bluuebunny/crossref_metadata_2025 huggingface dataset:
Disseminate and Recurrent Infundibulofolliculitis in Childhood: A Rarely Reported Entity
Authors: Kline Amy , Relic John
Published: January 2015

Disseminate and recurrent infundibulofolliculitis (DRIF) is a term used to describe a micropapular skin disorder, most commonly occurring in young men with Fitzpatrick skin type V and VI. We present the case of two young Sudanese brothers with a clinical and histologic picture typical of this condition, which has been infrequently reported in children and has not previously been reported in related individuals. The etiology remains uncertain and there is no clear consensus on treatment.
A Unique Association of Unilateral Idiopathic Calcinosis Cutis with Ipsilateral Porokeratotic Eccrine Ostial and Dermal Duct Nevus
Authors: Vasudevan Biju , Sondhi Vishal , Verma Rajesh , Neema Shekhar
Published: January 2015

An 11‐year‐old boy presented with complaints of multiple skin‐colored hard lumps on the right side of his body and progressive deformity of the right leg of 7‐years duration. His parents had also noticed multiple asymptomatic pits over his right arm, palms, and soles since childhood. Examination revealed skin‐colored nontender nodules on the right half of his body and shortening of his right leg. The multiple hyperpigmented pits over the right arm, palm, and sole raised diagnostic difficulties, but histopathologic, radiologic, and biochemical investigations confirmed the features of idiopathic calcinosis cutis and porokeratotic eccrine ostial and dermal duct nevus. Unilateral idiopathic calcinosis cutis has not been previously reported in the literature, and the association with ipsilateral porokeratotic eccrine ostial and dermal duct nevus makes this case unique. Diagnostic difficulties and limited options for treatment make this case interesting academically.
Solar Spectral Irradiance and Summary Outputs Using Excel
Authors: Diffey Brian
Published: January 2015

The development of an Excel spreadsheet is described that calculates solar spectral irradiance between 290–3000 nm on an unshaded, horizontal surface under a cloudless sky at sea level, together with summary outputs such as global UV index, illuminance and percentage of energy in different wavebands. A deliberate goal of the project was to adopt the principle of Ockham's razor and to develop a model that is as simple as it can be commensurate with delivering results of adequate accuracy. Consequently, just four inputs are required—geographical latitude, month, day of month and time of day—resulting in a spreadsheet that is easily usable by anyone with an interest in sunlight and solar power irrespective of their background. The accuracy of the calculated data is sufficient for many applications where knowledge of the ultraviolet, visible and infrared levels in sunlight is of interest.
Blood flow restricted and traditional resistance training performed to fatigue produce equal muscle hypertrophy
Authors: Farup J. , de Paoli F. , Bjerg K. , Riis S. , Ringgard S. , Vissing K.
Published: January 2015

This study investigated the hypertrophic potential of load‐matched blood‐flow restricted resistance training (BFR) vs free‐flow traditional resistance training (low‐load TRT) performed to fatigue. Ten healthy young subjects performed unilateral BFR and contralateral low‐load TRT elbow flexor dumbbell curl with 40% of one repetition maximum until volitional concentric failure 3 days per week for 6 weeks. Prior to and at 3 (post‐3) and 10 (post‐10) days post‐training, magnetic resonance imaging (MRI) was used to estimate elbow flexor muscle volume and muscle water content accumulation through training. Acute changes in muscle thickness following an early vs a late exercise bout were measured with ultrasound to determine muscle swelling during the immediate 0–48 h post‐exercise. Total work was threefold lower for BFR compared with low‐load TRT (P < 0.001). Both BRF and low‐load TRT increased muscle volume by approximately 12% at post‐3 and post‐10 (P < 0.01) with no changes in MRI‐determined water content. Training increased muscle thickness during the immediate 48 h post‐exercise (P < 0.001) and to greater extent with BRF (P < 0.05) in the early training phase. In conclusion, BFR and low‐load TRT, when performed to fatigue, produce equal muscle hypertrophy, which may partly rely on transient exercise‐induced increases in muscle water content.
Real‐time symptomatic case of transfusion‐transmitted dengue
Authors: Levi José Eduardo , Nishiya Anna , Félix Alvina Clara , Salles Nanci Alves , Sampaio Luciana Ribeiro , Hangai Fátima , Sabino Ester Cerdeira , Mendrone Alfredo
Published: January 2015

Background

Dengue virus transmission by blood transfusion is a rarely reported event.

Case Report

During a dengue outbreak in São Paulo city, a regular plateletpheresis donor informed the blood bank of being diagnosed a few days after donation. The recipient was hospitalized and displayed symptoms and laboratory evidence of dengue after transfusion.

Results

The donor was immunoglobulin (Ig)G, IgM, and polymerase chain reaction nonreactive on the index sample, seroconverting 20 days later. The platelet units were transfused into two patients. One of them developed fever 3 days after transfusion, with high viral load. His pretransfusion sample was negative for IgG, IgM, and dengue RNA, while the second recipient did not show any symptoms nor laboratory evidence of dengue infection.

Conclusions

This case brings additional evidence that dengue is indeed transmissible by blood transfusion and clinical manifestations, although rare, do occur.
COMPUTED TOMOGRAPHIC FINDINGS IN 57 CATS WITH PRIMARY PULMONARY NEOPLASIA
Authors: Aarsvold Stacie , Reetz Jennifer A. , Reichle Jean K. , Jones Ian D. , Lamb Christopher R. , Evola Maria G. , Keyerleber Michele A. , Marolf Angela J.
Published: January 2015

Primary pulmonary neoplasia is relatively uncommon in cats and generally has a poor prognosis. In this multicenter, retrospective study of 57 cats with pulmonary neoplasia, the most frequent presenting signs were anorexia/inappetence (39%) and cough (37%). The pulmonary tumors were considered to be incidental findings in 9% cats. In computed tomographic (CT) images, primary pulmonary tumors appeared as a pulmonary mass in 55 (96%) cats and as a disseminated pulmonary lesion without a defined mass in two (4%) cats. Most pulmonary tumors were in the caudal lobes, with 28 (49%) in the right caudal lobe and 17 (30%) in the left caudal lobe. CT features associated with pulmonary tumors included mass in contact with visceral pleura (96%), irregular margins (83%), well‐defined borders (79%), bronchial compression (74%), gas‐containing cavities (63%), foci of mineral attenuation (56%), and bronchial invasion (19%). The mean (range) maximal dimension of the pulmonary masses was 3.5 cm (1.1–11.5 cm). Additional foci of pulmonary disease compatible with metastasis were observed in 53% cats. Pleural fluid was evident in 30% cats and pulmonary thrombosis in 12% cats. The histologic diagnoses were 47 (82%) adenocarcinomas, six (11%) tumors of bronchial origin, three (5%) adenosquamous cell carcinomas, and one (2%) squamous cell carcinoma. In this series, adenocarcinoma was the predominant tumor type, but shared many features with less common tumor types. No associations were identified between tumor type and CT features. Prevalence of suspected intrapulmonary metastasis was higher than in previous radiographic studies of cats with lung tumors.
On an early proposal for a unified system of units
Authors: Mendelson Kenneth S.
Published: January 2015

In the present SI system, the units of length and time are related by defining the speed of light as exactly 299,792,458 m/s. In 1857, Wilhelm Weber and Rudolf Kohlrausch proposed a system of units in which the units of length and time were also related by defining a speed, although not the speed of light. The system was extended to include a unit of mass. The Weber-Kohlrausch system was impractical and was apparently never adopted. Nevertheless, it remains of historical interest as an early attempt at a systematic treatment of physical units.
Research as a guide for curriculum development: An example from introductory spectroscopy. II. Addressing student difficulties with atomic emission spectra
Authors: Ivanjek L. , Shaffer P. S. , McDermott L. C. , Planinic M. , Veza D.
Published: January 2015

This is the second of two closely related articles (Paper I and Paper II) that together illustrate how research in physics education has helped guide the design of instruction that has proved effective in improving student understanding of atomic spectroscopy. Most of the more than 1000 students who participated in this four-year investigation were science majors enrolled in the introductory calculus-based physics course at the University of Washington (UW) in Seattle, WA, USA. The others included graduate and undergraduate teaching assistants at UW and physics majors in introductory and advanced physics courses at the University of Zagreb, Zagreb, Croatia. About half of the latter group were preservice high school physics teachers. Paper I describes how several conceptual and reasoning difficulties were identified among university students as they tried to relate a discrete line spectrum to the energy levels of atoms in a light source. This second article (Paper II) illustrates how findings from this research informed the development of a tutorial that led to improvement in student understanding of atomic emission spectra.
Cancer and the gut microbiota: An unexpected link
Authors: Zitvogel Laurence , Galluzzi Lorenzo , Viaud Sophie , Vétizou Marie , Daillère Romain , Merad Miriam , Kroemer Guido
Published: January 2015

Gut microbiota and its interactions with the host immune system play a role in oncogenesis and can alter the effectiveness of anticancer agents.
Breathing fresh: Rare stems cells repair injured lung
Authors: Sun Jie
Published: January 2015

Lung lineage-negative epithelial progenitor cells mediate tissue regeneration following major injury.
Streptococcus gallolyticus subsp. gallolyticus from Human and Animal Origins: Genetic Diversity, Antimicrobial Susceptibility, and Characterization of a Vancomycin-Resistant Calf Isolate Carrying a
vanA
-Tn
1546
-Like Element
Authors: Romero-Hernández Beatriz , Tedim Ana P. , Sánchez-Herrero José Francisco , Librado Pablo , Rozas Julio , Muñoz Gloria , Baquero Fernando , Cantón Rafael , del Campo Rosa
Published: January 2015

The aim of this work was to characterize the antibiotic susceptibility and genetic diversity of 41
Streptococcus gallolyticus
subsp.
gallolyticus
isolates: 18 isolates obtained from animals and 23 human clinical isolates. Antibiotic susceptibility was determined by the semiautomatic Wider system and genetic diversity by pulsed-field gel electrophoresis (PFGE) with SmaI. Animal isolates grouped separately in the PFGE analysis, but no statistical differences in antimicrobial resistance were found between the two groups. The LMG 17956 sequence type 28 (ST28) strain recovered from the feces of a calf exhibited high levels of resistance to vancomycin and teicoplanin (MIC, ≥256 mg/liter). Its glycopeptide resistance mechanism was characterized by Southern blot hybridization and a primer-walking strategy, and finally its genome, determined by whole-genome sequencing, was compared with four closely related
S. gallolyticus
subsp.
gallolyticus
genomes. Hybridization experiments demonstrated that a Tn
1546
-like element was integrated into the bacterial chromosome. In agreement with this finding, whole-genome sequencing confirmed a partial deletion of the
vanY-vanZ
region and partial duplication of the
vanH
gene. The comparative genomic analyses revealed that the LMG 17956 ST28 strain had acquired an unusually high number of transposable elements and had experienced extensive chromosomal rearrangements, as well as gene gain and loss events. In conclusion,
S. gallolyticus
subsp.
gallolyticus
isolates from animals seem to belong to lineages separate from those infecting humans. In addition, we report a glycopeptide-resistant isolate from a calf carrying a Tn
1546
-like element integrated into its chromosome.
Impact of the Combination of Daptomycin and Trimethoprim-Sulfamethoxazole on Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Infections
Authors: Claeys Kimberly C. , Smith Jordan R. , Casapao Anthony M. , Mynatt Ryan P. , Avery Lisa , Shroff Anjali , Yamamura Deborah , Davis Susan L. , Rybak Michael J.
Published: January 2015

Complicated
Staphylococcus aureus
infections, including bacteremia, are often associated with treatment failures, prolonged hospital stays, and the emergence of resistance to primary and even secondary therapies. Daptomycin is commonly used as salvage therapy after vancomycin failure for the treatment of methicillin-resistant
S. aureus
(MRSA) infections. Unfortunately, the emergence of daptomycin resistance, especially in deep-seated infections, has been reported, prompting the need for alternative or combination therapy. Numerous antibiotic combinations with daptomycin have been investigated clinically and
in vitro
. Of interest, the combination of daptomycin and trimethoprim-sulfamethoxazole (TMP-SMX) has proved to be rapidly bactericidal
in vitro
to strains that are both susceptible and nonsusceptible to daptomycin. However, to date, there is limited clinical evidence supporting the use of this combination. This was a multicenter, retrospective case series of patients treated with the combination of daptomycin and TMP-SMX for at least 72 h. The objective of this study was to describe the safety and effectiveness of this regimen in clinical practice. The most commonly stated reason that TMP-SMX was added to daptomycin was persistent bacteremia and/or progressive signs and symptoms of infection. After the initiation of combination therapy, the median time to clearance of bacteremia was 2.5 days. Microbiological eradication was demonstrated in 24 out of 28 patients, and
in vitro
synergy was demonstrated in 17 of the 17 recovered isolates. Further research with this combination is necessary to describe the optimal role and its impact on patient outcomes.
Subtle Changes in Endochin-Like Quinolone Structure Alter the Site of Inhibition within the Cytochrome
bc
1
Complex of Plasmodium falciparum
Authors: Stickles Allison M. , de Almeida Mariana Justino , Morrisey Joanne M. , Sheridan Kayla A. , Forquer Isaac P. , Nilsen Aaron , Winter Rolf W. , Burrows Jeremy N. , Fidock David A. , Vaidya Akhil B. , Riscoe Michael K.
Published: January 2015

The cytochrome
bc
1
complex (cyt
bc
1
) is the third component of the mitochondrial electron transport chain and is the target of several potent antimalarial compounds, including the naphthoquinone atovaquone (ATV) and the 4(1
H
)-quinolone ELQ-300. Mechanistically, cyt
bc
1
facilitates the transfer of electrons from ubiquinol to cytochrome
c
and contains both oxidative (Q
o
) and reductive (Q
i
) catalytic sites that are amenable to small-molecule inhibition. Although many antimalarial compounds, including ATV, effectively target the Q
o
site, it has been challenging to design selective Q
i
site inhibitors with the ability to circumvent clinical ATV resistance, and little is known about how chemical structure contributes to site selectivity within cyt
bc
1
. Here, we used the proposed Q
i
site inhibitor ELQ-300 to generate a drug-resistant
Plasmodium falciparum
clone containing an I22L mutation at the Q
i
region of cyt
b
. Using this D1 clone and the Y268S Q
o
mutant strain,
P. falciparum
Tm90-C2B, we created a structure-activity map of Q
i
versus Q
o
site selectivity for a series of endochin-like 4(1
H
)-quinolones (ELQs). We found that Q
i
site inhibition was associated with compounds containing 6-position halogens or aryl 3-position side chains, while Q
o
site inhibition was favored by 5,7-dihalogen groups or 7-position substituents. In addition to identifying ELQ-300 as a preferential Q
i
site inhibitor, our data suggest that the 4(1
H
)-quinolone scaffold is compatible with binding to either site of cyt
bc
1
and that minor chemical changes can influence Q
o
or Q
i
site inhibition by the ELQs.
Small-Molecule Inhibitors of Staphylococcus aureus RnpA-Mediated RNA Turnover and tRNA Processing
Authors: Eidem Tess M. , Lounsbury Nicole , Emery John F. , Bulger Jeffrey , Smith Andrew , Abou-Gharbia Magid , Childers Wayne , Dunman Paul M.
Published: January 2015

New agents are urgently needed for the therapeutic treatment of
Staphylococcus aureus
infections. In that regard,
S. aureus
RNase RnpA may represent a promising novel dual-function antimicrobial target that participates in two essential cellular processes, RNA degradation and tRNA maturation. Accordingly, we previously used a high-throughput screen to identify small-molecule inhibitors of the RNA-degrading activity of the enzyme and showed that the RnpA inhibitor RNPA1000 is an attractive antimicrobial development candidate. In this study, we used a series of
in vitro
and cellular assays to characterize a second RnpA inhibitor, RNPA2000, which was identified in our initial screening campaign and is structurally distinct from RNPA1000. In doing so, it was found that
S. aureus
RnpA does indeed participate in 5′-precursor tRNA processing, as was previously hypothesized. Further, we show that RNPA2000 is a bactericidal agent that inhibits both RnpA-associated RNA degradation and tRNA maturation activities both
in vitro
and within
S. aureus
. The compound appears to display specificity for RnpA, as it did not significantly affect the
in vitro
activities of unrelated bacterial or eukaryotic ribonucleases and did not display measurable human cytotoxicity. Finally, we show that RNPA2000 exhibits antimicrobial activity and inhibits tRNA processing in efflux-deficient Gram-negative pathogens. Taken together, these data support the targeting of RnpA for antimicrobial development purposes, establish that small-molecule inhibitors of both of the functions of the enzyme can be identified, and lend evidence that RnpA inhibitors may have broad-spectrum antimicrobial activities.
Examining the Use of Ceftaroline in the Treatment of Streptococcus pneumoniae Meningitis with Reference to Human Cathelicidin LL-37
Authors: Sakoulas George , Nonejuie Poochit , Kullar Ravina , Pogliano Joseph , Rybak Michael J. , Nizet Victor
Published: January 2015

Five cases of bacterial meningitis treated with ceftaroline (4
Streptococcus pneumoniae
and 1
Staphylococcus aureus
) are summarized here. The pharmacodynamics of human cathelicidin LL-37 and ceftaroline were evaluated against
S. pneumoniae
. Patients who received ceftaroline 600 mg every 8 h (q8h) (1
S. aureus
and 3
S. pneumoniae
) were successfully treated; treatment failed in 1 patient with
S. pneumoniae
who received 600 mg q12h. Ceftaroline increased the negative surface charge and sensitized
S. pneumoniae
to killing by LL-37, a peptide implicated in blood-brain barrier defense.
Global Analysis of Posttranscriptional Regulation by GlmY and GlmZ in Enterohemorrhagic Escherichia coli O157:H7
Authors: Gruber Charley C. , Sperandio Vanessa
Published: January 2015

Enterohemorrhagic
Escherichia coli
(EHEC) is a significant human pathogen and is the cause of bloody diarrhea and hemolytic-uremic syndrome. The virulence repertoire of EHEC includes the genes within the locus of enterocyte effacement (LEE) that are largely organized in five operons,
LEE1
to
LEE5
, which encode a type III secretion system, several effectors, chaperones, and regulatory proteins. In addition, EHEC also encodes several non-LEE-encoded effectors and fimbrial operons. The virulence genes of this pathogen are under a large amount of posttranscriptional regulation. The small RNAs (sRNAs) GlmY and GlmZ activate the translation of glucosamine synthase (GlmS) in
E. coli
K-12, and in EHEC they destabilize the 3′ fragments of the
LEE4
and
LEE5
operons and promote translation of the non-LEE-encoded effector EspFu. We investigated the global changes of EHEC gene expression governed by GlmY and GlmZ using RNA sequencing and gene arrays. This study extends the known effects of GlmY and GlmZ regulation to show that they promote expression of the curli adhesin, repress the expression of tryptophan metabolism genes, and promote the expression of acid resistance genes and the non-LEE-encoded effector NleA. In addition, seven novel EHEC-specific sRNAs were identified using RNA sequencing, and three of them—sRNA56, sRNA103, and sRNA350—were shown to regulate urease, fimbria, and the LEE, respectively. These findings expand the knowledge of posttranscriptional regulation in EHEC.
Evidence that TP_0144 of Treponema pallidum Is a Thiamine-Binding Protein
Authors: Bian Jiang , Tu Youbin , Wang Song-Mei , Wang Xuan-Yi , Li Chunhao
Published: January 2015

Thiamine pyrophosphate (TPP), the biologically active form of thiamine (also known as vitamin B1), is an essential cofactor for several important enzymes involved in carbohydrate metabolism, and therefore, it is required for all living organisms. We recently found that a thiamine-binding protein (TDE_0143) is essential for the survival ofTreponema denticola, an important bacterial pathogen that is associated with human periodontitis. In this report, we provide experimental evidence showing that TP_0144, a homolog of TDE_0143 from the syphilis spirocheteTreponema pallidum, is a thiamine-binding protein that has biochemical features and functions that are similar to those of TDE_0143. First, structural modeling analysis reveal that both TDE_0143 and TP_0144 contain a conserved TPP-binding site and share similar structures to the thiamine-binding protein ofEscherichia coli. Second, biochemical analysis shows that these two proteins bind to TPP with similar dissociation constant (Kd) values (TDE_0143,Kdof 36.50 nM; TP_0144,Kdof 32.62 nM). Finally, heterologous expression of TP_0144 in a ΔTDE_0143 strain, a previously constructedTDE_0143mutant ofT. denticola, fully restores its growth and TPP uptake when exogenous thiamine is limited. Collectively, these results indicate that TP_0144 is a thiamine-binding protein that is indispensable forT. pallidumto acquire exogenous thiamine, a key nutrient for bacterial survival. In addition, the studies shown in this report further underscore the feasibility of usingT. denticolaas a platform to study the biology and pathogenicity ofT. pallidumand probably other uncultivable treponemal species as well.
Identification of a Putative Flavin Adenine Dinucleotide-Binding Monooxygenase as a Regulator for Myxococcus xanthus Development
Authors: Cao Shanshan , Wu Miaomiao , Xu Shihui , Yan Xiuwen , Mao Xiaohua
Published: January 2015

Gene clusters coding for the chaperone/usher (CU) pathway are widely distributed in many important environmental and pathogenic microbes; however, information about the regulatory machineries controlling CU gene expression during multicellular morphogenesis is missing. TheMyxococcus xanthusMcu system, encoded by themcuABCDgene cluster, represents a prototype of the archaic CU family that functions in spore coat formation. Using genome-wide transposon mutagenesis, we identified MXAN2872 to be a potential regulator of themcuABCoperon and demonstrated the necessity of MXAN2872 formcuABCexpression and fruiting body morphogenesis in early development.In silico, biochemical, and genetic analyses suggest that MXAN2872 encodes a Baeyer-Villiger monooxygenase (BVMO) of flavoproteins, and the potential cofactor-binding site as well as the BVMO fingerprint sequence is important for the regulatory role of the MXAN2872 protein. The expression profile ofmcuAin strains with an MXAN2872 deletion and point mutation agrees well with the timing of cell aggregation of these mutants. Furthermore, McuA could not be detected either in afruA-null mutant, where starvation-induced aggregation was completely blocked, or in the glycerol-induced spores, where sporulation was uncoupled from cell aggregation. In sum, the present work uncovers a positive role for MXAN2872, a metabolic enzyme-encoding gene, in controllingM. xanthusdevelopment. MXAN2872 functions by affecting the onset of cell aggregation, thereby leading to a secondary effect on the timing ofmcuABCexpression of this model organism.

IMPORTANCEIdentification of the players that driveMyxococcus xanthusfruiting body formation is necessary for studying the mechanism of multicellular morphogenesis in this model organism. This study identifies MXAN2872, a gene encoding a putative flavin adenine dinucleotide-binding monooxygenase, to be a new interesting regulator regulating the timing of developmental aggregation. In addition, MXAN2872 seems to affect the expression of the chaperone/usher gene clustermcuin a manner that is aggregation dependent. Thus, in organisms characterized by a developmental cycle, expression of the chaperone/usher pathway can be controlled by morphological checkpoints, demonstrating another layer of complexity in the regulation of this conserved protein secretion pathway.
Many Means to a Common End: the Intricacies of (p)ppGpp Metabolism and Its Control of Bacterial Homeostasis
Authors: Gaca Anthony O. , Colomer-Winter Cristina , Lemos José A.
Published: January 2015

In nearly all bacterial species examined so far, amino acid starvation triggers the rapid accumulation of the nucleotide second messenger (p)ppGpp, the effector of the stringent response. While for years the enzymes involved in (p)ppGpp metabolism and the significance of (p)ppGpp accumulation to stress survival were considered well defined, a recent surge of interest in the field has uncovered an unanticipated level of diversity in how bacteria metabolize and utilize (p)ppGpp to rapidly synchronize a variety of biological processes important for growth and stress survival. In addition to the classic activation of the stringent response, it has become evident that (p)ppGpp exerts differential effects on cell physiology in an incremental manner rather than simply acting as a biphasic switch that controls growth or stasis. Of particular interest is the intimate relationship of (p)ppGpp with persister cell formation and virulence, which has spurred the pursuit of (p)ppGpp inhibitors as a means to control recalcitrant infections. Here, we present an overview of the enzymes responsible for (p)ppGpp metabolism, elaborate on the intricacies that link basal production of (p)ppGpp to bacterial homeostasis, and discuss the implications of targeting (p)ppGpp synthesis as a means to disrupt long-term bacterial survival strategies.
Diffusion of Antibiotics through the PilQ Secretin in Neisseria gonorrhoeae Occurs through the Immature, Sodium Dodecyl Sulfate-Labile Form
Authors: Nandi Sobhan , Swanson Shauna , Tomberg Joshua , Nicholas Robert A.
Published: January 2015

In strains of
Neisseria gonorrhoeae
harboring the
mtr
and
penB
determinants that decrease permeation of antibiotics into the periplasm, mutation or deletion of the PilQ secretin of type IV pili increases resistance to penicillin by ∼3-fold, indicating a role for PilQ in antibiotic permeation. In this study, we examined spontaneously arising mutants with decreased susceptibility to penicillin. One class of mutants had a phenotype indistinguishable from that of a previously characterized
pilQ2
mutation that interfered with the formation of SDS-resistant PilQ multimers. A second class of mutants contained frameshift mutations in genes upstream of
pilQ
in the
pilMNOPQ
operon that increased resistance to levels similar to those of the
pilQ2
mutation. In-frame deletions of these genes were constructed, but only the frameshift mutations increased antibiotic resistance, suggesting that the mutations had polar effects on PilQ. Consistent with this result, titration of wild-type PilQ levels revealed a direct correlation between resistance and expression levels of PilQ. To determine which form of PilQ, the monomer or the multimer, was responsible for antibiotic permeation, we manipulated and quantified these forms in different mutants. Deletion of PilW, which is responsible for the maturation of PilQ into SDS-resistant multimers, had no effect on resistance. Moreover, Western blot analysis revealed that while SDS-resistant multimer levels were decreased by 26% in frameshift mutants, the levels of PilQ monomers were decreased by 48%. These data suggest that immature, SDS-labile complexes, not mature, SDS-resistant PilQ complexes, serve as the route of entry of antibiotics into the periplasm.

IMPORTANCE
The capacity of antibiotics to reach their target is crucial for their activity. In
Neisseria gonorrhoeae
, the PilQ secretin of type IV pili plays an important role in antibiotic influx when diffusion of antibiotics through porins is limited (e.g., in most resistant strains). On Western blots, PilQ exists both as a mature higher-order multimer and an immature, SDS-labile monomer. In this study, we examined spontaneously arising mutations in PilQ and in the genes upstream of PilQ in the
pilMNOPQ
operon that increase resistance to penicillin. We provide evidence that PilQ monomers associate by mass action to form immature multimers and that these complexes likely mediate the diffusion of antibiotics across the outer membrane.
Degradation Products of the Extracellular Pathogen Streptococcus pneumoniae Access the Cytosol via Its Pore-Forming Toxin
Authors: Lemon Jamie K. , Weiser Jeffrey N.
Published: January 2015

Streptococcus pneumoniae
is a leading pathogen with an extracellular lifestyle; however, it is detected by cytosolic surveillance systems of macrophages. The innate immune response that follows cytosolic sensing of cell wall components results in recruitment of additional macrophages, which subsequently clear colonizing organisms from host airways. In this study, we monitored cytosolic access by following the transit of the abundant bacterial surface component capsular polysaccharide, which is linked to the cell wall. Confocal and electron microscopy visually characterized the location of cell wall components in murine macrophages outside membrane-bound organelles. Quantification of capsular polysaccharide through cellular fractionation demonstrated that cytosolic access of bacterial cell wall components is dependent on phagocytosis, bacterial sensitivity to the host’s degradative enzyme lysozyme, and release of the pore-forming toxin pneumolysin. Activation of p38 mitogen-activated protein kinase (MAPK) signaling is important for limiting access to the cytosol; however, ultimately, these are catastrophic events for both the bacteria and the macrophage, which undergoes cell death. Our results show how expression of a pore-forming toxin ensures the death of phagocytes that take up the organism, although cytosolic sensing results in innate immune detection that eventually allows for successful host defense. These findings provide an example of how cytosolic access applies to an extracellular microbe and contributes to its pathogenesis.

IMPORTANCE
 
Streptococcus pneumoniae
(the pneumococcus) is a bacterial pathogen that is a leading cause of pneumonia. Pneumococcal disease is preceded by colonization of the nasopharynx, which lasts several weeks before being cleared by the host’s immune system. Although S. pneumoniae is an extracellular microbe, intracellular detection of pneumococcal components is critical for bacterial clearance. In this study, we show that following bacterial uptake and degradation by phagocytes, pneumococcal products access the host cell cytosol via its pore-forming toxin. This phenomenon of cytosolic access results in phagocyte death and may serve to combat the host cells responsible for clearing the organism. Our results provide an example of how intracellular access and subsequent immune detection occurs during infection with an extracellular pathogen.
Malaria Induces Anemia through CD8+T Cell-Dependent Parasite Clearance and Erythrocyte Removal in the Spleen
Authors: Safeukui Innocent , Gomez Noé D. , Adelani Aanuoluwa A. , Burte Florence , Afolabi Nathaniel K. , Akondy Rama , Velazquez Peter , Holder Anthony , Tewari Rita , Buffet Pierre , Brown Biobele J. , Shokunbi Wuraola A. , Olaleye David , Sodeinde Olugbemiro , Kazura James , Ahmed Rafi , Mohandas Narla , Fernandez-Reyes Delmiro , Haldar Kasturi
Published: January 2015

Severe malarial anemia (SMA) in semi-immune individuals eliminates both infected and uninfected erythrocytes and is a frequent fatal complication. It is proportional not to circulating parasitemia but total parasite mass (sequestered) in the organs. Thus, immune responses that clear parasites in organs may trigger changes leading to anemia. Here, we use an outbred-rat model where increasing parasite removal in the spleen escalated uninfected-erythrocyte removal. Splenic parasite clearance was associated with activated CD8+T cells, immunodepletion of which prevented parasite clearance. CD8+T cell repletion and concomitant reduction of the parasite load was associated with exacerbated (40 to 60%) hemoglobin loss and changes in properties of uninfected erythrocytes. Together, these data suggest that CD8+T cell-dependent parasite clearance causes erythrocyte removal in the spleen and thus anemia. In children infected with the human malaria parasite Plasmodium falciparum, elevation of parasite biomass (not the number of circulating parasites) increased the odds ratio for SMA by 3.5-fold (95% confidence intervals [CI95%], 1.8- to 7.5-fold). CD8+T cell expansion/activation independently increased the odds ratio by 2.4-fold (CI95%, 1.0- to 5.7-fold). Concomitant increases in both conferred a 7-fold (CI95%, 1.9- to 27.4-fold)-greater risk for SMA. Together, these data suggest that CD8+-dependent parasite clearance may predispose individuals to uninfected-erythrocyte loss and SMA, thus informing severe disease diagnosis and strategies for vaccine development.

IMPORTANCEMalaria is a major global health problem. Severe malaria anemia (SMA) is a complex disease associated with partial immunity. Rapid hemoglobin reductions of 20 to 50% are commonly observed and must be rescued by transfusion (which can carry a risk of HIV acquisition). The causes and risk factors of SMA remain poorly understood. Recent studies suggest that SMA is linked to parasite biomass sequestered in organs. This led us to investigate whether immune mechanisms that clear parasites in organs trigger anemia. In rats, erythropoiesis is largely restricted to the bone marrow, and critical aspects of the spleen expected to be important in anemia are similar to those in humans. Therefore, using a rat model, we show that severe anemia is caused through CD8+T cell-dependent parasite clearance and erythrocyte removal in the spleen. CD8 activation may also be a new risk factor for SMA in African children.
Necrotising pneumonia and bronchiectasis in a previously healthy 30-year-old man
Authors: Blauvelt David G , Castellanos Angela , Stern Theodore A , Puig Alberto
Published: January 2015

We present a case of a previously healthy 30-year-old man who presented with a necrotising pneumonia and bronchiectasis. His infectious workup revealed aStaphylococcus aureuspneumonia. Since bronchiectasis and necrotising pneumonia are unusual findings in an otherwise healthy person, further investigation was pursued. His workup revealed non-classic cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis (ABPA). This case discusses the differential diagnosis of bronchiectasis, the diagnosis and treatment of ABPA, and the role of CF mutations in the pathogenesis of ABPA.
Myocardial infarction associated with eosinophilia and plasma extravasation at multiple sites. A variant of Kounis syndrome
Authors: Gunawardena Mudalige Don Vajira Malin , Weerasinghe Anura , Herath Jagath , Amarasena Naomali
Published: January 2015

Myocardial infarction occurring during the course of type I hypersensitivity constitutes Kounis syndrome. We report a case of a 38-year-old man who presented with anterior ST elevation myocardial infarction and peripheral blood eosinophilia. He had rhinitis and malaise for several days prior to presentation. There was no urticarial rash or pruritus to suggest hypersensitivity. Coronary angiogram revealed only mild plaque disease. Blood investigations revealed moderate eosinophilia and elevated IgE levels. CT of the thorax revealed fluid extravasation at multiple sites. Screening for a possible secondary cause for eosinophilia revealed hypersensitivity to multiple antigens. A diagnosis of Kounis syndrome was made. Within days of starting steroids and antihistamines, the patient's eosinophil count returned to normal with improvement of clinical picture. This case differs from classical Kounis syndrome as there was no acute allergic reaction (except atopic rhinitis). Fluid extravasation at multiple sites has not been described in previous cases.
Tracheal intubation related complications in the prehospital setting
Authors: Caruana Emmanuel , Duchateau François-Xavier , Cornaglia Carole , Devaud Marie-Laure , Pirracchio Romain
Published: January 2015

Background

Prehospital tracheal intubation (TI) is associated with morbidity and mortality, particularly in cases of difficult intubation. The goal of the present study was to describe factors associated with TI related complications in the prehospital setting.

Methods

This was a prospective cohort study including all patients intubated on scene in a prehospital emergency medical service over a 4 year period. TI related complications included oxygen desaturation, aspiration, vomiting, bronchospasm and/or laryngospasm, and mechanical complications (mainstem intubation, oesophageal intubation and airway lesion— that is, dental or laryngeal trauma caused by the laryngoscope). Difficult intubation was defined as >2 failed laryngoscopic attempts, or the need for any alternative TI method. A multivariate logistic regression was used to identify the risk factors for TI related complications.

Results

1251 patients were included; 208 complications occurred in 165 patients (13.1%). Among the 208 complications, the most frequent were oesophageal intubation (n=69, 29.7%), desaturation (n=58, 25.0%) and mainstem intubation (n=37, 15.9%). In multivariate analysis, difficult intubation (OR=6.13, 3.93 to 9.54), Cormack and Lehane grades 3 and 4 (OR=2.23, 1.26 to 3.96 for Cormack and Lehane grade 3 and OR=2.61, 1.28 to 5.33 for Cormack and Lehane grade 4 compared with Cormack and Lehane grade 1) and a body mass index >30 kg/m2(OR=2.22, 1.38 to 3.56) were significantly associated with TI related complications.

Conclusions

Despite specific guidelines, TI related complications are more frequent in the prehospital setting when intubation is deemed difficult, the Cormack and Lehane grade is greater than grade 1 and the patient is overweight. In such situations, particular attention is needed to avoid complications.
Epidemiology of bicycle injuries and risk factors for serious injury
Authors: Rivara Frederick P , Thompson Diane C , Thompson Robert S
Published: January 2015

Objective

To determine the risk factors for serious injury to bicyclists, aside from helmet use.

Design

Prospective case-control study.

Setting

Seven Seattle area hospital emergency departments and two county medical examiner's offices.

Patients

Individuals treated in the emergency department or dying from bicycle related injuries.

Measurements

Information collected from injured bicyclists or their parents by questionnaire on circumstances of the crash; abstract of medical records for injury data. Serious injury defined as an injury severity score>8.

Analysis

Odd ratios computed using the maximum likelihood method, and adjusted using unconditional logistic regression.

Results

There were 3854 injured cyclists in the three year period; 3390 (88%) completed questionnaires were returned. 51% wore helmets at the time of crash. Only 22.3% of patients had head injuries and 34% had facial injuries. Risk of serious injury was increased by collision with a motor vehicle (odds ratio (OR)=4.6), self reported speed >15 mph (OR=1.2), young age (<6 years), and age >39 years (OR=2.1 and 2.2 respectively, compared with adults 20-39 years). Risk for serious injury was not affected by helmet use (OR=0.9). Risk of neck injury was increased in those struck by motor vehicles (OR=4.0), hospitalized for any injury (OR=2.0), and those who died (OR=15.1), but neck injury was not affected by helmet use.

Conclusions

Prevention of serious bicycle injuries cannot be accomplished through helmet use alone, and may require separation of cyclists from motor vehicles, and delaying cycling until children are developmentally ready.
Does research into contraceptive method discontinuation address women's own reasons? A critical review
Authors: Inoue Kumiyo , Barratt Alexandra , Richters Juliet
Published: January 2015

Objective

To examine the clinical and epidemiological literature addressing contraceptive method change or discontinuation and to assess whether the documented reasons reflected women's experiences.

Methods

Major databases including Medline and PsycINFO were searched using keywords related to contraception and discontinuation, adherence and satisfaction, for articles published between January 2003 and February 2013. Studies in developed countries that focused on women of reproductive age and reasons for method change or discontinuation were included. Reasons reported were categorised and examined.

Results

A total of 123 papers were reviewed in detail. Medical terminology was generally used to describe reasons for method discontinuation. The top two reported reasons were bleeding and pregnancy, but there was a lack of consensus about the categorisation of reasons. Broad categories that were not self-explanatory were included in more than half of the papers, often without further explanation. Only 12 studies expanded on categories containing ‘other’, ‘non-medical’ or ‘personal’ reasons. Eight papers included categories that attributed discontinuation to the participant, such as ‘dissatisfied with method’.

Conclusions

Studies of reasons for discontinuation of contraceptives do not well describe women's specific reasons. Studies rely heavily on medical terms and often fail to document women's subjective experiences. Future studies should create an opportunity for women to articulate their non-medical reasons in their own words, including those related to their sexual lives. Furthermore, researchers should distinguish, if possible, between reasons for discontinuation of a method and reasons for ceasing participation in a research study.
Propagation of the Gabor wave front set for Schrödinger equations with non-smooth potentials
Authors: Cordero Elena , Nicola Fabio , Rodino Luigi
Published: January 2015

We consider Schrödinger equations with real-valued smooth Hamiltonians, and non-smooth bounded pseudo-differential potentials, whose symbols may not even be differentiable. The well-posedness of the Cauchy problem is proved in the frame of the modulation spaces, and results of micro-local propagation of singularities are given in terms of Gabor wave front sets.
Problems of massive gravities
Authors: Deser S. , Izumi K. , Ong Y. C. , Waldron A.
Published: January 2015

The method of characteristics is a key tool for studying consistency of equations of motion; it allows issues such as predictability, maximal propagation speed, superluminality, unitarity and acausality to be addressed without requiring explicit solutions. We review this method and its application to massive gravity (mGR) theories to show the limitations of these models' physical viability: Among their problems are loss of unique evolution, superluminal signals, matter coupling inconsistencies and micro-acausality (propagation of signals around local closed time-like curves (CTCs)/closed causal curves (CCCs)). We extend previous no-go results to the entire three-parameter range of mGR theories. It is also argued that bimetric models suffer a similar fate.
Quarks and anomalies
Authors: Crewther R. J.
Published: January 2015

A nonperturbative understanding of neutral pion decay was an essential step towards the idea that strong interactions are governed by a color gauge theory for quarks. Some aspects of this work and related problems are still important.
Anisotropic pressure and hyperons in neutron stars
Authors: Sulaksono A.
Published: January 2015

We study the effects of anisotropic pressure (AI-P) on properties of the neutron stars (NSs) with hyperons inside its core within the framework of extended relativistic mean field. It is found that the main effects of AI-P on NS matter is to increase the stiffness of the equation of state EOS, which compensates for the softening of the EOS due to the hyperons. The maximum mass and redshift predictions of anisotropic neutron star with hyperonic core are quite compatible with the result of recent observational constraints if we use the parameter of AI-P model h ≤ 0.8 [L. Herrera and W. Barreto, Phys. Rev. D 88 (2013) 084022.] and Λ ≤ -1.15 [D. D. Doneva and S. S. Yazadjiev, Phys. Rev. D 85 (2012) 124023.]. The radius of the corresponding NS at M = 1.4 M⊙ is more than 13 km, while the effect of AI-P on the minimum mass of NS is insignificant. Furthermore, due to the AI-P in the NS, the maximum mass limit of higher than 2.1 M⊙ cannot rule out the presence of hyperons in the NS core.
FORCE SUMMATION AND TWITCH POTENTIATION CAPACITY IN HUMAN ANKLE PLANTAR- AND DORSI-FLEXOR MUSCLES
Authors: Ohta Yoichi , Yotani Kengo
Published: January 2015

Purpose: The present study aimed to clarify inter-individual correlation between the magnitudes of force summation and the post-activation potentiation (PAP), in human ankle plantar- and dorsi-flexor muscles. Methods: We analyzed 10 male participants plantar-flexor muscles and the 12 male participants dorsi-flexor muscles using a database from a previous study. Before and after maximum voluntary contraction, we measured the amount of isometric torque evoked by a single, double- and triple-pulse train stimulus. Results: The magnitude of PAP was significantly positively correlated with the magnitude of force summation in both the plantar- and dorsi-flexor muscles. Conclusions: The present study confirmed the correlation between the magnitudes of force summation and PAP in human ankle plantar- and dorsi-flexor muscles. This suggests that muscle characteristics affecting the force summation capacity depend on the PAP, to some degree. These results suggest that the combination of both parameters might enhance the usefulness of evaluating changes in muscle function using intrinsic contractile properties.
OPTIMAL CREDIT ALLOCATION UNDER REGIME UNCERTAINTY WITH SENSITIVITY ANALYSIS
Authors: BERNIS GUILLAUME , CARASSUS LAURENCE , DOCQ GRÉGOIRE , SCOTTI SIMONE
Published: January 2015

We consider the problem of credit allocation in a regime-switching model. The global evolution of the credit market is driven by a benchmark, the drift of which is given by a two-state continuous-time hidden Markov chain. We apply filtering techniques to obtain the diffusion of the credit assets under partial observation and show that they have a specific excess return with respect to the benchmark. The investor performs a simple mean–variance allocation on credit assets. However, returns and variance matrix have to be computed by a numerical method such as Monte Carlo, because of the dynamics of the system and the non-linearity of the asset prices. We use the theory of Dirichlet forms to deal with the uncertainty on the excess returns. This approach provides an estimation of the bias and the variance of the optimal allocation, and return. We propose an application in the case of a sectorial allocation with Credit Default Swaps (CDS), fully calibrated with observable data or direct input given by the portfolio manager.