bluuebunny/crossref_metadata_2025 huggingface dataset:
Dating Violence Among Urban, Minority, Middle School Youth and Associated Sexual Risk Behaviors and Substance Use
Authors: Lormand Donna K. , Markham Christine M. , Peskin Melissa F. , Byrd Theresa L. , Addy Robert C. , Baumler Elizabeth , Tortolero Susan R.
Published: April 2013

BACKGROUND

Whereas dating violence among high school students has been linked with sexual risk‐taking and substance use, this association has been understudied among early adolescents. We estimated the prevalence of physical and nonphysical dating violence in a sample of middle school students and examined associations between dating violence, sexual, and substance use behaviors.

METHODS

Logistic regression models for clustered data from 7th grade students attending 10 Texas urban middle schools were used to examine cross‐sectional associations between dating violence victimization and risk behaviors.

RESULTS

The sample (N = 950) was 48.5% African American, 36.0% Hispanic, 55.7% female, mean age 13.1 years (SD 0.64). About 1 in 5 reported physical dating violence victimization, 48.1% reported nonphysical victimization, and 52.6% reported any victimization. Adjusted logistic regression analyses indicated that physical, nonphysical, and any victimization was associated with ever having sex, ever using alcohol, and ever using drugs.

CONCLUSIONS

Over 50% of sampled middle school students had experienced dating violence, which may be associated with early sexual initiation and substance use. Middle school interventions that prevent dating violence are needed.
Is It Bullying or Sexual Harassment? Knowledge, Attitudes, and Professional Development Experiences of Middle School Staff
Authors: Charmaraman Linda , Jones Ashleigh E. , Stein Nan , Espelage Dorothy L.
Published: April 2013

BACKGROUND

This study fills a gap in the literature by examining how school staff members view bullying and sexual harassment and their role in preventing both. Given recent legislation, increasingly more attention is paid to bully prevention; however, student‐on‐student sexual harassment is less addressed.

METHODS

Four focus groups were conducted with 32 staff members from 4 midwestern public middle schools. Questions assessed professional development opportunities on bullying and sexual harassment prevention/intervention, personal definitions of these behaviors, and their perceptions of school norms regarding such behavior.

RESULTS

Staff members recalled receiving more professional development on bullying than sexual harassment. They tended to define sexual harassment as something that occurs between adults and/or adults and students and did perceive their role in enforcing a “sexual harassment‐free” peer‐to‐peer school zone.

CONCLUSION

When school administrators fail to provide professional development on both bullying and sexual harassment, staff members do not understand that sexual harassment occurs between students. Thus, they are unaware of policies to protect students from harmful experiences in educational settings and are not likely to understand their own role in preventing them.
Relationships Among Cyberbullying, School Bullying, and Mental Health in Taiwanese Adolescents
Authors: Chang Fong‐Ching , Lee Ching‐Mei , Chiu Chiung‐Hui , Hsi Wen‐Yun , Huang Tzu‐Fu , Pan Yun‐Chieh
Published: April 2013

BACKGROUND

This study examined the relationships among cyberbullying, school bullying, and mental health in adolescents.

METHODS

In 2010, a total of 2992 10th grade students recruited from 26 high schools in Taipei, Taiwan completed questionnaires.

RESULTS

More than one third of students had either engaged in cyberbullying or had been the target (cybervictim) of it in the last year. About 18.4% had been cyberbullied (cybervictim); 5.8% had cyberbullied others (cyberbully); 11.2% had both cyberbullied others and been cyberbullied (cyberbully‐victim). About 8.2% had been bullied in school (victim); 10.6% had bullied others (bully); and, 5.1% had both bullied others and had been bullied in school (bully‐victim). Students with Internet risk behaviors were more likely to be involved in cyberbullying and/or cybervictimization; students who had cyberbullying or victimization experiences also tended to be involved in school bullying/victimization. After controlling for sex, academic performance, and household poverty, cyber/school victims and bully‐victims were more likely to have lower self‐esteem, and cyber/school victims, bullies and bully‐victims were at a greater risk for serious depression.

CONCLUSIONS

Both cyberbullying and school bullying and/or victimization experiences were independently associated with increased depression.
Perception of Thickness, Mouth Coating and Mouth Drying of Dairy Beverages by Younger and Older Volunteers
Authors: Withers Caroline , Gosney Margot A. , Methven Lisa
Published: April 2013

Sensory perception has been found to change during ageing. The perception of mouthfeel by older adults, and the role of ageing on the sensory perception of texture attributes is uncertain. This study investigated perception of the textural attributes of thickness, mouth coating and mouth drying, in the context of dairy beverages, by older and younger adults. Just noticeable differences of a starch thickener and for cream concentration within milk were established for thickness and mouth‐coating perception, finding no age‐related differences between participant groups. Mouth drying was assessed through the directional paired comparison of a mouth‐drying milk beverage to a skimmed milk sample. The older adults were found to be more sensitive to mouth drying (P = 0.03) than the younger adults. This study found no age‐related decline in texture perception with older adults finding perception of some attributes such as mouth drying enhanced by ageing.

Practical Applications

Texture is an important attribute of food and beverages at any age. The decline of olfaction, flavor and taste perception with age may force older adults to put more emphasis on texture attributes; therefore, understanding the perception of textural cues in the mouth is very important. This study found texture perception of thickness, mouth coating and mouth drying may not only be preserved but in the case of mouth drying enhanced during ageing. This may impact on the enjoyment and consumption of foods of older adults, especially during illness or when taking medication. This research study is essential in showing the impact of ageing on texture perception and highlight to the food industry, hospitals and care homes the importance of texture attributes when developing foods and meals for older adults and patients.
Lipopolysaccharide of Aggregatibacter actinomycetemcomitans up‐regulates inflammatory cytokines, prostaglandin E2 synthesis and osteoclast formation in interleukin‐1 receptor antagonist‐deficient mice
Authors: Mizutani H. , Ishihara Y. , Izawa A. , Fujihara Y. , Kobayashi S. , Gotou H. , Okabe E. , Takeda H. , Ozawa Y. , Kamiya Y. , Kamei H. , Kikuchi T. , Yamamoto G. , Mitani A. , Nishihara T. , Noguchi T.
Published: April 2013

Background and Objective

The interleukin (IL)‐1 receptor antagonist (Ra) binds to IL‐1 receptors and inhibits IL‐1 activity. However, it is unclear whether the IL‐1Ra plays a protective role in periodontal disease. The purpose of this study was to compare IL‐1Ra knockout (KO) and wild‐type (WT) mice in regard to proinflammatory cytokine production, osteoclast formation and bone resorption in response to periodontal bacterial lipopolysaccharide (LPS).

Material and Methods

Peritoneal macrophages (Mφs) were obtained from 13‐wk‐old IL‐1Ra KO and WT mice. Peritoneal Mφs were cultured with or without 10 μg/mL of Aggregatibacter actinomycetemcomitans LPS for 24 h. The levels of IL‐1alpha (IL‐1α), IL‐1beta (IL‐1β), tumor necrosis factor‐α (TNF‐α) and IL‐6 were measured in periotoneal Mφs supernatant fluid (PM‐SF) using an ELISA. Bone marrow cells were obtained from the mice and stimulated with PM‐SF for 9 d, then stained with TRAP. The frequency of TRAP‐positive multinucleated giant cell formation was calculated based on a fusion index. PM‐SF‐stimulated calvarial bone resorption was analyzed using micro‐computed tomography, and calvarial histological analysis was performed using hematoxylin and eosin and TRAP staining. The expression of cyclooxygenase‐2 (Cox2), prostanoid receptor EP4 (Ep4) and Rank mRNAs in bone marrow cells were measured using real‐time quantitative PCR, while prostaglandin E2 (PGE2) production was determined by ELISA.

Results

The levels of IL‐1α, IL‐1β, TNF‐α and IL‐6 in IL‐1Ra KO mice PM‐SF stimulated with A. actinomycetemcomitans LPS were significantly increased by approximately 4‐ (p < 0.05), 5‐ (p < 0.05), 1.3‐ (p < 0.05) and 6‐ (p < 0.05) fold, respectively, compared with the levels in WT mice. Moreover, osteoclast formation, expression of Rank, Ep4 and Cox2 mRNAs and production of PGE2 were significantly increased by approximately 2‐ (p < 0.05), 1.6‐ (p < 0.05), 2.5‐ (p < 0.05), 1.6‐ (p < 0.05) and 1.9‐ (p < 0.05) fold, respectively, in IL‐1Ra KO mice stimulated with A. actinomycetemcomitans LPS compared with WT mice.

Conclusion

IL‐1Ra regulates IL‐1 activity and appears to reduce the levels of other inflammatory cytokines, including TNF‐α and IL‐6, while it also reduces expression of the EP4 receptor related to prostanoid sensitivity and osteoclast formation. These results suggest that IL‐1Ra is an important molecule for inhibition of inflammatory periodontal bone resorption.
Is there a link between deep‐sea biodiversity and ecosystem function?
Authors: Leduc Daniel , Rowden Ashley A. , Pilditch Conrad A. , Maas Elizabeth W. , Probert P. Keith
Published: April 2013

Studying the diversity‐ecosystem function relationship in the deep sea is of primary importance in the face of biodiversity loss and for our understanding of how the deep sea functions. Results from the first study of diversity‐ecosystem function relationships in the deep sea (Danovaroet al. 2008; Current Biology, 18, 1–8) are unexpected and show an exponential relationship between deep‐sea nematode diversity and ecosystem function and efficiency, although this relationship appears largely restricted to relatively low diversities [ES(51) <25]. Here, we investigate the relationship between nematode diversity and several independent measures/proxies of ecosystem function (sediment community oxygen consumption, bacterial biomass, bacterial extracellular enzyme activity) and efficiency (ratio of bacterial/nematode carbon to organic C content of the sediment) on the New Zealand continental slope. Nematode diversity at our study sites was relatively high [ES(51) = 30–42], and there was no relationship between species/functional diversity and ecosystem function/efficiency after accounting for the effects of water depth and food availability. Our results are consistent with a breakdown of the exponential diversity‐function relationship at high levels of diversity, which may be due to increased competition or greater functional redundancy. Future studies need to take into account as many environmental factors and as wide a range of diversities as possible to provide further insights into the diversity‐ecosystem function relationship in the largest ecosystem on Earth.
Copper speciation and isotopic fractionation in plants: uptake and translocation mechanisms
Authors: Ryan Brooke M. , Kirby Jason K. , Degryse Fien , Harris Hugh , McLaughlin Mike J. , Scheiderich Kathleen
Published: April 2013

The fractionation of stable copper (Cu) isotopes during uptake into plant roots and translocation to shoots can provide information on Cu acquisition mechanisms.

Isotope fractionation (65Cu/63Cu) and intact tissue speciation techniques (X‐ray absorption spectroscopy, XAS) were used to examine the uptake, translocation and speciation of Cu in strategy I (tomato–Solanum lycopersicum) and strategy II (oat–Avena sativa) plant species. Plants were grown in controlled solution cultures, under varied iron (Fe) conditions, to test whether the stimulation of Fe‐acquiring mechanisms can affect Cu uptake in plants.

Isotopically light Cu was preferentially incorporated into tomatoes (Δ65Cuwhole plant‐solution = c. −1‰), whereas oats showed minimal isotopic fractionation, with no effect of Fe supply in either species. The heavier isotope was preferentially translocated to shoots in tomato, whereas oat plants showed no significant fractionation during translocation. The majority of Cu in the roots and leaves of both species existed as sulfur‐coordinated Cu(I) species resembling glutathione/cysteine‐rich proteins.

The presence of isotopically light Cu in tomatoes is attributed to a reductive uptake mechanism, and the isotopic shifts within various tissues are attributed to redox cycling during translocation. The lack of isotopic discrimination in oat plants suggests that Cu uptake and translocation are not redox selective.
Laterality in the gestural communication of wild chimpanzees
Authors: Hobaiter Catherine , Byrne Richard W.
Published: April 2013

We examined hand preference in the intentional gestural communication of wild chimpanzees in the Budongo forest, Uganda. Individuals showed some tendency to be lateralized, although less than has been reported for begging and pointing gestures in captivity; on average, their absolute bias was around 0.25 (where 1.0 represents complete right‐ or left‐hand use and 0.0 represents no bias). Lateralization was incomplete even in individuals with major manual disabilities. Where individuals had a stronger preference, this was more often toward the right hand; moreover, as age increased, the direction (but not the extent) of hand preference shifted toward the right. While the gestural repertoire as a whole was largely employed ambilateraly, object‐manipulation gestures showed a strong right‐hand bias.
Measurements of Personal UV Exposure on Different Parts of the Body During Various Activities
Authors: Weihs Philipp , Schmalwieser Alois , Reinisch Corinna , Meraner Elisabeth , Walisch Silvia , Harald Maier
Published: April 2013

Within this study, the erythemal ultraviolet (UV) exposure received by different parts of the body during four different activities is determined. Optoelectronic devices were used to measure the erythemal UV exposure at 10 different positions of the body. The measuring devices were fixed on the forehead, on the shoulders, on the arms, on the chest, on the thighs and on the lower legs. The measurements were performed during the following activities of the test persons: walking, sitting, lying and sitting up. The measurements were performed on four clear sky days in the early afternoon at 1 s interval. One measurement sequence was taking 30–40 min. For the analysis of the measured UV exposures, the ambient UV is taken as a reference to remove the atmospheric fluctuations on the measured UV exposure. The strong dependence of the UV exposure on the activity and on the orientation of the test person is shown. Most of the body parts receive the highest exposure, when the test subject is sitting up or lying. The shoulders are most at risk when the test person is walking, whereas during the activities sitting up and lying the legs are most at risk.
Lectin‐Binding Pattern in Ovarian Structures of Rats with Experimental Polycystic Ovaries
Authors: Barbeito CG , Ortega HH , Matiller V , Gimeno EJ , Salvetti NR
Published: April 2013

Contents

Numerous experimental models in different species have been developed for the study of polycystic ovarian syndrome. In this study, we used a model of induction of polycystic ovaries (PO) in rats by exposure to constant light to study the distribution and variations of glycosylated residues present in the different ovarian structures. Seven biotinylated lectins were used (Con‐A, WGA, DBA, SBA, PNA, RCA and UEA‐I) on tissue sections, and detection was performed using the streptavidin/peroxidase method. In tissue sections was observed an increase in affinity for Con‐A in the granulosa and theca interna of growing follicles and cysts in animals with PO in relation to the control group. Follicular cysts showed higher affinity for WGA and RCA‐I which growing follicles in the same group, and there was a decrease in affinity for PNA in the cysts in relation to the growth of follicles in both groups. Atretic follicles in both groups showed greater labelling with lectins PNA, SBA and RCA‐I in relation to healthy follicles. It could also be noted that the zona pellucida of cystic follicles lost the affinity for the lectin Con‐A. There was no staining on follicles in any category with the lectins DBA and UEA‐I, although it was staining in the corpus luteum (control group) and in the mesothelium and interstitial glands of both groups with DBA. These observations probably reflect changes in the glycosaminoglycans present in the different ovarian compartments or in the glycosylation of cellular components essential for proper follicular dynamics.
Diagnostic yield of combined bronchoscopy and endobronchial ultrasonography, under LungPoint guidance for small peripheral pulmonary lesions
Authors: Tamiya Motohiro , Okamoto Norio , Sasada Shinji , Shiroyama Takayuki , Morishita Naoko , Suzuki Hidekazu , Yoshida Emi , Hirashima Tomonori , Kawahara Kunimitu , Kawase Ichiro
Published: April 2013

Background and objective

The yield of biopsy performed during bronchoscopy is reduced if the lesion is smaller than 30 mm. We evaluated the performance of a new diagnostic technique combining endobronchial ultrasonography with a guide sheath (EBUS‐GS) and a virtual bronchoscopic navigation system, LungPoint (Broncus Technologies, Inc., Mountain View, CA, USA), for the diagnosis of small (≤30 mm) peripheral pulmonary lesions (PPL).

Methods

Between May 2011 and December 2011, we recruited 68 consecutive patients presenting with a PPL 30 mm or less in diameter determined by chest computed tomography. We used the LungPoint system before bronchoscopy to identify the bronchus into which the bronchoscope should be advanced. We used a thin bronchoscope. EBUS‐GS was performed using an endoscope ultrasonography system equipped with a 20‐MHz mechanical radial‐type probe. We used a guide sheath with an external diameter of 1.95 mm, thin forceps and brushing.

Results

The diagnostic yield of the 68 PPL was 77.9%; it was 83.7% and 68.0% for the malignant and benign lesions, respectively. Notably, three cases were diagnosed by transbronchial needle‐aspiration cytology alone. Univariate and multivariate analyses showed that the EBUS probe localization was the most significant contributor to successful diagnosis (diagnostic yield: within vs adjacent to the lesion = 92.1% vs 60.0%, respectively; P = 0.004 and P = 0.003, respectively).

Conclusions

The combination of EBUS‐GS and LungPoint was useful for diagnosing small PPL.
A novel HLA‐C allele, HLA‐C*06:45, identified by sequence‐based typing in a Chinese individual
Authors: Wang J. , Xia L. , Luo M. , Chen Q.
Published: April 2013

HLA‐C*06:45 differs from HLA‐C*06:02 by a single G to A substitution at position187.
Proficiency in Science: Assessment Challenges and Opportunities
Authors: Pellegrino James W.
Published: April 2013

Proficiency in science is being defined through performance expectations that intertwine science practices, cross-cutting concepts, and core content knowledge. These descriptions of what it means to know and do science pose challenges for assessment design and use, whether at the classroom instructional level or the system level for monitoring the progress of science education. There are systematic ways to approach assessment development that can address design challenges, as well as examples of the application of such principles in science assessment. This Review considers challenges and opportunities that exist for design and use of assessments that can support science teaching and learning consistent with a contemporary view of what it means to be proficient in science.
External Quantum Efficiency Above 100% in a Singlet-Exciton-Fission–Based Organic Photovoltaic Cell
Authors: Congreve Daniel N. , Lee Jiye , Thompson Nicholas J. , Hontz Eric , Yost Shane R. , Reusswig Philip D. , Bahlke Matthias E. , Reineke Sebastian , Van Voorhis Troy , Baldo Marc A.
Published: April 2013

Splitting Singlets

Solar cell efficiency is limited because light at wavelengths shorter than the cell's absorption threshold does not channel any of its excess energy into the generated electricity.

Congreve
et al.

(p.
334
) have developed a method to harvest the excess energy in carbon-based absorbers through a process termed “singlet fission.” In this process, high-energy photons propel two current carriers, rather than just one, by populating a singlet state that spontaneously divides into a pair of triplet states. Although it works in a functioning organic solar cell, the efficiency needs improving.
Climate's Dark Forcings
Authors: Andreae Meinrat O. , Ramanathan V.
Published: April 2013

Uncertainties about the properties and amounts of atmospheric black carbon complicate efforts to understand its regional and global effects on climate.
Did You Feel It?
The Earthquake Observers
Disaster Science from Lisbon to Richter

by Deborah R. Coen

University of Chicago Press, Chicago, 2013. 356 pp. $35, £24.50. ISBN 9780226111810.
Authors: Beroza Gregory C.
Published: April 2013

In this history of seismology and its impact, Coen focuses on the contributions of human observers—citizens as well as scientists.
Fire in the Ocean
Authors: Masiello C. A. , Louchouarn P.
Published: April 2013

Exposure to fire alters the properties of dissolved organic carbon in ways that affect how it decomposes in rivers and in the ocean.

[Also see Report by

Jaffé
et al.

]
Wild Cards Remain After Proposed Reshuffle of STEM Education
Authors: Mervis Jeffrey
Published: April 2013

Most people agree that the U.S. government could do a better job of managing the $3 billion being spent by a dozen federal agencies on science education, but few are lining up behind a White House plan to accomplish that goal.
Charged Membranes
Authors: Thatcher Jack D.
Published: April 2013

Animated lessons describe how Na
+
- and K
+
-dependent adenosine triphosphatase (Na
+
/K
+
–ATPase) generates an electrochemical gradient across a membrane and provides two examples of how the energy of charged membranes is utilized.
Transcriptional Reprogramming by TOR
Authors: Gough Nancy R.
Published: April 2013

Photosynthesis or glucose stimulates TOR signaling to activate the root meristem.
Pathway of Neurotoxicity
Authors: Gough Nancy R.
Published: April 2013

Two hallmarks of Alzheimer’s disease are connected through a CAMKK2-AMPK pathway.
Modulation of PF10_0355 (MSPDBL2) Alters Plasmodium falciparum Response to Antimalarial Drugs
Authors: Van Tyne Daria , Uboldi Alessandro D. , Healer Julie , Cowman Alan F. , Wirth Dyann F.
Published: April 2013

Malaria's ability to rapidly adapt to new drugs has allowed it to remain one of the most devastating infectious diseases of humans. Understanding and tracking the genetic basis of these adaptations are critical to the success of treatment and intervention strategies. The novel antimalarial resistance locus
PF10
_
0355
(
Pfmspdbl2
) was previously associated with the parasite response to halofantrine, and functional validation confirmed that overexpression of this gene lowered parasite sensitivity to both halofantrine and the structurally related antimalarials mefloquine and lumefantrine, predominantly through copy number variation. Here we further characterize the role of
Pfmspdbl2
in mediating the antimalarial drug response of
Plasmodium falciparum
. Knockout of
Pfmspdbl2
increased parasite sensitivity to halofantrine, mefloquine, and lumefantrine but not to unrelated antimalarials, further suggesting that this gene mediates the parasite response to a specific class of antimalarial drugs. A single nucleotide polymorphism encoding a C591S mutation within
Pfmspdbl2
had the strongest association with halofantrine sensitivity and showed a high derived allele frequency among Senegalese parasites. Transgenic parasites expressing the ancestral
Pfmspdbl2
allele were more sensitive to halofantrine and structurally related antimalarials than were parasites expressing the derived allele, revealing an allele-specific effect on drug sensitivity in the absence of copy number effects. Finally, growth competition experiments showed that under drug pressure, parasites expressing the derived allele of
Pfmspdbl2
outcompeted parasites expressing the ancestral allele within a few generations. Together, these experiments demonstrate that modulation of
Pfmspdbl2
affects malaria parasite responses to antimalarial drugs.
Induced Resistance to Methionyl-tRNA Synthetase Inhibitors in Trypanosoma brucei Is Due to Overexpression of the Target
Authors: Ranade Ranae M. , Gillespie J. Robert , Shibata Sayaka , Verlinde Christophe L. M. J. , Fan Erkang , Hol Wim G. J. , Buckner Frederick S.
Published: April 2013

New classes of antiparasitic drugs active against
Trypanosoma brucei
are needed to combat human African trypanosomiasis. Inhibitors of methionyl-tRNA synthetase (MetRS) have excellent potential to be developed for this purpose (S. Shibata, J. R. Gillespie, A. M. Kelley, A. J. Napuli, Z. Zhang, K. V. Kovzun, R. M. Pefley, J. Lam, F. H. Zucker, W. C. Van Voorhis, E. A. Merritt, W. G. Hol, C. L. Verlinde, E. Fan, and F. S. Buckner, Antimicrob. Agents Chemother.
55
:1982–1989, 2011). In order to assess the potential for resistance to develop against this new class of inhibitors,
T. brucei
cultures were grown in the presence of MetRS inhibitors or comparison drugs. Resistance up to ∼50 times the baseline 50% inhibitory concentration (IC
50
) was induced against a MetRS inhibitor after ∼120 days. A similar level of resistance to the clinical drug eflornithine was induced after ∼50 days and for pentamidine after ∼80 days. Thus, resistance was induced more slowly against MetRS inhibitors than against clinically used drugs. The parasites resistant to the MetRS inhibitor were shown to overexpress MetRS mRNA by a factor of 35 over the parental strain. Southern analysis indicated that the MetRS gene was amplified in the genome by nearly 8-fold. When injected into mice, the MetRS inhibitor-resistant parasites caused a reduced level of infection, indicating that the changes associated with resistance attenuated their virulence. This finding and the fact that resistance to MetRS inhibitors developed relatively slowly are encouraging for further development of this class of compounds. Published studies on other antitrypanosomal drugs have primarily shown that alterations in membrane transporters were the mechanisms responsible for resistance. This is the first published report of induced drug resistance in the African trypanosome due to overexpression of the target enzyme.
Redefining the Role of the β-Lactamase Locus in Methicillin-Resistant Staphylococcus aureus: β-Lactamase Regulators Disrupt the MecI-Mediated Strong Repression on
mecA
and Optimize the Phenotypic Expression of Resistance in Strains with Constitutive
mecA
Expression
Authors: Arêde Pedro , Ministro Joana , Oliveira Duarte C.
Published: April 2013

In response to β-lactam chemotherapy,
Staphylococcus aureus
has acquired two resistance determinants:
blaZ
, coding for β-lactamase, which confers resistance to penicillins only, and
mecA
, coding for an extra cell wall cross-linking enzyme with reduced affinity for virtually all other β-lactams. The transcriptional control of both resistance determinants is regulated by homologous repressors (BlaI and MecI, respectively) and sensor inducers (BlaR1 and MecR1, respectively). There is a cross-talk between the two regulatory systems, and it has been demonstrated that
bla
regulators stabilize the
mecA
acquisition. In a recent study, we have unexpectedly observed that in most MRSA strains, there was no significant change in the resistance phenotype upon the overexpression in
trans
of a MecI repressor, whereas in those few strains negative for the
bla
locus, there was a massive decrease of resistance (D. C. Oliveira and H. de Lencastre, PLoS One 6:e23287, 2011). Here, we demonstrate that, contrary to what is currently accepted, the
bla
regulatory system efficiently disrupts the strong MecI-mediated repression on
mecA
, enabling the optimal expression of resistance. This effect appears to be due to the formation of MecI::BlaI heterodimers that might bind less efficiently to the
mecA
promoter and become nonfunctional due to the proteolytic inactivation of the BlaI monomer. In addition, we have also observed that the presence of
bla
regulators may enhance dramatically the expression of β-lactam resistance in MRSA strains with constitutive
mecA
expression, compensating for the fitness cost imposed by the large β-lactamase plasmid. These observations point to important unrecognized roles of the
bla
locus for the expression of the methicillin-resistant
S. aureus
(MRSA) phenotype.
Roseomonas Spinal Epidural Abscess Complicating Instrumented Posterior Lumbar Interbody Fusion
Authors: Maraki Sofia , Bantouna Vasiliki , Lianoudakis Efstratios , Stavrakakis Ioannis , Scoulica Efstathia
Published: April 2013

The first case of a spinal epidural abscess caused by
Roseomonas mucosa
following instrumented posterior lumbar fusion is presented. Although rare, because of its highly resistant profile,
Roseomonas
species should be included in the differential diagnosis of epidural abscesses in both immunocompromised and immunocompetent hosts.
Identical Miniature Inverted Repeat Transposable Elements Flank Class 1 Integrons in Clinical Isolates of Acinetobacter spp
Authors: Domingues Sara , Toleman Mark A. , Nielsen Kaare M. , da Silva Gabriela J.
Published: April 2013

Miniature inverted repeat transposable elements (MITEs) have been identified flanking class 1 integrons. We have identified and characterized a 439-bp MITE-like structure in seven
Acinetobacter
species isolates from Portugal and Brazil. The complete sequence similarity of the elements and flanking regions suggests that MITEs may act as mobilizable vectors for the dissemination of integrons.
Direct Comparison of Xpert MTB/RIF Assay with Liquid and Solid Mycobacterial Culture for Quantification of Early Bactericidal Activity
Authors: Kayigire Xavier A. , Friedrich Sven O. , Venter Amour , Dawson Rodney , Gillespie Stephen H. , Boeree Martin J. , Heinrich Norbert , Hoelscher Michael , Diacon Andreas H.
Published: April 2013

The early bactericidal activity of antituberculosis agents is usually determined by measuring the reduction of the sputum mycobacterial load over time on solid agar medium or in liquid culture. This study investigated the value of a quantitative PCR assay for early bactericidal activity determination. Groups of 15 patients were treated with 6 different antituberculosis agents or regimens. Patients collected sputum for 16 h overnight at baseline and at days 7 and 14 after treatment initiation. We determined the sputum bacterial load by CFU counting (log CFU/ml sputum, reported as mean ± standard deviation [SD]), time to culture positivity (TTP, in hours [mean ± SD]) in liquid culture, and Xpert MTB/RIF cycle thresholds (

C
T

,
n
[mean ± SD]). The ability to discriminate treatment effects between groups was analyzed with one-way analysis of variance (ANOVA). All measurements showed a decrease in bacterial load from mean baseline (log CFU, 5.72 ± 1.00; TTP, 116.0 ± 47.6;

C
T

, 19.3 ± 3.88) to day 7 (log CFU, −0.26 ± 1.23,
P
= 0.2112; TTP, 35.5 ± 59.3,
P
= 0.0002;

C
T

, 0.55 ± 3.07,
P
= 0.6030) and day 14 (log CFU, −0.55 ± 1.24,
P
= 0.0006; TTP, 54.8 ± 86.8,
P
< 0.0001;

C
T

, 2.06 ± 4.37,
P
= 0.0020). The best discrimination between group effects was found with TTP at day 7 and day 14 (
F
= 9.012,
P
< 0.0001, and
F
= 11.580,
P
< 0.0001), followed by log CFU (
F
= 4.135,
P
= 0.0024, and
F
= 7.277,
P
< 0.0001).

C
T

was not significantly discriminative (
F
= 1.995,
P
= 0.091, and
F
= 1.203,
P
= 0.316, respectively). Culture-based methods are superior to PCR for the quantification of early antituberculosis treatment effects in sputum.
Development and Evaluation of an Affordable Real-Time Qualitative Assay for Determining HIV-1 Virological Failure in Plasma and Dried Blood Spots
Authors: Aitken Susan C. , Kliphuis Aletta , Bronze Michelle , Wallis Carole L. , Kityo Cissy , Balinda Sheila , Stevens Wendy , Spieker Nicole , de Oliveira Tulio , Rinke de Wit Tobias F. , Schuurman Rob
Published: April 2013

Virological failure (VF) has been identified as the earliest, most predictive determinant of HIV-1 antiretroviral treatment (ART) failure. Due to the high cost and complexity of virological monitoring, VF assays are rarely performed in resource-limited settings (RLS). Rather, ART failure is determined by clinical monitoring and to a large extent immunological monitoring. This paper describes the development and evaluation of a low-cost, dried blood spot (DBS)-compatible qualitative assay to determine VF, in accordance with current WHO guideline recommendations for therapy switching in RLS. The assay described here is an internally controlled qualitative real-time PCR targeting the conserved long terminal repeat domain of HIV-1. This assay was applied to HIV-1 subtypes A to H and further evaluated on HIV-1 clinical plasma samples from South Africa (
n
= 191) and Tanzania (
n
= 42). Field evaluation was performed in Uganda using local clinical plasma samples (
n
= 176). Furthermore, assay performance was evaluated for DBS. This assay is able to identify VF for all major HIV-1 group M subtypes with equal specificity and has a lower detection limit of 1.00E+03 copies/ml for plasma samples and 5.00E+03 copies/ml for DBS. Comparative testing yielded accurate VF determination for therapy switching in 89% to 96% of samples compared to gold standards. The assay is robust and flexible, allowing for “open platform” applications and producing results comparable to those of commercial assays. Assay design enables application in laboratories that can accommodate real-time PCR equipment, allowing decentralization of testing to some extent. Compatibility with DBS extends access of sampling and thus access to this test to remote settings.
Spectrum of Bacterial Colonization Associated with Urothelial Cells from Patients with Chronic Lower Urinary Tract Symptoms
Authors: Khasriya Rajvinder , Sathiananthamoorthy Sanchutha , Ismail Salim , Kelsey Michael , Wilson Mike , Rohn Jennifer L. , Malone-Lee James
Published: April 2013

Chronic lower urinary tract symptoms (LUTS), such as urgency and incontinence, are common, especially among the elderly, but their etiology is often obscure. Recent studies of acute urinary tract infections implicated invasion by
Escherichia coli
into the cytoplasm of urothelial cells, with persistence of long-term bacterial reservoirs, but the role of infection in chronic LUTS is unknown. We conducted a large prospective study with eligible patients with LUTS and controls over a 3-year period, comparing routine urine cultures of planktonic bacteria with cultures of shed urothelial cells concentrated in centrifuged urinary sediments. This comparison revealed large numbers of bacteria undetected by routine cultures. Next, we typed the bacterial species cultured from patient and control sediments under both aerobic and anaerobic conditions, and we found that the two groups had complex but significantly distinct profiles of bacteria associated with their shed bladder epithelial cells. Strikingly,
E. coli
, the organism most responsible for acute urinary tract infections, was not the only or even the main offending pathogen in this more-chronic condition. Antibiotic protection assays with shed patient cells and
in vitro
infection studies using patient-derived strains in cell culture suggested that LUTS-associated bacteria are within or extremely closely associated with shed epithelial cells, which explains how routine cultures might fail to detect them. These data have strong implications for the need to rethink our common diagnoses and treatments of chronic urinary tract symptoms.
Both TRIF and IPS-1 Adaptor Proteins Contribute to the Cerebral Innate Immune Response against Herpes Simplex Virus 1 Infection
Authors: Menasria Rafik , Boivin Nicolas , Lebel Manon , Piret Jocelyne , Gosselin Jean , Boivin Guy
Published: April 2013

Toll-like receptors (TLRs) and RNA helicases (RLHs) are important cell sensors involved in the immunological control of viral infections through production of type I interferon (IFN). The impact of a deficiency in the TRIF and IPS-1 adaptor proteins, respectively, implicated in TLR3 and RLH signaling pathways, was investigated during herpes simplex virus 1 (HSV-1) encephalitis. TRIF
−/−
, IPS-1
−/−
, and C57BL/6 wild-type (WT) mice were infected intranasally with 7.5 × 10
5
PFU of HSV-1. Mice were monitored for neurological signs and survival over 20 days. Groups of mice were sacrificed on days 3, 5, 7, 9, and 11 postinfection for determination of brain viral replication by quantitative PCR (qPCR), plaque assay, and immunohistochemistry and for alpha/beta interferon (IFN-α/β) levels and phosphorylation of interferon regulatory factors 3 and 7 (IRF-3 and -7) in brain homogenates by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. TRIF
−/−
and IPS-1
−/−
mice had higher mortality rates than WT mice (
P
= 0.02 and
P
= 0.09, respectively). Viral antigens were more disseminated throughout the brain, correlating with a significant increase in brain viral load for TRIF
−/−
(days 5 to 9) and IPS-1
−/−
(days 7 and 9) mice compared to results for the WT. IFN-β production was reduced in brain homogenates of TRIF
−/−
and IPS-1
−/−
mice on day 5 compared to results for the WT, whereas IFN-α levels were increased on day 7 in TRIF
−/−
mice. Phosphorylation levels of IRF-3 and IRF-7 were decreased in TRIF
−/−
and IPS-1
−/−
mice, respectively. These data suggest that both the TRIF and IPS-1 signaling pathways are important for the control of HSV replication in the brain and survival through IFN-β production.
Identification of the Human Herpesvirus 6A gQ1 Domain Essential for Its Functional Conformation
Authors: Maeki Takahiro , Hayashi Mayuko , Kawabata Akiko , Tang Huamin , Yamanishi Koichi , Mori Yasuko
Published: April 2013

Human herpesvirus 6 is a T lymphotropic herpesvirus, long classified into variants A and B (HHV-6A and HHV-6B) based on differences in sequence and pathogenicity. Recently, however, HHV-6A and HHV-6B were reclassified as different species. Here, we isolated a neutralizing monoclonal antibody (Mab) named AgQ 1-1 that was specific for HHV-6A glycoprotein Q1 (AgQ1), and we showed that amino acid residues 494 to 497 of AgQ1 were critical for its recognition by this Mab. This region was also essential for AgQ1's complex formation with gH, gL, and gQ2, which might be important for viral binding to the cellular receptor, CD46. In addition, amino acid residues 494 to 497 are essential for viral replication. Interestingly, this sequence corresponds to the domain on HHV-6B gQ1 that is critical for recognition by an HHV-6B-specific neutralizing Mab. Within this domain, only Q at position 496 of HHV-6A is distinct from the HHV-6B sequence; however, the mutant AgQ1(Q496E) was still clearly recognized by the Mab AgQ 1-1. Surprisingly, replacement of the adjacent amino acid, in mutant AgQ1(C495A), resulted in poor recognition by Mab AgQ 1-1, and AgQ1(C495A) could not form the gH/gL/gQ1/gQ2 complex. Furthermore, the binding ability of mutant AgQ1(L494A) with CD46 decreased, although it could form the gH/gL/gQ1/gQ2 complex and it showed clear reactivity to Mab AgQ 1-1. These data indicated that amino acid residues 494 to 497 of AgQ1 were critical for the recognition by Mab AgQ 1-1 and essential for AgQ1's functional conformation.
Persistent Enteric Murine Norovirus Infection Is Associated with Functionally Suboptimal Virus-Specific CD8 T Cell Responses
Authors: Tomov Vesselin T. , Osborne Lisa C. , Dolfi Douglas V. , Sonnenberg Gregory F. , Monticelli Laurel A. , Mansfield Kathleen , Virgin Herbert W. , Artis David , Wherry E. John
Published: April 2013

Norovirus (NV) gastroenteritis is a major contributor to global morbidity and mortality, yet little is known about immune mechanisms leading to NV control. Previous studies using the murine norovirus (MNV) model have established a key role for T cells in MNV clearance. Despite these advances, important questions remain regarding the magnitude, location, and dynamics of the MNV-specific T cell response. To address these questions, we identified MNV-specific major histocompatibility complex (MHC) class I immunodominant epitopes using an overlapping peptide screen. One of these epitopes (amino acids 519 to 527 of open reading frame 2 [ORF2519-527]) was highly conserved among all NV genogroups. Using MHC class I peptide tetramers, we tracked MNV-specific CD8 T cells in lymphoid and mucosal sites during infection with two MNV strains with distinct biological behaviors, the acutely cleared strain CW3 and the persistent strain CR6. Here, we show that enteric MNV infection elicited robust T cell responses primarily in the intestinal mucosa and that MNV-specific CD8 T cells dynamically regulated the expression of surface molecules associated with activation, differentiation, and homing. Furthermore, compared to MNV-CW3 infection, chronic infection with MNV-CR6 resulted in fewer and less-functional CD8 T cells, and this difference was evident as early as day 8 postinfection. Finally, MNV-specific CD8 T cells were capable of reducing the viral load in persistently infectedRag1−/−mice, suggesting that these cells are a crucial component of NV immunity. Collectively, these data provide fundamental new insights into the adaptive immune response to two closely related NV strains with distinct biological behaviors and bring us closer to understanding the correlates of protective antiviral immunity in the intestine.
Erdheim-Chester disease with isolated craniocerebral involvement
Authors: Jain Rajendra Singh , Sannegowda Raghavendra Bakki , Jain Rahul , Mathur Tarun
Published: April 2013

Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis with distinctive radiographic and pathological features. Intracranial involvement is further a rarity, usually producing diabetes insipidus or cerebellar-brainstem symptoms. We report a 40-year-old man presenting with recurrent secondarily generalised seizures. An MRI scan of the brain revealed multiple enhancing intracranial masses in frontal, temporal and parietal regions. Biopsy from the left frontotemporal lesion confirmed it to be a rare case of ECD. The patient received a short course of corticosteroids initially and subsequently remained well-controlled on antiepileptic therapy alone. A repeat MRI of his brain showed significant resolution of lesions. Osteolytic lesions in the skull vault were detected during follow-up which also disappeared. Interestingly, there was no involvement of long bones or any other system even after 12 years of follow-up.
Concomitant typhlitis andClostridium difficilecolitis developed after first R-CHOP chemotherapy in a non-Hodgkin lymphoma patient
Authors: Junpaparp Parichart , Buppajarntham Saranya , Madueno Fernando Vargas , Varadi Gabor
Published: April 2013

Typhlitis or neutropenic enterocolitis (NEC) is a life-threatening condition that occurs in neutropenic patients. Early recognition is crucial owing to high death rate. We present a case of a 54-year-old man, diagnosed with non-Hodgkin lymphoma who received a first cycle of rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), prednisolone (R-CHOP) chemotherapy 10 days prior presenting. He developed fever, mucositis, watery diarrhoea and right lower quadrant pain with rebound tenderness. He also had neutropenia, with an absolute neutrophil count of zero. CT abdomen confirmed the diagnosis of typhlitis, demonstrating characteristic terminal ileum, caecal and right-sided colon involvement. Moreover, stool PCR was also positive for toxigenicClostridium difficile. Therefore, the patient was diagnosed with concomitant typhlitis andC difficile-associated diarrhoea (CDAD). He was empirically treated with intravenous cefepime, intravenous metronidazole and oral vancomycin. His symptoms resolved in 10 days. This case illustrated a successful medical treatment of typhlitis in concomitance with CDAD.
Temporary recovery after resuscitation: delayed postanoxic encephalopathy
Authors: Goedee Stephan , van der Nat Gerarda A M , Roks Gerwin
Published: April 2013

Delayed postanoxic encephalopathy is reported infrequently and is characterised by a lucid interval of seemingly good recovery from an anoxic insult. Days or even weeks may pass before changes in behaviour, motor responses or consciousness occur. Neurological deterioration may progress to coma, death or severe disability, whereas some patients have a second recovery period. Pathogenesis is yet to be discovered. Prognosis is reportedly poor, treatment is symptomatic and at best anecdotal. We present a case report and available literature.
Characterising the progress in HIV/AIDS research in the Middle East and North Africa
Authors: Saba Hanan F , Kouyoumjian Silva P , Mumtaz Ghina R , Abu-Raddad Laith J
Published: April 2013

Objectives

The Middle East and North Africa (MENA) region is perceived to have limited HIV data. The objective of this study was to quantitatively characterise the progress in HIV research in this region since the discovery of the epidemic.

Methods

Four indices were defined and implemented to measure the progress of HIV research using the PubMed, Embase, MENA HIV/AIDS Epidemiology Synthesis Project and US Census Bureau HIV/AIDS Surveillance databases. The four indices provide complementary measures to characterise different aspects of the progress of HIV research.

Results

A total of 2118, 2352, 683 and 4889 records were identified through the PubMed, the Embase, the Synthesis Project and the HIV Prevalence indices, respectively. The proportion of the total global HIV records that relate to MENA is 1.2%. Overall, the indices show steady progress in the number of new records every year, with an accelerated pace in the last few years. The rate of progress in MENA was also higher than the rate of progress in HIV records globally. There is no evidence so far of stabilisation or a peak in the number of new records year by year. About half of the records were produced after the year 2005. The number of records shows large heterogeneity across countries.

Conclusions

MENA has witnessed a rapid growth in HIV research over the last decade. However, there are still large gaps in HIV scientific evidence in the region, and the progress is far from being uniform across countries. Ongoing and future research needs to be geared towards academic standard and production of scientific publications.
How to cope with changing demand conditions — The Swedish forest sector as a case study: an analysis of major drivers of change in the use of wood resources
Authors: Jonsson Ragnar
Published: April 2013

Promotion of renewable energy sources in Europe is foreseen to result in a dramatic increase in the demand for woody biomass. This paper assesses whether wood resources in the European Union (EU) will support future demand. Possible implications for countries with ample forest resources and a well-developed forest industry, such as Sweden, of an expected mounting demand pressure are discussed. Other drivers of change in global wood product markets posing challenges for the forest sector in general are also addressed. These drivers are reviewed and, together with the results from the EUwood project and econometric wood market models, analyzed as to their impacts on the Swedish forest sector. Demand is foreseen to vastly exceed the potential supply of woody biomass in Europe, putting a tremendous pressure on the Swedish forest resource and necessitating trade-offs between different ecosystem services. Further, projections suggest that Sweden will decrease in importance in production as well as consumption terms for all wood products.