bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital morbidity due to paracoccidioidomycosis in Brazil (1998–2006)
Authors: Coutinho Ziadir Francisco , Wanke Bodo , Travassos Claudia , Oliveira Rosely Magalhães , Xavier Diego Ricardo , Coimbra Carlos E. A. 
Published: February 2015

AbstractObjectiveTo analyse hospital morbidity records due to paracoccidioidomycosis in Brazil, including its nationwide distribution in time and space, as well as key epidemiological and sociodemographic characteristics.MethodsDescriptive analysis of hospital morbidity records due to paracoccidioidomycosis covering the period January 1998 to December 2006. Hospital records were obtained from the Hospital Information System of the Brazilian Unified Health System (SIH/SUS).ResultsThere were 6732 hospitalisations (82% male) due to paracoccidioidomycosis in the period, representing 4.3 per 1.0 million inhabitants. Admissions due to this mycosis were recorded in 27% of the 5560 Brazilian municipalities, covering 35% of the country. Ten municipalities concentrated 52% of all admissions. The temporal distribution of admissions for paracoccidioidomycosis showed a slight increase. The geographical analysis showed two distinct patterns of the disease: (i) traditional areas of southern and south‐eastern regions, covering 60% of admissions, and (ii) a second pattern in northern Brazil revealed a transverse band of higher concentration with about 27% of admissions, particularly along the southern border of the Amazon region.ConclusionThis first nationwide analysis of hospitalisation due to paracoccidioidomycosis in Brazil shows that it is the most prevalent systemic mycosis in Brazil. Despite its importance, there are major deficits in its proper registry, diagnostics and treatment. The particular epidemiological and medical challenges of paracoccidioidomycosis will not be met while the disease continues to be perceived as an isolated infectious entity restricted to a few faraway regions of the globe.
Lateral suppressor and Goblet act in hierarchical order to regulate ectopic meristem formation at the base of tomato leaflets
Authors: Rossmann Susanne , Kohlen Wouter , Hasson Alice , Theres Klaus 
Published: February 2015

SummaryIn seed plants, new axes of growth are established by the formation of meristems, groups of pluripotent cells that maintain themselves and initiate the formation of lateral organs. After embryonic development, secondary shoot meristems form in the boundary zones between the shoot apical meristem and leaf primordia, the leaf axils. In addition, many plant species develop ectopic meristems at different positions of the plant body. In the compound tomato leaf, ectopic meristems can initiate at the base of leaflets, which are delimited by two distinct boundary zones, referred to as the proximal (PLB) and distal (DLB) leaflet boundaries. We demonstrate that the two leaflet boundaries differ from each other and that ectopic meristem formation is strictly limited to the DLB. Our data suggest that the DLB harbours a group of pluripotent cells that seems to be the launching pad for meristem formation. Initiation of these meristems is dependent on the activities of the transcriptional regulators Goblet (Gob) and Lateral suppressor (Ls), specifically expressed in the DLB. Gob and Ls act in hierarchical order, because Ls transcript accumulation is dependent on Gob activity, but not vice versa. Ectopic meristem formation at the DLB is also observed in other seed plants, like Cardamine pratensis, indicating that it is part of a widespread developmental program. Ectopic meristem formation leads to an increase in the number of buds, enhances the capacity for survival and opens the route to vegetative propagation.
The use of autologous platelet‐rich plasma in the orthopedic setting
Authors: Cohn Claudia S. , Lockhart Evelyn , McCullough J. Jeffrey 
Published: February 2015

BACKGROUNDAutologous platelet‐rich plasma (aPRP) is widely used with orthopedic patients to help treat injuries to tendons, cartilage, ligaments, and muscle. A comprehensive review of the literature was conducted to evaluate aPRP's efficacy and compare available methods. In addition, the production and administration of aPRP were explored.STUDY DESIGN AND METHODSA literature search was performed. Randomized controlled clinical trials (RCTs) in orthopedic procedures on adult patients were included and assessed for methodologic quality. The main outcomes were pain relief, increase in function, structural integrity, and “healing” based on various validated scales.RESULTSTwelve RCTs and one controlled cohort were included (four lateral epicondylitis, two chronic Achilles tendinopathy, two anterior cruciate ligament injury, and five rotator cuff injuries). Four trials reported some benefit from aPRP versus controls while eight trials found no benefit from aPRP applications versus control. One study had too many patients withdraw from the control arm for acceptable data interpretation. All protocols used a different aPRP formulation or method of delivery or application.CONCLUSIONSDespite its popularity, there are no standardized criteria that define aPRP. Different techniques yield wide variability in terms of platelet count and concentration. These variations make it difficult to compare clinical trials that use aPRP or draw conclusions concerning its clinical efficacy in orthopedic procedures. Blood bankers have experience in the production of standardized blood components. This expertise may be used to develop and implement protocols for the production and administration of aPRP, as well as quality control measures.
Evidence for recent evolution in an invasive species, Microstegium vimineum, Japanese stiltgrass
Authors: Ziska L H , Tomecek M B , Valerio M , Thompson J P 
Published: February 2015

SummaryThe establishment and spread of invasive plants are often associated with a ‘general‐purpose genotype’, with a corresponding high degree of phenotypic plasticity when introduced to a new environment. Evolutionary potential of invasive species following introduction should also be considered, however, as such changes can facilitate rapid range expansion. In this study, we utilised seed from three geographically distinct mid‐Atlantic populations of an invasive species, Microstegium vimineum (Japanese stiltgrass), to assess whether populations varied in their biomass and reproductive responses to light and nitrogen under neutral glasshouse conditions. To assess evolutionary adaptation, we quantified and correlated the abiotic environment from each collection location with the final biomass and seed production of that population under common glasshouse conditions. For M. vimineum, growth and reproductive responses to a common set of abiotic parameters (e.g. light) under these conditions indicated considerable phenotypic variation between and within populations. Interestingly, the degree of variation of seed production and final biomass among populations in the glasshouse was strongly correlated with growing season length and cumulative degree days recorded near each population location. These latter data indicated that M. vimineum, introduced into this region <100 years ago, may be undergoing adaptive evolution. Although additional populations of M. vimineum need to be examined, this study suggests that local evolutionary adaptation may be occurring rapidly and could, potentially, be an important aspect in the establishment and spread of this invasive species.
Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development andIn VitroandIn VivoEvaluation
Authors: Jain Keerti , Verma Ashwni Kumar , Mishra Prabhat Ranjan , Jain Narendra Kumar 
Published: February 2015

ABSTRACTThe present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR),1H nuclear magnetic resonance (1H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency,in vitrodrug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellularLeishmania donovaniamastigotes,in vivopharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pH-sensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagicL. donovaniamastigotes. In thein vitrocell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs.In vivostudies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity.
In Vitro
Activity of Five Quinolones and Analysis of the Quinolone Resistance-Determining Regions of
gyrA
,
gyrB
,
parC
, and
parE
in Ureaplasma parvum and Ureaplasma urealyticum Clinical Isolates from Perinatal Patients in Japan
Authors: Kawai Yasuhiro , Nakura Yukiko , Wakimoto Tetsu , Nomiyama Makoto , Tokuda Tsugumichi , Takayanagi Toshimitsu , Shiraishi Jun , Wasada Kenshi , Kitajima Hiroyuki , Fujita Tomio , Nakayama Masahiro , Mitsuda Nobuaki , Nakanishi Isao , Takeuchi Makoto , Yanagihara Itaru 
Published: February 2015

ABSTRACT

Ureaplasma
spp. cause several disorders, such as nongonococcal urethritis, miscarriage, and preterm delivery with lung infections in neonates, characterized by pathological chorioamnionitis in the placenta. Although reports on antibiotic resistance in
Ureaplasma
are on the rise, reports on quinolone-resistant
Ureaplasma
infections in Japan are limited. The purpose of this study was to determine susceptibilities to five quinolones of
Ureaplasma urealyticum
and
Ureaplasma parvum
isolated from perinatal samples in Japan and to characterize the quinolone resistance-determining regions in the
gyrA
,
gyrB
,
parC
, and
parE
genes. Out of 28 clinical
Ureaplasma
strains, we isolated 9 with high MICs of quinolones and found a single
parC
gene mutation, resulting in the change S83L. Among 158 samples, the ParC S83L mutation was found in 37 samples (23.4%), including 1 sample harboring a ParC S83L–GyrB P462S double mutant. Novel mutations of ureaplasmal ParC (S83W and S84P) were independently found in one of the samples. Homology modeling of the ParC S83W mutant suggested steric hindrance of the quinolone-binding pocket (QBP), and
de novo
prediction of peptide structures revealed that the ParC S84P may break/kink the formation of the α4 helix in the QBP. Further investigations are required to unravel the extent and mechanism of antibiotic resistance of
Ureaplasma
spp. in Japan.
Variability of Voriconazole Plasma Concentrations after Allogeneic Hematopoietic Stem Cell Transplantation: Impact of Cytochrome P450 Polymorphisms and Comedications on Initial and Subsequent Trough Levels
Authors: Gautier-Veyret Elodie , Fonrose Xavier , Tonini Julia , Thiebaut-Bertrand Anne , Bartoli Mireille , Quesada Jean-Louis , Bulabois Claude-Eric , Cahn Jean-Yves , Stanke-Labesque Françoise 
Published: February 2015

ABSTRACT

Voriconazole (VRC) plasma trough concentrations (
C
min
) are highly variable, and this could affect treatment efficacy and safety in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). We aimed to describe the intra- and interindividual variation of VRC
C
min
throughout the course of VRC therapy and to identify the determinants of this variation. Clinical data, medications, and VRC
C
min
(
n
= 308) of 33 AHSCT patients were retrospectively collected. Cytochrome P450 (CYP450) genotypes of CYP2C19, CYP3A4, and CYP3A5 patients were retrospectively determined before allografting, and a combined genetic score was calculated for each patient. The higher the genetic score, the faster the metabolism of the patient. The VRC
C
min
inter- and intraindividual coefficients of variation were 84% and 68%, respectively. The VRC dose (
D
) was correlated to VRC
C
min
(
r
= 0.412,
P
< 0.0001) only for oral administration. The administration route and the genetic score significantly affected the initial VRC
C
min
. Considering oral therapy, patients with a genetic score of <2 had higher initial VRC
C
min
/
D
than patients with a genetic score of >2 (
P
= 0.009). Subsequent VRC
C
min
remained influenced by the genetic score (
P
= 0.004) but were also affected by pump proton inhibitor comedication (
P
< 0.0001). The high variability of VRC
C
min
in AHSCT patients is partially explained by the route of administration, treatment with pump proton inhibitors, and the combined genetic score. This study suggests the interest in combined genetic score determination to individualize
a priori
the VRC dose and underlines the need for longitudinal therapeutic drug monitoring to adapt subsequent doses to maintain the VRC
C
min
within the therapeutic range.
In Vitro
Activity of RX-P873 against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii
Authors: Flamm Robert K. , Rhomberg Paul R. , Jones Ronald N. , Farrell David J. 
Published: February 2015

ABSTRACT

RX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shown
in vitro
activity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis.
Enterobacteriaceae
(657),
Pseudomonas aeruginosa
(200), and
Acinetobacter baumannii
(202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were tested
in vitro
by broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC
90
, 0.5 μg/ml) was >32-fold more active than ceftazidime and inhibited 97.1% and 99.5% of
Enterobacteriaceae
isolates at MIC values of ≤1 and ≤4 μg/ml, respectively. There were only three isolates with an MIC value of >4 μg/ml (all were indole-positive
Protea
). RX-P873 (MIC
50/90
, 2/4 μg/ml) was highly active against
Pseudomonas aeruginosa
isolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active against
P. aeruginosa
than tobramycin (MIC
90
, 2 μg/ml; 91.0% susceptible) and colistin (MIC
90
, 2 μg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC
90
, 8 μg/ml; 93.5% susceptible) and meropenem (MIC
90
, 8 μg/ml; 76.0% susceptible). RX-P873, the most active agent against
Acinetobacter baumannii
(MIC
90
, 1 μg/ml), was 2-fold more active than colistin (MIC
90
, 2 μg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC
90
, 4 μg/ml). This novel agent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.
Search for Novel Candidate Mutations for Metronidazole Resistance in Helicobacter pylori Using Next-Generation Sequencing
Authors: Binh Tran Thanh , Suzuki Rumiko , Trang Tran Thi Huyen , Kwon Dong Hyeon , Yamaoka Yoshio 
Published: February 2015

ABSTRACT

Metronidazole resistance is a key factor associated with
Helicobacter pylori
treatment failure. Although this resistance is mainly associated with mutations in the
rdxA
and
frxA
genes, the question of whether metronidazole resistance is caused by the inactivation of
frxA
alone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptible
H. pylori
strain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistant
H. pylori
strains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations in
frxA
(
hp0642
),
rdxA
(
hp0954
), and
rpsU
(
hp0562
) were confirmed by the Sanger method. The mutated sequence in
rdxA
was successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation in
rdxA
showed a low MIC (16 mg/liter), while those containing mutations in both
rdxA
and
frxA
showed a higher MIC (48 mg/liter). No transformants containing a single mutation in
frxA
or
rpsU
were obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations in
rdxA
are mainly associated with metronidazole resistance, and mutations in
frxA
are able to enhance
H. pylori
resistance only in the presence of
rdxA
mutations. Moreover, mutations in
rpsU
may play a role in metronidazole resistance.
Modification of the CpsA Protein Reveals a Role in Alteration of the Streptococcus agalactiae Cell Envelope
Authors: Rowe Hannah M. , Hanson Brett R. , Runft Donna L. , Lin Qian , Firestine Steve M. , Neely Melody N. 
Published: February 2015

ABSTRACT

The bacterial cell envelope is a crucial first line of defense for a systemic pathogen, with production of capsular polysaccharides and maintenance of the peptidoglycan cell wall serving essential roles in survival in the host environment. The LytR-CpsA-Psr proteins are important for cell envelope maintenance in many Gram-positive species. In this study, we examined the role of the extracellular domain of the CpsA protein of the zoonotic pathogen group B
Streptococcus
in capsule production and cell wall integrity. CpsA has multiple functional domains, including a DNA-binding/transcriptional activation domain and a large extracellular domain. We demonstrated that episomal expression of extracellularly truncated CpsA causes a dominant-negative effect on capsule production when expressed in the wild-type strain. Regions of the extracellular domain essential to this phenotype were identified. The dominant-negative effect could be recapitulated by addition of purified CpsA protein or a short CpsA peptide to cultures of wild-type bacteria. Changes in cell wall morphology were also observed when the dominant-negative peptide was added to wild-type cultures. Fluorescently labeled CpsA peptide could be visualized bound at the mid-cell region near the division septae, suggesting a novel role for CpsA in cell division. Finally, expression of truncated CpsA also led to attenuation of virulence in zebrafish models of infection, to levels below that of a
cpsA
deletion strain, demonstrating the key role of the extracellular domain in virulence of GBS.
Essential Engagement of Toll-Like Receptor 2 in Initiation of Early Protective Th1 Response against Rough Variants of Mycobacterium abscessus
Authors: Kim Jong-Seok , Kang Min-Jung , Kim Woo Sik , Han Seung Jung , Kim Hong Min , Kim Ho Won , Kwon Kee Woong , Kim So Jeong , Cha Seung Bin , Eum Seok-Yong , Koh Won-Jung , Cho Sang-Nae , Park Jong-Hwan , Shin Sung Jae 
Published: February 2015

ABSTRACT

Although
Mycobacterium abscessus
(
M. abscessus
) is becoming more prevalent in patients without overt immunodeficiency, little is known about the factors that contribute to disease susceptibility. This study was undertaken to investigate how Toll-like receptor 2 (TLR2) functionally contributes to the generation of protective immunity against
M. abscessus
in a morphotype-specific manner. We found that
Tlr2
−/−
mice were extremely susceptible to an intravenous (i.v.) model of infection by
M. abscessus
rough variants, displaying uncontrolled infection in the lungs and a significantly lower survival rate than with wild-type (WT) mice. This uncontrolled infection resulted from failures in the following processes: (i) production of the crucial cytokines gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70); (ii) early infiltration of neutrophils, monocytes, and dendritic cells (DCs) in the lungs of
Tlr2
−/−
mice; (iii) rapid influx of CD4
+
and CD8
+
T cells; and (iv) the expansion of memory/effector T cells. Notably, systemic administration of
M. abscessus
culture filtrate-treated syngeneic DCs from WT mice greatly strengthened immune priming
in vivo
, resulting in a dramatic reduction in bacterial growth and improved long-term survival in
Tlr2
−/−
mice, with a recovery of protective immunity. Our findings demonstrate that TLR2 is an essential contributor to instructive and effector immunity during
M. abscessus
infection in a morphotype-specific manner.
Characterization of a Novel Two-Component Regulatory System, HptRS, the Regulator for the Hexose Phosphate Transport System in Staphylococcus aureus
Authors: Park Joo Youn , Kim Jong Wan , Moon Bo Youn , Lee Juyeun , Fortin Ye Ji , Austin Frank W. , Yang Soo-Jin , Seo Keun Seok 
Published: February 2015

ABSTRACT

Hexose phosphate is an important carbon source within the cytoplasm of host cells. Bacterial pathogens that invade, survive, and multiply within various host epithelial cells exploit hexose phosphates from the host cytoplasm through the
h
exose
p
hosphate
t
ransport (HPT) system to gain energy and synthesize cellular components. In
Escherichia coli
, the HPT system consists of a two-component regulatory system (UhpAB) and a phosphate sensor protein (UhpC) that tightly regulate expression of a hexose phosphate transporter (UhpT). Although growing evidence suggests that
Staphylococcus aureus
also can invade, survive, and multiply within various host epithelial cells, the genetic elements involved in the HPT system in
S. aureus
have not been characterized yet. In this study, we identified and characterized the HPT system in
S. aureus
that includes the
hptRS
(a novel two-component regulatory system), the
hptA
(a putative phosphate sensor), and the
uhpT
(a hexose phosphate transporter) genes. The
hptA
,
hptRS
, and
uhpT
markerless deletion mutants were generated by an allelic replacement method using a modified pMAD-CM-GFPuv vector system. We demonstrated that both
hptA
and
hptRS
are required to positively regulate transcription of
uhpT
in response to extracellular phosphates, such as glycerol-3-phosphate (G3P), glucose-6-phosphate (G6P), and fosfomycin. Mutational studies revealed that disruption of the
hptA
,
hptRS
, or
uhpT
gene impaired the growth of bacteria when the available carbon source was limited to G6P, impaired survival/multiplication within various types of host cells, and increased resistance to fosfomycin. The results of this study suggest that the HPT system plays an important role in adaptation of
S. aureus
within the host cells and could be an important target for developing novel antistaphylococcal therapies.