bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy drinks: What is all the hype? The dangers of energy drink consumption
Authors: Rath Mandy
Published: January 2012

Purpose: To describe the adverse effects associated with energy drink consumption among adolescents and young adults.

Data sources: Review of literature utilizing Medscape, the Internet, MD Consult, and CINAHL. The following search terms were used: Energy drinks, caffeine, guarana, taurine, ginseng, sugar, and caffeine toxicity. Search was limited to English language sources from 2005 to 2010.

Conclusions: The popularity of energy drinks and the rapid growth of their excessive consumption among adolescents and young adults have brought about great concern in regards to overall health and well‐being. Caffeine, which is readily available to minors, is the most commonly used psychoactive substance in the world and imposes a potentially harmful influence on health, academic performance, and personal adjustments. Teens and young adults account for nearly $2.3 billion of energy drink sales. Adolescents and young adults are often unaware that various products, such as energy drinks, herbal medications, and various other medications that promote alertness, contain caffeine. When these products are taken together, caffeine toxicity and severe adverse effects can occur.

Implications for practice: Practitioners need to be aware of the consequences of energy drink consumption and be prepared to provide appropriate patient education.
Conservation ofNeotropical primates:Ecuador – a case study
Authors: de la Torre S.
Published: January 2012

Neotropical primates are a highly diverse and ecologically important group that is facing several conservation problems. This review aims to contribute to understanding the nature and extent of these problems by presenting relevant information on the conservation status ofEcuadorian primates. In the recent evaluation for theRed Data Book of Ecuadorian Mammals, 53% of 21 primate taxa (20 species – 21 subspecies) were considered to be threatened (19% Vulnerable, 24% Endangered and 10% Critically Endangered), 43% are Near Threatened and 5% are Data Deficient; none were considered as Least Concern. Conservation actions need to rely on objective information that is not always available. Most primatological studies have been carried out in two protected areas in Ecuadorian Amazon (Cuyabeno Reserve and Yasuní National Park). There have been fewer studies in the west of the Andes. To enhance conservation actions, we need to determine the geographic distribution and to evaluate the impacts of habitat loss, hunting and illegal trade for all primate taxa. Collaboration between zoos and academic institutions to carry out studies with captive populations and to raise public awareness of conservation issues is fundamental. Direct participation of local communities may assure the continuity of the studies and the effectiveness of conservation actions.
Early cardiac dysfunction is rescued by upregulation of SERCA2a pump activity in a rat model of metabolic syndrome
Authors: Miklós Z. , Kemecsei P. , Bíró T. , Marincsák R. , Tóth B. I. , Op den Buijs J. , Benis É. , Drozgyik A. , Ivanics T.
Published: January 2012

Aim

Various components of metabolic syndrome associate with cardiac intracellular calcium () mishandling, a precipitating factor in the development of heart failure. We aimed to provide a thorough description of early stage ‐cycling alterations in the fructose‐fed rat, an experimental model of the disorder, where insulin resistance, hypertension and dyslipidaemia act cooperatively on the heart.

Method

Rats were fed with fructose‐rich chow. After 6 weeks, echocardiography was performed, which was followed by measurements of myocardial transients recorded by Indo‐1 surface fluorometry in isolated perfused hearts. Sarcoplasmic reticulum (SR) Ca2+‐ATPase (SERCA2a) activity was assessed by administration of its inhibitor cyclopiazonic acid (CPA). Mathematical model analysis of transients was used to estimate kinetic properties of SR Ca2+ transporters. Protein levels of key Ca2+ handling proteins were also measured.

Results

Echocardiography showed signs of cardiac hypertrophy, but in vivo and ex vivo haemodynamic performance of fructose‐fed rat hearts were unaltered. However, a decline in Ca2+ sequestration capacity ( and decay time of transients) was observed. Model estimation showed decreased affinity for Ca2+ (higher Km) and elevated Vmax for SERCA2a. Diseased hearts were more vulnerable to CPA application. Fructose feeding caused elevation in SERCA2a and phosphorylated phospholamban (PLB) expression, while total PLB level remained unchanged.

Conclusion

In early stage, metabolic syndrome primarily disturbs SERCA2a function in the heart, but consequential haemodynamic dysfunction is prevented by upregulation of SERCA2a protein level and phosphorylation pathways regulating PLB. However, this compensated state is very vulnerable to a further decline in SERCA2a function.
MM2‐Thalamic Creutzfeldt–Jakob Disease: Neuropathological, Biochemical and Transmission Studies Identify a Distinctive Prion Strain
Authors: Moda Fabio , Suardi Silvia , Di Fede Giuseppe , Indaco Antonio , Limido Lucia , Vimercati Chiara , Ruggerone Margherita , Campagnani Ilaria , Langeveld Jan , Terruzzi Alessandro , Brambilla Antonio , Zerbi Pietro , Fociani Paolo , Bishop Matthew T. , Will Robert G. , Manson Jean C. , Giaccone Giorgio , Tagliavini Fabrizio
Published: January 2012

In Creutzfeldt–Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease‐associated prion protein (PrPSc) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico‐pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrPSc and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrPSc are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia.

We observed two young patients with MM2‐thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrPSc. Challenge of transgenic mice expressing 129MM human PrP showed that MM2‐thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2‐cortical sCJD. The affected mice showed deposition of type 2A PrPSc, a scenario that is unprecedented in this mouse line. These data indicate that MM2‐thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2‐cortical form.
Restoration of lordosis and disk height after single‐level transforaminal lumbar interbody fusion
Authors: Kepler Christopher K , Rihn Jeffrey A , Radcliff Kristen E , Patel Amar A , Anderson D Greg , Vaccaro Alexander R , Hilibrand Alan S , Albert Todd J
Published: January 2012

Objective:  To study radiographic and clinical outcomes after transforaminal lumbar interbody fusion (TLIF) in order to determine the impact of TLIF on lumbar lordosis, intervertebral height and improvement in clinical outcome measures.

Methods:  Forty‐five patients who had undergone a single‐level TLIF procedure for a single‐level degenerative condition were retrospectively reviewed and their clinical histories, degree of pre‐ and post‐operative lumbar lordosis, intervertebral height, and cage position recorded. Clinical assessment included use of modified Odom's criteria and a visual analog scale (VAS) for back and leg pain.

Results:  At 21 months, the patients had gained an average of 3.6° of lumbar lordosis and 4.5 mm disc height. Change in disc height was significantly associated with an anterior cage position while lumbar lordosis was unaffected by cage position. A spondylolisthesis subgroup demonstrated 31% reduction in the magnitude of anterior slip. Less lordosis was associated with worse back and leg pain as assessed by VAS and greater disk heights were associated with higher Odom's criteria scores. Patients with persistent leg pain at final follow‐up had less lumbar lordosis and intervertebral height than patients without leg pain.

Conclusions:  Intervertebral height and lumbar lordosis reconstruction are important for achieving good surgical results; guidance regarding the likely changes in lumbar lordosis and disk height after TLIF is provided by our findings.
A Systematic Approach to Studying Fisheries Governance
Authors: Basurto Xavier , Nenadovic Mateja
Published: January 2012

How can policies for governing marine fisheries become more effective? How can we engage in developing a new science of fisheries governance that promotes knowledge accumulation and collective learning? We look into these issues by reviewing the current social‐ecological status of marine fisheries, common policy approaches in place to govern them, and key learned lessons and shortcomings. While great efforts have been made towards understanding marine governance in the last 50 years, if we are to meet the current and upcoming challenges facing global fisheries, we need to engage with systematic knowledge accumulation about governance performance. To this end we report on a novel classificatory framework which, while nascent, could offer the potential to help us move in that direction.
Endocannabinoids at the synapse a decade after the dies mirabilis (29 March 2001): what we still do not know
Authors: Alger Bradley E.
Published: January 2012

Abstract  Endogenous cannabinoids (endocannabinoids, eCBs) are ubiquitous regulators of synaptic transmission in the brain, mediating numerous forms of short‐ and long‐term plasticity, and having strong influences on synapse formation and neurogenesis. Their roles as retrograde messengers that suppress both excitatory and inhibitory transmission are well‐established. Yet, despite intensive investigation, many basic aspects of the eCB system are not understood. This brief review highlights recent advances, problems that remain unresolved, and avenues for future exploration. While 2‐arachidonoylglycerol (2‐AG) is probably the major eCB for intercellular CB1R‐dependent signalling, anandamide (AEA) has come to the forefront in several novel contexts, both as a dual endovanilloid/endocannabinoid that regulates synaptic transmission acutely and as the source of a steady eCB tone in hippocampus. Complexities in the cellular processing of 2‐AG are receiving renewed attention, as they are increasingly recognized as major determinants of how 2‐AG affects cells. Long‐standing fundamental issues such as the synthesis pathway for AEA and the molecular mechanism(s) underlying cellular uptake and release of eCBs remain problematical.
Muscle protein synthesis in response to nutrition and exercise
Authors: Atherton P. J. , Smith K.
Published: January 2012

Abstract  Muscle protein synthesis (MPS) is the driving force behind adaptive responses to exercise and represents a widely adopted proxy for gauging chronic efficacy of acute interventions, (i.e. exercise/nutrition). Recent findings in this arena have been progressive. Nutrient‐driven increases in MPS are of finite duration (∼1.5 h), switching off thereafter despite sustained amino acid availability and intramuscular anabolic signalling. Intriguingly, this ‘muscle‐full set‐point’ is delayed by resistance exercise (RE) (i.e. the feeding × exercise combination is ‘more anabolic’ than nutrition alone) even ≥24 h beyond a single exercise bout, casting doubt on the importance of nutrient timing vs. sufficiency per se. Studies manipulating exercise intensity/workload have shown that increases in MPS are negligible with RE at 20–40% but maximal at 70–90% of one‐repetition maximum when workload is matched (according to load × repetition number). However, low‐intensity exercise performed to failure equalises this response. Analysing distinct subcellular fractions (e.g. myofibrillar, sarcoplasmic, mitochondrial) may provide a readout of chronic exercise efficacy in addition to effect size in MPS per se, i.e. while ‘mixed’ MPS increases similarly with endurance and RE, increases in myofibrillar MPS are specific to RE, prophetic of adaptation (i.e. hypertrophy). Finally, the molecular regulation of MPS by exercise and its regulation via ‘anabolic’ hormones (e.g. IGF‐1) has been questioned, leading to discovery of alternative mechanosensing–signalling to MPS.
Science Signaling
Podcast: 31 January 2012
Authors: Cardon Caleb M. , Rutter Jared , VanHook Annalisa M.
Published: January 2012

Signaling through PAS kinases bypasses the pro-growth requirement of Tor2 in yeast.
Trapped in the Plaque
Authors: Adler Elizabeth M.
Published: January 2012

Netrin-1 enhances the retention of macrophages and the recruitment of smooth muscle cells, thereby promoting the progression of atherosclerotic lesions.
Expression of OXA-Type and SFO-1 β-Lactamases Induces Changes in Peptidoglycan Composition and Affects Bacterial Fitness
Authors: Fernández Ana , Pérez Astrid , Ayala Juan A. , Mallo Susana , Rumbo-Feal Soraya , Tomás Maria , Poza Margarita , Bou Germán
Published: January 2012

β-Lactamases and penicillin-binding proteins (PBPs) have evolved from a common ancestor. β-Lactamases are enzymes that degrade β-lactam antibiotics, whereas PBPs are involved in the synthesis and processing of peptidoglycan, which forms an elastic network in the bacterial cell wall. This study analyzed the interaction between β-lactamases and peptidoglycan and the impact on fitness and biofilm production. A representative set of all classes of β-lactamases was cloned in the expression vector pBGS18 under the control of the CTX-M promoter and expressed in
Escherichia coli
MG1655. The peptidoglycan composition of all clones was evaluated, and quantitative changes were found in
E. coli
strains expressing OXA-24, OXA-10-like, and SFO-1 (with its upstream regulator AmpR) β-lactamases; the level of cross-linked muropeptides decreased, and their average length increased. These changes were associated with a statistically significant fitness cost, which was demonstrated in both
in vitro
and
in vivo
experiments. The observed changes in peptidoglycan may be explained by the presence of residual
dd
-endopeptidase activity in these β-lactamases, which may result in hydrolysis of the peptide cross bridge. The biological cost associated with these changes provides important data regarding the interaction between β-lactamases and the metabolism of peptidoglycan and may provide an explanation for the epidemiology of these β-lactamases in
Enterobacteriaceae
.
Alterations of OprD in Carbapenem-Intermediate and -Susceptible Strains of Pseudomonas aeruginosa Isolated from Patients with Bacteremia in a Spanish Multicenter Study
Authors: Ocampo-Sosa Alain A. , Cabot Gabriel , Rodríguez Cristina , Roman Elena , Tubau Fe , Macia María D. , Moya Bartolomé , Zamorano Laura , Suárez Cristina , Peña Carmen , Domínguez María A. , Moncalián Gabriel , Oliver Antonio , Martínez-Martínez Luis ,   the Spanish Network for Research in Infectious Diseases (REIPI)
Published: January 2012

We investigated the presence of OprD mutations in 60 strains of metallo-ß-lactamase-negative
Pseudomonas aeruginosa
intermediately susceptible (IS [
n
= 12]; MIC = 8 μg/ml) or susceptible (S [
n
= 48]; MICs ≤ 1 to 4 μg/ml) to imipenem and/or meropenem that were isolated from patients with bacteremia in order to evaluate their impact on carbapenem susceptibility profiles. The presence of mutations in
oprD
was detected by sequencing analysis. OprD expression was assessed by both outer membrane protein (OMP) analysis and real-time PCR (RT-PCR). Fourteen (23%) isolates had an OprD identical to that of PAO1, and OprD modifications were detected in 46 isolates (77%). Isolates were classified as OprD “full-length types” (T1 [
n
= 40, including both wild-type OprD and variants showing several polymorphisms]) and OprD “deficient types” (T2 [
n
= 3 for OprD frameshift mutations] and T3 [
n
= 17 for premature stop codons in
oprD
]). RT-PCR showed that 5 OprD type T1 isolates presented reduced transcription of
oprD
(0.1- to 0.4-fold compared to PAO1), while
oprD
levels increased more than 2-fold over that seen with PAO1 in 4 OprD type T1 isolates. A total of 50% of the isolates belonging to OprD “deficient types” were susceptible to both carbapenems, and 40% were susceptible to meropenem and intermediately susceptible to imipenem. Only one isolate (5%) within this group was intermediately susceptible to both carbapenems, and one (5%) was susceptible to imipenem and intermediately susceptible to meropenem. We concluded that OprD inactivating mutations in clinical isolates of
P. aeruginosa
are not restricted only to carbapenem-resistant isolates but are also found in isolates with imipenem or meropenem MICs of only 0.06 to 4 μg/ml.
Complete Sequence of a Novel 178-Kilobase Plasmid Carrying
bla
NDM-1
in a Providencia stuartii Strain Isolated in Afghanistan
Authors: Mc Gann Patrick , Hang Jun , Clifford Robert J. , Yang Yu , Kwak Yoon I. , Kuschner Robert A. , Lesho Emil P. , Waterman Paige E.
Published: January 2012

In response to global concerns over the spread of the New Delhi metallo-β-lactamase gene 1,
bla
NDM-1
, a monthly surveillance program was initiated in September 2010. All carbapenem-resistant Gram-negative strains forwarded to our facility are screened for this gene. To date, 321 carbapenem-resistant isolates, encompassing 11 bacterial species, have been tested. In February 2011, two strains of
Providencia stuartii
, submitted from a military hospital in Afghanistan, tested positive for
bla
NDM-1
. Both strains were identical by pulsed-field gel electrophoresis (PFGE).
bla
NDM-1
was carried on a large plasmid, pMR0211, which was sequenced by emulsion PCR and pyrosequencing. pMR0211 is 178,277 bp in size and belongs to incompatibility group A/C. The plasmid consists of a backbone with considerable homology to pAR060302 from
Escherichia coli
, and it retains many of the antibiotic resistance genes associated with it. The plasmid also shares common elements with the pNDM-HK plasmid, including
bla
NDM-1
,
armA
, and
sul1
. However, gene orientation is reversed, and a 3-kb fragment from this region is absent from pMR0211. pMR0211 also contains additional genes, including the aminoglycoside-modifying enzyme loci
aadA
and
aac
(
6
′), the quinolone resistance gene
qnrA
, a gene with highest homology to a U32 family peptidase from
Shewanella amazonensis
, and the
bla
OXA-10
gene. The finding of this gene in an intrinsically colistin-resistant species such as
Providencia stuartii
is especially worrisome, as it renders the organism resistant to nearly every available antibiotic. The presence of multiple insertion sequences and transposons flanking the region containing the
bla
NDM-1
gene further highlights the potential mobility associated with this gene.
Pharmacokinetics of Different Dosing Strategies of Oral Posaconazole in Patients with Compromised Gastrointestinal Function and Who Are at High Risk for Invasive Fungal Infection
Authors: Cornely Oliver A. , Helfgott David , Langston Amelia , Heinz Werner , Vehreschild Jörg-Janne , Vehreschild Maria J. G. T. , Krishna Gopal , Ma Lei , Huyck Susan , McCarthy Michael C.
Published: January 2012

The aim of this study was to assess different dosing strategies that may result in increased posaconazole bioavailability in patients with compromised gastrointestinal function and at high risk for invasive fungal infections. Patients undergoing chemotherapy and at risk for compromised gastrointestinal function received open-label posaconazole at 200 mg three times daily (TID) on days 1 to 8. Patients were randomized to one of three open-label dosing regimens of posaconazole on days 9 to 15: 200 mg TID, 400 mg twice daily (BID), or 400 mg TID. The plasma concentrations of interest on days 8 and 15 were 500 and 700 ng/ml, respectively; day 2 plasma concentrations of 250 and 350 ng/ml were chosen as levels that might result in steady-state concentrations of >500 and >700 ng/ml, respectively. A total of 75 patients enrolled; 52/75 (69%) completed the study, and 49/75 were included in the pharmacokinetic analyses. Mean plasma concentrations were 230, 346, and 637 ng/ml on days 2, 3, and 8, respectively. The day 15 values were 660, 930, and 671 ng/ml for 200 mg TID, 400 mg BID, and 400 mg TID, respectively. In 12 patients with a day 8 posaconazole concentration of <250 ng/ml, an overall benefit of the higher two doses was not apparent, suggesting that a subset of patients has low steady-state plasma concentrations. A change in dosing regimen on day 9 did not lead to higher exposures in these “poor absorbers” on day 15. Poor absorption may be enhanced with a high-fat meal, a nutritional supplement, or acidification.
An Antibiotic That Inhibits a Late Step in Wall Teichoic Acid Biosynthesis Induces the Cell Wall Stress Stimulon in Staphylococcus aureus
Authors: Campbell Jennifer , Singh Atul K. , Swoboda Jonathan G. , Gilmore Michael S. , Wilkinson Brian J. , Walker Suzanne
Published: January 2012

Wall teichoic acids (WTAs) are phosphate-rich, sugar-based polymers attached to the cell walls of most Gram-positive bacteria. In
Staphylococcus aureus
, these anionic polymers regulate cell division, protect cells from osmotic stress, mediate host colonization, and mask enzymatically susceptible peptidoglycan bonds. Although WTAs are not required for survival
in vitro
, blocking the pathway at a late stage of synthesis is lethal. We recently discovered a novel antibiotic, targocil, that inhibits a late acting step in the WTA pathway. Its target is TarG, the transmembrane component of the ABC transporter (TarGH) that exports WTAs to the cell surface. We examined here the effects of targocil on
S. aureus
using transmission electron microscopy and gene expression profiling. We report that targocil treatment leads to multicellular clusters containing swollen cells displaying evidence of osmotic stress, strongly induces the cell wall stress stimulon, and reduces the expression of key virulence genes, including
dltABCD
and capsule genes. We conclude that WTA inhibitors that act at a late stage of the biosynthetic pathway may be useful as antibiotics, and we present evidence that they could be particularly useful in combination with beta-lactams.
MurAA Is Required for Intrinsic Cephalosporin Resistance of Enterococcus faecalis
Authors: Vesić Dušanka , Kristich Christopher J.
Published: January 2012

Enterococcus faecalis
is a low-GC Gram-positive bacterium that is intrinsically resistant to cephalosporins, antibiotics that target cell wall biosynthesis. To probe the mechanistic basis for intrinsic resistance, a library of transposon mutants was screened to identify
E. faecalis
strains that are highly susceptible to ceftriaxone, revealing a transposon mutant with a disruption in
murAA. murAA
is predicted to encode a UDP-
N
-acetylglucosamine 1-carboxyvinyl transferase that catalyzes the first committed step in peptidoglycan synthesis: phosphoenolpyruvate (PEP)-dependent conversion of UDP-
N
-acetylglucosamine to UDP-
N
-acetylglucosamine-enolpyruvate. In-frame deletion of
murAA
, but not its homolog in the
E. faecalis
genome (
murAB
), led to increased susceptibility of
E. faecalis
to cephalosporins. Furthermore, expression of
murAA
enhanced cephalosporin resistance in an
E. faecalis
mutant lacking IreK (formerly PrkC), a key kinase required for cephalosporin resistance. Further genetic analysis revealed that MurAA catalytic activity is necessary but not sufficient for this role. Collectively, our data indicate that MurAA and MurAB have distinct roles in
E. faecalis
physiology and suggest that MurAA possesses a unique property or activity that enables it to enhance intrinsic resistance of
E. faecalis
to cephalosporins.
Small Plasmids Harboring
qnrB19
: a Model for Plasmid Evolution Mediated by Site-Specific Recombination at
oriT
and Xer Sites
Authors: Tran Tung , Andres Patricia , Petroni Alejandro , Soler-Bistué Alfonso , Albornoz Ezequiel , Zorreguieta Angeles , Reyes-Lamothe Rodrigo , Sherratt David J. , Corso Alejandra , Tolmasky Marcelo E.
Published: January 2012

Plasmids pPAB19-1, pPAB19-2, pPAB19-3, and pPAB19-4, isolated from
Salmonella
and
Escherichia coli
clinical strains from hospitals in Argentina, were completely sequenced. These plasmids include the
qnrB19
gene and are 2,699, 3,082, 2,989, and 2,702 nucleotides long, respectively, and they share extensive homology among themselves and with other previously described small
qnrB19
-harboring plasmids. The genetic environment of
qnrB19
in all four plasmids is identical to that in these other plasmids and in transposons such as Tn
2012
, Tn
5387
, and Tn
5387
-like. Nucleotide sequence comparisons among these and previously described plasmids showed a variable region characterized by being flanked by an
oriT
locus and a Xer recombination site. We propose that this arrangement could play a role in the evolution of plasmids and present a model for DNA swapping between plasmid molecules mediated by site-specific recombination events at
oriT
and a Xer target site.
Dynamic Interaction between Fluconazole and Amphotericin B against Cryptococcus gattii
Authors: Santos Julliana Ribeiro Alves , Gouveia Ludmila Ferreira , Taylor Erika Linzi Silva , Resende-Stoianoff Maria Aparecida , Pianetti Gerson Antônio , César Isabela Costa , Santos Daniel Assis
Published: January 2012

Cryptococcus gattii
is the main pathogen of cryptococcosis in healthy patients and is treated mainly with fluconazole and amphotericin B. The combination of these drugs has been questioned because the mechanisms of action could lead to a theoretical antagonistic interaction. We evaluated distinct parameters involved in the
in vitro
combination of fluconazole and amphotericin B against
Cryptococcus gattii
. Fourteen strains of
C. gattii
were used for the determination of MIC, fractional inhibitory concentration, time-kill curve, and postantifungal effect (PAFE). Ergosterol quantification was performed to evaluate the influence of ergosterol content on the interaction between these antifungals. Interaction between the drugs varied from synergistic to antagonistic depending on the strain and concentration tested. Increasing fluconazole levels were correlated with an antagonistic interaction. A total of 48 h was necessary for reducing the fungal viability in the presence of fluconazole, while 12 h were required for amphotericin B. When these antifungals were tested in combination, fluconazole impaired the amphotericin B activity. The ergosterol content decreased with the increase of fluconazole levels and it was correlated with the lower activity of amphotericin B. The PAFE found varied from 1 to 4 h for fluconazole and from 1 to 3 h for amphotericin B. The interaction of fluconazole and amphotericin B was concentration-dependent and special attention should be directed when these drugs are used in combination against
C. gattii
.
Evolutionary Changes in Antimicrobial Resistance of Invasive Neisseria meningitidis Isolates in Belgium from 2000 to 2010: Increasing Prevalence of Penicillin Nonsusceptibility
Authors: Bertrand Sophie , Carion Françoise , Wintjens René , Mathys Vanessa , Vanhoof Raymond
Published: January 2012

This study was conducted to evaluate the evolution of the antimicrobial susceptibility of
Neisseria meningitidis
causing invasive diseases in Belgium in the period of January 2000 to December 2010. A total of 1,933 cases of
N. meningitidis
from invasive infections were analyzed by antimicrobial susceptibility testing at the Belgian Meningococcal Reference Centre. The majority of strains were susceptible to antibiotics that are currently used for the treatment and prophylaxis of meningococcal disease, but the prevalence of clinical isolates with reduced susceptibility to penicillin increased over the years. The phenotyping, genotyping, and determination of MICs of penicillin G were performed. The systematic shift of the curves toward higher penicillin MICs in the susceptible population indicated that this population became less sensitive to penicillin in this period. A 402-bp DNA fragment in the 3′ end of
penA
was sequenced for the 296 nonsusceptible meningococcal strains isolated between 2000 and 2010 to examine the genetic diversity and evolution of their
penA
gene. In conclusion, the data obtained in our study support the statement that the position of penicillin G as a first choice in the treatment of invasive meningococcal diseases in Belgium should be reexamined. Despite an important number of isolates displaying a reduced susceptibility to penicillin, at present the expanded-spectrum cephalosporins, such as ceftriaxone, are not affected. The follow-up of the evolutionary changes in antimicrobial resistance has also proved to be essential for the recommendation of an appropriate antimicrobial treatment for invasive meningococcal diseases.
Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice
Authors: Washino Takuya , Moroda Masataka , Iwakura Yoichiro , Aosai Fumie
Published: January 2012

Interleukin 1 receptor antagonist (IL-1Ra)-deficient BALB/c mice develop spontaneous arthritis resembling human rheumatoid arthritis. We herein report that infection withToxoplasma gondii, an intracellular protozoan, is capable of ameliorating the spontaneous development of arthritis in IL-1Ra-deficient mice. The onset of arthritis development was delayed and the severity score of arthritis was significantly suppressed inT. gondii-infected mice. Expression of IL-12p40 mRNA from CD11c+cells of mesenteric lymph nodes (mLN) and spleen markedly increased at 1 week after peroral infection. While CD11c+cells also produced IL-10, IL-1β, and IL-6, CD4+T cells fromT. gondii-infected mice expressed significantly high levels of T-bet and gamma interferon (IFN-γ) mRNA in both mLN and spleen. Levels of GATA-3/IL-4 mRNA or RORγt/IL-17 mRNA decreased in the infected mice, indicating Th1 cell polarization and the reduction of Th2 and Th17 cell polarization. The severity of arthritis was related to Th1 cell polarization accompanied by Th17 cell reduction, demonstrating the protective role of theT. gondii-derived Th1 response against Th17 cell-mediated arthritis in IL-1Ra-deficient mice.
Both Phthiocerol Dimycocerosates and Phenolic Glycolipids Are Required for Virulence of Mycobacterium marinum
Authors: Yu Jia , Tran Vanessa , Li Ming , Huang Xinghua , Niu Chen , Wang Decheng , Zhu Jianghua , Wang Jianping , Gao Qian , Liu Jun
Published: January 2012

Phthiocerol dimycocerosates (PDIMs) and structurally related phenolic glycolipids (PGLs) are complex cell wall lipids unique to pathogenic mycobacteria. While these lipids have been extensively studied in recent years, there are conflicting reports on some aspects of their biosynthesis and on the role of PDIMs and especially PGLs in virulence of
Mycobacterium tuberculosis
. This has been complicated by the natural deficiency of PGLs in many clinical strains of
M. tuberculosis
and the frequent loss of PDIMs in laboratory
M. tuberculosis
strains. In this study, we isolated seven mutants of
Mycobacterium marinum
deficient in PDIMs and/or PGLs in which multiple genes of the PDIM/PGL biosynthetic locus were disrupted by transposon insertion. Zebrafish infection experiments showed that
M. marinum
strains lacking one or both of these lipids were avirulent, suggesting that both PDIMs and PGLs are required for virulence. We also found that these strains were hypersensitive to antibiotics and exhibited increased cell wall permeability. Our studies provide new insights into the biosynthesis of PDIMs/PGLs and may help us to understand the role of PDIMs and PGLs in
M. tuberculosis
virulence.
Comparing CATCH, CHALICE and PECARN clinical decision rules for paediatric head injuries
Authors: Lyttle Mark D , Crowe Louise , Oakley Ed , Dunning Joel , Babl Franz E
Published: January 2012

Many children present to emergency departments following head injury (HI), with a small number at risk of avoidable poor outcome. Difficulty identifying such children, coupled with increased availability of cranial CT, has led to variation in practice and increased CT rates. Clinical decision rules (CDRs) have been derived for paediatric HI but there is no published comparison to assist in deciding which to implement. The content of the three of highest quality and accuracy are described and compared. Systematic reviews of paediatric HI CDRs were published in 2009 and 2011. To identify CDRs published since the most recent review, key databases were searched, selecting studies which included CDRs involving children aged 0–18 years with a history of HI. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies Tool, and performance evaluated by reported accuracy. Three high quality CDRs were identified: CATCH (Canadian Assessment of Tomography for Childhood Head Injury) CHALICE (Children's Head Injury Algorithm for the Prediction of Important Clinical Events) and PECARN (Paediatric Emergency Care Applied Research Network). All were derived with high methodological standards but differed in key areas, including study population, outcomes and severity of HI. Each stated different predictor variables and only PECARN provided a separate algorithm for young children. CATCH and CHALICE identify children requiring CT and PECARN those who do not. All perform with high sensitivity and low specificity. PECARN is the only validated CDR, and none has undergone impact analysis. These three CDRs should undergo validation and comparison in a single population, with analysis of their impact on practice and financial implications, to aid relevant bodies in deciding which to implement.
Willingness to use HIV pre-exposure prophylaxis and the likelihood of decreased condom use are both associated with unprotected anal intercourse and the perceived likelihood of becoming HIV positive among Australian gay and bisexual men
Authors: Holt Martin , Murphy Dean A , Callander Denton , Ellard Jeanne , Rosengarten Marsha , Kippax Susan C , de Wit John B F
Published: January 2012

Objectives

To investigate willingness to use HIV pre-exposure prophylaxis (PrEP) and the likelihood of decreased condom use among Australian gay and bisexual men.

Methods

A national, online cross-sectional survey was conducted in April to May 2011. Bivariate relationships were assessed with χ2or Fisher's exact test. Multivariate logistic regression analysis was performed to assess independent relationships with primary outcome variables.

Results

Responses from 1161 HIV-negative and untested men were analysed. Prior use of antiretroviral drugs as PrEP was rare (n=6). Just over a quarter of the sample (n=327; 28.2%) was classified as willing to use PrEP. Willingness to use PrEP was independently associated with younger age, having anal intercourse with casual partners (protected or unprotected), having fewer concerns about PrEP and perceiving oneself to be at risk of HIV. Among men who were willing to use PrEP (n=327), only 26 men (8.0%) indicated that they would be less likely to use condoms if using PrEP. The likelihood of decreased condom use was independently associated with older age, unprotected anal intercourse with casual partners (UAIC) and perceiving oneself to be at increased risk of HIV.

Conclusions

The Australian gay and bisexual men the authors surveyed were cautiously optimistic about PrEP. The minority of men who expressed willingness to use PrEP appear to be appropriate candidates, given that they are likely to report UAIC and to perceive themselves to be at risk of HIV.
Clinical Efficacy of Macrophage-Activating Chinese Mixed Herbs (MACH) in Improvement of Embryo Qualities in Women with Long-Term Infertility of Unknown Etiology
Authors: Ushiroyama Takahisa , Yokoyama Noriko , Hakukawa Midori , Sakuma Kou , Ichikawa Fumio , Yoshida Satoshi
Published: January 2012

Despite the recent technological advances in in vitro fertilization and embryo transfer (IVF-ET), a significant proportion of women still do not become pregnant after long-term infertility, whether it is originally due to older age or other undetermined factors. In the present study, macrophage activating Chinese herbs (MACH) were evaluated for their effects on embryo qualities in women who were undergoing repeated IVF-ET because of long-term infertility. Thirty women, who had significantly low rates of developing good quality cleaved embryos and did not become pregnant after three or more cycles of Assisted Reproductive Technology (ART) procedure, were included in the study. Oral administration of MACH significantly increased the percentage of good quality early stage blastocysts (the number of grade 1 or grade 2 cleaved embryos/the number of retrieved oocytes) from 18.7 ± 16.2% to 36.1 ± 27.1% (1.9-fold increase, p < 0.01). The rate of good quality early stage blastocysts increased in all patients. In 19 patients who desired embryo transfer using late stage blastocysts, MACH significantly increased the percentage of late stage blastocysts from the initial value of 14.8 ± 11.2% to 21.1 ± 23.1% (1.4-fold increase, p < 0.05). The rate of embryonic progress into late stage blastocyst increased in 52.6% (10/19) of the patients. Furthermore, treatment with MACH significantly decreased the plasma follicle stimulating hormone (FSH) concentration on the day of oocyte retrieval from 14.4 ± 3.2 to 10.5 ± 2.4 mIU/ml (p < 0.05). No adverse events were observed with MACH supplementation, and there was no patient dropout. Administration of MACH resulted in improved embryo quality in the difficult cases. The present study demonstrates a new benefit of this herbal blend in women with refractory infertility of unknown etiology.
Clinical Outcomes of Traditional Chinese Medicine Compound Formula in Treating Sleep-Disordered Breathing Patients
Authors: Wu Yi-Hong , Wei Yi-Chia , Tai Yu-Shan , Chen Kuan-Jen , Li Hsueh-Yu
Published: January 2012

Sleep-Disordered Breathing (SDB) is a prevalent affliction, which can range from simple snoring to severely obstructive sleep apnea. Compared to current treatment options of SDB, traditional Chinese medicine (TCM) provides a noninvasive way to relieve SDB-related symptoms and deaths. The purpose of this retrospective study was to observe the progression of adult SDB patients who had taken compound formula SZ + NUH (concentrated herbal granules) for four weeks. Depending on subjects’ individual needs, minor additions of formulas or single herbs were allowed. We found a significant amount of relief from snoring among the 118 enrolled subjects, according to before-after scores observed through the Snore Outcome Survey (SOS). Furthermore, as projected from the moderate linear correlation in before-after scores, we inferred that those cases with more severe snoring at baseline had greater improvement after treatment. Excessive daytime sleepiness was also significantly improved according to the results of the Epworth Sleepiness Scale (ESS). Assessment, using the SF-36 (Taiwanese version) revealed possible benefits of SZ + NUH in improving multiple facets of subjects’ quality of life. During treatment, no significant side effects occurred. In conclusion, the TCM compound formula based on SZ + NUH could be a safe and effective option for SDB treatment.
2 Hz Electro-Acupuncture at Yinlingquan (SP9) and Ququan (LR8) Acupoints Induces Changes in Blood Flow in the Liver and Spleen
Authors: Chou Wen-Cheng , Liu Hsu-Jan , Lin Yi-Wen , Cheng Chin-Yi , Li Tsai-Chung , Tang Nou-Ying , Hsieh Ching-Liang
Published: January 2012

According to the principles of traditional Chinese medicine, channels and collaterals within the body provide pathways through which qi and blood travel, and each channel or collateral is linked with a specific organ. The Yinlingquan (spleen 9, SP9) and Ququan (liver 8, LR8) acupoints represent the sea points of the spleen and liver meridians, respectively, from which qi and blood flow into their specific visceral organs. The purpose of this study was to investigate the changes in blood flow/perfusion in the liver and spleen resulting from the application of 2 Hz electro-acupuncture (EA) to the Yinlingquan (SP9) or Ququan (LR8) acupoints. A total of 18 Spragrue-Dawley rats were randomly divided into three groups of six rats each as follows: sham group receiving sham EA; Yinlingquan (SP9) group receiving 2 Hz EA, applied at bilateral Yinlingquan (SP9) acupoints; and Ququan (LR8) groups receiving 2 Hz EA, applied at bilateral Ququan (LR8) acupoints. The mean blood flow/perfusion of the spleen and liver was recorded using a laser Doppler blood flow monitor prior to EA (representing the baseline), during EA, and post-EA. Each measurement period lasted ten minutes. Nitric oxide levels were also measured from the right femoral arterial blood, following the conclusion of each series of blood flow/perfusion recordings. The results indicate that the sham EA did not increase the mean blood flow/perfusion in the liver or spleen; 2 Hz EA at bilateral Yinlingquan (SP9) acupoints increased the mean blood flow/perfusion in the spleen, but not in the liver. In contrast, 2 Hz EA at bilateral Ququan (LR8) acupoints increased the mean blood flow/perfusion in the liver, but not in the spleen. Nitric oxide levels showed no significant difference between any of the groups at any stage of the measurements. According to the results, we conclude that EA at the Yinlingquan (SP9) and Ququan (LR8) acupoints can increase the blood flow in the spleen and liver, respectively.
Scutellaria baicalensis Attenuates Blood-Brain Barrier Disruption after Intracerebral Hemorrhage in Rats
Authors: Shin Jung-Won , Kang Ho-Chang , Shim Jaewon , Sohn Nak-Won
Published: January 2012

Disruption of the blood-brain barrier (BBB) contributes to the inflammatory response and edema formation in the brain, exacerbating brain damage. The present study evaluated the effects of Scutellaria baicalensis (SR) water extracts on BBB disruption after intracerebral hemorrhage (ICH) in rats. ICH was induced by stereotaxic intrastriatal injection of bacterial type VII collagenase, and SR was administrated orally three times (50 mg/ml/kg) during the 48 h after ICH onset. SR treatment significantly reduced the degree of (1) hemorrhage volume and edema percentage of the ipsilateral hemisphere, (2) brain water content, (3) MPO-positive neutrophil infiltration in the peri-hematoma, and (4) BBB permeability measured by Evans blue leakage. In addition, expression of matrix metalloproteinase (MMP)-9, MMP-12, and tissue inhibitor of MMPs (TIMP)-1 were investigated with immunohistochemistry. SR treatment reduced MMP-9 and MMP-12 expression in the peri-hematoma after ICH. These results indicate that SR attenuates the BBB disruption through anti-inflammatory effects and suppression of MMP expression. These findings provide a pharmacological basis for the use of SR in the treatment of the BBB disruption following stroke and trauma.
Anti-Fatigue Effect ofZizania caudiflora (Turczaninow)Nakai
Authors: Kim Na-Hyung , Moon Phil-Dong , Pak Sok Cheon , Kim Hyung-Min , Jeong Hyun-Ja
Published: January 2012

The purpose of the present study was to investigate the anti-fatigue effect of Zizania caudiflora (Turczaninow) Nakai (ZC) and hydrolyzed ZC by malted barley (HZC) through a forced swimming test (FST) in mice. After the first measurement of immobility times, the mice were divided into control, fluoxetine, ZC, and HZC groups to match the swimming times in each group. The immobility times in the FST of the control as well as the fluoxetine, ZC, and HZC-administered groups after administration for three days were 135.3 ± 3.3,66.8 ± 3.9,120.2 ± 2.7, and 123.2 ± 2.9 sec, respectively. The immobility times in the FST of the ZC and HZC-administered groups for 14 days were significantly decreased in comparison with the control group (p < 0.01). In addition, the immobility times of ZC and HZC-administered groups for 14 days in the tail-suspension test were also significantly decreased in comparison with the control group (p < 0.05). The plasma levels of albumin, glucose, and total protein were significantly increased and creatine phosphokinase was significantly decreased in the ZC and HZC-administered groups compared to the control group. However, the levels of lactate dehydrogenase and blood urea nitrogen in the ZC and HZC-administered groups did not represent a significant difference compared to the control group. In summary, these results suggest that ZC or HZC might be a candidate for an anti-fatigue agent.
GENERALIZED YANG–BAXTER EQUATIONS AND BRAIDING QUANTUM GATES
Authors: CHEN REBECCA S.
Published: January 2012

Solutions to the Yang–Baxter equation — an important equation in mathematics and physics — and their afforded braid group representations have applications in fields such as knot theory, statistical mechanics, and, most recently, quantum information science. In particular, unitary representations of the braid group are desired because they generate braiding quantum gates. These are actively studied in the ongoing research into topological quantum computing. A generalized Yang–Baxter equation was proposed a few years ago by Eric Rowell et al. By finding solutions to the generalized Yang–Baxter equation, we obtain new unitary braid group representations. Our representations give rise to braiding quantum gates and thus have the potential to aid in the construction of useful quantum computers.
Statistical Soft Error Rate (SSER) Analysis for Scaled CMOS Designs
Authors: Peng Huan-Kai , Huang Hsuan-Ming , Kuo Yu-Hsin , Wen Charles H.-P.
Published: January 2012

This article re-examines the soft error effect caused by radiation-induced particles beyond the deep submicron regime. Considering the impact of process variations, voltage pulse widths of transient faults are found no longer monotonically diminishing after propagation, as they were formerly. As a result, the soft error rates in scaled electronic designs escape traditional static analysis and are seriously underestimated. In this article we formulate the statistical soft error rate (SSER) problem and present two frameworks to cope with the aforementioned sophisticated issues. The
table-lookup
framework captures the change of transient-fault distributions implicitly by using a Monte-Carlo approach, whereas the
SVR-learning
framework does the task explicitly by using statistical learning theory. Experimental results show that both frameworks can more accurately estimate SERs than static approaches do. Meanwhile, the SVR-learning framework outperforms the table-lookup framework in both SER accuracy and runtime.
Robust Vacuity for Branching Temporal Logic
Authors: Gurfinkel Arie , Chechik Marsha
Published: January 2012

There is a growing interest in techniques for detecting whether a logic specification is satisfied too easily, or
vacuously
. For example, the specification “every request is eventually followed by an acknowledgment” is satisfied vacuously by a system that never generates any requests. Vacuous satisfaction misleads users of model-checking into thinking that a system is correct. It is a serious problem in practice.

There are several existing definitions of vacuity. Originally, Beer et al. [1997] formalized
vacuity
as insensitivity to syntactic perturbation (
syntactic vacuity
). This formulation captures the intuition of “vacuity” when applied to a single occurrence of a subformula. Armoni et al. argued that vacuity must be
robust
; not affected by semantically invariant changes, such as extending a model with additional atomic propositions. They show that syntactic vacuity is not robust for subformulas of linear temporal logic, and propose an alternative definition;
trace vacuity
.

In this article, we continue this line of research. We show that trace vacuity is not robust for branching time logic. We further refine the notion of vacuity so that it applies uniformly to linear and branching time logic and does not suffer from the common pitfalls of prior definitions. Our new definition,
bisimulation vacuity
, is a proper and nontrivial extension of both syntactic and trace vacuity. We discuss the complexity of detecting bisimulation vacuity, and identify several practically-relevant subsets of CTL* for which vacuity detection problem is reducible to model-checking. We believe that in most practical applications, bisimulation vacuity provides both the desired theoretical properties and is tractable computationally.