bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prematch Salivary Secretory Immunoglobulin A in Soccer Players From the 2014 World Cup Qualifying Campaign
Authors: Morgans Ryland , Owen Adam , Doran Dominic , Drust Barry , Morton James P. 
Published: August 2014

Purpose:To monitor resting salivary secretory immunoglobulin A (SIgA) levels in international soccer players during the short-term training period that precedes international match play.Methods:In a repeated-measure design, saliva samples were obtained from 13 outfield soccer players who participated in the training camps preceding 7 games (5 home and 2 away) of the 2014 FIFA World Cup qualifying campaign. Samples were obtained daily for 4 d preceding each game (and analyzed for SIgA using the IPRO oral-fluid-collection system) at match day minus 1 (MD-1), minus 2 (MD-2), minus 3 (MD-3), and minus 4 (MD-4).Results:SIgA displayed a progressive decline (P = .01) during the 4-d training period (MD-4, 365 ± 127 μg/mL; MD-3, 348 ± 154 μg/mL; MD-2, 290 ± 138 μg/mL; MD-1, 256 ± 90 μg/mL) such that MD-1 values were significantly lower (P = .01) than both MD-4 and MD-3. The 95% confidence intervals for the differences between MD-1 and MD-4 were –191 to –26 and between MD-1 and MD-3 were –155 to –28.Conclusions:Data demonstrate that a short-term soccer-training camp in preparation for international competition induces detectable perturbations to mucosal immunity. Future studies should monitor SIgA (as a practical and noninvasive measure of immunity) alongside internal and external measures of training load in an attempt to strategically individualize training and nutritional strategies that may support optimal preparation for high-level competition.
Analysis of the Kenyan Distance-Running Phenomenon
Authors: Tucker Ross , Onywera Vincent O. , Santos-Concejero Jordan 
Published: August 2014

Purpose:To investigate the ethnicity of Kenya’s most successful international runners, tracking their evolution over the period of their international emergence and current dominance.Methods:The authors analyzed male track distance events from 800m upwards from all the major global athletics championships from 1964 to 2013, and the annual Top-25 world marathon performances since 1990.Results:The percentage of top-25 marathon performances and medals won by Kenyan and Kalenjin runners have increased over time with Nandi subtribe outperforming the rest of the world outside Africa (r > .70, large effect). However, Europe, North America, Oceania, Asia, and South America decreased over time in top marathon performances and track medals won (r > .70, large effect). The tribe and subtribe distribution was different in the marathon than in the track: Maasais were more likely to feature in medals won in shorter track events than in the top 25 of the world marathon rankings (risk ratio [RR] = 9.67, very large effect). This was also the case for Marakwets (RR = 6.44, very large effect) and Pokots (RR = 4.83, large effect). On the other hand, Keiyos, Kikuyus, Kipsigis, Sabaots, and Tugens were more likely to succeed in the marathon than in shorter track events (RR > 2.0, moderate effect).Conclusion:These data emphasize that the previously documented emergence of African distance runners is primarily a Kenyan phenomenon, driven by the Kalenjin tribe and in particular the Nandi subtribe. This supports the complex interaction between genotype, phenotype, and socioeconomic factors driving the remarkable dominance of Kenyan distance runners.
Resveratrol Is Active against Leishmania amazonensis:
In Vitro
Effect of Its Association with Amphotericin B
Authors: Ferreira Christian , Soares Deivid Costa , Nascimento Michelle Tanny Cunha do , Pinto-da-Silva Lucia Helena , Sarzedas Carolina Galvão , Tinoco Luzineide Wanderley , Saraiva Elvira Maria 
Published: August 2014

ABSTRACT

Resveratrol is a polyphenol found in black grapes and red wine and has many biological activities. In this study, we evaluated the effect of resveratrol alone and in association with amphotericin B (AMB) against
Leishmania amazonensis
. Our results demonstrate that resveratrol possesses both antipromastigote and antiamastigote effects, with 50% inhibitory concentrations (IC
50
s) of 27 and 42 μM, respectively. The association of resveratrol with AMB showed synergy for
L. amazonensis
amastigotes, as demonstrated by the mean sums of fractional inhibitory index concentration (mean ΣFIC) of 0.483, although for promastigotes, this association was indifferent. Treatment with resveratrol increased the percentage of promastigotes in the sub-G
0
/G
1
phase of the cell cycle, reduced the mitochondrial potential, and showed an elevated choline peak and CH
2
-to-CH
3
ratio in the nuclear magnetic resonance (NMR) spectroscopy analysis; all these features indicate parasite death. Resveratrol also decreased the activity of the enzyme arginase in uninfected and infected macrophages with and without stimulation with interleukin-4 (IL-4), also implicating arginase inhibition in parasite death. The anti-
Leishmania
effect of resveratrol and its potential synergistic association with AMB indicate that these compounds should be subjected to further studies of drug association therapy
in vivo
.
A Clinical Adverse Drug Reaction Prediction Model for Patients with Chagas Disease Treated with Benznidazole
Authors: Sperandio da Silva Gilberto Marcelo , Mediano Mauro Felippe Felix , Alvarenga Americano do Brasil Pedro Emmanuel , da Costa Chambela Mayara , da Silva Joyce Almeida , de Sousa Andrea Silvestre , Xavier Sergio Salles , Rodrigues da Costa Andrea , Magalhães Saraiva Roberto , Hasslocher-Moreno Alejandro Marcel 
Published: August 2014

ABSTRACT
Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease, and the evidence supporting the benefits of BZN use during the chronic phase of the disease will favor its use in millions of individuals. However, more than 30% of patients treated with BZN may suffer adverse drug reactions (ADRs), and the development of tools to identify those patients at risk is highly desirable. In the present study, we aimed to identify predictive factors for ADRs in Chagas disease patients treated with BZN. Among 195 patients included in the study, 48.7% experienced ADRs and 31.3% had ADRs that caused BZN treatment discontinuation. Overall ADRs and ADRs that caused BZN treatment discontinuation were more common among women and in those who graduated from elementary school. Overall ADRs were also less frequent among black individuals. Based on logistic regression analysis, female sex (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.5 to 5.4), graduation from elementary school (OR, 2.0; 95% CI, 1.1 to 3.8), and white (OR, 5.0; 95% CI, 1.0 to 24.1) and mulatto (OR, 5.6; 95% CI, 1.1 to 28.7) races were considered to predict overall ADRs, and female sex (OR, 2.3; 95% CI, 1.2 to 4.3) was considered to predict ADRs that caused BZN treatment discontinuation. Graduation from elementary school also presented a tendency to predict ADRs that caused BZN treatment discontinuation (OR, 1.8; 95% CI, 0.9 to 3.6). The logistic regression (LR) models to predict ADRs to BZN described in this study may become important tools to minimize ADRs and improve patients' compliance and thus assist physicians treating patients with Chagas disease with BZN.
In Vitro
Susceptibility of Plasmodium vivax to Antimalarials in Colombia
Authors: Fernández Diana , Segura César , Arboleda Margarita , Garavito Giovanny , Blair Silvia , Pabón Adriana 
Published: August 2014

ABSTRACT

The
in vitro
susceptibilities of 30 isolates of
Plasmodium vivax
to a number of antimalarials (chloroquine [CQ], mefloquine, amodiaquine, quinine, and artesunate [AS]) were evaluated. The isolates came from the region of Urabá in Colombia, in which malaria is endemic, and were evaluated by the schizont maturation test. The 50% inhibitory concentration (IC
50
) was 0.6 nM (95% confidence interval [CI], 0.3 to 1.0 nM) for artesunate, 8.5 nM (95% CI, 5.6 to 13.0 nM) for amodiaquine, 23.3 nM (95% CI, 12.4 to 44.1 nM) for chloroquine, 55.6 nM (95% CI, 36.8 to 84.1 nM) for mefloquine, and 115.3 nM (95% CI, 57.7 to 230.5 nM) for quinine. The isolates were classified according to whether the initial parasites were mature or immature trophozoites (Tfz). It was found that the IC
50
s for chloroquine and artesunate were significantly different in the two aforementioned groups (
P
< 0.001). The IC
50
s of CQ and AS were higher in the isolates from mature Tfz (CQ, 39.3 nM versus 17 nM; AS, 1.4 nM versus 0.3 nM), and 10% of the isolates showed lower susceptibilities to one of the antimalarial drugs, 13.3% to two antimalarial drugs, and 3.3% to more than three antimalarial drugs. It should be highlighted that despite the extensive use of chloroquine in Colombia,
P. vivax
continues to be susceptible to antimalarials. This is the first report, to our knowledge, showing
in vitro
susceptibilities of
P. vivax
isolates to antimalarials in Colombia.
Molecular Mechanism of MBX2319 Inhibition of Escherichia coli AcrB Multidrug Efflux Pump and Comparison with Other Inhibitors
Authors: Vargiu Attilio V. , Ruggerone Paolo , Opperman Timothy J. , Nguyen Son T. , Nikaido Hiroshi 
Published: August 2014

ABSTRACT

Efflux pumps of the resistance nodulation division (RND) superfamily, such as AcrB, make a major contribution to multidrug resistance in Gram-negative bacteria. The development of inhibitors of the RND pumps would improve the efficacy of current and next-generation antibiotics. To date, however, only one inhibitor has been cocrystallized with AcrB. Thus,
in silico
structure-based analysis is essential for elucidating the interaction between other inhibitors and the efflux pumps. In this work, we used computer docking and molecular dynamics simulations to study the interaction between AcrB and the compound MBX2319, a novel pyranopyridine efflux pump inhibitor with potent activity against RND efflux pumps of
Enterobacteriaceae
species, as well as other known inhibitors (D13-9001, 1-[1-naphthylmethyl]-piperazine, and phenylalanylarginine-β-naphthylamide) and the binding of doxorubicin to the efflux-defective F610A variant of AcrB. We also analyzed the binding of a substrate, minocycline, for comparison. Our results show that MBX2319 binds very tightly to the lower part of the distal pocket in the B protomer of AcrB, strongly interacting with the phenylalanines lining the hydrophobic trap, where the hydrophobic portion of D13-9001 was found to bind by X-ray crystallography. Additionally, MBX2319 binds to AcrB in a manner that is similar to the way in which doxorubicin binds to the F610A variant of AcrB. In contrast, 1-(1-naphthylmethyl)-piperazine and phenylalanylarginine-β-naphthylamide appear to bind to somewhat different areas of the distal pocket in the B protomer of AcrB than does MBX2319. However, all inhibitors (except D13-9001) appear to distort the structure of the distal pocket, impairing the proper binding of substrates.
Antimalarial Activity of the Myxobacterial Macrolide Chlorotonil A
Authors: Held Jana , Gebru Tamirat , Kalesse Markus , Jansen Rolf , Gerth Klaus , Müller Rolf , Mordmüller Benjamin 
Published: August 2014

ABSTRACT

Myxobacteria are Gram-negative soil-dwelling bacteria belonging to the phylum
Proteobacteria
. They are a rich source of promising compounds for clinical application, such as epothilones for cancer therapy and several new antibiotics. In the course of a bioactivity screening program of secondary metabolites produced by
Sorangium cellulosum
strains, the macrolide chlorotonil A was found to exhibit promising antimalarial activity. Subsequently, we evaluated chlorotonil A against
Plasmodium falciparum
laboratory strains and clinical isolates from Gabon. Chlorotonil A was highly active, with a 50% inhibitory concentration between 4 and 32 nM; additionally, no correlations between the activities of chlorotonil A and artesunate (rho, 0.208) or chloroquine (rho, −0.046) were observed.
Per os
treatment of
Plasmodium berghei
-infected mice with four doses of as little as 36 mg of chlorotonil A per kg of body weight led to the suppression of parasitemia with no obvious signs of toxicity. Chlorotonil A acts against all stages of intraerythrocytic parasite development, including ring-stage parasites and stage IV to V gametocytes, and it requires only a very short exposure to the parasite to exert its antimalarial action. Conclusively, chlorotonil A has an exceptional and unprecedented profile of action and represents an urgently required novel antimalarial chemical scaffold. Therefore, we propose it as a lead structure for further development as an antimalarial chemotherapeutic.
Overproduction of Ristomycin A by Activation of a Silent Gene Cluster in Amycolatopsis japonicum MG417-CF17
Authors: Spohn Marius , Kirchner Norbert , Kulik Andreas , Jochim Angelika , Wolf Felix , Muenzer Patrick , Borst Oliver , Gross Harald , Wohlleben Wolfgang , Stegmann Evi 
Published: August 2014

ABSTRACT

The emergence of antibiotic-resistant pathogenic bacteria within the last decades is one reason for the urgent need for new antibacterial agents. A strategy to discover new anti-infective compounds is the evaluation of the genetic capacity of secondary metabolite producers and the activation of cryptic gene clusters (genome mining). One genus known for its potential to synthesize medically important products is
Amycolatopsis
. However,
Amycolatopsis japonicum
does not produce an antibiotic under standard laboratory conditions. In contrast to most
Amycolatopsis
strains,
A. japonicum
is genetically tractable with different methods. In order to activate a possible silent glycopeptide cluster, we introduced a gene encoding the transcriptional activator of balhimycin biosynthesis, the
bbr
gene from
Amycolatopsis balhimycina
(
bbr
Aba
), into
A. japonicum
. This resulted in the production of an antibiotically active compound. Following whole-genome sequencing of
A. japonicum
, 29 cryptic gene clusters were identified by genome mining. One of these gene clusters is a putative glycopeptide biosynthesis gene cluster. Using bioinformatic tools, ristomycin (syn. ristocetin), a type III glycopeptide, which has antibacterial activity and which is used for the diagnosis of von Willebrand disease and Bernard-Soulier syndrome, was deduced as a possible product of the gene cluster. Chemical analyses by high-performance liquid chromatography and mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) spectroscopy confirmed the
in silico
prediction that the recombinant
A. japonicum
/pRM4-
bbr
Aba
synthesizes ristomycin A.
Bacterial Heterogeneity Is a Requirement for Host Superinfection by the Lyme Disease Spirochete
Authors: Rogovskyy Artem S. , Bankhead Troy 
Published: August 2014

ABSTRACTIn nature, mixedBorrelia burgdorferiinfections are common and possibly can be acquired by either superinfection or coinfection. Superinfection by heterologousB. burgdorferistrains has been established experimentally, although the ability of homologousB. burgdorfericlones to superinfect a host has not been studied in detail. Information regarding any potential immune barriers to secondary infection also currently is unavailable. In the present study, the ability to superinfect various mouse models by homologous wild-type clones was examined and compared to superinfection by heterologous strains. To assess the ability of homologousB. burgdorfericlones to successfully superinfect a mouse host, primary- and secondary-infecting spirochetes were recovered viain vitrocultivation of collected blood or tissue samples. This was accomplished by generating two different antibiotic-resistant versions of the wild-type B31-A3 clone in order to distinguish superinfectingB. burgdorferifrom primary-infecting spirochetes. The data demonstrate an inability of homologousB. burgdorferito superinfect immunocompetent mice as opposed to heterologous strains. Attempts to superinfect different types of immunodeficient mice with homologousB. burgdorferiindicate that the murine innate immune system represents a major barrier to intrastrain superinfection. Consequently, the possibility of innate immunity as a driving force forB. burgdorferiheterogeneity during the enzootic cycle is discussed.
BDCA1-Positive Dendritic Cells (DCs) Represent a Unique Human Myeloid DC Subset That Induces Innate and Adaptive Immune Responses to Staphylococcus aureus Infection
Authors: Jin Jun-O , Zhang Wei , Du Jiang-yuan , Yu Qing 
Published: August 2014

ABSTRACT

Staphylococcus aureus
bloodstream infection (bacteremia) is a major cause of morbidity and mortality and places substantial cost burdens on health care systems. The role of peripheral blood dendritic cells (PBDCs) in the immune responses against
S. aureus
infection has not been well characterized. In this study, we demonstrated that BDCA1
+
myeloid DCs (mDCs) represent a unique PBDC subset that can induce immune responses against
S. aureus
infection. BDCA1
+
mDCs could engulf
S. aureus
and strongly upregulated the expression of costimulatory molecules and production of proinflammatory cytokines. Furthermore, BDCA1
+
mDCs expressed high levels of major histocompatibility complex (MHC) class I and II molecules in response to
S. aureus
and greatly promoted proliferation and gamma interferon (IFN-γ) production in CD4 and CD8 T cells. Moreover, BDCA1
+
mDCs expressed higher levels of Toll-like receptor 2 (TLR-2) and scavenger receptor A (SR-A) than those on CD16
+
and BDCA3
+
mDCs, and these two receptors were both required for the recognition of
S. aureus
and the subsequent activation of BDCA1
+
mDCs. Finally, BDCA1
+
mDC-mediated immune responses against
S. aureus
were dependent on MyD88 signaling pathways. These results demonstrate that human BDCA1
+
mDCs represent a unique subset of mDCs that can respond to
S. aureus
to undergo maturation and activation and to induce Th1 and Tc1 immune responses.
The Disulfide Bonding System Suppresses CsgD-Independent Cellulose Production in Escherichia coli
Authors: Hufnagel David A. , DePas William H. , Chapman Matthew R. 
Published: August 2014

ABSTRACT

The bacterial extracellular matrix encases cells and protects them from host-related and environmental insults. The
Escherichia coli
master biofilm regulator CsgD is required for the production of the matrix components curli and cellulose. CsgD activates the diguanylate cyclase AdrA, which in turn stimulates cellulose production through cyclic di-GMP (c-di-GMP). Here, we identified and characterized a CsgD- and AdrA-independent cellulose production pathway that was maximally active when cultures were grown under reducing conditions or when the disulfide bonding system (DSB) was compromised. The CsgD-independent cellulose activation pathway was dependent on a second diguanylate cyclase, called YfiN. c-di-GMP production by YfiN was repressed by the periplasmic protein YfiR, and deletion of
yfiR
promoted CsgD-independent cellulose production. Conversely, when YfiR was overexpressed, cellulose production was decreased. Finally, we found that YfiR was oxidized by DsbA and that intraprotein YfiR disulfide bonds stabilized YfiR in the periplasm. Altogether, we showed that reducing conditions and mutations in the DSB system caused hyperactivation of YfiN and subsequent CsgD-independent cellulose production.
Treatment of cervical metaphyseal fractures due to delayed ossification in an adult dog with hypopituitarism
Authors: Iwata Munetaka , Hakozaki Takaharu , Hara Yasushi 
Published: August 2014

A four‐year‐old male toy poodle presented with signs of cervical pain over a period of two years, with subsequent progression to tetraparesis. Neurological examination suggested a transverse myelopathy in the cervical spinal cord. Radiographs of the cervical spine showed fractured endplates of the third through the sixth cervical vertebrae and delayed growth plate closure of all skeletal structures. Total serum thyroid‐stimulating hormone and T4 concentrations were very low, indicating hypothyroidism. MRI revealed a pituitary gland cyst and spinal cord compression by fractured metaphysis which were displaced dorsally into the spinal canal. Surgical treatment resulted in marked improvement in clinical signs. Open physes were nearly closed 16 months after continuous administration of levothyroxine sodium hydrate. Based on these findings, a presumed diagnosis of Salter–Harris type III fractures of the vertebral endplates associated with delayed ossification of the growth plates due to hypothyroidism was made.
Unusual manifestation of bromide toxicity (bromism) in an idiopathic epileptic dog already treated with phenobarbital
Authors: Stabile Fabio , de Stefani Alberta , De Risio Luisa 
Published: August 2014

A three‐year seven‐month‐old female spayed Cavalier King Charles spaniel was diagnosed with idiopathic epilepsy. Because of poor seizure control, the dog was started on oral treatment with potassium bromide as adjunctive treatment to phenobarbital. The dog presented eight days following bromide loading, having developed sedation, general proprioceptive ataxia and generalised appendicular repetitive myoclonus. The serum bromide concentration was 15.9 mg/ml (target range 1 mg/ml to 2.5 mg/ml), which was suggestive of a bromide overdose. The dog improved after reduction of bromide dosing and no similar episodes were reported by the owners at a follow up of 26 months. To the authors’ knowledge this is the first report describing generalised repetitive myoclonus related to bromide toxicity.
Iron oxide magnetic nanoparticles synthesized by atmospheric microplasmas
Authors: Wang Ying , Kaur Parvin , Tan Augustine Tuck Lee , Singh Rajveer , Lee Paul Choon Keat , Springham Stuart Victor , Ramanujan Raju V , Rawat R. S. 
Published: August 2014

This paper presents the synthesis of iron oxide nanoparticles using the atmospheric microplasma (AMP). The properties of iron oxide nanoparticles synthesized using AMP are compared with particles (i) formed in as-prepared solution and (ii) prepared using thermal decomposition method. Iron oxide nanoparticles prepared by all the 3 treatment methods exhibit quite soft ferromagnetic properties with coercivities less than 10 G. The AMP synthesis technique was found to be more efficient and better than thermal decomposition method due to ultra-shorter experiment time (around 2.5 min) as compared to 90 min required for thermal decomposition method. Moreover, AMP synthesized nanoparticles are better isolated and of smaller size than thermal decomposition ones. The effect of plasma discharge timings on synthesized nanoparticles has also been studied in this work. Coercivity of synthesized nanoparticles decreases with the increasing plasma discharge timings from 3 to 10 min. The nanoparticles synthesized using plasma discharge timing of 10 min exhibit the smallest coercivity of around 3 G. This suggests a high possibility of achieving super-paramagnetic nanoparticles by optimizing the plasma discharge timings of AMP.