bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of nasopharyngeal bacterial colonisation in HIV‐exposed young infants in Tanzania
Authors: Kinabo G. D. , van der Ven A. , Msuya L. J. , Shayo A. M. , Schimana W. , Ndaro A. , van Asten H. A. G. H. , Dolmans W. M. V. , Warris A. , Hermans P. W. M. 
Published: January 2013

AbstractObjectivesTo estimate the prevalence of nasopharyngeal bacterial colonisation (NPBC) patterns in young Tanzanian HIV‐exposed infants and to analyse the influence of maternal NPBC and of the infant's HIV status on the NPBC pattern.MethodsLongitudinal cohort study of neonates born to HIV‐infected mothers visiting Kilimanjaro Christian Medical Centre, Tanzania, between 2005 and 2009. Demographic and clinical data and nasopharyngeal bacterial cultures were obtained at the age of 6 weeks, 3 and 6 months, and at one time point, a paired mother–infant nasopharyngeal swab was taken.ResultsFour hundred and twenty‐two swabs were taken from 338 eligible infants. At 6 weeks of age, colonisation rates were 66% for Staphylococcus aureus, 56% for Streptococcus pneumoniae, 50% for Moraxella catarrhalis and 14% for Haemophilus influenzae. Colonisation with S. aureus diminished over time and was more common in HIV‐infected infants. S. pneumoniae and H. influenzae colonisation rose over time and was more prevalent in HIV‐uninfected children. Co‐colonisation of S. pneumoniae with H. influenzae or M. catarrhalis was mostly noticed in HIV‐infected infants. S. pneumoniae and M.catarrhalis colonisation of the mother was a risk factor for colonisation in HIV‐uninfected infants, while maternal S. aureus colonisation was a risk factor for colonisation in HIV‐infected infants. Among the 104 S. pneumoniae isolates, 19F was most prevalent, and 57 (55%) displayed capsular serotypes represented in the 13‐valent pneumococcal conjugate vaccine.ConclusionsNPBC was common in Tanzanian HIV‐exposed infants. The significant prevalence of pneumococcal vaccine serotypes colonising this paediatric population justifies the use of the 13‐valent pneumococcal vaccine to reduce the burden of pneumococcal invasive disease.
Characterization of various blood and graft sources: a prospective series
Authors: Chevallier Patrice , Robillard Nelly , Illiaquer Marina , Esbelin Julie , Mohty Mohamad , Bodin‐Bressollette Celine , Guillaume Thierry , Stocco Veronique , Auffray Fabienne , Derenne Sophie , Planche Lucie , Bene Marie‐Christine , Imbert‐Marcille Berthe‐Marie 
Published: January 2013

BackgroundStudies comparing cell components of blood and graft sources are very scarce. We present here a thorough study examining the cellular content of various sources of blood and cell therapy products.Study Design and MethodsWe have prospectively compared by fluorescence‐activated cell sorting analyses the cellular composition of three blood sources on the one hand—peripheral blood (PB; n = 10) versus granulocyte–colony‐stimulating factor (G‐CSF)‐mobilized PB (GCSF‐PB, n = 10) versus cord blood (CB, n = 10)—and of three graft sources on the other hand—unmanipulated bone marrow (uBM, n = 5) versus leukapheresis product (LP, n = 10) versus thawed CB graft (n = 7).ResultsAll median absolute numbers of cell subsets were found significantly higher in GCSF‐PB and LP, except for monocytoid dendritic cells (mDCs) in CB and uBM. The most impressive results were the median quantities of memory T and B lymphocytes but also of plasmacytoid DCs (pDCs) contained in LP compared to thawed CB graft, with ratios of 375, 318, and 247, respectively. The proportions of naive and CD4+/CD8− T cells, transitional B cells, and CD5+ and naive B lymphocytes were found significantly higher in CB samples while the proportions of mDCs and pDCs were found significantly lower.ConclusionOur study shows strong differences in terms of quantitative and qualitative cellular composition between several blood or graft sources, possibly explaining the differences observed in terms of outcomes after transplant.
Inactivation of Plasmodium spp. in plasma and platelet concentrates using riboflavin and ultraviolet light
Authors: Keil Shawn D. , Kiser Patti , Sullivan James J. , Kong Amy S. , Reddy Heather L. , Avery Anne , Goodrich Raymond P. 
Published: January 2013

BackgroundPhotochemical treatment of blood products could help prevent transfusion‐transmitted malaria and reduce the need for donor deferrals. In this study we evaluated the effectiveness of riboflavin and ultraviolet (UV) light against both Plasmodium falciparum, which causes the most severe form of human malaria, and Plasmodium yoelii, an in vivo murine model for malaria.Study Design and MethodsPlasma and platelet (PLT) concentrates were inoculated with either P. falciparum– or P. yoelii–infected red blood cells (RBCs). Aliquots from each unit were collected after inoculation, after addition of riboflavin, and after treatment. In vitro P. falciparum growth was assessed using thin blood films of duplicate samples at 24, 48, 72, and 96 hours. P. yoelii parasitemia was followed in mice for 14 days postinoculation.ResultsIn the in vitro studies, the mean P. falciparum parasitemia increased 12‐ to 19‐fold in pretreatment samples, both before and after addition of riboflavin, after 96‐hour culture. Few parasites were observed in Mirasol‐treated units at 24 hours; those that were observed were degenerating. Through the remainder of the 96‐hour culture period, cultures of treated samples were negative. In the in vivo study, mouse plasma containing P. yoelii–infected RBCs had a mean starting titer of 4.6 log mouse infectious dose 50%/mL. No infectious parasite was detected in treated samples.ConclusionTreatment with riboflavin and UV light was effective at reducing viable P. falciparum in both PLT and plasma products by at least 3.2 logs. Additionally, an at least 4.4‐log reduction was observed with P. yoelii.
Tonic inhibition sets the state of excitability in olfactory bulb granule cells
Authors: Labarrera Christina , London Michael , Angelo Kamilla 
Published: January 2013

Key points
Granule cells are the main source of inhibition in the olfactory bulb (i.e. the first station of odour processing in the mammalian brain), but very little is known about the inhibition that acts upon them.
Using in vivo whole cell patch clamp recordings in anaesthetized mice we report the following new findings:
Abstract  GABAergic granule cells (GCs) regulate, via mitral cells, the final output from the olfactory bulb to piriform cortex and are central for the speed and accuracy of odour discrimination. However, little is known about the local circuits in which GCs are embedded and how GCs respond during functional network activity. We recorded inhibitory and excitatory currents evoked during a single sniff‐like odour presentation in GCs in vivo. We found that synaptic excitation was extensively activated across cells, whereas phasic inhibition was rare. Furthermore, our analysis indicates that GCs are innervated by a persistent firing of deep short axon cells that mediated the inhibitory evoked responses. Blockade of GABAergic synaptic input onto GCs revealed a tonic inhibitory current mediated by furosemide‐sensitive GABAA receptors. The average current associated with this tonic GABAergic conductance was 3‐fold larger than that of phasic inhibitory postsynaptic currents. We show that the pharmacological blockage of tonic inhibition markedly increased the occurrence of supra‐threshold responses during an odour‐stimulated sniff. Our findings suggest that GCs mediate recurrent or lateral inhibition, depending on the ambient level of extracellular GABA.
Comparison of
In Vitro
Antifungal Activities of Efinaconazole and Currently Available Antifungal Agents against a Variety of Pathogenic Fungi Associated with Onychomycosis
Authors: Jo Siu William J. , Tatsumi Yoshiyuki , Senda Hisato , Pillai Radhakrishnan , Nakamura Takashi , Sone Daisuke , Fothergill Annette 
Published: January 2013

ABSTRACT

Onychomycosis is a common fungal nail infection in adults that is difficult to treat. The
in vitro
antifungal activity of efinaconazole, a novel triazole antifungal, was evaluated in recent clinical isolates of
Trichophyton rubrum
,
Trichophyton mentagrophytes
, and
Candida albicans
, common causative onychomycosis pathogens. In a comprehensive survey of 1,493 isolates, efinaconazole MICs against
T. rubrum
and
T. mentagrophytes
ranged from ≤0.002 to 0.06 μg/ml, with 90% of isolates inhibited (MIC
90
) at 0.008 and 0.015 μg/ml, respectively. Efinaconazole MICs against 105
C. albicans
isolates ranged from ≤0.0005 to >0.25 μg/ml, with 50% of isolates inhibited (MIC
50
) by 0.001 and 0.004 μg/ml at 24 and 48 h, respectively. Efinaconazole potency against these organisms was similar to or greater than those of antifungal drugs currently used in onychomycosis, including amorolfine, ciclopirox, itraconazole, and terbinafine. In 13
T. rubrum
toenail isolates from onychomycosis patients who were treated daily with topical efinaconazole for 48 weeks, there were no apparent increases in susceptibility, suggesting low potential for dermatophytes to develop resistance to efinaconazole. The activity of efinaconazole was further evaluated in another 8 dermatophyte, 15 nondermatophyte, and 10 yeast species (a total of 109 isolates from research repositories). Efinaconazole was active against
Trichophyton
,
Microsporum
,
Epidermophyton
,
Acremonium
,
Fusarium
,
Paecilomyces
,
Pseudallescheria
,
Scopulariopsis
,
Aspergillus
,
Cryptococcus
,
Trichosporon
, and
Candida
and compared favorably to other antifungal drugs. In conclusion, efinaconazole is a potent antifungal with a broad spectrum of activity that may have clinical applications in onychomycosis and other mycoses.
Phylogenetic Analysis of Chromosomally Determined Qnr and Related Proteins
Authors: Jacoby George A. , Hooper David C. 
Published: January 2013

ABSTRACT

qnr
genes were discovered on plasmids by their ability to reduce quinolone susceptibility, but homologs can be found in the genomes of at least 92 Gram-negative, Gram-positive, and strictly anaerobic bacterial species. The related pentapeptide repeat protein-encoding
mfpA
gene is present in the genome of at least 19 species of
Mycobacterium
and 10 other
Actinobacteria
species. The native function of these genes is not yet known.
Role of Matrix β-1,3 Glucan in Antifungal Resistance of Non-albicans Candida Biofilms
Authors: Mitchell K. F. , Taff H. T. , Cuevas M. A. , Reinicke E. L. , Sanchez H. , Andes D. R. 
Published: January 2013

ABSTRACT

Candida
biofilm infections pose an increasing threat in the health care setting due to the drug resistance associated with this lifestyle. Several mechanisms underlie the resistance phenomenon. In
Candida albicans
, one mechanism involves drug impedance by the biofilm matrix linked to β-1,3 glucan. Here, we show this is important for other
Candida
spp. We identified β-1,3 glucan in the matrix, found that the matrix sequesters antifungal drug, and enhanced antifungal susceptibility with matrix β-1,3 glucan hydrolysis.
Cryptococcus neoformans Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses
Authors: O'Meara Teresa R. , Holmer Stephanie M. , Selvig Kyla , Dietrich Fred , Alspaugh J. Andrew 
Published: January 2013

ABSTRACTInfectious microorganisms often play a role in modulating the immune responses of their infected hosts. We demonstrate thatCryptococcus neoformanssignals through the Rim101 transcription factor to regulate cell wall composition and the host-pathogen interface. In the absence of Rim101,C. neoformansexhibits an altered cell surface in response to host signals, generating an excessive and ineffective immune response that results in accelerated host death. This host immune response to therim101Δ mutant strain is characterized by increased neutrophil influx into the infected lungs and an altered pattern of host cytokine expression compared to the response to wild-type cryptococcal infection. To identify genes associated with the observed phenotypes, we performed whole-genome RNA sequencing experiments under capsule-inducing conditions. We defined the downstream regulon of the Rim101 transcription factor and determined potential cell wall processes involved in the capsule attachment defects and altered mechanisms of virulence in therim101Δ mutant. The cell wall generates structural stability for the cell and allows the attachment of surface molecules such as capsule polysaccharides. In turn, the capsule provides an effective mask for the immunogenic cell wall, shielding it from recognition by the host immune system.IMPORTANCECryptococcus neoformansis an opportunistic human pathogen that is a significant cause of death in immunocompromised individuals. There are two major causes of death due to this pathogen: meningitis due to uncontrolled fungal proliferation in the brain in the face of a weakened immune system and immune reconstitution inflammatory syndrome characterized by an overactive immune response to subclinical levels of the pathogen. In this study, we examined howC. neoformansuses the conserved Rim101 transcription factor to specifically remodel the host-pathogen interface, thus regulating the host immune response. These studies explored the complex ways in which successful microbial pathogens induce phenotypes that ensure their own survival while simultaneously controlling the nature and degree of the associated host response.
Kinetics of Facultative Heterochromatin and Polycomb Group Protein Association with the Herpes Simplex Viral Genome during Establishment of Latent Infection
Authors: Cliffe Anna R. , Coen Donald M. , Knipe David M. 
Published: January 2013

ABSTRACT
The herpes simplex virus (HSV) genome is associated with heterochromatic histone modifications, including trimethylation of the lysine 27 residue of histone H3 (H3K27me3), during latent infection of neurons. Here we have examined the kinetics of general chromatin and H3K27me3 association with the viral genome during establishment of latent infection. Using both wild-type virus and a mutant virus that is unable to undergo replication in neurons, we found that histone H3 associates with viral gene promoters by 7 days postinfection (dpi). Levels of H3K27me3 were low at 7 dpi but increased dramatically by 14 dpi. Hence, general chromatin association and/or other factors may play a key role(s) in the initial silencing of lytic genes, and H3K27me3 may play a role in further suppression of the genome and/or the maintenance of latency. A component of Polycomb repressive complex 2 (PRC2), which mediates the addition of K27me3 to histone H3 (Suz12), was also recruited by 14 dpi. We have shown previously that the levels of H3K27me3 during latent infection are increased in the presence of the latency-associated transcript (LAT). However, the initial targeting of PRC2 was not found to be dependent on the LAT. We found that a component of the PRC1 complex (Bmi1), which binds to H3K27me3, was not enriched at promoters found previously to be enriched for H3K27me3. Our results are consistent with (i) chromatinization of viral DNA or other mechanisms causing the initial silencing of HSV lytic genes and (ii) facultative heterochromatin maintaining that silencing during latent infection of neurons.

IMPORTANCE
The human pathogen herpes simplex virus (HSV) hides for the lifetime of the host in peripheral neurons. The mechanism by which HSV is able to shut off its gene expression and persist in neurons is not known. Here we show that the HSV DNA first associates with histone H3, with later recruitment of Polycomb repressor complex 2 (PRC2) and trimethylation of the lysine 27 residue of histone H3 (H3K27me3), a modification associated with heterochromatin. This work indicates that the initial silencing of HSV gene expression is not correlated with enrichment of H3K27me3 and that PRC2 may be recruited to already-silenced genes to further silence gene expression and/or maintain gene silencing. We demonstrate that recruitment of PRC2 is not dependent upon expression of the noncoding HSV latency-associated transcripts, indicating the presence of unknown triggers for PRC2 recruitment during the establishment of latent infection.
Development and validation of the Bowel Cleansing Impact Review (BOCLIR)
Authors: Doward Lynda , Wilburn Jeanette , McKenna Stephen P , Leicester Roger , Epstein Owen , Hedley Vicki , Korala Sanjeeva , Twiss James , Jones Deborah , Geraint Mike 
Published: January 2013

ObjectiveAcceptability and tolerability of bowel cleansers influence whether patients are able to complete the prescribed dose and, consequently, the quality of the cleansing achieved. No standardised means of assessing patients’ experience of using bowel cleansing is currently available. The aim of the study was to develop the Bowel Cleansing Impact Review (BOCLIR) to assess patient response to bowel cleansing products.DesignContent was derived from qualitative interviews. Face and content validity were assessed via cognitive-debriefing interviews. Finally, patients completed the BOCLIR and a demographic questionnaire. Item response theory (Rasch analysis) was employed for item reduction and assessment of unidimensionality. Internal consistency and construct validity were also assessed.ResultsAnalysis of 40 interviews resulted in the production of three scales; patient satisfaction, symptomatic impact and activity limitations. Scales were designed to be used alone or together. 19 debriefing interviews demonstrated BOCLIR acceptability, relevance and ease of completion. The validation survey involved 166 patients (52% male, mean (SD) age 54.3 (15.2) years). After misfitting and redundant items were removed all scales fit the Rasch model confirming their unidimensionality. Cronbach's α-coefficients were high (0.77–0.94) indicating good internal consistency. Scores on the BOCLIR were related to patients’ willingness to use the product in future and ease of drinking the full preparation (p<0.01 for each scale).ConclusionsThe BOCLIR is a new measure consisting of three unidimensional scales (satisfaction, symptoms and activity limitations) with good psychometric and scaling properties. The BOCLIR will allow accurate assessment of patients’ response to bowel cleansing preparations.
Geographical disparities in child mortality in the rural areas of Iran: 16-years trend
Authors: Moradi-Lakeh Maziar , Bijari Bita , Namiranian Nasim , Olyaeemanesh Ali-Reza , Khosravi Ardeshir 
Published: January 2013

PurposeWe performed this study to assess the trend of geographical disparities between rural areas located in the catchment areas of 41 medical universities in Iran from 1993 to 2008. We evaluated four indicators including rates for neonatal mortality (NMR), infant mortality (IMR), under-5 mortality (U5MR) and crude death (CDR).MethodsWe got about 656 university-year data points for each of the indicators (missing data <0.5%). The people under assessment were between 16.7 (in 1993) to 20.1 million (in 2008). We measured disparities through the calculation of index of disparities (IDisp) and assessed the trends using the Cuzick non-parametric test for trend.FindingsExcept for the increasing trend of CDR (Z=+2.83, p=0.005), the others had decreasing trends: NMR (Z=−3.23, p=0.001), IMR (Z=−3.84, p<0.001) and U5MR (Z=−3.84, p<0.001). The IDisptrends of IMR (Z=−2.2, p=0.027) and U5MR (Z=−2.84, p=0.005) were decreasing, while the IDisptrends for NMR (Z=+2.19, p=0.028) and CDR (Z=+2.39, p=0.017) were increasing.ConclusionsThe results show that at least for IMR and U5MR, in addition to improvement in average national levels, the geographical disparities have decreased. In the cases of NMR and CDR, inspite of the improvements in national levels, the trends of health disparities are not as good. We need to use strategies to provide more specialised care fairly in addition to primary healthcare to reduce disparities in CDR and NMR and influence them more.
A Novel Inhibitor of STAT3 Homodimerization Selectively Suppresses STAT3 Activity and Malignant Transformation
Authors: Zhang Xiaolei , Sun Ying , Pireddu Roberta , Yang Hua , Urlam Murali K. , Lawrence Harshani R. , Guida Wayne C. , Lawrence Nicholas J. , Sebti Saïd M. 
Published: January 2013

Abstract
STAT3–STAT3 dimerization, which involves reciprocal binding of the STAT3-SH2 domain to phosphorylated tyrosine-705 (Y-705), is required for STAT3 nuclear translocation, DNA binding, and transcriptional regulation of downstream target genes. Here, we describe a small molecule S3I-1757 capable of disrupting STAT3–STAT3 dimerization, activation, and malignant transforming activity. Fluorescence polarization assay and molecular modeling suggest that S3I-1757 interacts with the phospho-Y-705–binding site in the SH2 domain and displaces fluorescein-labeled GpYLPQTV phosphotyrosine peptide from binding to STAT3. We generated hemagglutinin (HA)-tagged STAT3 and FLAG-tagged STAT3 and showed using coimmunoprecipitation and colocalization studies that S3I-1757 inhibits STAT3 dimerization and STAT3–EGF receptor (EGFR) binding in intact cells. Treatment of human cancer cells with S3I-1757 (but not a closely related analog, S3I-1756, which does not inhibit STAT3 dimerization), inhibits selectively the phosphorylation of STAT3 over AKT1 and ERK1/2 (MAPK3/1), nuclear accumulation of P-Y705-STAT3, STAT3–DNA binding, and transcriptional activation and suppresses the expression levels of STAT3 target genes, such as Bcl-xL (BCL2L1), survivin (BIRC5), cyclin D1 (CCND1), and matrix metalloproteinase (MMP)-9. Furthermore, S3I-1757, but not S3I-1756, inhibits anchorage-dependent and -independent growth, migration, and invasion of human cancer cells, which depend on STAT3. Finally, STAT3-C, a genetically engineered mutant of STAT3 that forms a constitutively dimerized STAT3, rescues cells from the effects of S3I-1757 inhibition. Thus, we have developed S3I-1757 as a STAT3–STAT3 dimerization inhibitor capable of blocking hyperactivated STAT3 and suppressing malignant transformation in human cancer cells that depend on STAT3. Cancer Res; 73(6); 1922–33. ©2012 AACR.
Cyclooxygenase-2 Generates the Endogenous Mutagen trans-4-Hydroxy-2-nonenal in Enterococcus faecalis–Infected Macrophages
Authors: Wang Xingmin , Allen Toby D. , Yang Yonghong , Moore Danny R. , Huycke Mark M. 
Published: January 2013

Abstract
Infection of macrophages by the human intestinal commensal Enterococcus faecalis generates DNA damage and chromosomal instability in mammalian cells through bystander effects. These effects are characterized by clastogenesis and damage to mitotic spindles in target cells and are mediated, in part, by trans-4-hydroxy-2-nonenal (4-HNE). In this study, we investigated the role of COX and lipoxygenase (LOX) in producing this reactive aldehyde using E. faecalis–infected macrophages and interleukin (IL)-10–knockout mice colonized with this commensal. 4-HNE production by E. faecalis–infected macrophages was significantly reduced by COX and LOX inhibitors. The infection of macrophages led to decreased Cox1 and Alox5 expression whereas COX-2 and 4-HNE increased. Silencing Alox5 and Cox1 with gene-specific siRNAs had no effect on 4-HNE production. In contrast, silencing Cox2 significantly decreased 4-HNE production by E. faecalis–infected macrophages. Depleting intracellular glutathione increased 4-HNE production by these cells. Next, to confirm COX-2 as a source for 4-HNE, we assayed the products generated by recombinant human COX-2 and found 4-HNE in a concentration-dependent manner using arachidonic acid as a substrate. Finally, tissue macrophages in colon biopsies from IL-10–knockout mice colonized with E. faecalis were positive for COX-2 by immunohistochemical staining. This was associated with increased staining for 4-HNE protein adducts in surrounding stroma. These data show that E. faecalis, a human intestinal commensal, can trigger macrophages to produce 4-HNE through COX-2. Importantly, it reinforces the concept of COX-2 as a procarcinogenic enzyme capable of damaging DNA in target cells through bystander effects that contribute to colorectal carcinogenesis. Cancer Prev Res; 6(3); 206–16. ©2013 AACR.