bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Epidemiology of Repeat Chlamydia trachomatis Detection after Treatment by Using C. trachomatis OmpA Genotyping
Authors: Kapil Richa , Press Christen G. , Hwang M. Lisa , Brown LaDraka , Geisler William M.
Published: December 2014

Repeat
Chlamydia trachomatis
detection frequently occurs within months after
C. trachomatis
infection treatment. The origins of such infection (persistence versus reinfection from untreated or new partners) are varied and difficult to determine.
C. trachomatis
strains can be differentiated by sequencing the
ompA
gene encoding the outer membrane protein A (OmpA). We used OmpA genotyping to investigate the epidemiology of repeat
C. trachomatis
detection after treatment in
C. trachomatis
-infected subjects seen at a sexually transmitted diseases clinic. Subjects were enrolled, tested for
C. trachomatis
, treated with azithromycin, and scheduled for a 6-month follow-up for repeat
C. trachomatis
testing. OmpA genotyping was performed on
C. trachomatis
-positive urogenital specimens obtained from patients at enrollment and follow-up. The enrollment visit OmpA genotypes for
C. trachomatis
were determined for 162 subjects (92% female, 94% African American).
C. trachomatis
was detected at follow-up in 39 subjects (24%). The OmpA genotype distribution at enrollment did not differ in those with versus those without repeat
C. trachomatis
detection. Of the 35 subjects with
C. trachomatis
strains genotyped at enrollment and follow-up, 7 (20%) had the same
ompA
sequence at both visits, while 28 (80%) had discordant sequences. A new sexual partner was reported more often in subjects with discordant
C. trachomatis
strains than in those with concordant strains (13 [46%] versus 1 [14%];
P
= 0.195). Half of the subjects with discordant
C. trachomatis
strains who reported sexual activity since treatment denied a new sexual partner; 62% of these subjects reported that their partner was treated. Our study demonstrates that most repeat
C. trachomatis
detections after treatment were new infections with a different
C. trachomatis
strain rather than reinfection with the same strain. OmpA genotyping can be a useful tool in understanding the origins of repeat
C. trachomatis
detection after treatment.
What DNA Viral Genomic Rearrangements Tell Us about Persistence
Authors: Imperiale Michael J. , Jiang Mengxi
Published: December 2014

Understanding the life cycle and pathogenesis of animal viruses requires that we have systems in which the viruses can replicate and cause disease. For the latter, we rely upon animal models or information that we can obtain from studying natural infections of humans and other animals. For the former, however, we are largely dependent on the availability of cell culture systems in which viruses can be propagated to investigate the molecular mechanisms of viral replication. For many years, it was assumed that replication in culture provided an accurate description of the life cycle of the organism. In this Gem, we will discuss two viruses, polyomavirus and cytomegalovirus, in which cell culture systems have accidentally provided unique potential insights into viral replication and persistence in their hosts.
The Amphipathic Helix of Adenovirus Capsid Protein VI Contributes to Penton Release and Postentry Sorting
Authors: Martinez Ruben , Schellenberger Pascale , Vasishtan Daven , Aknin Cindy , Austin Sisley , Dacheux Denis , Rayne Fabienne , Siebert Alistair , Ruzsics Zsolt , Gruenewald Kay , Wodrich Harald
Published: December 2014

Nuclear delivery of the adenoviral genome requires that the capsid cross the limiting membrane of the endocytic compartment and traverse the cytosol to reach the nucleus. This endosomal escape is initiated upon internalization and involves a highly coordinated process of partial disassembly of the entering capsid to release the membrane lytic internal capsid protein VI. Using wild-type and protein VI-mutated human adenovirus serotype 5 (HAdV-C5), we show that capsid stability and membrane rupture are major determinants of entry-related sorting of incoming adenovirus virions. Furthermore, by using electron cryomicroscopy, as well as penton- and protein VI-specific antibodies, we show that the amphipathic helix of protein VI contributes to capsid stability by preventing premature disassembly and deployment of pentons and protein VI. Thus, the helix has a dual function in maintaining the metastable state of the capsid by preventing premature disassembly and mediating efficient membrane lysis to evade lysosomal targeting. Based on these findings and structural data from cryo-electron microscopy, we suggest a refined disassembly mechanism upon entry.

IMPORTANCE
In this study, we show the intricate connection of adenovirus particle stability and the entry-dependent release of the membrane-lytic capsid protein VI required for endosomal escape. We show that the amphipathic helix of the adenovirus internal protein VI is required to stabilize pentons in the particle while coinciding with penton release upon entry and that release of protein VI mediates membrane lysis, thereby preventing lysosomal sorting. We suggest that this dual functionality of protein VI ensures an optimal disassembly process by balancing the metastable state of the mature adenovirus particle.
Model of the TVA Receptor Determinants Required for Efficient Infection by Subgroup A Avian Sarcoma and Leukosis Viruses
Authors: Melder Deborah C. , Pike Gennett M. , VanBrocklin Matthew W. , Federspiel Mark J.
Published: December 2014

The study of the interactions of subgroup A avian sarcoma and leucosis viruses [ASLV(A)] with the TVA receptor required to infect cells offers a powerful experimental model of retroviral entry. Several regions and specific residues in the TVA receptor have previously been identified to be critical determinants of the binding affinity with ASLV(A) envelope glycoproteins and to mediate efficient infection. Two homologs of the TVA receptor have been cloned: the original quail TVA receptor, which has been the basis for most of the initial characterization of the ASLV(A) TVA, and the chicken TVA receptor, which is 65% identical to the quail receptor overall but identical in the region thought to be critical for infection. Our previous work characterized three mutant ASLV(A) isolates that could efficiently bind and infect cells using the chicken TVA receptor homolog but not using the quail TVA receptor homolog, with the infectivity of one mutant virus being >500-fold less with the quail TVA receptor. The mutant viruses contained mutations in the hr1 region of the surface glycoprotein. Using chimeras of the quail and chicken TVA receptors, we have identified new residues of TVA critical for the binding affinity and entry of ASLV(A) using the mutant glycoproteins and viruses to probe the function of those residues. The quail TVA receptor required changes at residues 10, 14, and 31 of the corresponding chicken TVA residues to bind wild-type and mutant ASLV(A) glycoproteins with a high affinity and recover the ability to mediate efficient infection of cells. A model of the TVA determinants critical for interacting with ASLV(A) glycoproteins is proposed.

IMPORTANCE
A detailed understanding of how retroviruses enter cells, evolve to use new receptors, and maintain efficient entry is crucial for identifying new targets for combating retrovirus infection and pathogenesis, as well as for developing new approaches for targeted gene delivery. Since all retroviruses share an envelope glycoprotein organization, they likely share a mechanism of receptor triggering to begin the entry process. Multiple, noncontiguous interaction determinants located in the receptor and the surface (SU) glycoprotein hypervariable domains are required for binding affinity and to restrict or broaden receptor usage. In this study, further mechanistic details of the entry process were elucidated by characterizing the ASLV(A) glycoprotein interactions with the TVA receptor required for entry. The ASLV(A) envelope glycoproteins are organized into functional domains that allow changes in receptor choice to occur by mutation and/or recombination while maintaining a critical level of receptor binding affinity and an ability to trigger glycoprotein conformational changes.
The P25 Protein of Potato Virus X (PVX) Is the Main Pathogenicity Determinant Responsible for Systemic Necrosis in PVX-Associated Synergisms
Authors: Aguilar Emmanuel , Almendral David , Allende Lucía , Pacheco Remedios , Chung Bong Nam , Canto Tomás , Tenllado Francisco
Published: December 2014

Most plant viruses counter the RNA silencing-based antiviral defense by expressing viral suppressors of RNA silencing (VSRs). In this sense, VSRs may be regarded as virulence effectors that can be recognized by the host as avirulence (avr) factors to induce
R
-mediated resistance. We made use of
Agrobacterium
-mediated transient coexpression of VSRs in combination with
Potato virus X
(PVX) to recapitulate in local tissues the systemic necrosis (SN) caused by PVX-potyvirus synergistic infections in
Nicotiana benthamiana
. The hypersensitive response (HR)-like response was associated with an enhanced accumulation of PVX subgenomic RNAs. We further show that expression of P25, the VSR of PVX, in the presence of VSR from different viruses elicited an HR-like response in
Nicotiana
spp. Furthermore, the expression of P25 by a
Plum pox virus
(PPV) vector was sufficient to induce an increase of PPV pathogenicity that led to necrotic mottling. A frameshift mutation in the P25 open reading frame (ORF) of PVX did not lead to necrosis when coexpressed with VSRs. These findings indicate that P25 is the main PVX determinant involved in eliciting a systemic HR-like response in PVX-associated synergisms. Moreover, we show that silencing of
SGT1
and
RAR1
attenuated cell death in both PVX-potyvirus synergistic infection and the HR-like response elicited by P25. Our study underscores that P25 variants that have impaired ability to suppress RNA silencing cannot act as elicitors when synergized by the presence of other VSRs. These findings highlight the importance of RNA silencing suppression activity in the HR-like response elicited by VSRs in certain hosts.

IMPORTANCE
The work presented here describes how the activity of the PVX suppressor P25 elicits an HR-like response in
Nicotiana
spp. when overexpressed with other VSR proteins. This finding suggests that the SN response caused by PVX-associated synergisms is a delayed immune response triggered by P25, once it reaches a threshold level by the action of other VSRs. Moreover, this work supports the contention that the silencing suppressor activity of PVX P25 protein is a prerequisite for HR elicitation. We propose that unidentified avr determinants could be involved in other cases of viral synergisms in which heterologous “helper” viruses encoding strong VSRs exacerbate the accumulation of the avr-encoding virus.
Thymic HIV-2 Infection Uncovers Posttranscriptional Control of Viral Replication in Human Thymocytes
Authors: Nunes-Cabaço Helena , Matoso Paula , Foxall Russell B. , Tendeiro Rita , Pires Ana R. , Carvalho Tânia , Pinheiro Ana I. , Soares Rui S. , Sousa Ana E.
Published: December 2014

A unique HIV-host equilibrium exists in untreated HIV-2-infected individuals. This equilibrium is characterized by low to undetectable levels of viremia throughout the disease course, despite the establishment of disseminated HIV-2 reservoirs at levels comparable to those observed in untreated HIV-1 infection. Although the clinical spectrum is similar in the two infections, HIV-2 infection is associated with a much lower rate of CD4 T-cell decline and has a limited impact on the mortality of infected adults. Here we investigated HIV-2 infection of the human thymus, the primary organ for T-cell production. Human thymic tissue and suspensions of total or purified CD4 single-positive thymocytes were infected with HIV-2 or HIV-1 primary isolates using either CCR5 or CXCR4 coreceptors. We found that HIV-2 infected both thymic organ cultures and thymocyte suspensions, as attested to by the total HIV DNA and cell-associated viral mRNA levels. Nevertheless, thymocytes featured reduced levels of intracellular Gag viral protein, irrespective of HIV-2 coreceptor tropism and cell differentiation stage, in agreement with the low viral load in culture supernatants. Our data show that HIV-2 is able to infect the human thymus, but the HIV-2 replication cycle in thymocytes is impaired, providing a new model to identify therapeutic targets for viral replication control.

IMPORTANCE
HIV-1 infects the thymus, leading to a decrease in CD4 T-cell production that contributes to the characteristic CD4 T-cell loss. HIV-2 infection is associated with a very low rate of progression to AIDS and is therefore considered a unique naturally occurring model of attenuated HIV disease. HIV-2-infected individuals feature low to undetectable plasma viral loads, in spite of the numbers of circulating infected T cells being similar to those found in patients infected with HIV-1. We assessed, for the first time, the direct impact of HIV-2 infection on the human thymus. We show that HIV-2 is able to infect the thymus but that the HIV-2 replication cycle in thymocytes is impaired. We propose that this system will be important to devise immunotherapies that target viral production, aiding the design of future therapeutic strategies for HIV control.
Targeting Cellular Squalene Synthase, an Enzyme Essential for Cholesterol Biosynthesis, Is a Potential Antiviral Strategy against Hepatitis C Virus
Authors: Saito Kyoko , Shirasago Yoshitaka , Suzuki Tetsuro , Aizaki Hideki , Hanada Kentaro , Wakita Takaji , Nishijima Masahiro , Fukasawa Masayoshi
Published: December 2014

Hepatitis C virus (HCV) exploits host membrane cholesterol and its metabolism for progeny virus production. Here, we examined the impact of targeting cellular squalene synthase (SQS), the first committed enzyme for cholesterol biosynthesis, on HCV production. By using the HCV JFH-1 strain and human hepatoma Huh-7.5.1-derived cells, we found that the SQS inhibitors YM-53601 and zaragozic acid A decreased viral RNA, protein, and progeny production in HCV-infected cells without affecting cell viability. Similarly, small interfering RNA (siRNA)-mediated knockdown of SQS led to significantly reduced HCV production, confirming the enzyme as an antiviral target. A metabolic labeling study demonstrated that YM-53601 suppressed the biosynthesis of cholesterol and cholesteryl esters at antiviral concentrations. Unlike YM-53601, the cholesterol esterification inhibitor Sandoz 58-035 did not exhibit an antiviral effect, suggesting that biosynthesis of cholesterol is more important than that of cholesteryl esters for HCV production. YM-53601 inhibited transient replication of a JFH-1 subgenomic replicon and entry of JFH-1 pseudoparticles, suggesting that at least suppression of viral RNA replication and entry contributes to the antiviral effect of the drug. Collectively, our findings highlight the importance of the cholesterol biosynthetic pathway in HCV production and implicate SQS as a potential target for antiviral strategies against HCV.

IMPORTANCEHepatitis C virus (HCV) is known to be closely associated with host cholesterol and its metabolism throughout the viral life cycle. However, the impact of targeting cholesterol biosynthetic enzymes on HCV production is not fully understood. We found that squalene synthase, the first committed enzyme for cholesterol biosynthesis, is important for HCV production, and we propose this enzyme as a potential anti-HCV target. We provide evidence that synthesis of free cholesterol is more important than that of esterified cholesterol for HCV production, highlighting a marked free cholesterol dependency of HCV production. Our findings also offer a new insight into a role of the intracellular cholesterol pool that is coupled to its biosynthesis in the HCV life cycle.
Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes
Authors: Tjeerdema Nathanja , Georgiadi Anastasia , Jonker Jacqueline T , van Glabbeek Marjolijn , Dehnavi Reza Alizadeh , Tamsma Jouke T , Smit Johannes W A , Kersten Sander , Rensen Patrick C N
Published: December 2014

Background

Angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and associates with dyslipidemia. The expression of ANGPTL4 is regulated by free fatty acids (FFA) that activate lipid-sensing peroxisome proliferator-activated receptors (PPARs), but FFA can also activate pattern recognition receptors including Toll-like receptor 4 (TLR4) in macrophages.

Objective

To assess whether systemic low-grade inflammation is a determinant for plasma ANGPTL4 levels in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM).

Design

We studied 335 male participants: healthy controls (Controls), patients with the MetS without inflammation (MetS−I) and with low-grade inflammation (MetS+I), and patients with T2DM. All patients without diabetes included in the present study were initially matched for waist circumference. In plasma, ANGPTL4, C reactive protein (CRP) and metabolic parameters were determined. Underlying mechanisms were examined using human macrophages in vitro.

Results

As compared with Controls, plasma ANGPTL4 levels were increased in patients with MetS−I, MetS+I, and T2DM. Furthermore, ANGPTL4 was increased in T2DM compared with MetS−I. In fact, plasma CRP correlated positively with plasma ANGPTL4. In vitro studies showed that TLR 3/4 activation largely increased the expression and release of ANGPTL4 by macrophages.

Conclusions

Plasma ANGPTL4 levels in humans are predicted by CRP, a marker of inflammation, and ANGPTL4 expression by macrophages is increased by inflammatory stimuli.
National survey to determine current practices, training and attitudes towards advanced polypectomy in the UK
Authors: Geraghty Joe , O'Toole Paul , Anderson John , Valori Roland , Sarkar Sanchoy
Published: December 2014

Objective

Developments in advanced polypectomy technique provide an alternative to surgery in the management of large and complex colorectal polyps. These endoscopic techniques require expertise and can potentially incur high complication rates. This survey evaluates current UK practice, attitudes and training in advanced polypectomy.

Design

Anonymous online questionnaire.

Setting

Colonoscopists within the UK were asked about their approach to large polyps (>2 cm).

Results

Among the 268 respondents (64% of whom were BCSP accredited), 86% were confident in removing lesions >2 cm by endoscopic mucosal resection (EMR). Of these, 27% were classed as low volume operators (<10 lesions resected/annum) and 14% as high volume operators (>50/annum). By comparison, only 3% currently performed endoscopic submucosal dissection (ESD). Referring one or more benign polyps for surgery a year was common among responders of all levels (11–68%). Training deficiencies were common: only 21% of responders had received a period of training dedicated to advanced polypectomy; 58% of responders would welcome a national training scheme and a majority supported the implementation of advanced polypectomy accreditation with national guidelines. However, while 41% wanted nominated regional EMR experts, only 18% would welcome an integrated national referral network for large/complex polyps.

Conclusions

EMR is practised widely while ESD service provision is very limited. Most experienced colonoscopists are confident to perform piecemeal EMR, even if their training is suboptimal and annual numbers low. Practices and attitudes were variable, even among self-defined level 4 operators. Improving training and implementation of accreditation were welcomed, but there was little appetite for mandated referral to subspecialist ‘experts' and national networks.
The effect of participatory women's groups on infant feeding and child health knowledge, behaviour and outcomes in rural Bangladesh: a controlled before-and-after study
Authors: Younes Leila , Houweling Tanja A J , Azad Kishwar , Kuddus Abdul , Shaha Sanjit , Haq Bedowra , Nahar Tasmin , Hossen Munir , Beard James , Copas Andrew , Prost Audrey , Costello Anthony , Fottrell Edward
Published: December 2014

Background

Despite efforts to reduce under-5 mortality rates worldwide, an estimated 6.6 million under-5 children die every year. Community mobilisation through participatory women's groups has been shown to improve maternal and newborn health in rural settings, but little is known about the potential of this approach to improve care and health in children after the newborn period.

Methods

Following on from a cluster-randomised controlled trial to assess the effect of participatory women's groups on maternal and neonatal health outcomes in rural Bangladesh, 162 women's groups continued to meet between April 2010 and December 2011 to identify, prioritise and address issues that affect the health of children under 5 years. A controlled before-and-after study design and difference-in-difference analysis was used to assess morbidity outcomes and changes in knowledge and practices related to child feeding, hygiene and care-seeking behaviour.

Findings

Significant improvements were measured in mothers’ knowledge of disease prevention and management, danger signs and hand washing at critical times. Significant increases were seen in exclusive breast feeding for at least 6 months (15.3% (4.2% to 26.5%)), and mean duration of breast feeding (37.9 days (17.4 to 58.3)). Maternal reports of under-5 morbidities fell in intervention compared with control areas, including reports of fever (−10.5% (−15.1% to −6.0%)) and acute respiratory infections (−12.2% (−15.6% to −8.8%)). No differences were observed in dietary diversity scores or immunisation uptake.

Conclusions

Community mobilisation through participatory women's groups can be successfully adapted to address health knowledge and practice in relation to child's health, leading to improvements in a number of child health indicators and behaviours.
Influence of wind, wave, and water level dynamics on walleye eggs in a north temperate lake
Authors: Raabe Joshua K. , Bozek Michael A.
Published: December 2014

Walleye (Sander vitreus) populations are cyclic because of biotic and abiotic factors, and wind activity, wave energy, and water levels may be influential given walleye spawn close to shore. We installed an anemometer and tridirectional velocimeter on a spawning reef in Big Crooked Lake, Wisconsin, in 2005 to determine wind–wave relationships and wave energy exceedance of critical velocities of both egg (affecting transport) and substrates (affecting abrasion or burial). To evaluate egg movement, we delineated egg locations at adhesive, postspawn, and black-eyed stages and surveyed on-shore for stranded eggs. We monitored water level with a staff gauge. Wind and wave velocities were significantly (p < 0.01) correlated, and wave velocities were significantly higher (p < 0.01) nearshore (2.0 m) than further from shore (4.6 m). Mean nearshore wave velocities were often sufficient to initiate movement of nonadhesive eggs (45% of records) and fine sand (39%) during egg incubation. Surveys indicated waves moved eggs closer to shore and some onto shore. Water level fluctuations (range = 2.4 cm) likely did not strand or desiccate eggs. We documented that wind and wave activity transports eggs and substrates and should be considered a critical factor in annual walleye egg survival and year-class strength.
An embedding theorem of 𝔼0 with model theoretic applications
Authors: Kaplan Itay , Miller Benjamin D.
Published: December 2014

We provide a new criterion for embedding 𝔼0, and apply it to equivalence relations in model theory. This generalize the results of the authors and Pierre Simon on the Borel cardinality of Lascar strong types equality, and Newelski's results about pseudo Fσ groups.
A Note on a Class of Solutions for Games with Externalities Generalizing the Shapley Value
Authors: Sánchez-Pérez Joss
Published: December 2014

In this paper we study a family of extensions of the Shapley value for games in partition function form with n players. In particular, we provide a complete characterization for all linear, symmetric, efficient and null solutions in these environments. Finally, we relate our characterization result with other ways to extend the Shapley value in the literature.
In vitro evidence that phosphatidylcholine protects against indomethacin/bile acid-induced injury to cells
Authors: Dial Elizabeth J. , Dawson Paul A. , Lichtenberger Lenard M.
Published: December 2014

Indomethacin is a powerful analgesic nonsteroidal anti-inflammatory drug (NSAID), but is limited in use by its primary side effect to cause gastrointestinal bleeding and serious injury. One factor important for exacerbating NSAID injury is the presence of bile acids, which may interact with indomethacin to form toxic mixed micelles in the gut. The development of a safer gastrointestinal formulation of indomethacin that is chemically complexed with phosphatidylcholine (PC-indomethacin) may offer an improved therapeutic agent, particularly in the presence of bile acid, but its potential protective mechanism is incompletely understood. Intestinal epithelial cells (IEC-6) were tested for injury with indomethacin (alone and plus various bile acids) compared with PC-indomethacin (alone and plus bile acids). To explore a role for bile acid uptake into cells as a requirement for NSAID injury, studies were performed using Madin-Darby canine kidney cells transfected with the apical sodium-dependent bile acid transporter (ASBT). Indomethacin, but not PC-indomethacin, was directly and dose-dependently injurious to IEC-6 cells. Similarly, the combination of any bile acid plus indomethacin, but not PC-indomethacin, induced cell injury. The expression of ASBT had a modest effect on the acute cytotoxicity of indomethacin in the presence of some conjugated bile acids. Complexing PC with indomethacin protected against the acute intestinal epithelial injury caused by indomethacin regardless of the presence of bile acids. The presence of luminal bile acid, but not its carrier-mediated uptake into the enterocyte, is required for acute indomethacin-induced cell injury. It is likely that initial cell damage induced by indomethacin occurs at or near the cell membrane, an effect exacerbated by bile acids and attenuated by PC.
Blocking central pathways in the primate motor system using high-frequency sinusoidal current
Authors: Fisher Karen M. , Jillani Ngalla E. , Oluoch George O. , Baker Stuart N.
Published: December 2014

Electrical stimulation with high-frequency (2–10 kHz) sinusoidal currents has previously been shown to produce a transient and complete nerve block in the peripheral nervous system. Modeling and in vitro studies suggest that this is due to a prolonged local depolarization across a broad section of membrane underlying the blocking electrode. Previous work has used cuff electrodes wrapped around the peripheral nerve to deliver the blocking stimulus. We extended this technique to central motor pathways, using a single metal microelectrode to deliver focal sinusoidal currents to the corticospinal tract at the cervical spinal cord in anesthetized adult baboons. The extent of conduction block was assessed by stimulating a second electrode caudal to the blocking site and recording the antidromic field potential over contralateral primary motor cortex. The maximal block achieved was 99.6%, similar to findings of previous work in peripheral fibers, and the optimal frequency for blocking was 2 kHz. Block had a rapid onset, being complete as soon as the transient activation associated with the start of the sinusoidal current was over. High-frequency block was also successfully applied to the pyramidal tract at the medulla, ascending sensory pathways in the dorsal columns, and the descending systems of the medial longitudinal fasciculus. High-frequency sinusoidal stimulation produces transient, reversible lesions in specific target locations and therefore could be a useful alternative to permanent tissue transection in some experimental paradigms. It also could help to control or prevent some of the hyperactivity associated with chronic neurological disorders.
Synaptic mechanisms for generating temporal diversity of auditory representation in the dorsal cochlear nucleus
Authors: Zhou Mu , Li Ya-Tang , Yuan Wei , Tao Huizhong W. , Zhang Li I.
Published: December 2014

In central auditory pathways, neurons exhibit a great diversity of temporal discharge patterns, which may contribute to the parallel processing of auditory signals. How such response diversity emerges in the central auditory circuits remains unclear. Here, we investigated whether synaptic mechanisms can contribute to the generation of the temporal response diversity at the first stage along the central auditory neuraxis. By in vivo whole-cell voltage-clamp recording in the dorsal cochlear nucleus of rats, we revealed excitatory and inhibitory synaptic inputs underlying three different firing patterns of fusiform/pyramidal neurons in response to auditory stimuli: “primary-like,” “pauser,” and “buildup” patterns. We found that primary-like neurons received strong, fast-rising excitation, whereas pauser and buildup neurons received accumulating excitation with a relatively weak fast-rising phase, followed by a slow-rising phase. Pauser neurons received stronger fast-rising excitation than buildup cells. On the other hand, inhibitory inputs to the three types of cells exhibited similar temporal patterns, all with a strong fast-rising phase. Dynamic-clamp recordings demonstrated that the differential temporal patterns of excitation could primarily account for the different discharge patterns. In addition, discharge pattern in a single neuron varied in a stimulus-dependent manner, which could be attributed to the modulation of excitation/inhibition balance by different stimuli. Further examination of excitatory inputs to vertical/tuberculoventral and cartwheel cells suggested that fast-rising and accumulating excitation might be conveyed by auditory nerve and parallel fibers, respectively. A differential summation of excitatory inputs from the two sources may thus contribute to the generation of response diversity.
Utility of Intraoperative Neuromonitoring during Minimally Invasive Fusion of the Sacroiliac Joint
Authors: Woods Michael , Birkholz Denise , MacBarb Regina , Capobianco Robyn , Woods Adam
Published: December 2014

Study Design. Retrospective case series.Objective. To document the clinical utility of intraoperative neuromonitoring during minimally invasive surgical sacroiliac joint fusion for patients diagnosed with sacroiliac joint dysfunction (as a direct result of sacroiliac joint disruptions or degenerative sacroiliitis) and determine stimulated electromyography thresholds reflective of favorable implant position.Summary of Background Data. Intraoperative neuromonitoring is a well-accepted adjunct to minimally invasive pedicle screw placement. The utility of intraoperative neuromonitoring during minimally invasive surgical sacroiliac joint fusion using a series of triangular, titanium porous plasma coated implants has not been evaluated.Methods. A medical chart review of consecutive patients treated with minimally invasive surgical sacroiliac joint fusion was undertaken at a single center. Baseline patient demographics and medical history, intraoperative electromyography thresholds, and perioperative adverse events were collected after obtaining IRB approval.Results. 111 implants were placed in 37 patients. Sensitivity of EMG was 80% and specificity was 97%. Intraoperative neuromonitoring potentially avoided neurologic sequelae as a result of improper positioning in 7% of implants.Conclusions. The results of this study suggest that intraoperative neuromonitoring may be a useful adjunct to minimally invasive surgical sacroiliac joint fusion in avoiding nerve injury during implant placement.
Credibility Test for Frequency Estimation of Sinusoid Using Chebyshev’s Inequality
Authors: Guobing Hu , LiZhong Xu , Yan Gao , Shanshan Wu
Published: December 2014

Estimation of sinusoid frequency is a key research problem related to radar, sonar, and communication systems. The results of numerous investigations on frequency estimation have been reported in the literature. Nevertheless, to the best of our knowledge, none of them have dealt with credibility evaluation, which is used to decide whether an individual frequency estimate of the sinusoid is accurate or not. In this study, the credibility problem is modeled as a hypothesis test based on Chebyshev’s inequality (CI). The correlation calculated from the received signal and the reference signal generated according to the frequency estimate is used as a test statistic. A threshold is determined based on CI, and the analytical expression for the frequency estimation credibility detection performance is derived. Simulations show that the proposed method performs well even at low signal‐to‐noise ratios.
Malignant Peripheral Nerve Sheath Tumors of the Head and Neck: A Case Series and Literature Review
Authors: Mullins Brandon T. , Hackman Trevor
Published: December 2014

Background. Malignant peripheral nerve sheath tumors (MPNSTs) of the head and neck are rare aggressive neoplasms with a poor prognosis. This study describes the management and outcomes of 3 of our patients with MPNSTs of the head and neck.Methods. We identified 3 patients presenting with MPNST of the head and neck and treated at the University of North Carolina. We compared our results to the literature from 1963 to 2014.Results. Mean follow-up was 31 months. Average age at diagnosis was 44.7 years of age. All patients received wide-local excision and adjuvant radiotherapy. No patients recurred during the series. Recurrence-free survival time for the patients was 45, 37, and 3 months, respectively.Conclusions. Our data series confirms that a combined-modality approach with complete surgical resection and adjuvant radiotherapy leads to improved outcomes in MPNSTs of the head and neck. Nonetheless, due to historically poor outcomes, continued research into newer therapies needs to be explored.
Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective
Authors: Homaira Nusrat , Rawlinson William , Snelling Thomas L. , Jaffe Adam
Published: December 2014

Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups.
Experimental Study on the Cause of Inorganic Scale Formation in the Water Injection Pipeline of Tarim Oilfield
Authors: Pei Guihong , Wang Chunyang , Liu Lili
Published: December 2014

Scale formation of water injection pipeline will cause the pipeline to be corroded and increase frictional drag, which will induce the quality and quantity cannot meet the need of oil production process. The cause of scale formation in different oilfield is different because of the complex formation conditions. Taking one operation area of Tazhong oilfield as research object, the authors studied the water quality in different point along water injection pipeline through experiment studies, and analyzed the cause of inorganic scale formation and influence factors. The research results can provide theoretical guidance to anticorrosion and antiscale of oilfield pipeline.
An Introspective Update on the Influence of miRNAs in Breast Carcinoma and Neuroblastoma Chemoresistance
Authors: Carta Alessia , Chetcuti Rachel , Ayers Duncan
Published: December 2014

Chemoresistance to conventional cytotoxic drugs may occur in any type of cancer and this can either be inherent or develop through time. Studies have linked this acquired resistance to the abnormal expression of microRNAs (miRNAs) that normally silence genes. At abnormal levels, miRNAs can either gain ability to silence tumour suppressor genes or else lose ability to silence oncogenes. miRNAs can also affect pathways that are involved in drug metabolism, such as drug efflux pumps, resulting in a resistant phenotype. The scope of this review is to provide an introspective analysis on the specific niches of breast carcinoma and neuroblastoma research.
Giant Malignant Phyllodes Tumour of Breast
Authors: Krishnamoorthy Ramakrishnan , Savasere Thejas , Prabhuswamy Vinod Kumar , Babu Rajashekhara , Shivaswamy Sadashivaiah
Published: December 2014

The term phyllodes tumour includes lesions ranging from completely benign tumours to malignant sarcomas. Clinically phyllodes tumours are smooth, rounded, and usually painless multinodular lesions indistinguishable from fibroadenomas. Percentage of phyllodes tumour classified as malignant ranges from 23% to 50%. We report a case of second largest phyllodes tumour in a 35-year-old lady who presented with swelling of right breast since 6 months, initially small in size, that progressed gradually to present size. Examination revealed mass in the right breast measuring36×32 cms with lobulated firm surface and weighing 10 kgs. Fine needle aspiration cytology was reported as borderline phyllodes; however core biopsy examination showed biphasic neoplasm with malignant stromal component. Simple mastectomy was done and specimen was sent for histopathological examination which confirmed the core biopsy report. Postoperatively the patient received chemotherapy and radiotherapy. The patient is on follow-up for a year and has not shown any evidence of metastasis or recurrence.
A Five-Gene Hedgehog Signature Developed as a Patient Preselection Tool for Hedgehog Inhibitor Therapy in Medulloblastoma
Authors: Shou Yaping , Robinson Douglas M. , Amakye Dereck D. , Rose Kristine L. , Cho Yoon-Jae , Ligon Keith L. , Sharp Thad , Haider Asifa S. , Bandaru Raj , Ando Yuichi , Geoerger Birgit , Doz François , Ashley David M. , Hargrave Darren R. , Casanova Michela , Tawbi Hussein A. , Rodon Jordi , Thomas Anne L. , Mita Alain C. , MacDonald Tobey J. , Kieran Mark W.
Published: December 2014

Purpose: Distinct molecular subgroups of medulloblastoma, including hedgehog (Hh) pathway–activated disease, have been reported. We identified and clinically validated a five-gene Hh signature assay that can be used to preselect patients with Hh pathway–activated medulloblastoma.

Experimental Design: Gene characteristics of the Hh medulloblastoma subgroup were identified through published bioinformatic analyses. Thirty-two genes shown to be differentially expressed in fresh-frozen and formalin-fixed paraffin-embedded tumor samples and reproducibly analyzed by RT-PCR were measured in matched samples. These data formed the basis for building a multi-gene logistic regression model derived through elastic net methods from which the five-gene Hh signature emerged after multiple iterations. On the basis of signature gene expression levels, the model computed a propensity score to determine Hh activation using a threshold set a priori. The association between Hh activation status and tumor response to the Hh pathway inhibitor sonidegib (LDE225) was analyzed.

Results: Five differentially expressed genes in medulloblastoma (GLI1, SPHK1, SHROOM2, PDLIM3, and OTX2) were found to associate with Hh pathway activation status. In an independent validation study, Hh activation status of 25 medulloblastoma samples showed 100% concordance between the five-gene signature and Affymetrix profiling. Further, in medulloblastoma samples from 50 patients treated with sonidegib, all 6 patients who responded were found to have Hh-activated tumors. Three patients with Hh-activated tumors had stable or progressive disease. No patients with Hh-nonactivated tumors responded.

Conclusions: This five-gene Hh signature can robustly identify Hh-activated medulloblastoma and may be used to preselect patients who might benefit from sonidegib treatment. Clin Cancer Res; 21(3); 585–93. ©2014 AACR.
Choroid Plexus Tumors in Children: A Population-Based Study
Authors: Lam Sandi , Lin Yimo , Cherian Jacob , Qadri Usama , Harris Dominic A. , Melkonian Stephanie , Jea Andrew
Published: December 2014

Background: Choroid plexus tumors are rare neoplasms that primarily occur in children. The use of the SEER (Surveillance, Epidemiology and End Results) database allows for the analysis of the relationship between prognostic factors and survival. Methods: We analyzed the SEER database to select pediatric patients (<18 years old) with histologically confirmed diagnoses of choroid plexus papillomas (CPP; WHO Grade 0), atypical CPP (WHO Grade I) and choroid plexus carcinomas (CPC; WHO grade III). In univariate and multivariate analysis, we analyzed the relationship between demographic (age, gender, race, date of diagnosis) and treatment factors (extent of surgical resection, use of adjuvant radiation) on survival. Results: Overall, 168 pediatric subjects with choroid plexus tumors were identified as follows: 75 cases of CPP, 12 cases of atypical CPP and 81 cases of CPC. The median follow-up time was 3.5 years for CPP and 7.7 years for CPC. The median age at diagnosis was 4 years for CPP (10-90th percentile 0-16 years) and 1 year for CPC (10-90th percentile 0-10 years). In univariate regression analysis, CPC histology (β = -3.2, 95% confidence interval, CI -4.8 to -1.5, p < 0.001) was significantly associated with younger age at diagnosis in comparison to CPP. The mean tumor size was 3.7 cm for CPP and 6.0 cm for CPC (p < 0.001). A higher-grade tumor was associated with significantly increased mortality (hazard ratio, HR = 28.90, 95% CI 3.94-211.83, p = 0.001). Overall survival at 5 years was 98.7% for CPP and 58.5% for CPC (p < 0.001). Among those patients with CPC, gross total resection (GTR) was associated with a significantly lower mortality (HR = 0.21, 95% CI 0.07-0.66, p = 0.007). Overall survival at 5 years was 70.9% after GTR, significantly better than 35.9% after subtotal resection (p = 0.012) and 30% after no surgery (p = 0.003). Radiation treatment was not found to confer a survival benefit in CPC. No demographic characteristics (age, sex, race, date of diagnosis) were significantly associated with mortality. Conclusions: Analysis of a pediatric cohort of choroid plexus tumors in children in the SEER database shows that tumor grade is predictive of survival. In cases of CPC, the extent of surgical resection, especially GTR, is significantly associated with increased survival. Radiation did not confer survival benefit.
Changes in the Retinal Vascular Network Morphology (Diameter and Tortuosity) after Administration of Intravitreal Bevacizumab in a Patient with Ischaemic Branch Retinal Vein Occlusion
Authors: Kelkar Aditya , Shah Rachana , Kelkar Jai , Kelkar Shreekant , Bhirud Shilpa , Gandhi Poonam
Published: December 2014

We report a case of transient reduction in the diameter and tortuosity of an occluded vessel after intravitreal administration of 1.25 mg (0.05 ml) bevacizumab in a patient with ischaemic branch retinal vein occlusion. A 64-year-old hypertensive female presented with chief complaints of reduced vision in her right eye for 3 months. Her vision in the right eye was evaluated as counting fingers at 2 m. Fundus examination revealed superotemporal branch retinal vein occlusion. On fluorescein angiography, in the superotemporal quadrant, there was hyperfluorescence that increased in size and intensity in the late phase, suggestive of a leaking neovascular frond. In addition, there was capillary non-perfusion in the adjacent area. The patient was administered 1.25 mg (0.05 ml) of bevacizumab intravitreally in her right eye, under all aseptic precautions. After 1 week, her right eye fundus showed regression of neovascularisation. Fluorescein angiography also demonstrated regression of neovascularisation in addition to a decrease in the diameter and tortuosity of the retinal vessel.
Cutaneous Squamous Cell Carcinoma with Perineural Invasion: Report on Eight Cases and Review of the Literature
Authors: Verburg Maurice , Lang Martin , Mühlstädt Michael , Klein Annette , Schauber Jürgen , Sattler Elke C. , Kunte Christian
Published: December 2014

Background: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) is considered to be a negative prognostic factor. A lot of uncertainty remains regarding the classification, diagnosis, treatment and prognosis of SCC with PNI. Objective: To describe typical courses of SCC with PNI and associated findings in order to suggest an optimized diagnostic and therapeutic approach. Methods: We present eight cases of SCC with PNI, considering patient and tumor characteristics, histology, treatment and clinical course regarding local recurrence and metastasization. Results: SCC patients with PNI have a higher rate of local recurrences and greater risk for metastasization than SCC patients without PNI. Age ranged from 68 to 77 years, 6 patients were male and 2 female, with all tumors localized on the head. Three patients had chronic lymphocytic leukemia. Conclusion: Based on the data of this series and the current literature, we make suggestions for better diagnostic and therapeutic management.
Epidemiology and pathophysiology of venous thromboembolism: similarities with atherothrombosis and the role of inflammation
Authors: Riva Nicoletta , Donadini Marco P. , Ageno Walter
Published: December 2014

Venous thromboembolism (VTE) is a multifactorial disease. Major provoking factors (e. g. surgery, cancer, major trauma, and immobilisation) are identified in 50–60 % of patients, while the remaining cases are classified as unprovoked. However, minor predisposing conditions may be detectable in these patients, possibly concurring to the pathophysiology of the disease, especially when co-existing. In recent years, the role of chronic inflammatory disorders, infectious diseases and traditional cardiovascular risk factors has been extensively investigated. Inflammation, with its underlying prothrombotic state, could be the potential link between these risk factors, as well as the explanation for the reported association between arterial and venous thromboembolic events.