bluuebunny/crossref_metadata_2025 huggingface dataset:
Destabilization of α-Helical Structure in Solution Improves Bactericidal Activity of Antimicrobial Peptides: Opposite Effects on Bacterial and Viral Targets
Authors: Ulaeto David O. , Morris Christopher J. , Fox Marc A. , Gumbleton Mark , Beck Konrad
Published: January 2016

We have previously examined the mechanism of antimicrobial peptides on the outer membrane of vaccinia virus. We show here that the formulation of peptides LL37 and magainin-2B amide in polysorbate 20 (Tween 20) results in greater reductions in virus titer than formulation without detergent, and the effect is replicated by substitution of polysorbate 20 with high-ionic-strength buffer. In contrast, formulation with polysorbate 20 or high-ionic-strength buffer has the opposite effect on bactericidal activity of both peptides, resulting in lesser reductions in titer for both Gram-positive and Gram-negative bacteria. Circular dichroism spectroscopy shows that the differential action of polysorbate 20 and salt on the virucidal and bactericidal activities correlates with the α-helical content of peptide secondary structure in solution, suggesting that the virucidal and bactericidal activities are mediated through distinct mechanisms. The correlation of a defined structural feature with differential activity against a host-derived viral membrane and the membranes of both Gram-positive and Gram-negative bacteria suggests that the overall helical content in solution under physiological conditions is an important feature for consideration in the design and development of candidate peptide-based antimicrobial compounds.
Nitazoxanide Inhibits Pilus Biogenesis by Interfering with Folding of the Usher Protein in the Outer Membrane
Authors: Chahales Peter , Hoffman Paul S. , Thanassi David G.
Published: January 2016

Many bacterial pathogens assemble surface fibers termed pili or fimbriae that facilitate attachment to host cells and colonization of host tissues. The chaperone/usher (CU) pathway is a conserved secretion system that is responsible for the assembly of virulence-associated pili by many different Gram-negative bacteria. Pilus biogenesis by the CU pathway requires a dedicated periplasmic chaperone and an integral outer membrane (OM) assembly and secretion platform termed the usher. Nitazoxanide (NTZ), an antiparasitic drug, was previously shown to inhibit the function of aggregative adherence fimbriae and type 1 pili assembled by the CU pathway in enteroaggregative
Escherichia coli
, an important causative agent of diarrhea. We show here that NTZ also inhibits the function of type 1 and P pili from uropathogenic
E. coli
(UPEC). UPEC is the primary causative agent of urinary tract infections, and type 1 and P pili mediate colonization of the bladder and kidneys, respectively. By analysis of the different stages of the CU pilus biogenesis pathway, we show that treatment of bacteria with NTZ causes a reduction in the number of usher molecules in the OM, resulting in a loss of pilus assembly on the bacterial surface. In addition, we determine that NTZ specifically prevents proper folding of the usher β-barrel domain in the OM. Our findings demonstrate that NTZ is a pilicide with a novel mechanism of action and activity against diverse CU pathways. This suggests that further development of the NTZ scaffold may lead to new antivirulence agents that target the usher to prevent pilus assembly.
Is Aerosolized Pentamidine for Pneumocystis Pneumonia Prophylaxis in Renal Transplant Recipients Not as Safe as We Might Think?
Authors: Macesic N. , Urbancic K. , Ierino F. , Grayson M. L.
Published: January 2016

Outbreaks of
Pneumocystis
pneumonia have been described in renal transplant recipients. Aerosolized pentamidine is frequently used for prophylaxis in this setting. We report our experience with aerosolized pentamidine use in 56 renal transplant recipients. We found high rates of adverse reactions in patients with chronic respiratory disease.
Inhibition of Hippocampal Regeneration by Adjuvant Dexamethasone in Experimental Infant Rat Pneumococcal Meningitis
Authors: Bally Lia , Grandgirard Denis , Leib Stephen L.
Published: January 2016

Pneumococcal meningitis (PM) causes neurological sequelae in up to half of surviving patients. Neuronal damage associated with poor outcome is largely mediated by the inflammatory host response. Dexamethasone (DXM) is used as an adjuvant therapy in adult PM, but its efficacy in the treatment of pneumococcal meningitis in children is controversially discussed. While DXM has previously been shown to enhance hippocampal apoptosis in experimental PM, its impact on hippocampal cell proliferation is not known. This study investigated the impact of DXM on hippocampal proliferation in infant rat PM. Eleven-day-old nursing Wistar rats (n= 90) were intracisternally infected withStreptococcus pneumoniaeto induce experimental meningitis. Treatment with DXM or vehicle was started 18 h after infection, concomitantly with antibiotics (ceftriaxone 100 mg/kg of body weight twice a day [b.i.d.]). Clinical parameters were monitored, and the amount of cells with proliferating activity was assessed usingin vivoincorporation of bromodeoxyuridine (BrdU) and anin vitroneurosphere culture system at 3 and 4 d postinfection. DXM significantly worsened weight loss and survival. Density of BrdU-positive cells, as an index of cells with proliferating activity, was significantly lower in DXM-treated animals compared to vehicle controls (P< 0.0001). In parallel, DXM reduced neurosphere formation as an index for stem/progenitor cell density compared to vehicle treatment (P= 0.01). Our findings provide clear evidence that DXM exerts an antiproliferative effect on the hippocampus in infant rat PM. We conclude that an impairment of regenerative hippocampal capacity should be taken into account when considering adjuvant DXM in the therapeutic regimen for PM in children.
Incidence and Risk Factors of Ocular Infection Caused by Staphylococcus aureus Bacteremia
Authors: Jung Jiwon , Lee Junyeop , Yu Shi Nae , Kim Yong Kyun , Lee Ju Young , Sung Heungsup , Kim Mi-Na , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Woo Jun Hee , Lee Joo Yong , Kim Yang Soo , Chong Yong Pil
Published: January 2016

Staphylococcus aureus
bacteremia (SAB) often leads to ocular infections, including endophthalmitis and chorioretinitis. However, the incidence, risk factors, and outcomes of ocular infections complicated by SAB are largely unknown. We retrospectively analyzed the incidence and risk factors of ocular involvement in a prospective cohort of patients with SAB at a tertiary-care hospital. Ophthalmologists reviewed the fundoscopic findings and classified the ocular infections as endophthalmitis or chorioretinitis. During the 5-year study period, 1,109 patients had SAB, and data for 612 (55%) who underwent ophthalmic examinations within 14 days after SAB onset were analyzed. Of those 612 patients, 56 (9% [95% confidence interval [CI], 7 to 12%]) had ocular involvement, including 15 (2.5%) with endophthalmitis and 41 (6.7%) with chorioretinitis. In a multivariate analysis, infective endocarditis (adjusted odds ratio [aOR], 5.74 [95% CI, 2.25 to 14.64]) and metastatic infection (aOR, 2.38 [95% CI, 1.29 to 4.39]) were independent risk factors for ocular involvement. Of the 47 patients with ocular involvement who could communicate, only 17 (36%) had visual disturbances. Two-thirds of the patients with endophthalmitis (10/15 patients) were treated with intravitreal antibiotics combined with parenteral antibiotics, whereas all of the patients with chorioretinitis were treated only with systemic antibiotics. No patients became blind. Among 42 patients for whom follow-up assessments were available, the ocular lesions improved in 29 (69%) but remained the same in the others. Ocular involvement was independently associated with death within 30 days after SAB onset. Ocular involvement is not uncommon among patients with SAB. Routine ophthalmic examinations should be considered for patients with infective endocarditis or metastatic infections caused by SAB.
Characterization of VCC-1, a Novel Ambler Class A Carbapenemase from Vibrio cholerae Isolated from Imported Retail Shrimp Sold in Canada
Authors: Mangat Chand S. , Boyd David , Janecko Nicol , Martz Sarah-Lynn , Desruisseau Andrea , Carpenter Michael , Reid-Smith Richard J. , Mulvey Michael R.
Published: January 2016

One of the core goals of the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) is to monitor major meat commodities for antimicrobial resistance. Targeted studies with methodologies based on core surveillance protocols are used to examine other foods, e.g., seafood, for antimicrobial resistance to detect resistances of concern to public health. Here we report the discovery of a novel Ambler class A carbapenemase that was identified in a nontoxigenic strain ofVibrio cholerae(N14-02106) isolated from shrimp that was sold for human consumption in Canada.V. choleraeN14-02106 was resistant to penicillins, carbapenems, and monobactam antibiotics; however, PCR did not detect common β-lactamases. Bioinformatic analysis of the whole-genome sequence ofV. choleraeN14-02106 revealed on the large chromosome a novel carbapenemase (referred to here as VCC-1, forVibriocholeraecarbapenemase1) with sequence similarity to class A enzymes. Two copies ofblaVCC-1separated and flanked by ISVch9(i.e., 3 copies of ISVch9) were found in an acquired 8.5-kb region inserted into a VrgG family protein gene. ClonedblaVCC-1conferred a β-lactam resistance profile similar to that inV. choleraeN14-02106 when it was transformed into a susceptible laboratory strain ofEscherichia coli. Purified VCC-1 was found to hydrolyze penicillins, 1st-generation cephalosporins, aztreonam, and carbapenems, whereas 2nd- and 3rd-generation cephalosporins were poor substrates. Using nitrocefin as a reporter substrate, VCC-1 was moderately inhibited by clavulanic acid and tazobactam but not EDTA. In this report, we present the discovery of a novel class A carbapenemase from the food supply.
Characterization of SXT/R391 Integrative and Conjugative Elements in Proteus mirabilis Isolates from Food-Producing Animals in China
Authors: Lei Chang-Wei , Zhang An-Yun , Wang Hong-Ning , Liu Bi-Hui , Yang Li-Qin , Yang Yong-Qiang
Published: January 2016

SXT/R391 integrative and conjugative elements (ICEs) were detected in 8 out of 125
Proteus mirabilis
isolates from food-producing animals in China. Whole-genome sequencing revealed that seven ICEs were identical to ICE
Pmi
Jpn1, carrying the cephalosporinase gene
bla
CMY-2
. Another one, designated ICE
Pmi
Chn1, carried five resistance genes. All eight ICEs could be transferred to
Escherichia coli
via conjugation. The results highlight the idea that animal farms are important reservoir of the SXT/R391 ICE-containing
P. mirabilis
.
Natural History of Francisella tularensis in Aerosol-Challenged BALB/c Mice
Authors: Heine Henry S. , Chuvala Lara , Riggins Renaldo , Cirz Ryan , Cass Robert , Louie Arnold , Drusano G. L.
Published: January 2016

The objective of this study was to evaluate the natural history and pathogenesis of
Francisella tularensis
in a murine model of inhalational tularemia with the SchuS4 strain. Before the efficacy of antimicrobials could be assessed in this model, further model development was required to determine the optimal time to start therapy. This study helped define the time course of infection after aerosol challenge by quantifying the presence of bacteria in lung, blood, and spleen at multiple harvest points. In this study, mice were infected via a targeted inhaled dose of 100 50% lethal doses (LD
50
s) (LD
50
= 300 CFU) of
F. tularensis
by whole-body aerosol. At 1, 24, 36, 48, 60, 72, 75, 78, 81, 84, 87, and 90 h postchallenge, groups of 15 animals were sacrificed and blood, lung, and splenic tissue samples were harvested, homogenized, plated, and incubated to evaluate the bacterial load in those tissues. It was determined that of the 3 sample types harvested, splenic tissue provided the most consistent bacterial counts, which steadily increased with the progressing infection. Further, it was determined that lung samples from all (15/15) animals were positive for infection at 75 h postaerosolization and that 14/15 animals had positive splenic tissue counts. Bacterial levels in blood were not predictive of treatment initiation. For future therapeutic evaluation studies in this model using
F. tularensis
(SchuS4), it was determined that therapy should be initiated at 75 h postchallenge and validated by spleen involvement.
Nonselective Persistence of a Rickettsia conorii Extrachromosomal Plasmid during Mammalian Infection
Authors: Riley Sean P. , Fish Abigail I. , Garza Daniel A. , Banajee Kaikhushroo H. , Harris Emma K. , del Piero Fabio , Martinez Juan J.
Published: January 2016

Scientific analysis of the genus
Rickettsia
is undergoing a rapid period of change with the emergence of viable genetic tools. The development of these tools for the mutagenesis of pathogenic bacteria will permit forward genetic analysis of
Rickettsia
pathogenesis. Despite these advances, uncertainty still remains regarding the use of plasmids to study these bacteria in
in vivo
mammalian models of infection, namely, the potential for virulence changes associated with the presence of extrachromosomal DNA and nonselective persistence of plasmids in mammalian models of infection. Here, we describe the transformation of
Rickettsia conorii
Malish 7 with the plasmid pRam18dRGA[AmTrCh]. Transformed
R. conorii
stably maintains this plasmid in infected cell cultures, expresses the encoded fluorescent proteins, and exhibits growth kinetics in cell culture similar to those of nontransformed
R. conorii
. Using a well-established murine model of fatal Mediterranean spotted fever, we demonstrate that
R. conorii
(pRam18dRGA[AmTrCh]) elicits the same fatal outcomes in animals as its untransformed counterpart and, importantly, maintains the plasmid throughout infection in the absence of selective antibiotic pressure. Interestingly, plasmid-transformed
R. conorii
was readily observed both in endothelial cells and within circulating leukocytes. Together, our data demonstrate that the presence of an extrachromosomal DNA element in a pathogenic rickettsial species does not affect either
in vitro
proliferation or
in vivo
infectivity in models of disease and that plasmids such as pRam18dRGA[AmTrCh] are valuable tools for the further genetic manipulation of pathogenic rickettsiae.
Intestinal Epithelial Toll-Like Receptor 4 Signaling Affects Epithelial Function and Colonic Microbiota and Promotes a Risk for Transmissible Colitis
Authors: Dheer Rishu , Santaolalla Rebeca , Davies Julie M. , Lang Jessica K. , Phillips Matthew C. , Pastorini Cristhine , Vazquez-Pertejo Maria T. , Abreu Maria T.
Published: January 2016

Evidence obtained from gene knockout studies supports the role of Toll-like receptor 4 (TLR4) in intestinal inflammation and microbiota recognition. Increased epithelial TLR4 expression is observed in patients with inflammatory bowel disease. However, little is known of the effect of increased TLR4 signaling on intestinal homeostasis. Here, we examined the effect of increased TLR4 signaling on epithelial function and microbiota by using transgenic villin-TLR4 mice that overexpress TLR4 in the intestinal epithelium. Our results revealed that villin-TLR4 mice are characterized by increases in the density of mucosa-associated bacteria and bacterial translocation. Furthermore, increased epithelial TLR4 signaling was associated with an impaired epithelial barrier, altered expression of antimicrobial peptide genes, and altered epithelial cell differentiation. The composition of the colonic luminal and mucosa-associated microbiota differed between villin-TLR4 and wild-type (WT) littermates. Interestingly, WT mice cohoused with villin-TLR4 mice displayed greater susceptibility to acute colitis than singly housed WT mice did. The results of this study suggest that epithelial TLR4 expression shapes the microbiota and affects the functional properties of the epithelium. The changes in the microbiota induced by increased epithelial TLR4 signaling are transmissible and exacerbate dextran sodium sulfate-induced colitis. Together, our findings imply that host innate immune signaling can modulate intestinal bacteria and ultimately the host's susceptibility to colitis.
Succinic Semialdehyde Promotes Prosurvival Capability of Agrobacterium tumefaciens
Authors: Wang Chao , Tang Desong , Gao Yong-Gui , Zhang Lian-Hui
Published: January 2016

Succinic semialdehyde (SSA), an important metabolite of γ-aminobutyric acid (GABA), is a ligand of the repressor AttJ regulating the expression of the
attJ-attKLM
gene cluster in the plant pathogen
Agrobacterium tumefaciens
. While the response of
A. tumefaciens
to GABA and the function of
attKLM
have been extensively studied, genetic and physiological responses of
A. tumefaciens
to SSA remain unknown. In combination with microarray and genetic approaches, this study sets out to explore new roles of the SSA-AttJKLM regulatory mechanism during bacterial infection. The results showed that SSA plays a key role in regulation of several bacterial activities, including C
4
-dicarboxylate utilization, nitrate assimilation, and resistance to oxidative stress. Interestingly, while the SSA relies heavily on the functional AttKLM in mediating nitrate assimilation and oxidative stress resistance, the compound could regulate utilization of C
4
-dicarboxylates independent of AttJKLM. We further provide evidence that SSA controls C
4
-dicarboxylate utilization through induction of an SSA importer and that disruption of
attKLM
attenuates the tumorigenicity of
A. tumefaciens
. Taken together, these findings indicate that SSA could be a potent plant signal which, together with AttKLM, plays a vital role in promoting the bacterial prosurvival abilities during infection.

IMPORTANCE
Agrobacterium tumefaciens
is a plant pathogen causing crown gall diseases and has been well known as a powerful tool for plant genetic engineering. During the long history of microbe-host interaction,
A. tumefaciens
has evolved the capabilities of recognition and response to plant-derived chemical metabolites. Succinic semialdehyde (SSA) is one such metabolite. Previous results have demonstrated that SSA functions to activate a quorum-quenching mechanism and thus to decrease the level of quorum-sensing signals, thereby avoiding the elicitation of a plant defense. Here, we studied the effect of SSA on gene expression at a genome-wide level and reported that SSA also promotes bacterial survival during infection. These findings provide a new insight on the biological significance of chemical signaling between agrobacteria and plant hosts.
Inositol-Requiring Enzyme 1-Dependent Activation of AMPK Promotes Brucella abortus Intracellular Growth
Authors: Liu Ning , Li Yingying , Dong Chunyan , Xu Xiaohan , Wei Pan , Sun Wanchun , Peng Qisheng
Published: January 2016

AMP-activated protein kinase (AMPK) is a serine/threonine kinase that is well conserved during evolution. AMPK activation inhibits production of reactive oxygen species (ROS) in cells via suppression of NADPH oxidase. However, the role of AMPK during the process of
Brucella
infection remains unknown. Our data demonstrate that
B. abortus
infection induces AMPK activation in HeLa cells in a time-dependent manner. The known AMPK kinases LKB1, CAMKKβ, and TAK1 are not required for the activation of AMPK by
B. abortus
infection. Instead, this activation is dependent on the RNase activity of inositol-requiring enzyme 1 (IRE1). Moreover, we also found that
B. abortus
infection-induced IRE1-dependent activation of AMPK promotes
B. abortus
intracellular growth with peritoneal macrophages via suppression of NADPH-derived ROS production.

IMPORTANCE
Previous studies showed that
B. abortus
infection does not promote any oxidative burst regulated by NADPH oxidase. However, the underlying mechanism remains elusive. We report for the first time that AMPK activation caused by
B. abortus
infection plays important role in NADPH oxidase-derived ROS production.
Impact of Different Target Sequences on Type III CRISPR-Cas Immunity
Authors: Maniv Inbal , Jiang Wenyan , Bikard David , Marraffini Luciano A.
Published: January 2016

Clustered regularly interspaced short palindromic repeat (CRISPR) loci encode an adaptive immune system of prokaryotes. Within these loci, sequences intercalated between repeats known as “spacers” specify the targets of CRISPR immunity. The majority of spacers match sequences present in phages and plasmids; however, it is not known whether there are differences in the immunity provided against these diverse invaders. We studied this issue using the
Staphylococcus epidermidis
CRISPR system, which harbors spacers matching both phages and plasmids. We determined that this CRISPR system provides similar levels of defense against the conjugative plasmid pG0400 and the bacteriophage CNPX. However, whereas antiplasmid immunity was very sensitive to the introduction of mismatches in the target sequence, mutations in the phage target were largely tolerated. Placing the phage and plasmid targets into a vector that can be both conjugated and transduced, we demonstrated that the route of entry of the target has no impact on the effect of the mismatches on immunity. Instead, we established that the specific sequences of each spacer/target determine the susceptibility of the
S. epidermidis
CRISPR system to mutations. Therefore, spacers that are more resistant to mismatches would provide long-term immunity against phages and plasmids that otherwise would escape CRISPR targeting through the accumulation of mutations in the target sequence. These results uncover an unexpected complexity in the arms race between CRISPR-Cas systems and prokaryotic infectious genetic elements.

IMPORTANCE
CRISPR-Cas loci protect bacteria and archaea from both phage infection and plasmid invasion. These loci harbor short sequences of phage and plasmid origin known as “spacers” that specify the targets of CRISPR-Cas immunity. The presence of a spacer sequence matching a phage or plasmid ensures host immunity against infection by these genetic elements. In turn, phages and plasmids constantly mutate their targets to avoid recognition by the spacers of the CRISPR-Cas immune system. In this study, we demonstrated that different spacer sequences vary in their ability to tolerate target mutations that allow phages and plasmids to escape from CRISPR-Cas immunity. These results uncover an unexpected complexity in the arms race between CRISPR-Cas systems and prokaryotic infectious genetic elements.
An avulsion fracture of the calcaneal tuberosity: delay of treatment causes the ‘Achilles heel’ of optimal recovery
Authors: Bosman Willem-Maarten , Leijnen Michiel , van den Bremer Jephta , Ritchie Ewan D
Published: January 2016

A 72-year-old woman was diagnosed with an avulsion fracture of the tuberosity of the calcaneus. The fracture was planned for elective fixation 12 days after the accident. The planned open reduction and internal fixation was not possible due to a decubital wound on the Achilles heel as a result of pressure on the skin of the fractured tuberosity. Closed reduction and internal fixation was performed, leading to an acceptable outcome. Avulsion fractures of the tuberosity of the calcaneus are rare injuries, and delay in treatment should be avoided as it may lead to preventable complications.
Uncommon inflammatory swelling of the lips: orofacial granulomatosis
Authors: Hafiz Abdul , Mufeed Abdulla , Kandasamy Gopinath , Krishnapillai Rekha
Published: January 2016

Orofacial granulomatosis (OFG) is an unusual condition associated with permanent or recurrent swelling of orofacial tissues together with oral mucosal ulceration and a variety of orofacial characteristics. The chronic inflammation inherent to OFG often displays granulomas in the subepithelial stroma. We present a case of OFG and its management. The patient responded to intralesional injections of corticosteroids.
Pigmented spherical body floating within the globe
Authors: Hassan Ali S , Hoffman Jeremy , Kirthi Varo
Published: January 2016

Vitreous cysts are rare ocular malformations. We report an unusual case of a pigmented free-floating vitreous cyst incidentally detected in a highly myopic 28-year-old woman who was referred by her optometrist.
Somatic symptom disorder, a new DSM-5 diagnosis of an old clinical challenge
Authors: Rosic Tea , Kalra Sameer , Samaan Zainab
Published: January 2016

Somatic symptom disorder (SSD) is characterised by a dysfunctional preoccupation with one or more physical symptoms. Patients with SSD often pursue excessive and unnecessary investigations, hospitalisations and treatments that significantly affect quality of life and drain healthcare resources. Thus, appropriate diagnosis and careful management are required to mitigate the patient's distress and to reduce the burden to the healthcare system. SSD is a new disorder defined in the Diagnostic and Statistical Manual Fifth Edition (DSM-5), replacing somatoform and related disorders in the DSM-4-Text Revision with diagnostic criteria that are inclusive of a broad array of presentations. This report presents a detailed clinical case of an elderly man with a history of frequent hospital visits presenting with SSD. We discuss diagnostic challenges and evidence-based management in acute inpatient as well as in outpatient settings. We also review data on healthcare utilisation associated with SSD.
Bronchial anthracofibrosis with interstitial lung disease: an association yet to be highlighted
Authors: Kunal Shekhar , Pilaniya Vikas , Shah Ashok
Published: January 2016

Bronchial anthracofibrosis (BAF), an emerging pulmonary disease due to long-standing exposure to biomass fuel smoke, is predominantly seen in females from developing nations. BAF is known to be associated with tuberculosis, pneumonia, chronic obstructive pulmonary disease and lung cancer, but the association of BAF with interstitial lung disease (ILD) is rare and yet to be highlighted. A 72-year-old woman with a 30-year history of exposure to biomass fuel smoke presented with dry cough and exertional dyspnoea. Imaging demonstrated interlobular, intralobular and peribronchovascular interstitial thickening and honeycombing adjoining the subpleural regions, suggestive of the usual interstitial pneumonia pattern. A restrictive pattern with diffusion defect was noted. Fibrebronchoscopy revealed a bluish-black anthracotic pigmentation with a narrowed and distorted left upper lobe, and apical segment of left lower lobe bronchus, confirming BAF. A diagnosis of BAF with ILD was made. To the best of our knowledge, this is the first detailed description of this association.
Group B streptococcal meningitis in a previously healthy man
Authors: Li Lucy Qian , Cheema Sanjay , Goel Nupur
Published: January 2016

Group BStreptococcus(GBS) is an infrequent cause of meningitis in adults, usually affecting elderly patients and those with serious underlying disease. It is more commonly recognised as one of the leading aetiological agents of neonatal sepsis following maternally derived infection during pregnancy. We report a case of a previously healthy 26-year-old man who presented with fevers, confusion and headache. Lumbar puncture results were consistent with bacterial meningitis, and blood cultures grew GBS. To the best of our knowledge, our patient represents one of the few reported cases of GBS meningitis in a previously healthy young man. Interestingly, our patient had a significant family history of central nervous system infection including a son with herpes simplex virus encephalitis, a sister with meningococcal meningitis and a great-uncle with meningitis of unknown cause. We discuss genetic factors that may predispose certain people to develop meningitis with normally harmless microorganisms such as GBS.
Using qualitative insights to change practice: exploring the culture of antibiotic prescribing and consumption for urinary tract infections
Authors: Duane Sinead , Domegan Christine , Callan Aoife , Galvin Sandra , Cormican Martin , Bennett Kathleen , Murphy Andrew W , Vellinga Akke
Published: January 2016

Objectives

The aim of this paper is to explore the culture of antibiotic prescribing and consumption in the community for urinary tract infections (UTI) from the perspective of the general practitioners (GPs) and community member.

Design

Indepth interviews were conducted with GPs, and focus groups were held with community members.

Setting

General practice and community setting.

Participants

15 GPs practising in rural and urban locations in Ireland participated in the indepth interviews. 6 focus groups (n=42) with participants who had direct or indirect experiences with UTI were also undertaken.

Results

The decision to prescribe or consume an antibiotic for a UTI is a set of complex processes including need recognition, information search and evaluation processes governed by the relationship and interactions between the GP and the patient. Different GP and patient decision-making profiles emerged emphasising the diversity and variety of general practice in real-life settings. The GP findings showed a requirement for more microbiological information on antibiotic resistance patterns to inform prescribing decisions. Focus group participants wanted a conversation with the GP about their illness and the treatment options available.

Conclusions

Collectively, this research identified the consultation as a priority intervention environment for stimulating change in relation to antibiotics. This paper demonstrates how qualitative research can identify the interacting processes which are instrumental to the decision to prescribe or consume an antibiotic for a suspected UTI. Qualitative research empowers researchers to investigate the what, how and why of interventions in real-life setting. Qualitative research can play a critical and instrumental role in designing behavioural change strategies with high impact on practice. The results of this research were used to design a complex intervention informed by social marketing.

Trial registration number

NCT01913860; Pre-results.
Cellulitis: Home Or Inpatient in Children from the Emergency Department (CHOICE): protocol for a randomised controlled trial
Authors: Ibrahim Laila F , Babl Franz E , Orsini Francesca , Hopper Sandy M , Bryant Penelope A
Published: January 2016

Introduction

Children needing intravenous antibiotics for cellulitis are usually admitted to hospital, whereas adults commonly receive intravenous treatment at home. This is a randomised controlled trial (RCT) of intravenous antibiotic treatment of cellulitis in children comparing administration of ceftriaxone at home with standard care of flucloxacillin in hospital. The study aims to compare (1) the rate of treatment failure at home versus hospital (2) the safety of treatment at home versus hospital; and (3) the effect of exposure to short course ceftriaxone versus flucloxacillin on nasal and gut micro-organism resistance patterns and the clinical implications.

Methods and analysis

Inclusion criteria: children aged 6 months to <18 years with uncomplicated moderate/severe cellulitis, requiring intravenous antibiotics. Exclusions: complicated cellulitis (eg, orbital, foreign body) and immunosuppressed or toxic patients. The study is a single-centre, open-label, non-inferiority RCT. It is set in the emergency department (ED) at the Royal Children's Hospital (RCH) in Melbourne, Australia and the Hospital-in-the-Home (HITH) programme; a home-care programme, which provides outreach from RCH. Recruitment will occur in ED from January 2015 to December 2016. Participants will be randomised to either treatment in hospital, or transfer home under the HITH programme. The calculated sample size is 188 patients (94 per group) and data will be analysed by intention-to-treat.Primary outcome: treatment failure defined as a change in treatment due to lack of clinical improvement according to the treating physician or adverse events, within 48 hSecondary outcomes: readmission to hospital, representation, adverse events, length of stay, microbiological results, development of resistance, cost-effectiveness, patient/parent satisfaction. This study has started recruitment.

Ethics and dissemination

This study has been approved by the Human Research Ethics Committee of the RCH Melbourne (34254C) and registered with the ClinicalTrials.gov registry (NCT02334124). We aim to disseminate the findings through international peer-reviewed journals and conferences.

Clinical trial

Pre-results.
Comparing NICU teamwork and safety climate across two commonly used survey instruments
Authors: Profit Jochen , Lee Henry C , Sharek Paul J , Kan Peggy , Nisbet Courtney C , Thomas Eric J , Etchegaray Jason M , Sexton Bryan
Published: January 2016

Background and objectives

Measurement and our understanding of safety culture are still evolving. The objectives of this study were to assess variation in safety and teamwork climate and in the neonatal intensive care unit (NICU) setting, and compare measurement of safety culture scales using two different instruments (Safety Attitudes Questionnaire (SAQ) and Hospital Survey on Patient Safety Culture (HSOPSC)).

Methods

Cross-sectional survey study of a voluntary sample of 2073 (response rate 62.9%) health professionals in 44 NICUs. To compare survey instruments, we used Spearman's rank correlation coefficients. We also compared similar scales and items across the instruments using t tests and changes in quartile-level performance.

Results

We found significant variation across NICUs in safety and teamwork climate scales of SAQ and HSOPSC (p<0.001). Safety scales (safety climate and overall perception of safety) and teamwork scales (teamwork climate and teamwork within units) of the two instruments correlated strongly (safety r=0.72, p<0.001; teamwork r=0.67, p<0.001). However, the means and per cent agreements for all scale scores and even seemingly similar item scores were significantly different. In addition, comparisons of scale score quartiles between the two instruments revealed that half of the NICUs fell into different quartiles when translating between the instruments.

Conclusions

Large variation and opportunities for improvement in patient safety culture exist across NICUs. Important systematic differences exist between SAQ and HSOPSC such that these instruments should not be used interchangeably.
Why do we still page each other? Examining the frequency, types and senders of pages in academic medical services
Authors: Carlile Narath , Rhatigan Joseph J , Bates David W
Published: January 2016

Background

Paging still represents an important form of communication within hospitals, but it results in interruptions, and other more modern approaches could be superior. This study aims to describe how paging is currently used in an academic medical centre, including the frequency, type, urgency and sender of pages, so that improvements in communication can be better informed.

Study sample

In order to understand what communication needs paging fulfils in a modern academic medical centre, we analysed a database of 1252 pages sent to internal medicine residents within an academic medical centre. We assessed all pages from 3 separate general medicine rotations over a total of 56 days encompassing 602 h.

Results

Residents were paged an average of 22.4 times per day, with a maximum of 50 pages per day. Most pages were deemed clinically relevant (76%) and important (76%) to patient care. Overall, 59% of pages required a response. A mean of 7.7 pages were sent per patient, up to a maximum of 70 pages for one patient. Nurses (28%), consultants (16%) and the clinical laboratory (15%) were responsible for the majority of pages. Almost all pages from nurses (82%) and consultants (82%) required a response. Regionalised services had significantly fewer pages per day than non-regionalised services (19 vs 37, p≤0.00001).

Conclusions

Paging remains widely used for communications within hospitals about patient care. Although the majority of pages were judged to be clinically relevant and important, they frequently required a response potentially leading to interruptions in workflow, and communication waste. Paging rate and volume has not decreased in 25 years despite significant penetration of newer technologies. For the majority of current uses of pages, we believe other approaches may now be more appropriate. Regionalisation significantly reduces the number and urgency of the pages.
Impact of the 2011 ACGME resident duty hour reform on hospital patient experience and processes-of-care
Authors: Rajaram Ravi , Saadat Lily , Chung Jeanette , Dahlke Allison , Yang Anthony D , Odell David D , Bilimoria Karl Y
Published: January 2016

Introduction

In 2011, the Accreditation Council for Graduate Medical Education (ACGME) expanded restrictions on resident duty hours. While studies have shown no association between these restrictions and improved outcomes, process-of-care and patient experience measures may be more sensitive to resident performance, and thus may be impacted by duty hour policies. The objective of this study was to evaluate the association between the 2011 resident duty hour reform and measures of processes-of-care and patient experience.

Methods

Hospital Consumer Assessment of Healthcare Providers and Systems survey data and process-of-care scores were obtained from the Centers for Medicare and Medicaid Services Hospital Compare website for 1 year prior to (1 July 2010 to 30 June 2011) and 1 year after (1 July 2011 to 30 June 2012) duty hour reform implementation. Using a difference-in-differences model, non-teaching and teaching hospitals were compared before and after the 2011 reform to test the association of this policy with changes in process-of-care and patient experience measure scores.

Results

Duty hour reform was not associated with a change in the five patient experience measures evaluated, including patients rating a hospital 9 or 10 (coefficient −0.003, 95% CI −0.79 to 0.79) or stating they would ‘definitely recommend’ a hospital (coefficient −0.28, 95% CI −1.01 to 0.44). For all 10 process-of-care measures examined, such as antibiotic timing (coefficient −0.462, 95% CI −1.502 to 0.579) and discontinuation (0.188, 95% CI −0.529 to 0.904), duty hour reform was not associated with a change in scores.

Conclusions

The 2011 ACGME duty hour reform was not associated with improvements in process-of-care and patient experience measures. These data should be considered when considering reform of resident duty hour policies.
Continuity of care and 30-day readmission for patients evaluated in the emergency room after cerebral aneurysm treatment
Authors: Bekelis Kimon , Missios Symeon , MacKenzie Todd A
Published: January 2016

Background

The association between continuity of care and the rate of 30-day readmissions after surgical procedures continues to be debated.

Objective

To investigate the association of 30-day readmissions with evaluation in the hospital where the original procedure was performed for patients presenting to the emergency department (ED) after cerebral aneurysm treatment.

Methods

We performed a cohort study of patients with cerebral aneurysms, who were evaluated in the ED within 30 days after discharge following surgical clipping or endovascular coiling between 2009 and 2013, and were registered in the Statewide Planning and Research Cooperative System database. A propensity score adjusted model was used to control for confounding, whereas mixed effects accounted for clustering at the hospital level.

Results

Of the 452 patients presenting to the ED, 218 (48.2%) were evaluated in a different hospital from that in which the original procedure was performed (7.7% readmitted), and 234 (51.8%) were evaluated at the original hospital (18.4% readmitted). In a multivariable analysis, we showed that evaluation in the ED of the original hospital was associated with decreased rate of 30-day readmission (OR=0.41; 95% CI 0.22 to 0.78). We found similar associations in a mixed-effects logistic regression model (OR=0.46; 95% CI 0.35 to 0.84) and a propensity score adjusted model (OR=0.41; 95% CI 0.22 to 0.77). This corresponds to10 patients needing to be evaluated in the hospital at which the original procedure was performed to prevent one readmission.

Conclusions

Using a comprehensive all-payer cohort of patients in New York State, who were evaluated in the ED after cerebral aneurysm treatment, we identified an association between assessment in the hospital at which the original procedure was performed and a lower rate of 30-day readmissions. This underlines the potential importance of continuity of care for surgical patients to prevent readmission.
Diagnostic impact of routine Lyme serology in recent-onset arthritis: results from the ESPOIR cohort
Authors: Guellec Dewi , Narbonne Valérie , Cornec Divi , Marhadour Thierry , Varache Sophie , Dougados Maxime , Daurès Jean Pierre , Jousse-Joulin Sandrine , Devauchelle-Pensec Valérie , Saraux Alain
Published: January 2016

Objectives

Lyme disease may be considered by rheumatologists in patients with recent-onset arthritis, even in the absence of suggestive symptoms. The aim of this study was to determine the diagnostic impact of routine Lyme serology in a French cohort of patients with recent-onset arthritis affecting at least 2 joints.

Methods

We performed an ancillary study of a French prospective multicentre cohort established to monitor clinical, biological and radiographic data in patients with inflammatory arthritis in at least 2 joints, lasting for 6 weeks to 6 months.BorreliaIgM and IgG antibodies were sought routinely at baseline, using ELISA tests, independently from the physician's strategy for detecting a spirochetal infection. We recorded the proportion of patients with a final diagnosis of Lyme arthritis and evaluated the diagnostic performance of Lyme serology in this particular context. The clinical and biological characteristics of patients according to the Lyme serology results were analysed.

Results

Of 810 patients, 657 (81.1%) were negative for IgM and IgG antibodies, 91 (11.2%) had only IgM antibodies, 49 (6%) had only IgG antibodies, and 13 (1.6%) had IgG and IgM antibodies. Thus, 7.6% had IgG positivity, consistent with exposure toBorrelia infection. IgG positivity was significantly more prevalent in the North and North-East regions of France (χ2=14.6, p<0.001). No patients received a definite diagnosis of Lyme arthritis.

Conclusions

This study does not support routine Lyme serological testing in patients with recent-onset inflammatory arthritis affecting more than 1 joint.
Impact of Funneliformis mosseae on the growth, lead uptake, and localization of Sophora viciifolia
Authors: Xu Zhouying , Ban Yihui , Yang Ren , Zhang Xiangyu , Chen Hui , Tang Ming
Published: January 2016

On the basis of a pot experiment under lead (Pb) stress, we investigated the effects of an arbuscular mycorrhizal (AM) fungus (Funneliformis mosseae) on the growth and Pb uptake of Sophora viciifolia L., and explored the Pb localization in AM roots using transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). The results showed that high Pb levels (500 and 1000 μg/g) inhibited the growth of S. viciifolia seedlings. Compared with the noninoculation treatment, F. mosseae inoculation decreased the Pb concentrations above- and belowground by 61.0% and 15.2%, when exposed to Pb at a concentration of 1000 μg/g. The root length, fork number, tip number, surface area, and volume of mycorrhizal S. viciifolia were higher than those of the corresponding nonmycorrhizal plants. These parameters of mycorrhizal plants increased by 220%, 219%, 157%, 225%, and 278% when plants were exposed to Pb at 1000 μg/g compared with nonmycorrhizal plants. The ratio of root length with diameters between 0–0.2 mm to the total root length significantly increased under Pb stress, and F. mosseae inoculation significantly reduced the ratio. Under Pb stress, F. mosseae increased the ratios of root length with 0.61–0.8 and 0.81–1.0 mm diameters to the total root length, indicating that F. mosseae tended to thicken the roots of S. viciifolia under Pb additions. The combined results of TEM and EDS indicated that Pb deposited in not only plant cells but also the cell walls and vacuoles of the AM fungal intracellular hyphae, thus revealing the subcellular-level mechanism of AM fungi in alleviating the Pb toxicity to the host plant.
Who speaks for AI?
Authors: Eaton Eric , Dietterich Tom , Gini Maria , Grosz Barbara J. , Isbell Charles L. , Kambhampati Subbarao , Littman Michael , Rossi Francesca , Russell Stuart , Stone Peter , Walsh Toby , Wooldridge Michael
Published: January 2016

These are boom times for AI. Articles celebrating the success of AI research appear frequently in the international press. Every day, millions of people routinely use AI-based systems that the founders of the field would hail as miraculous. And there is a palpable sense of excitement about impending applications of AI technologies.
Interview with Eelco Herder
Authors: Atzenbeck Claus
Published: January 2016

Eelco Herder works as a senior researcher at the L3S Research Center in Hannover, Germany. His main research interests include Web personalization, User Modeling, usability and HCI in general. Other research topics include Web usage analysis and the development of tools for Personal Information Management. His Ph.D. research at the University of Twente focused on the observation, modeling and prediction of user navigation on the Internet. His work on context-aware revisitation support received the Douglas Engelbart Best Paper Award at Hypertext 2011. Eelco serves as general chair for Hypertext 2016 and served as program, workshop, poster, publicity and local chair at various conferences, among which Hypertext 2014, IUI 2014, CHI 2012, UMAP 2010--2013 and Adaptive Hypermedia 2008.
"Modeling aspects of human trails on the web" by Philipp Singer, with Prateek Jain as coordinator
Authors: Singer Philipp
Published: January 2016

Philipp Singer is a now post-doctoral researcher at the Computational Social Science Department of GESIS in Cologne. In the last few years, his research has focused on modeling aspects of human sequences on the Web. To that end, he has been dedicated to provide insights and tools that facilitate future research concerned with the study of regularities, patterns and strategies in human sequences on the Web. Philipp has published in several renowned conferences and journals such as WWW, CIKM, ISWC, IJSWIS or EPJDS and received the best paper award in last year's WWW'15 conference. He received his PhD in computer Science from the Technical University of Graz (Austria). For more information see http://www.philippsinger.info/
Upcoming SIGWEB supported conferences
Authors: Samuel Hamman
Published: January 2016

The Special Interest Group on Hypertext and the Web, SIGWEB was created in 1989 to support the community participating in the annual ACM Hypertext Conference. Now in its third decade, SIGWEB has grown considerably and now sponsors six annual conferences of different sizes and covering a wide range of topics. SIGWEB supports several specialized conferences, short courses, and workshops, as well as the Annual Hypertext Conference. SIGWEB sponsored conferences focus on timely topics in applied and computational hypertext and Web disciplines and provide a place for members and the entire applied Hypermedia and Web community to exchange ideas and to meet with and expand their network of colleagues. In this article, we provide a brief overview of SIGWEB sponsored conferences, in addition to events that are in cooperation with SIGWEB.