bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Intravenous Peramivir for Treatment of Seasonal Influenza Virus Infection
Authors: Kohno Shigeru , Kida Hiroshi , Mizuguchi Masashi , Shimada Jingoro 
Published: August 2010

ABSTRACTPeramivir, a sialic acid analogue, is a selective inhibitor of neuraminidases produced by influenza A and B viruses. We evaluated the efficacy and safety of a single intravenous dose of peramivir in outpatients with uncomplicated seasonal influenza virus infection. A total of 300 previously healthy adult subjects aged 20 to 64 years with a positive influenza virus rapid antigen test were recruited within 48 h of the onset of influenza symptoms and randomized to three groups: single intravenous infusion of either 300 mg peramivir per kg of body weight, 600 mg peramivir, or matching placebo on study day 1. Influenza symptoms and body temperature were self-assessed for 14 days. Nasal and pharyngeal swabs were collected to determine the viral titer. The primary endpoint was the time to alleviation of symptoms. Of the 300 subjects, 296 were included in the intent-to-treat infected population (300 mg peramivir,n= 99; 600 mg peramivir,n= 97; and placebo,n= 100). Peramivir significantly reduced the time to alleviation of symptoms at both 300 mg (hazard ratio, 0.681) and 600 mg (hazard ratio, 0.666) compared with placebo (adjustedPvalue, 0.0092 for both comparisons). No serious adverse events were reported. Peramivir was well tolerated, and its adverse-event profile was similar to that of placebo. A single intravenous dose of peramivir is effective and well tolerated in subjects with uncomplicated seasonal influenza virus infection.
Emergence and Molecular Characterization of Extensively Drug-Resistant
Mycobacterium tuberculosis
Clinical Isolates from the Delhi Region in India
Authors: Khanna Alka , Raj V. Samuel , Tarai Bansidhar , Sood Ruchi , Pareek Pawan Kumar , Upadhyay Dilip J. , Sharma Pawan , Rattan Ashok , Saini Kulvinder Singh , Singh Harpal 
Published: August 2010

ABSTRACT

We screened 194
Mycobacterium tuberculosis
strains isolated from tuberculosis (TB) patients in Delhi and neighboring regions in India to identify the prevalence of extensive drug resistance (XDR) in clinical isolates. Among these, 104 isolates were found to be multidrug resistant (MDR), and 6 were identified as XDR isolates, which was later confirmed by antimicrobial susceptibility testing against the respective drug screening panel. Genotyping was carried out by amplifying and sequencing the following genes:
rpoB
(rifampin),
katG
(isoniazid),
gyrA
(fluoroquinolones), and
rrs
(amikacin, kanamycin, and capreomycin). Our analyses indicated that mutations at the hot spots of these genes were positively correlated with drug resistance in clinical isolates. The key mutation observed for
rpoB
was in the codon for amino acid position 531 (S531L), and other mutations were seen in the hot spot, including those encoding Q510P, L511H, D516V, and H526Y mutations. We identified S315T and R463L substitutions encoded in the
katG
locus. An S95T substitution encoded in the
gyrA
locus was the most common mutation observed in fluoroquinolone-resistant isolates. In addition, we saw D94G and D94N mutations encoded in the QRDR region. The 16S rRNA (
rrs
) gene encoded mainly the A1401G mutation and an additional mutation, G1484T, resulting in ribosomal modifications. Taken together, the data in this report clearly establish the presence of phenotypically distinct XDR strains in India by molecular profiling and further identify specific mutational hot spots within key genes of XDR-TB strains.
CD28 Exerts Protective and Detrimental Effects in a Pulmonary Model of Paracoccidioidomycosis
Authors: Felonato Maíra , Pina Adriana , Bernardino Simone , Loures Flávio V. , de Araujo Eliseu Frank , Calich Vera L. G. 
Published: August 2010

ABSTRACTT-cell immunity has been claimed as the main immunoprotective mechanism againstParacoccidioides brasiliensisinfection, the most important fungal infection in Latin America. As the initial events that control T-cell activation in paracoccidioidomycosis (PCM) are not well established, we decided to investigate the role of CD28, an important costimulatory molecule for the activation of effector and regulatory T cells, in the immunity against this pulmonary pathogen. Using CD28-deficient (CD28−/−) and normal wild-type (WT) C57BL/6 mice, we were able to demonstrate that CD28 costimulation determines in pulmonary paracoccidioidomycosis an early immunoprotection but a late deleterious effect associated with impaired immunity and uncontrolled fungal growth. Up to week 10 postinfection, CD28−/−mice presented increased pulmonary and hepatic fungal loads allied with diminished production of antibodies and pro- and anti-inflammatory cytokines besides impaired activation and migration of effector and regulatory T (Treg) cells to the lungs. Unexpectedly, CD28-sufficient mice progressively lost the control of fungal growth, resulting in an increased mortality associated with persistent presence of Treg cells, deactivation of inflammatory macrophages and T cells, prevalent presence of anti-inflammatory cytokines, elevated fungal burdens, and extensive hepatic lesions. As a whole, our findings suggest that CD28 is required for the early protective T-cell responses toP. brasiliensisinfection, but it also induces the expansion of regulatory circuits that lately impair adaptive immunity, allowing uncontrolled fungal growth and overwhelming infection, which leads to precocious mortality of mice.
Interleukin-4 Regulates the Expression of CD209 and Subsequent Uptake ofMycobacterium lepraeby Schwann Cells in Human Leprosy
Authors: Teles Rosane M. B. , Krutzik Stephan R. , Ochoa Maria T. , Oliveira Rosane B. , Sarno Euzenir N. , Modlin Robert L. 
Published: August 2010

ABSTRACTThe ability of microbial pathogens to target specific cell types is a key aspect of the pathogenesis of infectious disease.Mycobacterium leprae, by infecting Schwann cells, contributes to nerve injury in patients with leprosy. Here, we investigated mechanisms of host-pathogen interaction in the peripheral nerve lesions of leprosy. We found that the expression of the C-type lectin, CD209, known to be expressed on tissue macrophages and to mediate the uptake ofM. leprae, was present on Schwann cells, colocalizing with the Schwann cell marker, CNPase (2′,3′-cyclic nucleotide 3′-phosphodiesterase), along with theM. lepraeantigen PGL-1 in the peripheral nerve biopsy specimens.In vitro, human CD209-positive Schwann cells, both from primary cultures and a long-term line, have a higher binding ofM. lepraecompared to CD209-negative Schwann cells. Interleukin-4, known to be expressed in skin lesions from multibacillary patients, increased CD209 expression on human Schwann cells and subsequent Schwann cell binding toM. leprae, whereas Th1 cytokines did not induce CD209 expression on these cells. Therefore, the regulated expression of CD209 represents a common mechanism by which Schwann cells and macrophages bind and take upM. leprae, contributing to the pathogenesis of leprosy.
RssAB-FlhDC-ShlBA as a Major Pathogenesis Pathway in
Serratia marcescens
Authors: Lin Chuan-Sheng , Horng Jim-Tong , Yang Chun-Hung , Tsai Yu-Huan , Su Lin-Hui , Wei Chia-Fong , Chen Chang-Chieh , Hsieh Shang-Chen , Lu Chia-Chen , Lai Hsin-Chih 
Published: August 2010

ABSTRACT

Serratia marcescens
has long been recognized as an important opportunistic pathogen, but the underlying pathogenesis mechanism is not completely clear. Here, we report a key pathogenesis pathway in
S. marcescens
comprising the RssAB two-component system and its downstream elements, FlhDC and the dominant virulence factor hemolysin ShlBA. Expression of
shlBA
is under the positive control of FlhDC, which is repressed by RssAB signaling. At 37°C, functional RssAB inhibits swarming, represses hemolysin production, and promotes
S. marcescens
biofilm formation. In comparison, when
rssBA
is deleted,
S. marcescens
displays aberrant multicellularity favoring motile swarming with unbridled hemolysin production. Cellular and animal infection models further demonstrate that loss of
rssBA
transforms this opportunistic pathogen into hypervirulent phenotypes, leading to extensive inflammatory responses coupled with destructive and systemic infection. Hemolysin production is essential in this context. Collectively, a major virulence regulatory pathway is identified in
S. marcescens
.
Vitamin B
6
Is Required for Full Motility and Virulence in
Helicobacter pylori
Authors: Grubman Alexandra , Phillips Alexandra , Thibonnier Marie , Kaparakis-Liaskos Maria , Johnson Chad , Thiberge Jean-Michel , Radcliff Fiona J. , Ecobichon Chantal , Labigne Agnès , de Reuse Hilde , Mendz George L. , Ferrero Richard L. 
Published: August 2010

ABSTRACT

Despite recent advances in our understanding of how
Helicobacter pylori
causes disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors in
H. pylori
, we generated low-infectivity variants of a mouse-colonizing
H. pylori
strain using the classical technique of
in vitro
attenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of the
Escherichia coli
vitamin B
6
biosynthesis enzymes PdxA and PdxJ. Functional complementation studies with
E. coli
confirmed
H. pylori
PdxA and PdxJ to be
bona fide
homologs of vitamin B
6
biosynthesis enzymes. Importantly,
H. pylori
PdxA was required for optimal growth
in vitro
and was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B
6
is necessary for the synthesis of glycosylated flagella and for flagellum-based motility in
H. pylori
. Thus, for the first time, we identify vitamin B
6
biosynthesis enzymes as novel virulence factors in bacteria. Interestingly,
pdxA
and
pdxJ
orthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.

IMPORTANCE
Approximately half of the world’s population is infected with
H. pylori
, yet how
H. pylori
bacteria establish chronic infections in human hosts remains elusive. From gene array studies, we identified two genes as representing potentially novel colonization factors for
H. pylori
. These genes encoded enzymes involved in the synthesis of vitamin B
6
, an important molecule for many metabolic reactions in living organisms. Little is currently known regarding vitamin B
6
biosynthesis in human pathogens. We showed that mutant
H. pylori
bacteria lacking an enzyme involved in
de novo
vitamin B
6
biosynthesis, PdxA, were unable to synthesize motility appendages (flagella) and were unable to establish chronic colonization in mice. Thus, this work identifies vitamin B
6
biosynthesis enzymes as novel virulence factors for bacterial pathogens. Interestingly, a number of human pathogens, but not their mammalian hosts, possess these genes, which suggests that Pdx enzymes may represent ideal candidates for new therapeutic targets.
Recent advances in imaging epilepsy
Authors: Craven Ian , Kotsarini Christina , Hoggard Nigel 
Published: August 2010

Abstract
Around 30 000 people are diagnosed with epilepsy every year in the UK. While many of these respond well to antiepileptic drugs, 20–30% have seizures that are resistant to best medical treatment. For these patients it is important to identify any structural abnormalities responsible for generating seizure activity that may be amenable to surgical resection. There are many imaging modalities available to investigate epilepsy including computed tomography (CT), nuclear medicine and magnetic resonance imaging (MRI). Additional techniques are available in specific circumstances including single positron emission CT, diffusion imaging, MR spectroscopy, perfusion imaging and functional MRI. Clearly with so many options, a targeted approach is required to reach a diagnosis efficiently. In this article, each modality is discussed along with the imaging options for the common causes of focal seizure activity.
Aquatic community metabolism response to municipal effluent inputs in rivers quantified using diel δ18O values of dissolved oxygen
Authors: Wassenaar L. I. , Venkiteswaran J. J. , Schiff S. L. , Koehler G. 
Published: August 2010

The spatial footprint over which municipal wastewater effluents cause changes to aquatic community structure and metabolism is key information required for the management of discharges into rivers. Longitudinal studies were undertaken on the Bow and South Saskatchewan rivers, Canada, to assess a new isotopic and modelling approach that combined O2and δ18O-O2diel (24 h) response curves to quantify changes in integrated community aquatic metabolism as a result of point-source wastewater inputs. Diel samplings were conducted over four seasons along 50 km transects at Calgary (Bow River) and Saskatoon (South Saskatchewan River). Diel O2and δ18O-O2cycles grew in magnitude downstream of effluent inputs in all seasons compared with upstream control sites. δ18O-O2depletions clearly revealed the stimulating effect of effluent on aquatic photosynthesis. Diel isotopic mass balance modelling showed community metabolic responses to effluent inputs were most pronounced in the spring and summer when photosynthesis and respiration rates were about two- to three-fold higher than at upstream control sites. Our findings revealed that sewage treatment plant nutrient additions resulted in an enhanced metabolic footprint that extended beyond 50 km downstream.
Sex differences in linear and nonlinear heart rate variability during early recovery from supramaximal exercise
Authors: Mendonca Goncalo V. , Heffernan Kevin S. , Rossow Lindy , Guerra Myriam , Pereira Fernando D. , Fernhall Bo 
Published: August 2010

Women demonstrate greater RR interval variability than men of similar age. Enhanced parasympathetic input into cardiac regulation appears to be not only greater in women, but also protective during periods of cardiac stress. Even though women may have a more favorable autonomic profile after exercise, little research has been conducted on this issue. This study was designed to examine the cardiac autonomic response, in both male and female participants, during the early recovery from supramaximal exercise. Twenty-five individuals, aged 20 to 33 years (13 males and 12 females), performed a 30-s Wingate test. Beat-to-beat RR series were recorded before and 5 min after exercise, with the participants in the supine position and under paced breathing. Linear (spectral analysis) and nonlinear analyses (detrended fluctuation analysis (DFA)) were performed on the same RR series. At rest, women presented lower raw low frequency (LF) power and higher normalized high frequency (HF) power. Under these conditions, the LF/HF ratio of women was also lower than that of men (p < 0.05), but there were no differences in the short-term scaling exponent (α1). Even though both sexes showed a significant modification in linear and nonlinear measures of heart rate variability (HRV) (p < 0.05), women had a greater change in LF/HF ratio and α1 than men from rest to recovery. This study demonstrates that the cardiac autonomic function of women is more affected by supramaximal exercise than that of men. Additionally, DFA did not provide additional information about sexual dimorphisms, compared with conventional spectral HRV techniques.
Aerobic capacity of rats recovered from fetal malnutrition with a fructose-rich diet
Authors: Cambri Lucieli Teresa , Dalia Rodrigo Augusto , Ribeiro Carla , Rostom de Mello Maria Alice 
Published: August 2010

The objective of this study was to analyze the aerobic capacity, through the maximal lactate steady-state (MLSS) protocol, of rats subjected to fetal protein malnutrition and recovered with a fructose-rich diet. Pregnant adult Wistar rats that were fed a balanced (17% protein) diet or a low-protein (6% protein) diet were used. After birth, the offspring were distributed into groups according to diet until 60 days of age: balanced (B), balanced diet during the whole experimental period; balanced–fructose (BF), balanced diet until birth and fructose-rich diet (60% fructose) until 60 days; low protein–balanced (LB), low-protein diet until birth and balanced diet until 60 days; and low protein–fructose (LF), low protein diet until birth and fructose-rich diet until 60 days. It was verified that the fructose-rich diet reduced body growth, mainly in the BF group. There was no difference among the groups in the load corresponding to the MLSS (B, 7.5 ± 0.5%; BF, 7.4 ± 0.6%; LB, 7.7 ± 0.4%; and LF, 7.7 ± 0.6% relative to body weight). However, the BF group presented higher blood lactate concentrations (4.8 ± 0.9 mmol·L–1) at 25 min in the load corresponding to the MLSS (B, 3.2 ± 0.9 mmol·L–1; LB, 3.4 ± 0.9 mmol·L–1; and LF, 3.2 ± 1.0 mmol·L–1). Taken together, these results indicate that the ability of young rats to perform exercise was not altered by intrauterine malnutrition or a fructose-rich diet, although the high fructose intake after the balanced diet in utero increased blood lactate during swimming exercises in rats.
Noninvasive measures of vascular health are reliable in preschool-aged children
Authors: Currie Katharine D. , Proudfoot Nicole A. , Timmons Brian W. , MacDonald Maureen J. 
Published: August 2010

Measures of vascular health are known to be important predictors of cardiovascular disease in adulthood. The reliability of commonly used measures of vascular health has been demonstrated in school-aged children, adolescents, and adults; however, their reliability in preschool-aged children remains to be determined. Twenty 2- to 6-year-old children participated in 2 identical testing sessions on different days. Following 10 min of supine rest, carotid artery blood pressures and common carotid artery images were assessed simultaneously for 10 heart cycles, using applanation tonometry and B-mode ultrasound, respectively, while electrocardiogram (ECG) and infrared measures of arterial pressure waves at the dorsalis pedis were recorded continuously. Brachial artery blood pressures were determined using an automated oscillometric device. Carotid artery diameters and intima-media thickness (IMT) were analyzed using a semiautomated detection software program. Carotid compliance, distensibility, and stiffness index were calculated from carotid diameters and carotid blood pressures. Whole-body pulse-wave velocity (PWV) was determined from the time delay between the R spike of the ECG and the foot of the dorsalis pedis arterial pressure wave. Reliability of all measures was assessed using the coefficient of variation (CV) and the intraclass correlation coefficient (ICC). The most reliable measures were carotid artery IMT and PWV with CVs of 2.6% and 3.5% and ICCs of 0.86 and 0.76, respectively. The lower reliability of carotid compliance and distensibility (ICC ≤ 0.63) is likely attributable to the variability of blood pressure measurements. This study confirms that vascular measurements demonstrate substantial reliability in preschool-aged children as young as 2 years.
Ab initio studies of the vibrational spectra of some hydrogen-bonded complexes of fluoroacetylene
Authors: Ramasami Ponnadurai , Ford Thomas A. 
Published: August 2010

Ab initio molecular orbital theory has been used to compute the properties of a number of hydrogen-bonded complexes between fluoroacetylene as proton donor and ammonia, water, hydrogen fluoride, phosphine, hydrogen sulfide, and hydrogen chloride as proton acceptors. The properties considered were the vibrational spectra, the molecular structures, the hydrogen-bond energies, and the electron densities, and one of the aims of the study was to ascertain whether there was any evidence of blue-shifting hydrogen-bond character in the complexes formed. The adducts with NH3, H2O, PH3, and H2S were of the conventional CH···X kind (X = N, O, P, S), with hydrogen-bond energies decreasing in the order NH3 > H2O > PH3≈ H2S. Those formed with HF and HCl showed the presence of three alternative structures; in addition to the CH···F(Cl) complexes, adducts of the F(Cl)H···F and F(Cl)H···π type were also found to be stationary points on the potential energy surfaces, with stabilities in the order F(Cl)H···π > CH···F(Cl) > F(Cl)H···F. The hydrogen-bond energies of the CH···X series correlated with the gas-phase basicities of the proton acceptors; moreover, the CH bond-length changes, the wavenumber shifts, the complex–monomer infrared intensity ratios of the CH stretching modes, and the amounts of charge transferred on complex formation were all found to track with the hydrogen-bond energies. All those properties considered here are consistent with the formation of red-shifting hydrogen bonds, to the exclusion of the blue-shifting alternatives.
Theoretical study of the rovibrational spectrum of He2–OCS
Authors: Wang Xiao-Gang , Carrington, Tucker 
Published: August 2010

We report calculated microwave and infrared rovibrational transitions of the van der Waals complex He2–OCS. The calculations were done using a product basis, a Lanczos eigensolver, and potentials built from He–OCS, and He–He potential functions taken from the literature. All five of the large amplitude coordinates are treated exactly and calculations are done for J values up to five. All rovibrational levels are converged to 0.001 cm–1 by using basis sets with as many as 87 million funcions. Good agreement is found with previously reported experimental results. Although we assume that the dipole moment is along the OCS axis, we find transitions with appreciable intensity between different torsion states.
Homoselenocysteine — An oxygen or selenium acid in the gas phase?
Authors: Hurtado Marcela , Mó Otilia , Yáñez Manuel 
Published: August 2010

The potential energy surface of l-homoselenocysteine (HSEC) has been explored through the use of B3LYP/6-311+G(d,p) calculations. In this survey, seventy-seven different conformers have been located. These local minima can be classified in four groups, A–D. Structures A, B, and D are stabilized by intramolecular hydrogen bonds (IMHBs) with the amino group acting as the hydrogen bond (HB) donor and the carbonyl group (structures A and D) or the hydroxyl group (structure B) as HB acceptors. The structures in set C present an IMHB with the amino group acting as the HB acceptor and the hydroxyl group as the HB donor. The stability order decreases in the following order: A > B > C > D. From their relative stabilities it can be concluded that only three of these conformers, namely A1, A4, and A5, would exist in the gas phase at room temperature. The most stable deprotonated form corresponds to a Se-deprotated species stabilized by a strong IMHB between the hydroxyl group and the Se atom. However, a direct deprotonation of the most stable neutrals lead to O-deprotonated species, which eventually isomerize to yield the global minimum. Hence, we can conclude that, quite unexpectedly, HSEC behaves as a Se acid in the gas phase, its intrinsic acidity being 1374 kJ mol–1at the B3LYP/6-311++G(3df,2p) level of theory. The most stable protonated forms are systematically the N-protonated ones, the global minimum being a structure stabilized through an IMHB involving the protonated amino group as the HB donor and the SeH group as the HB acceptor. The calculated gas-phase proton affinity (PA) at the B3LYP/6-311++G(3df,2p) level of theory is 930 kJ mol–1.