bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional benefit of the bone‐anchored hearing aid with different auditory profiles: objective and subjective measures
Authors: van Wieringen A. , De Voecht K. , Bosman A.J. , Wouters J. 
Published: March 2011

Clin. Otolaryngol. 2011, 36, 114–120Objectives:  To examine sentence recognition and self‐report outcomes in hearing‐impaired persons with different auditory profiles and who were fitted unilaterally with a bone‐anchored hearing aid.Study‐design:  Prospective cohort study.Setting:  Tertiary referral unit.Patients:  Data were collected of six patients with single‐sided deafness (SSD), seven with a mild to severe hearing loss at the bone‐anchored hearing aid side and (near‐)normal hearing at the other side and six with a severe bilateral hearing loss.Main outcome measurements:  Sound field thresholds, and sentence recognition in noise (presented from different angles) with bone‐anchored hearing aid, without bone‐anchored hearing aid and with bone‐anchored hearing aid and other ear occluded. In addition, the Speech, Spatial and Qualities of hearing scale and the Abbreviated Profile of Hearing Aid Benefit questionnaire were administered as self‐report measures.Results:  Patients with single‐sided deafness listened mainly with their non‐bone‐anchored hearing aid ear, although the bone‐anchored hearing aid lifted the head shadow effect. Patients with mild to severe hearing loss at the bone‐anchored hearing aid side and (near‐)normal hearing at the other side performed significantly differently in aided and unaided conditions and even regained limited binaural sensitivity with the device. The latter was also true for the patients with severe bilateral hearing loss. However, their hearing loss at the non‐bone‐anchored hearing aid side was too great to contribute to hearing and they listened predominantly with their bone‐anchored hearing aid. Self‐report outcomes provided useful information on hearing disability, although this information was not significantly differently for the 3 groups of patients.Conclusions:  The bone‐anchored hearing aid enhanced performance in different hearing configurations, albeit to different extents.
Melanoma cell invasiveness is regulated by miR‐211 suppression of the BRN2 transcription factor
Authors: Boyle Glen M. , Woods Susan L. , Bonazzi Vanessa F. , Stark Mitchell S. , Hacker Elke , Aoude Lauren G. , Dutton‐Regester Ken , Cook Anthony L. , Sturm Richard A. , Hayward Nicholas K. 
Published: March 2011

SummaryTo identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR‐211. We focused on this pigment‐cell‐enriched miRNA as it is derived from the microphthalmia‐associated transcription factor (MITF)‐regulated gene, TRPM1 (melastatin). We find that miR‐211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR‐211, including POU3F2 (BRN2). Inhibition of miR‐211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR‐211 represses BRN2 in differentiated cells. Over‐expression of miR‐211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non‐overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR‐211 expression.
Differences in Antibody Responses of Individuals with Natural Infection and Those Vaccinated against Pandemic H1N1 2009 Influenza
Authors: Chan Kwok-Hung , To Kelvin K. W. , Hung Ivan F. N. , Zhang Anna J. X. , Chan Jasper F. W. , Cheng Vincent C. C. , Tse Herman , Che Xiao-Yan , Chen Honglin , Yuen Kwok-Yung 
Published: March 2011

ABSTRACTThe differential antibody response measured by the commonly used hemagglutination inhibition (HI) and microneutralization (MN) assays in patients with natural infection and vaccination has not been fully assessed. HI and conventional MN (CMN) assays were performed on sera from 651 patients with natural infection by pandemic H1N1 2009 influenza virus and on sera from 567 recipients of the corresponding vaccine. Surprisingly, the overall seroprotection rates determined by CMN and HI assays in vaccine recipients were only 44.8 and 35.1%, respectively. Antibody titers measured by the CMN assay was significantly higher than that obtained by HI assay in vaccine recipients aged ≥50 years, but these titers were not significantly different among younger vaccine recipients. In contrast, the HI titer was greater than the CMN titer for the age group from 16 to 29 years but was not significantly different in other age groups for natural infection. Lower antibody levels were found in both naturally infected patients and immunized recipients in the older than in the younger age groups, but naturally infected patients exhibited higher HI and CMN titers than did the corresponding vaccine recipients. In addition, we developed a rapid fluorescent focus microneutralization (FFMN) assay to test sera from naturally infected patients. The FFMN assay has a better correlation with CMN than with HI (ρ = 0.810 versus 0.684), which is expected of neutralizing antibody mainly targeted toward the inhibition of viral entry into cells. The higher antibody level elicited by natural infection than by vaccination may be related to differences between antigen presentation by the intramuscular route of vaccination and mucosal viral replication in mucosal cells of the respiratory tract.
Activity of TDT 067 (Terbinafine in Transfersome) against Agents of Onychomycosis, as Determined by Minimum Inhibitory and Fungicidal Concentrations
Authors: Ghannoum Mahmoud , Isham Nancy , Herbert Jacqueline , Henry William , Yurdakul Sam 
Published: March 2011

ABSTRACT

TDT 067 is a novel carrier-based dosage form (liquid spray) of 15 mg/ml of terbinafine in Transfersome that has been developed to deliver terbinafine to the nail bed to treat onychomycosis. In this study, we report the
in vitro
activities of TDT 067 against dermatophytes, compared with those of the Transfersome vehicle, naked terbinafine, and commercially available terbinafine (1%) spray. The MICs of TDT 067 and comparators against 25 clinical strains each of
Trichophyton rubrum
,
T. mentagrophytes
, and
Epidermophyton floccosum
were determined according to the CLSI M38–A2 susceptibility method (2008). Minimum fungicidal concentrations (MFCs) were determined by subculturing visibly clear wells from the MIC microtiter plates. TDT 067 demonstrated potent activity against the dermatophyte strains tested, with an MIC range of 0.00003 to 0.015 μg/ml. Overall, TDT 067 MIC
50
values (defined as the lowest concentrations to inhibit 50% of the strains tested) were 8-fold and 60-fold lower than those of naked terbinafine and terbinafine spray, respectively. The Transfersome vehicle showed minimal inhibitory activity. TDT 067 demonstrated lower MFC values for
T. rubrum
and
E. floccosum
than naked terbinafine and terbinafine spray. TDT 067 has more potent antifungal activity against dermatophytes that cause nail infection than conventional terbinafine preparations. The Transfersome vehicle appears to potentiate the antifungal activity of terbinafine. Clinical investigation of TDT 067 for the topical treatment of onychomycosis is warranted.
Transfer of KPC-2 Carbapenemase from Klebsiella pneumoniae to Escherichia coli in a Patient: First Case in Europe
Authors: Richter Sara N. , Frasson Ilaria , Bergo Cristina , Parisi Saverio , Cavallaro Antonietta , Palù Giorgio 
Published: March 2011

ABSTRACT

The first case in Europe of
Klebsiella pneumoniae
carbapenemase (KPC) 2 transfer from
K. pneumoniae
to
Escherichia coli
in the same patient is described. KPC-positive plasmids from the two species were identical, indicating horizontal plasmid transfer. Selection of the KPC-producing
E. coli
strain was triggered by therapy with meropenem.
Use of a Novel Real-Time PCR Assay To Detect Oral Polio Vaccine Shedding and Reversion in Stool and Sewage Samples after a Mexican National Immunization Day
Authors: Troy Stephanie B. , Ferreyra-Reyes Leticia , Huang ChunHong , Mahmud Nadim , Lee Yu-Jin , Canizales-Quintero Sergio , Flaster Harry , Báez-Saldaña Renata , García-García Lourdes , Maldonado Yvonne 
Published: March 2011

ABSTRACT
During replication, oral polio vaccine (OPV) can revert to neurovirulence and cause paralytic poliomyelitis. In individual vaccinees, it can acquire specific revertant point mutations, leading to vaccine-associated paralytic poliomyelitis (VAPP). With longer replication, OPV can mutate into vaccine-derived poliovirus (VDPV), which causes poliomyelitis outbreaks similar to those caused by wild poliovirus. After wild poliovirus eradication, safely phasing out vaccination will likely require global use of inactivated polio vaccine (IPV) until cessation of OPV circulation. Mexico, where children receive routine IPV but where OPV is given biannually during national immunization days (NIDs), provides a natural setting to study the duration of OPV circulation in a population primarily vaccinated with IPV. We developed a real-time PCR assay to detect and distinguish revertant and nonrevertant OPV serotype 1 (OPV-1), OPV-2, and OPV-3 from RNA extracted directly from stool and sewage. Stool samples from 124 children and 8 1-liter sewage samples from Orizaba, Veracruz, Mexico, collected 6 to 13 weeks after a NID were analyzed. Revertant OPV-1 was found in stool at 7 and 9 weeks, and nonrevertant OPV-2 and OPV-3 were found in stool from two children 10 weeks after the NID. Revertant OPV-1 and nonrevertant OPV-2 and -3 were detected in sewage at 6 and 13 weeks after the NID. Our real-time PCR assay was able to detect small amounts of OPV in both stool and sewage and to distinguish nonrevertant and revertant serotypes and demonstrated that OPV continues to circulate at least 13 weeks after a NID in a Mexican population routinely immunized with IPV.
First Reported Isolation of Neisseria canis from a Deep Facial Wound Infection in a Dog
Authors: Cantas Hasan , Pekarkova Marta , Kippenes Hege S. , Brudal Espen , Sorum Henning 
Published: March 2011

ABSTRACTNeisseria caniswas isolated in pure culture from a mandibular abscess in a dog. Ultrasound-guided fine-needle aspiration was used to obtain a sample from the abscess. Conventional bacteriological examination techniques followed by 16S rRNA gene sequencing from pure subculture and construction of a phylogenetic tree verified the isolate asN. canis. 16S rRNA sequence analysis revealed that a broader phylogenetic platform is needed in the part of the phylogenetic tree where the canine pathogenicN. canisisolate is located. The canine pathogenic isolate was found to be resistant to cephalexin and trimethoprim.
Residues of the UL25 Protein of Herpes Simplex Virus That Are Required for Its Stable Interaction with Capsids
Authors: Cockrell Shelley K. , Huffman Jamie B. , Toropova Katerina , Conway James F. , Homa Fred L. 
Published: March 2011

ABSTRACT
The herpes simplex virus 1 (HSV-1) UL25 gene product is a minor capsid component that is required for encapsidation, but not cleavage, of replicated viral DNA. UL25 is located on the capsid surface in a proposed heterodimer with UL17, where five copies of the heterodimer are found at each of the capsid vertices. Previously, we demonstrated that amino acids 1 to 50 of UL25 are essential for its stable interaction with capsids. To further define the UL25 capsid binding domain, we generated recombinant viruses with either small truncations or amino acid substitutions in the UL25 N terminus. Studies of these mutants demonstrated that there are two important regions within the capsid binding domain. The first 27 amino acids are essential for capsid binding of UL25, while residues 26 to 39, which are highly conserved in the UL25 homologues of other alphaherpesviruses, were found to be critical for stable capsid binding. Cryo-electron microscopy reconstructions of capsids containing either a small tag on the N terminus of UL25 or the green fluorescent protein (GFP) fused between amino acids 50 and 51 of UL25 demonstrate that residues 1 to 27 of UL25 contact the hexon adjacent to the penton. A second region, most likely centered on amino acids 26 to 39, contacts the triplex that is one removed from the penton. Importantly, both of these UL25 capsid binding regions are essential for the stable packaging of full-length viral genomes.
Cardiomyopathy Syndrome of Atlantic Salmon (Salmo salar L.) Is Caused by a Double-Stranded RNA Virus of the Totiviridae Family
Authors: Haugland Øyvind , Mikalsen Aase B. , Nilsen Pål , Lindmo Karine , Thu Beate J. , Eliassen Trygve M. , Roos Norbert , Rode Marit , Evensen Øystein 
Published: March 2011

ABSTRACT

Cardiomyopathy syndrome (CMS) of farmed and wild Atlantic salmon (
Salmo salar
L.) is a disease of yet unknown etiology characterized by a necrotizing myocarditis involving the atrium and the spongious part of the heart ventricle. Here, we report the identification of a double-stranded RNA virus likely belonging to the family
Totiviridae
as the causative agent of the disease. The proposed name of the virus is piscine myocarditis virus (PMCV). On the basis of the RNA-dependent RNA polymerase (RdRp) sequence, PMCV grouped with
Giardia lamblia
virus and infectious myonecrosis virus of penaeid shrimp. The genome size of PMCV is 6,688 bp, with three open reading frames (ORFs). ORF1 likely encodes the major capsid protein, while ORF2 encodes the RdRp, possibly expressed as a fusion protein with the ORF1 product. ORF3 seems to be translated as a separate protein not described for any previous members of the family
Totiviridae
. Following experimental challenge with cell culture-grown virus, histopathological changes are observed in heart tissue by 6 weeks postchallenge (p.c.), with peak severity by 9 weeks p.c. Viral genome levels detected by real-time reverse transcription (RT)-PCR peak earlier at 6 to 7 weeks p.c. The virus genome is detected by
in situ
hybridization in degenerate cardiomyocytes from clinical cases of CMS. Virus genome levels in the hearts from clinical field cases correlate well with the severity of histopathological changes in heart tissue. The identification of the causative agent for CMS is important for improved disease surveillance and disease control and will serve as a basis for vaccine development against the disease.
A New Ebola Virus Nonstructural Glycoprotein Expressed through RNA Editing
Authors: Mehedi Masfique , Falzarano Darryl , Seebach Jochen , Hu Xiaojie , Carpenter Michael S. , Schnittler Hans-Joachim , Feldmann Heinz 
Published: March 2011

ABSTRACT

Ebola virus (EBOV), an enveloped, single-stranded, negative-sense RNA virus, causes severe hemorrhagic fever in humans and nonhuman primates. The EBOV glycoprotein (GP) gene encodes the nonstructural soluble glycoprotein (sGP) but also produces the transmembrane glycoprotein (GP
1,2
) through transcriptional editing. A third GP gene product, a small soluble glycoprotein (ssGP), has long been postulated to be produced also as a result of transcriptional editing. To identify and characterize the expression of this new EBOV protein, we first analyzed the relative ratio of GP gene-derived transcripts produced during infection
in vitro
(in Vero E6 cells or Huh7 cells) and
in vivo
(in mice). The average percentages of transcripts encoding sGP, GP
1,2
, and ssGP were approximately 70, 25, and 5%, respectively, indicating that ssGP transcripts are indeed produced via transcriptional editing. N-terminal sequence similarity with sGP, the absence of distinguishing antibodies, and the abundance of sGP made it difficult to identify ssGP through conventional methodology. Optimized 2-dimensional (2D) gel electrophoresis analyses finally verified the expression and secretion of ssGP in tissue culture during EBOV infection. Biochemical analysis of recombinant ssGP characterized this protein as a disulfide-linked homodimer that was exclusively N glycosylated. In conclusion, we have identified and characterized a new EBOV nonstructural glycoprotein, which is expressed as a result of transcriptional editing of the GP gene. While ssGP appears to share similar structural properties with sGP, it does not appear to have the same anti-inflammatory function on endothelial cells as sGP.
The Breadth and Potency of Passively Acquired Human Immunodeficiency Virus Type 1-Specific Neutralizing Antibodies Do Not Correlate with the Risk of Infant Infection
Authors: Lynch John B. , Nduati Ruth , Blish Catherine A. , Richardson Barbra A. , Mabuka Jennifer M. , Jalalian-Lechak Zahra , John-Stewart Grace , Overbaugh Julie 
Published: March 2011

ABSTRACT
Although a major goal of human immunodeficiency virus type 1 (HIV-1) vaccine efforts is to elicit broad and potent neutralizing antibodies (NAbs), there are no data that directly demonstrate a role for such NAbs in protection from HIV-1 infection in exposed humans. The setting of mother-to-child transmission provides an opportunity to examine whether NAbs provide protection from HIV-1 infection because infants acquire passive antibodies from their mothers prior to exposure to HIV-1 through breastfeeding. We evaluated the characteristics of HIV-1-specific NAbs in 100 breast-fed infants of HIV-1-positive mothers who were HIV-1 negative at birth and monitored them until age 2. A panel of eight viruses that included variants representative of those in the study region as well as more diverse strains was used to determine the breadth of the infant NAbs. From their mothers, infants acquired broad and potent NAbs that were capable of recognizing heterologous circulating HIV-1 variants of diverse subtypes, but the presence of NAbs of broad HIV-1 specificity was not associated with transmission risk. There was also no correlation between responses to any particular virus tested, which included a range of diverse variants that demonstrated different neutralization profiles, including recognition by specific antibodies with known epitope targets. The eight viruses tested exhibited neutralization profiles to a variety of monoclonal antibodies (2F5, PG9, and VRC01) similar to those of viruses present in pregnant women in the cohort. These results suggest that the breadth and potency of the heterologous antibody response in exposed infants, measured against a virus panel comprised of variants typical of those circulating in the population, does not predict protection.
Valproic Acid Antagonizes the Capacity of Other Histone Deacetylase Inhibitors To Activate the Epstein-Barr Virus Lytic Cycle
Authors: Daigle Derek , Gradoville Lyn , Tuck David , Schulz Vince , Wang'ondu Ruth , Ye Jianjiang , Gorres Kelly , Miller George 
Published: March 2011

ABSTRACTDiverse stimuli reactivate the Epstein-Barr virus (EBV) lytic cycle in Burkitt lymphoma (BL) cells. In HH514-16 BL cells, two histone deacetylase (HDAC) inhibitors, sodium butyrate (NaB) and trichostatin A (TSA), and the DNA methyltransferase inhibitor azacytidine (AzaCdR) promote lytic reactivation. Valproic acid (VPA), which, like NaB, belongs to the short-chain fatty acid class of HDAC inhibitors, fails to induce the EBV lytic cycle in these cells. Nonetheless, VPA behaves as an HDAC inhibitor; it causes hyperacetylation of histone H3 (J. K. Countryman, L. Gradoville, and G. Miller, J. Virol.82:4706–4719, 2008). Here we show that VPA blocked the induction of EBV early lytic proteins ZEBRA and EA-D in response to NaB, TSA, or AzaCdR. The block in lytic activation occurred prior to the accumulation of BZLF1 transcripts. Reactivation of EBV in Akata cells, in response to anti-IgG, and in Raji cells, in response to tetradecanoyl phorbol acetate (TPA), was also inhibited by VPA. MS-275 and apicidin, representing two additional classes of HDAC inhibitors, and suberoylanilide hydroxamic acid (SAHA) reactivated EBV in HH514-16 cells; this activity was also inhibited by VPA. Although VPA potently blocked the expression of viral lytic-cycle transcripts, it did not generally block the transcription of cellular genes and was not toxic. The levels and kinetics of specific cellular transcripts, such as Stat3, Frmd6, Mad1, Sepp1, c-fos, c-jun, andegr1, which were activated by NaB and TSA, were similar in HH514-16 cells treated with VPA. When combined with NaB or TSA, VPA did not inhibit the activation of these cellular genes. Changes in cellular gene expression in response to VPA, NaB, or TSA were globally similar as assessed by human genome arrays; however, VPA selectively stimulated the expression of some cellular genes, such as MEF2D, YY1, and ZEB1, that could repress the EBV lytic cycle. We describe a novel example of functional antagonism between HDAC inhibitors.
Enhanced Chemotherapy of Cancer Using pH-Sensitive Mesoporous Silica Nanoparticles to Antagonize P-Glycoprotein–Mediated Drug Resistance
Authors: Huang I-Ping , Sun Shu-Pin , Cheng Shih-Hsun , Lee Chia-Hung , Wu Chia-Yan , Yang Chung-Shi , Lo Leu-Wei , Lai Yiu-Kay 
Published: March 2011

Abstract
Multidrug resistance (MDR) is the major clinical obstacle in the management of cancer by chemotherapy. Overexpression of ATP-dependent efflux transporter P-glycoprotein (PGP) is a key factor contributing to multidrug resistance of cancer cells. The purpose of the present study was to use the endosomal pH-sensitive MSN (mesoporous silica nanoparticles; MSN-Hydrazone-Dox) for controlled release of doxorubicin (Dox) in an attempt to overcome the PGP-mediated MDR. In vitro cell culture studies indicate that uptake of MSN-Hydrazone-Dox by the human uterine sarcoma MES-SA/Dox-resistant tumor (MES-SA/Dx-5) cell occurs through endocytosis, thus bypassing the efflux pump resistance. This improves the efficacy of the drug and leads to significant cytotoxicity and DNA fragmentation evidenced by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and DNA laddering assays. In vivo studies show that the intratumor injection of MSN-Hydrazone-Dox induces significant apoptosis of MES-SA/Dox-resistant cancer cells. This is validated by active caspase-3 immunohistochemical analysis. However, MSN-Hydrazone, without doxorubicin conjugation, cannot induce apoptosis in vitro and in vivo. In conclusion, both in vitro and in vivo studies show that MSN could serve as an efficient nanocarrier entering cell avidly via endocytosis, thus bypassing the PGP efflux pump to compromise the PGP-mediated MDR. MSN-Hydrazone-Dox could further respond to endosomal acidic pH to release doxorubicin in a sustained manner. Besides the cell study, this is the first report that successfully shows the therapeutic efficacy of using MSN against MDR cancer in vivo. Mol Cancer Ther; 10(5); 761–9. ©2011 AACR.