authors: Dinh Christine T. , Chen Si , Dinh John , Goncalves Stefania , Bas Esperanza , Padgett Kyle , Johnson Perry , Elsayyad Nagy , Telischi Fred , Van De Water Thomas
Published: November 2016

Background:

Stereotactic radiosurgery for lateral skull base tumors can cause hearing loss when the cochleae are exposed to high doses of single-fraction radiation. Currently, there are no known nondosimetric preventative treatments for radiation-induced ototoxicity.

Hypothesis:

Intratympanic (IT) dexamethasone (DXM), a synthetic steroid, protects against radiation-induced auditory hair cell (HC) and hearing losses in rats in vivo.

Methods:

Seven rats received radiation (12 Gy) to both cochleae. In irradiated rats and six nonirradiated rats, IT DXM was randomized to one ear, while tympanic puncture without DXM was performed on the contralateral ear. Baseline and 4-week postradiation auditory-evoked potential tests were performed. The cochleae were processed for HC viability.

Results:

Cochleae exposed to radiation demonstrated more outer HC (OHC) loss in all turns than nonirradiated ears (p <0.05). OHCs were more susceptible to radiation injury than inner HCs in the middle and basal turns (p <0.05). In irradiated cochleae, there was a nonsignificant trend for less OHC loss with IT DXM in the basal turn when compared with placebo. IT DXM did not improve radiation-induced hearing threshold shifts; however, a high rate of tympanic membrane perforations occurred with irradiated ears which may contribute to this finding.

Conclusion:

Radiation induced loss of OHCs in all turns of the cochlea. IT DXM reduced OHC loss in the basal turn of irradiated ears; however, this finding did not achieve statistical significance. Although IT DXM did not affect radiation-induced hearing threshold shifts in adult rats in vivo, this may be due to a high rate of tympanic membrane perforations.
Facial Nerve Meningioma: A Cause of Pediatric Facial Weakness
Authors: Deep Nicholas L. , Gnagi Sharon H. , Carpentieri David F. , Adelson P. David , Weisskopf Peter A.
Published: November 2016

Objective:

To present an unusual case of a temporal bone meningioma with intrafascicular spread throughout the temporal facial nerve from cerebellopontine angle (CPA) to stylomastoid foramen.

Patient:

Four-year-old female with progressive facial weakness and normal hearing.

Main Outcome Measure:

Clinical, radiological, and histopathological findings of temporal bone meningiomas.

Results:

A patient presented with progressive facial weakness and normal hearing. Imaging demonstrated a mass within the left internal auditory canal radiologically consistent with a schwannoma. Asymmetric enlargement with enhancement of the left facial nerve from CPA to the stylomastoid foramen suggested facial schwannoma. At surgery, gross tumor was noted in the internal auditory canal, the fallopian canal seemed expanded and the facial nerve was enlarged and had an irregular contour. Resection of the facial nerve from the CPA to just proximal to its exit at the stylomastoid foramen was necessary to achieve negative margins. Cable grafting was performed. The histopathologic diagnosis was transitional meningioma with intraneural growth throughout the length of the resected facial nerve segment.

Conclusion:

Meningiomas involving the temporal bone are exceedingly rare. We report a rare case of a child presenting with progressive facial weakness due to a presumed facial schwannoma spreading along the facial nerve throughout its intratemporal course that at surgery was found to be an intrafascicular CN VII meningioma.