bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Lactation on Post‐Partum Uterine Involution in Holstein Dairy Cows
Authors: Scully S , Maillo V , Duffy P , Kelly AK , Crowe MA , Rizos D , Lonergan P 
Published: May 2013

ContentsThe objective was to examine the effect of lactation on uterine involution in post‐partum dairy cows. Holstein primiparous cows were used (n = 19, mean age: 3.9 ± 0.1 years). At calving, cows were randomly assigned to one of two treatment groups, lactating (n = 11) or non‐lactating (i.e. dried off at calving, n = 8). Examination of the reproductive tract was carried out by ultrasonography twice weekly until week 7 post‐partum. Blood samples were collected twice weekly for the analysis of progesterone to indicate the resumption of cyclicity and metabolites indicative of energy status. Uterine involution was assessed in terms of size of the uterine horns, uterine body diameter and uterine fluid volume as assessed by the amount of non‐echogenic material measured by ultrasound and position of the uterus. Vaginal mucous score was taken on day 28 post‐partum for the assessment of uterine inflammation. Resumption of cyclicity (serum progesterone > 1 ng/ml) had occurred in both groups on average by day 21 post‐partum. Concentrations of non‐esterified fatty acids and beta‐hydroxybutyrate were higher, whereas concentrations of glucose, insulin and IGF‐1 were lower (p < 0.05) in lactating compared to non‐lactating cows. Lactating cows had a smaller mean uterine body diameter (p < 0.05) than non‐lactating cows from days 28 to 42 post‐partum (day 28: 20.2 ± 1.3 vs 24.9 ± 1.5 mm, respectively) and had a lower mean uterine fluid volume up to day 49 (p < 0.05). By day 49, there was no difference in uterine diameter (15.2 ± 1.8 vs 15.2 ± 1.6 mm) or uterine fluid volume (0.11 ± 0.38 vs 0.18 ± 0.46) between lactating and non‐lactating cows, respectively. Vaginal mucous score revealed no evidence of uterine inflammation in either group. In conclusion, while lactation induced significant alterations in metabolic status, it did not have a major effect on the rate of uterine involution as defined in this study.
Polymorphism in the Interleukin‐7 Receptor‐alpha and Outcome after Allogeneic Hematopoietic Cell Transplantation with Matched Unrelated Donor
Authors: Shamim Z. , Spellman S. , Haagenson M. , Wang T. , Lee S. J. , Ryder L. P. , Müller K. 
Published: May 2013

AbstractInterleukin‐7 (IL‐7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α‐chain of the IL‐7R is polymorphic with the existence of SNPs that give rise to non‐synonymous amino acid substitutions. We previously found an association between donor genotypes and increased treatment‐related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation (HCT). Some studies have confirmed an association between rs6897932C and multiple sclerosis. In this study, we evaluated the prognostic significance of IL‐7Rα SNP genotypes in 590‐recipient/donor pairs that received HLA‐matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis. The Tallele of rs6897932 was suggestive of an association with increased frequency of relapse by univariate analysis (P = 0.017) and multivariate analysis (P = 0.015). In conclusion, this study provides further evidence of a role of the IL‐7 pathway and IL‐7Rα SNPs in HCT.
Epstein–Barr virus (EBV) load in cerebrospinal fluid and peripheral blood of patients with EBV‐associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation
Authors: Liu Q.‐F. , Ling Y.‐W. , Fan Z.‐P. , Jiang Q.‐L. , Sun J. , Wu X.‐L. , Zhao J. , Wei Q. , Zhang Y. , Yu G.‐P. , Wu M.‐Q. , Feng R. 
Published: May 2013

AbstractBackgroundTo evaluate the diagnostic and prognostic utility of monitoring the Epstein–Barr virus (EBV) load in the cerebrospinal fluid (CSF) and peripheral blood for the patients with EBV‐associated central nervous system (CNS) diseases after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), 172 patients undergoing allo‐HSCT were enrolled in the study.MethodsThe EBV DNA levels of blood were monitored regularly in recipients of transplants for 3 years post transplantation. The EBV DNA levels of CSF were monitored in patients with EBV‐associated CNS diseases before the treatment and at different points following the treatment.ResultsPost‐transplant EBV‐associated diseases developed in 27 patients, including 12 patients with EBV‐associated CNS diseases. The 3‐year cumulative incidences of EBV‐associated diseases and EBV‐associated CNS diseases were 19.5 ± 3.5% and 8.6 ± 2.4%, respectively. Patients with EBV‐associated diseases showed higher loads of EBV DNA in their blood compared with patients with EBV DNA‐emia. No difference was seen between the EBV DNA levels of blood in patients with CNS involvement and patients without CNS involvement. The EBV DNA loads of blood increased 3–14 days before the clinical manifestations of EBV‐associated diseases emerged. The EBV DNA loads of CSF were higher than that of blood in patients with EBV‐associated CNS diseases. In 12 patients with EBV‐associated CNS diseases, EBV DNA levels were declining in both blood and CSF with the control of diseases, and the EBV DNA loads of CSF decreased faster than that of blood in 5 patients who responded to treatment, and the EBV DNA levels of CSF increased in 5 patients who were unresponsive to treatment. On multivariate analysis, the use of anti‐thymocyte globulin and intensified conditioning regimens were independent risk factors for EBV‐associated diseases and EBV‐associated CNS diseases.ConclusionsEBV‐associated CNS diseases are not rare after allo‐HSCT. The EBV DNA loads of CSF could act as an important indicator, but the EBV DNA loads of blood could not, for the diagnosis, prognosis, and therapeutic evaluation of EBV‐associated CNS diseases.
Independent control of reciprocal and lateral inhibition at the axon terminal of retinal bipolar cells
Authors: Tanaka Masashi , Tachibana Masao 
Published: May 2013

Key points
Two different forms of feedback inhibition, reciprocal and lateral inhibition, are ubiquitously observed throughout the nervous system.
In the retina, the axon terminal of bipolar cells receives reciprocal and lateral GABAergic inhibitory inputs from amacrine cells, but how a variety of visual inputs activate each inhibition remains largely unexplored.
Here we show that each inhibition is independently controlled by different types of bipolar cell outputs; reciprocal inhibition is driven by strong output from each bipolar cell, whereas lateral inhibition is driven by outputs from multiple bipolar cells even when each output is weak.
Composition of transmitter receptors and localization of Na+ channels were different between two inhibitory pathways, suggesting that different amacrine cells may mediate each inhibition.
The dual feedback inhibition can cooperatively reduce bipolar cell outputs in response to various visual inputs without deteriorating the quality of visual signals, thereby contributing to efficient signal transmission in the visual pathway.
Abstract  Bipolar cells (BCs), the second order neurons in the vertebrate retina, receive two types of GABAergic feedback inhibition at their axon terminal: reciprocal and lateral inhibition. It has been suggested that two types of inhibition may be mediated by different pathways. However, how each inhibition is controlled by excitatory BC output remains to be clarified. Here, we applied single/dual whole cell recording techniques to the axon terminal of electrically coupled BCs in slice preparation of the goldfish retina, and found that each inhibition was regulated independently. Activation voltage of each inhibition was different: strong output from a single BC activated reciprocal inhibition, but could not activate lateral inhibition. Outputs from multiple BCs were essential for activation of lateral inhibition. Pharmacological examinations revealed that composition of transmitter receptors and localization of Na+ channels were different between two inhibitory pathways, suggesting that different amacrine cells may mediate each inhibition. Depending on visual inputs, each inhibition could be driven independently. Model simulation showed that reciprocal and lateral inhibition cooperatively reduced BC outputs as well as background noise, thereby preserving high signal‐to‐noise ratio. Therefore, we conclude that excitatory BC output is efficiently regulated by the dual operating mechanisms of feedback inhibition without deteriorating the quality of visual signals.
Epidemiology of Isoniazid Resistance Mutations and Their Effect on Tuberculosis Treatment Outcomes
Authors: Huyen Mai N. T. , Cobelens Frank G. J. , Buu Tran N. , Lan Nguyen T. N. , Dung Nguyen H. , Kremer Kristin , Tiemersma Edine W. , van Soolingen Dick 
Published: May 2013

ABSTRACT

Isoniazid resistance is highly prevalent in Vietnam. We investigated the molecular and epidemiological characteristics and the association with first-line treatment outcomes of the main isoniazid resistance mutations in
Mycobacterium tuberculosis
in codon 315 of the
katG
and in the promoter region of the
inhA
gene.
Mycobacterium tuberculosis
strains with phenotypic resistance to isoniazid from consecutively diagnosed smear-positive tuberculosis patients in rural Vietnam were subjected to Genotype MTBDR
plus
testing to identify
katG
and
inhA
mutations. Treatment failure and relapse were determined by sputum culture. In total, 227 of 251 isoniazid-resistant strains (90.4%) had detectable mutations: 75.3% in
katG
codon 315 (
katG
315
) and 28.2% in the
inhA
promoter region.
katG
315
mutations were significantly associated with pretreatment resistance to streptomycin, rifampin, and ethambutol but not with the Beijing genotype and predicted both unfavorable treatment outcome (treatment failure or death) and relapse;
inhA
promoter region mutations were only associated with resistance to streptomycin and relapse. In tuberculosis patients,
M. tuberculosis
katG
315
mutations but not
inhA
mutations are associated with unfavorable treatment outcome.
inhA
mutations do, however, increase the risk of relapse, at least with treatment regimens that contain only isoniazid and ethambutol in the continuation phase.
Potentiation of Azole Antifungals by 2-Adamantanamine
Authors: LaFleur Michael D. , Sun Lingmei , Lister Ida , Keating John , Nantel Andre , Long Lisa , Ghannoum Mahmoud , North Jeffrey , Lee Richard E. , Coleman Ken , Dahl Thomas , Lewis Kim 
Published: May 2013

ABSTRACT

Azoles are among the most successful classes of antifungals. They act by inhibiting α-14 lanosterol demethylase in the ergosterol biosynthesis pathway. Oropharyngeal candidiasis (OPC) occurs in about 90% of HIV-infected individuals, and 4 to 5% are refractory to current therapies, including azoles, due to the formation of resistant biofilms produced in the course of OPC. We reasoned that compounds affecting a different target may potentiate azoles to produce increased killing and an antibiofilm therapeutic. 2-Adamantanamine (AC17) was identified in a screen for compounds potentiating the action of miconazole against biofilms of
Candida albicans
. AC17, a close structural analog to the antiviral amantadine, did not affect the viability of
C. albicans
but caused the normally fungistatic azoles to become fungicidal. Transcriptome analysis of cells treated with AC17 revealed that the ergosterol and filamentation pathways were affected. Indeed, cells exposed to AC17 had decreased ergosterol contents and were unable to invade agar.
In vivo
, the combination of AC17 and fluconazole produced a significant reduction in fungal tissue burden in a guinea pig model of cutaneous candidiasis, while each treatment alone did not have a significant effect. The combination of fluconazole and AC17 also showed improved efficacy (
P
value of 0.018) compared to fluconazole alone when fungal lesions were evaluated. AC17 is a promising lead in the search for more effective antifungal therapeutics.
MBX-500 Is Effective for Treatment of Clostridium difficile Infection in Gnotobiotic Piglets
Authors: Steele Jennifer , Zhang Quanshun , Beamer Gillian , Butler Michelle , Bowlin Terry , Tzipori Saul 
Published: May 2013

ABSTRACT

The novel antibiotic MBX-500, dosed at 100, 200, or 400 mg/kg twice daily for 7 days, was evaluated for the treatment of
Clostridium difficile
infection (CDI) in the gnotobiotic pig model. MBX-500 increased survival at all doses and at high doses improved clinical signs and reduced lesion severity, similar to vancomycin. Our results show that MBX-500 is an effective antibiotic for the treatment of diarrhea associated with CDI and prevents severe systemic disease.
Identification and Mechanism of Action of the Plant Defensin NaD1 as a New Member of the Antifungal Drug Arsenal against Candida albicans
Authors: Hayes Brigitte M. E. , Bleackley Mark R. , Wiltshire Jennifer L. , Anderson Marilyn A. , Traven Ana , van der Weerden Nicole L. 
Published: May 2013

ABSTRACT

In recent decades, pathogenic fungi have become a serious threat to human health, leading to major efforts aimed at characterizing new agents for improved treatments. Promising in this context are antimicrobial peptides produced by animals and plants as part of innate immune systems. Here, we describe an antifungal defensin, NaD1, with activity against the major human pathogen
Candida albicans
, characterize the mechanism of killing, and identify protection strategies used by the fungus to survive defensin treatment. The mechanism involves interaction between NaD1 and the fungal cell surface followed by membrane permeabilization, entry into the cytoplasm, hyperproduction of reactive oxygen species, and killing induced by oxidative damage. By screening
C. albicans
mutant libraries, we identified that the high-osmolarity glycerol (HOG) pathway has a unique role in protection against NaD1, while several other stress-responsive pathways are dispensable. The involvement of the HOG pathway is consistent with induction of oxidative stress by NaD1. The HOG pathway has been reported to have a major role in protection of fungi against osmotic stress, but our data indicate that osmotic stress does not contribute significantly to the adverse effects of NaD1 on
C. albicans
. Our data, together with previous studies with human beta-defensins and salivary histatin 5, indicate that inhibition of the HOG pathway holds promise as a broad strategy for increasing the activity of antimicrobial peptides against
C. albicans
.
High-Throughput Screening of a Collection of Known Pharmacologically Active Small Compounds for Identification of Candida albicans Biofilm Inhibitors
Authors: Siles Samuel A. , Srinivasan Anand , Pierce Christopher G. , Lopez-Ribot José L. , Ramasubramanian Anand K. 
Published: May 2013

ABSTRACT

Candida albicans
is the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective against
C. albicans
biofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting of 1,200 off-patent drugs already approved by the Food and Drug Administration (FDA), the Prestwick Chemical Library, to identify inhibitors of
C. albicans
biofilm formation. According to their pharmacological applications that are currently known, we classified these bioactive compounds as antifungal drugs, as antimicrobials/antiseptics, or as miscellaneous drugs, which we considered to be drugs with no previously characterized antifungal activity. Using a 96-well microtiter plate-based high-content screening assay, we identified 38 pharmacologically active agents that inhibit
C. albicans
biofilm formation. These drugs were subsequently tested for their potency and efficacy against preformed biofilms, and we identified three drugs with novel antifungal activity. Thus, repurposing FDA-approved drugs opens up a valuable new avenue for identification and potentially rapid development of antifungal agents, which are urgently needed.
The Bordetella pertussis Type III Secretion System Tip Complex Protein Bsp22 Is Not a Protective Antigen and Fails To Elicit Serum Antibody Responses during Infection of Humans and Mice
Authors: Villarino Romero Rodrigo , Bibova Ilona , Cerny Ondrej , Vecerek Branislav , Wald Tomas , Benada Oldrich , Zavadilova Jana , Osicka Radim , Sebo Peter 
Published: May 2013

ABSTRACT

The type III secretion system (T3SS) of pathogenic bordetellae employs a self-associating tip complex protein Bsp22. This protein is immunogenic during infections by
Bordetella bronchiseptica
and could be used as a protective antigen to immunize mice against
B. bronchiseptica
challenge. Since low-passage clinical isolates of the human pathogen
Bordetella pertussis
produce a highly homologous Bsp22 protein (97% homology), we examined its vaccine and diagnostic potential. No Bsp22-specific antibodies were, however, detected in serum samples from 36 patients with clinically and serologically confirmed whooping cough disease (pertussis syndrome). Moreover, although the induction of Bsp22 secretion by the laboratory-adapted 18323 strain in the course of mice lung infection was observed, the
B. pertussis
18323-infected mice did not mount any detectable serum antibody response against Bsp22. Furthermore, immunization with recombinant Bsp22 protein yielded induction of high Bsp22-specific serum antibody titers but did not protect mice against an intranasal challenge with
B. pertussis
18323. Unlike for
B. bronchiseptica
, hence, the Bsp22 protein is nonimmunogenic, and/or the serum antibody response to it is suppressed, during
B. pertussis
infections of humans and mice.
Malaria-Associatedl-Arginine Deficiency Induces Mast Cell-Associated Disruption to Intestinal Barrier Defenses against Nontyphoidal Salmonella Bacteremia
Authors: Chau Jennifer Y. , Tiffany Caitlin M. , Nimishakavi Shilpa , Lawrence Jessica A. , Pakpour Nazzy , Mooney Jason P. , Lokken Kristen L. , Caughey George H. , Tsolis Renee M. , Luckhart Shirley 
Published: May 2013

ABSTRACTCoinfection with malaria and nontyphoidalSalmonellaserotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, developl-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal ofl-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasiveEscherichia coliNissle andSalmonella entericaserotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice withl-arginine orl-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation withl-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasingl-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans.
Fitness, Stress Resistance, and Extraintestinal Virulence in Escherichia coli
Authors: Bleibtreu Alexandre , Gros Pierre-Alexis , Laouénan Cédric , Clermont Olivier , Le Nagard Hervé , Picard Bertrand , Tenaillon Olivier , Denamur Erick 
Published: May 2013

ABSTRACT

The extraintestinal virulence of
Escherichia coli
is dependent on numerous virulence genes. However, there is growing evidence for a role of the metabolic properties and stress responses of strains in pathogenesis. We assessed the respective roles of these factors in strain virulence by developing phenotypic assays for measuring
in vitro
individual and competitive fitness and the general stress response, which we applied to 82 commensal and extraintestinal pathogenic
E. coli
strains previously tested in a mouse model of sepsis. Individual fitness properties, in terms of maximum growth rates in various media (Luria-Bertani broth with and without iron chelator, minimal medium supplemented with gluconate, and human urine) and competitive fitness properties, estimated as the mean relative growth rate per generation in mixed cultures with a reference fluorescent
E. coli
strain, were highly diverse between strains. The activity of the main general stress response regulator, RpoS, as determined by iodine staining of the colonies, H
2
O
2
resistance, and
rpoS
sequencing, was also highly variable. No correlation between strain fitness and stress resistance and virulence in the mouse model was found, except that the maximum growth rate in urine was higher for virulent strains. Multivariate analysis showed that the number of virulence factors was the only independent factor explaining the virulence in mice. At the species level, growth capacity and stress resistance are heterogeneous properties that do not contribute significantly to the intrinsic virulence of the strains.
Assessment of the validity of the English National Health Service Adult In-Patient Survey for use within individual specialties
Authors: Sullivan P J , Harris M L , Doyle C , Bell D 
Published: May 2013

BackgroundHealthcare improvement requires rigorous measurement. Patient experience is a key healthcare outcome and target for improvement. Its measurement requires psychometrically validated questionnaires. In England, the Adult In-Patient Survey (AIPS), which is validated for use across the entire acute inpatient population, is administered to unselected patients after discharge from National Health Service acute Trusts. The AIPS is reported at an organisational level, but subhospital level data are needed for local quality improvement; it is currently uncertain whether the AIPS retains validity in local specialty subgroups.MethodsWe analysed the results of AIPS for 2010 (n=56 931 returns) by specialty (medicine, surgery, orthopaedics, renal medicine, neurosurgery, obstetrics-gynaecology and oncology) to determine whether validity is retained at a suborganisational level.ResultsCriterion validity and internal consistency of AIPS were retained for most specialty subgroups. When small local samples were excluded, the results for Trust level specialty groups were similar over a 2-year period, indicating test stability. For oncology there was poor internal consistency in the ‘doctors’ domain and criterion validity, expressed as the relationship elements of experience and overall rating of care, was less than for other specialties.ConclusionsThe AIPS is suitable for use within many specialties, but our findings question some elements of validity for oncology inpatients. We recommend that future surveys are administered and reported by specialty, to inform local improvement and permit comparison of specialty units.