bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Offense, Defense, and Ball Possession on Mobility Performance in Wheelchair Basketball
Authors: de Witte Annemarie M.H. , Berger Monique A.M. , Hoozemans Marco J.M. , Veeger Dirkjan H.E.J. , van der Woude Lucas H.V.
Published: October 2017

The aim of this study was to determine to what extent mobility performance is influenced by offensive or defensive situations and ball possession and to what extent these actions are different for the field positions. From video analysis, the relative duration of the various wheelchair movements during team offense/defense and individual ball possession was compared in 56 elite wheelchair basketball players. A two-way analysis of variance indicated that during offense, the guards and forwards performed longer driving forward than during defense. Overall, centers stood still longer during offense than during defense. Without ball, centers performed driving forward longer than with ball possession. It is concluded that offense, defense, and ball possession influenced mobility performance for the different field positions. These differences can be used to design specific training protocols. Furthermore, field positions require potentially different specific wheelchair configurations to improve performance.
Pathogen-induced mitochondrial fragmentation
Authors: VanHook Annalisa M.
Published: October 2017

Legionella pneumophila
promotes activation of the mitochondrial fission machinery to metabolically reprogram host macrophages.
Sustained
Ex Vivo
Susceptibility of Plasmodium falciparum to Artemisinin Derivatives but Increasing Tolerance to Artemisinin Combination Therapy Partner Quinolines in The Gambia
Authors: Amambua-Ngwa Alfred , Okebe Joseph , Mbye Haddijatou , Ceesay Sukai , El-Fatouri Fatima , Joof Fatou , Nyang Haddy , Janha Ramatoulie , Affara Muna , Ahmad Abdullahi , Kolly Olimatou , Nwakanma Davis , D'Alessandro Umberto
Published: October 2017

Antimalarial interventions have yielded a significant decline in malaria prevalence in The Gambia, where artemether-lumefantrine (AL) has been used as a first-line antimalarial for a decade. Clinical
Plasmodium falciparum
isolates collected from 2012 to 2015 were analyzed
ex vivo
for antimalarial susceptibility and genotyped for drug resistance markers (
pfcrt
K76T,
pfmdr1
codons 86, 184, and 1246, and
pfk13
) and microsatellite variation. Additionally, allele frequencies of single nucleotide polymorphisms (SNPs) from other drug resistance-associated genes were compared from genomic sequence data sets from 2008 (
n
= 79) and 2014 (
n
= 168). No artemisinin resistance-associated
pfk13
mutation was found, and only 4% of the isolates tested in 2015 showed significant growth after exposure to dihydroartemisinin. Conversely, the 50% inhibitory concentrations (IC
50
s) of amodiaquine and lumefantrine increased within this period.
pfcrt
76T and
pfmdr1
184F mutants remained at a prevalence above 80%.
pfcrt
76T was positively associated with higher IC
50
s to chloroquine.
pfmdr1
NYD increased in frequency between 2012 and 2015 due to lumefantrine selection. The TNYD (
pfcrt
76T and
pfmdr1
NYD wild-type haplotype) also increased in frequency following AL implementation in 2008. These results suggest selection for
pfcrt
and
pfmdr1
genotypes that enable tolerance to lumefantrine. Increased tolerance to lumefantrine calls for sustained chemotherapeutic monitoring in The Gambia to minimize complete artemisinin combination therapy (ACT) failure in the future.
ABCI3 Is a New Mitochondrial ABC Transporter from Leishmania major Involved in Susceptibility to Antimonials and Infectivity
Authors: Arcari Talia , Manzano José Ignacio , Gamarro Francisco
Published: October 2017

We have identified and characterized ABCI3 as a new mitochondrial ABC transporter from
Leishmania major
. Localization studies using confocal microscopy, a surface biotinylation assay, and trypsin digestion after digitonin permeabilization suggested that ABCI3 presents a dual localization in both mitochondria and the plasma membrane. From studies using parasites with a single knockout of
ABCI3
(
ABCI3
+/−
), we provide evidence that ABCI3 is directly involved in susceptibility to the trivalent form of antimony (SbIII) and metal ions. Attempts to obtain parasites with a double knockout of
ABCI3
were unsuccessful, suggesting that
ABCI3
could be an essential gene in
L. major
.
ABCI3
+/−
promastigotes were 5-fold more resistant to Sb
III
than the wild type, while
ABCI3
+/−
amastigotes were approximately 2-fold more resistant to pentavalent antimony (Sb
V
). This resistance phenotype was associated with decreased Sb
III
accumulation due to decreased Sb
III
uptake.
ABCI3
+/−
parasites presented higher ATP levels and generated less mitochondrial superoxide after Sb
III
incubation. Finally, we observed that
ABCI3
+/−
parasites showed a slightly higher infection capacity than wild-type and add-back
ABCI3
+/−
::3×FABCI3 parasites; however, after 72 h the number of
ABCI3
+/−
intracellular parasites per macrophage increased significantly. Our results show that ABCI3 is responsible for Sb
III
transport inside mitochondria, where it contributes to enhancement of the general toxic effects caused by Sb
III
. To our knowledge, ABCI3 is the first ABC transporter which is involved in susceptibility toward antimony, conferring Sb
III
resistance to parasites when it is partially deleted.
A Cohort Study of Risk Factors That Influence Empirical Treatment of Patients with Acute Pyelonephritis
Authors: Bosch-Nicolau Pau , Falcó Vicenç , Viñado Belén , Andreu Antonia , Len Oscar , Almirante Benito , Pigrau Carles
Published: October 2017

The aim of the current study was to compare community-acquired acute pyelonephritis (CA-APN) with health care-associated acute pyelonephritis (HCA-APN), describe the outcomes, and identify variables that could predict antimicrobial susceptibility. We conducted an observational study that included all consecutive episodes of acute pyelonephritis (APN) in adults during 2014 at a Spanish university hospital. From each episode, demographic data, comorbidities, clinical presentation, microbiological data, antimicrobial therapy, and outcome were recorded. A multivariable logistic regression model was performed to define the variables associated with antimicrobial resistance. A total of 607 patients, 503 (82.9%) with CA-APN and 104 (17.1%) with HCA-APN, were included in the study. Patients with HCA-APN were older than patients with CA-APN (70.4 versus 50.6 years;
P
< 0.001) and had higher rates of previous urinary tract infections (UTIs) (56.5% versus 24.5%;
P
< 0.001) and previous antibiotic use (56.8% versus 22.8%;
P
< 0.001).
Escherichia coli
was more frequently isolated from patients with CA-APN than from patients with HCA-APN (79.9% versus 50.5%;
P
< 0.001). The rates of resistance of
Escherichia coli
strains from CA-APN patients versus HCA-APN patients were as follows: amoxicillin-clavulanic acid, 22.4% versus 53.2% (
P
= 0.001); cefuroxime, 7.7% versus 43.5% (
P
= 0.001); cefotaxime, 4.3% versus 32.6% (
P
< 0.001); ciprofloxacin, 22.8% versus 74.5% (
P
< 0.001); and co-trimoxazole, 34.5% versus 58.7% (
P
= 0.003). The site of acquisition, recurrent UTIs, and previous antibiotic use were independent risk factors for antimicrobial resistance. Relapse rates were significantly higher when definitive antimicrobial treatment was not adequate (37.1% versus 9.3% when definitive antimicrobial treatment was adequate;
P
< 0.001). Our study reflects the rise of resistance to commonly used antibiotics in acute pyelonephritis. In order to choose the adequate empirical antibiotic therapy, risk factors for resistance should be considered.
Pharmacokinetic Properties of Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis
Authors: Boonstra J. M. , van der Elst K. C. , Veringa A. , Jongedijk E. M. , Brüggemann R. J. , Koster R. A. , Kampinga G. A. , Kosterink J. G. , van der Werf T. S. , Zijlstra J. G. , Touw D. J. , Alffenaar J. W. C.
Published: October 2017

The estimated attributable mortality rate for invasive candidiasis (IC) in the intensive care unit (ICU) setting varies from 30 to 40%. Physiological changes in critically ill patients may affect the distribution and elimination of micafungin, and therefore, dosing adjustments might be mandatory. The objective of this study was to determine the pharmacokinetic parameters of micafungin in critically ill patients and assess the probability of target attainment. Micafungin plasma concentrations were measured to estimate the pharmacokinetic properties of micafungin. MIC values for
Candida
isolates were determined to assess the probability of target attainment for patients. Data from 19 patients with suspected or proven invasive candidiasis were available for analysis. The median area under the concentration-time curve from 0 to 24 h at steady state (AUC
0–24
) was 89.6 mg · h/liter (interquartile range [IQR], 75.4 to 113.6 mg · h/liter); this was significantly lower than the median micafungin AUC
0–24
values of 152.0 mg · h/liter (IQR, 136.0 to 162.0 mg · h/liter) and 134.0 mg · h/liter (IQR, 118.0 to 148.6 mg · h/liter) in healthy volunteers (
P
= <0.0001 and
P
= <0.001, respectively). All
Candida
isolates were susceptible to micafungin, with a median MIC of 0.016 mg/liter (IQR, 0.012 to 0.023 mg/liter). The median AUC
0–24
/MIC ratio was 5,684 (IQR, 4,325 to 7,578), and 3 of the 17 evaluable patients (17.6%) diagnosed with proven invasive candidiasis did not meet the AUC/MIC ratio target of 5,000. Micafungin exposure was lower in critically ill patients than in healthy volunteers. The variability in micafungin exposure in this ICU population could be explained by the patients' body weight. Our findings suggest that healthier patients (sequential organ failure assessment [SOFA] score of <10) weighing more than 100 kg and receiving 100 mg micafungin daily are at risk for inappropriate micafungin exposure and potentially inadequate antifungal treatment. (This study has been registered at ClinicalTrials.gov under identifier NCT01716988.)
Multicenter Study of the Risk Factors for Colonization or Infection with Carbapenem-Resistant Enterobacteriaceae in Children
Authors: Chiotos Kathleen , Tamma Pranita D. , Flett Kelly B. , Naumann Matthew , Karandikar Manjiree V. , Bilker Warren B. , Zaoutis Theoklis , Han Jennifer H.
Published: October 2017

Carbapenem-resistant
Enterobacteriaceae
(CRE) are increasingly identified in children in the United States, but data on the epidemiology of CRE in this population are limited. The objectives of this study were to characterize the risk factors for colonization or infection with CRE and describe the microbiologic characteristics of pediatric CRE isolates. We performed a multicenter matched case-control study from January 2011 to October 2015 at three tertiary care pediatric centers. Case patients were hospitalized children with CRE isolated from clinical cultures and were matched in a 2:1 ratio to control patients with carbapenem-susceptible
Enterobacteriaceae
(CSE). Risk factors for colonization or infection with CRE were then evaluated using a multivariable conditional logistic regression. Additionally, we comprehensively reported the antimicrobial susceptibility pattern for CRE isolates. Sixty-three case patients were identified and matched to 126 control patients. On multivariable analysis, antipseudomonal antibiotic exposure within the previous 3 months (odds ratio [OR], 5.20; 95% confidence interval [CI], 1.71 to 15.9;
P
= 0.004), prior surgery (OR, 6.30; 95% CI, 1.83 to 21.6;
P
= 0.003), and mechanical ventilation (OR, 12.4; 95% CI, 1.26 to 122;
P
= 0.031) were identified as risk factors for colonization or infection with CRE. Pediatric CRE isolates demonstrated relatively low rates of resistance to amikacin (5%) and ciprofloxacin (25%). Our findings support an important role for antibiotic stewardship interventions limiting the unnecessary use of antipseudomonal antibiotics as a strategy to prevent widespread emergence of CRE in children. Future studies should further characterize molecular determinants of antibiotic resistance among pediatric CRE isolates.
Diversity of Mosaic
pbp2x
Families in Penicillin-Resistant Streptococcus pneumoniae from Iran and Romania
Authors: Mousavi Seyed Fazlollah , Pana Marina , Feizabadi Mohammad , Jalali Pantea , Ghita Maria , Denapaite Dalia , Hakenbeck Regine
Published: October 2017

Penicillin-resistant
Streptococcus pneumoniae
strains are found at high rates in Romania and Iran. The mosaic structure of PBP2x was investigated in 9 strains from Iran and in 15 strains from Romania to understand their evolutionary history. Mutations potentially important for β-lactam resistance were identified by comparison of the PBP2x sequences with the sequence of the related PBP2x of reference penicillin-sensitive
S. mitis
strains. Two main PBP2x mosaic gene families were recognized. Eight Iranian strains expressed PBP2x variants in group 1, which had a mosaic block highly related to PBP2x of the Spain
23F
-1 clone, which is widespread among international penicillin-resistant
S. pneumoniae
clones. A second unique PBP2x group was observed in Romanian strains; furthermore, three PBP2x single mosaic variants were found. Sequence blocks of penicillin-sensitive strain
S. mitis
658 were common among PBP2x variants from strains from both countries. Each PBP2x group contained specific signature mutations within the transpeptidase domain, documenting the existence of distinct mutational pathways for the development of penicillin resistance.
Kinetics of Sulbactam Hydrolysis by β-Lactamases, and Kinetics of β-Lactamase Inhibition by Sulbactam
Authors: Shapiro Adam B.
Published: October 2017

Sulbactam is one of four β-lactamase inhibitors in current clinical use to counteract drug resistance caused by degradation of β-lactam antibiotics by these bacterial enzymes. As a β-lactam itself, sulbactam is susceptible to degradation by β-lactamases. I investigated the Michaelis-Menten kinetics of sulbactam hydrolysis by 14 β-lactamases, representing clinically widespread groups within all four Ambler classes, i.e., CTX-M-15, KPC-2, SHV-5, and TEM-1 for class A; IMP-1, NDM-1, and VIM-1 for class B;
Acinetobacter baumannii
ADC-7,
Pseudomonas aeruginosa
AmpC, and
Enterobacter cloacae
P99 for class C; and OXA-10, OXA-23, OXA-24, and OXA-48 for class D. All of the β-lactamases were able to hydrolyze sulbactam, although they varied widely in their kinetic constants for the reaction, even within each class. I also investigated the inactivation kinetics of the inhibition of these enzymes by sulbactam. The class A β-lactamases varied widely in their susceptibility to inhibition, the class C and D enzymes were very weakly inhibited, and the class B enzymes were essentially or completely unaffected. In addition, we measured the sulbactam turnover number, the sulbactam/enzyme molar ratio required for complete inhibition of each enzyme. Class C enzymes had the lowest turnover numbers, class A enzymes varied widely, and class D enzymes had very high turnover numbers. These results are valuable for understanding which β-lactamases ought to be well inhibited by sulbactam. Moreover, since sulbactam has intrinsic antibacterial activity against
Acinetobacter
species pathogens, these results contribute to understanding β-lactamase-mediated sulbactam resistance in
Acinetobacter
, especially due to the action of the widespread class D enzymes.
Concentration and Variety of Carbapenemase Producers in Recreational Coastal Waters Showing Distinct Levels of Pollution
Authors: Paschoal Raphael P. , Campana Eloiza H. , Corrêa Laís L. , Montezzi Lara F. , Barrueto Lina R. L. , da Silva Isadora R. , Bonelli Raquel R. , Castro Laura de S. , Picão Renata C.
Published: October 2017

Carbapenemase-producing bacteria cause difficult-to-treat infections related to increased mortality in health care settings. Their occurrence has been reported in raw sewage, sewage-impacted rivers, and polluted coastal waters, which may indicate their spread to the community. We assessed the variety and concentration of carbapenemase producers in coastal waters with distinct pollution levels for 1 year. We describe various bacterial species producing distinct carbapenemases not only in unsuitable waters but also in waters considered suitable for primary contact.
Disruption of a Transcriptional Repressor by an Insertion Sequence Element Integration Leads to Activation of a Novel Silent Cellobiose Transporter in Lactococcus lactis MG1363
Authors: Solopova Ana , Kok Jan , Kuipers Oscar P.
Published: October 2017

Lactococcus lactis
subsp.
cremoris
strains typically carry many dairy niche-specific adaptations. During adaptation to the milk environment these former plant strains have acquired various pseudogenes and insertion sequence elements indicative of ongoing genome decay and frequent transposition events in their genomes. Here we describe the reactivation of a silenced plant sugar utilization cluster in an
L. lactis
MG1363 derivative lacking the two main cellobiose transporters, PtcBA-CelB and PtcBAC, upon applying selection pressure to utilize cellobiose. A disruption of the transcriptional repressor gene
llmg_1239
by an insertion sequence (IS) element allows expression of the otherwise silent novel cellobiose transporter Llmg_1244 and leads to growth of mutant strains on cellobiose. Llmg_1239 was labeled CclR, for
c
ellobiose
cl
uster
r
epressor.

IMPORTANCE
Insertion sequences (ISs) play an important role in the evolution of lactococci and other bacteria. They facilitate DNA rearrangements and are responsible for creation of new genetic variants with selective advantages under certain environmental conditions.
L. lactis
MG1363 possesses 71 copies in a total of 11 different types of IS elements. This study describes yet another example of an IS-mediated adaptive evolution. An integration of IS
981
or IS
905
into a gene coding for a transcriptional repressor led to activation of the repressed gene cluster coding for a plant sugar utilization pathway. The expression of the gene cluster allowed assembly of a novel cellobiose-specific transporter and led to cell growth on cellobiose.
Wide but Variable Distribution of a Hypervirulent Campylobacter jejuni Clone in Beef and Dairy Cattle in the United States
Authors: Tang Yizhi , Meinersmann Richard J. , Sahin Orhan , Wu Zuowei , Dai Lei , Carlson James , Plumblee Lawrence Jodie , Genzlinger Linda , LeJeune Jeffrey T. , Zhang Qijing
Published: October 2017

Campylobacter jejuniclone SA is the major cause of sheep abortion and contributes significantly to foodborne illnesses in the United States. Clone SA is hypervirulent because of its distinct ability to produce systemic infection and its predominant role in clinical sheep abortion. Despite the importance of clone SA, little is known about its distribution and epidemiological features in cattle. Here we describe a prospective study onC. jejuniclone SA prevalence in 35 feedlots in 5 different states in the United States and a retrospective analysis of clone SA inC. jejuniisolates collected by National Animal Health Monitoring System (NAHMS) dairy studies in 2002, 2007, and 2014. In feedlot cattle feces, the overall prevalence ofCampylobacterorganisms was 72.2%, 82.1% of which wereC. jejuni. Clone SA accounted for 5.8% of the totalC. jejuniisolates, but its prevalence varied by feedlot and state. Interestingly, starlings on the feedlots harboredC. jejuniin feces, including clone SA, suggesting that these birds may play a role in the transmission ofCampylobacter. In dairy cattle, the overall prevalence of clone SA was 7.2%, but a significant decrease in the prevalence was observed from 2002 to 2014. Whole-genome sequence analysis of the dairy clone SA isolates revealed that it was genetically stable over the years and most of the isolates carried the tetracycline resistance genetet(O) in the chromosome. These findings indicate that clone SA is widely distributed in both beef and dairy cattle and provide new insights into the molecular epidemiology of clone SA in ruminants.

IMPORTANCEC. jejuniclone SA is a major cause of small-ruminant abortion and an emerging threat to food safety because of its association with foodborne outbreaks. Cattle appear to serve as a major reservoir for this pathogenic organism, but there is a major gap in our knowledge about the epidemiology of clone SA in beef and dairy cattle. By taking advantage of surveillance studies conducted on a national scale, we found a wide but variable distribution of clone SA in feedlot cattle and dairy cows in the United States. Additionally, the work revealed important genomic features of clone SA isolates from cattle. These findings provide critically needed information for the development of preharvest interventions to control the transmission of this zoonotic pathogen. Control ofC. jejuniclone SA will benefit both animal health and public health, as it is a zoonotic pathogen causing disease in both ruminants and humans.
Ectomycorrhizal Fungal Communities in Urban Parks Are Similar to Those in Natural Forests but Shaped by Vegetation and Park Age
Authors: Hui Nan , Liu Xinxin , Kotze D. Johan , Jumpponen Ari , Francini Gaia , Setälä Heikki
Published: October 2017

Ectomycorrhizal (ECM) fungi are important mutualists for the growth and health of most boreal trees. Forest age and its host species composition can impact the composition of ECM fungal communities. Although plentiful empirical data exist for forested environments, the effects of established vegetation and its successional trajectories on ECM fungi in urban greenspaces remain poorly understood. We analyzed ECM fungi in 5 control forests and 41 urban parks of two plant functional groups (conifer and broadleaf trees) and in three age categories (10, ∼50, and >100 years old) in southern Finland. Our results show that although ECM fungal richness was marginally greater in forests than in urban parks, urban parks still hosted rich and diverse ECM fungal communities. ECM fungal community composition differed between the two habitats but was driven by taxon rank order reordering, as key ECM fungal taxa remained largely the same. In parks, the ECM communities differed between conifer and broadleaf trees. The successional trajectories of ECM fungi, as inferred in relation to the time since park construction, differed among the conifers and broadleaf trees: the ECM fungal communities changed over time under the conifers, whereas communities under broadleaf trees provided no evidence for such age-related effects. Our data show that plant-ECM fungus interactions in urban parks, in spite of being constructed environments, are surprisingly similar in richness to those in natural forests. This suggests that the presence of host trees, rather than soil characteristics or even disturbance regime of the system, determine ECM fungal community structure and diversity.

IMPORTANCE
In urban environments, soil and trees improve environmental quality and provide essential ecosystem services. ECM fungi enhance plant growth and performance, increasing plant nutrient acquisition and protecting plants against toxic compounds. Recent evidence indicates that soil-inhabiting fungal communities, including ECM and saprotrophic fungi, in urban parks are affected by plant functional type and park age. However, ECM fungal diversity and its responses to urban stress, plant functional type, or park age remain unknown. The significance of our study is in identifying, in greater detail, the responses of ECM fungi in the rhizospheres of conifer and broadleaf trees in urban parks. This will greatly enhance our knowledge of ECM fungal communities under urban stresses, and the findings can be utilized by urban planners to improve urban ecosystem services.
High-Quality Genome Sequence of Bacillus anthracis Strain 14RA5914 Isolated during an Outbreak in Germany in 2014
Authors: Elschner Mandy C. , Busch Anne , Schliephake Annette , Gaede Wolfgang , Zuchantke Eric , Tomaso Herbert
Published: October 2017

Bacillus anthracis
is a zoonotic agent causing anthrax, a notifiable disease in animals. The last anthrax outbreak among cattle in Germany occurred in April 2014 in Saxony-Anhalt. Here we report a high-quality genome sequence of the
Bacillus anthracis
strain 14RA5914 Dobichau isolated from the spleen of a dead cow.
Complete Genome Sequence of a Novel Bastrovirus Isolated from Raw Sewage
Authors: dos Anjos Karoline , Nagata Tatsuya , Melo Fernando Lucas de
Published: October 2017

The complete genome sequence of a novel bastrovirus was determined. The genome has 5,875 nucleotides and shares 56% nucleotide identity with a bastrovirus-like virus found in bat feces.
Fluorescence-Reported Allelic Exchange Mutagenesis Reveals a Role for Chlamydia trachomatis TmeA in Invasion That Is Independent of Host AHNAK
Authors: McKuen M. J. , Mueller K. E. , Bae Y. S. , Fields K. A.
Published: October 2017

Development of approaches to genetically manipulate
Chlamydia
is fostering important advances in understanding pathogenesis.
F
luorescence-
r
eported
a
llelic
e
xchange
m
utagenesis (FRAEM) now enables the complete deletion of specific genes in
C. trachomatis
L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to
ct694-ctl0063
t
ranslocated
m
embrane-associated
e
ffector A (TmeA). Deletion of
tmeA
did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity in both tissue culture and murine infection models. The
in vitro
defect was reflected by impaired invasion of host cells. TmeA binds human AHNAK, and we demonstrate here that AHNAK is transiently recruited by invading chlamydiae. TmeA, however, is not required for endogenous AHNAK recruitment. TmeA also impairs AHNAK-dependent actin bundling activity. This TmeA-mediated effect likely does not explain impaired invasion displayed by the
tmeA
strain of
Chlamydia
, since AHNAK-deficient cells revealed no invasion phenotype. Overall, our data indicate the efficacy of FRAEM and reveal a role of TmeA during chlamydial invasion that manifests independently of effects on AHNAK.
Inflammasome Activation by Bacterial Outer Membrane Vesicles Requires Guanylate Binding Proteins
Authors: Finethy Ryan , Luoma Sarah , Orench-Rivera Nichole , Feeley Eric M. , Haldar Arun K. , Yamamoto Masahiro , Kanneganti Thirumala-Devi , Kuehn Meta J. , Coers Jörn
Published: October 2017

The Gram-negative bacterial cell wall component lipopolysaccharide (LPS) is recognized by the noncanonical inflammasome protein caspase-11 in the cytosol of infected host cells and thereby prompts an inflammatory immune response linked to sepsis. Host guanylate binding proteins (GBPs) promote infection-induced caspase-11 activation in tissue culture models, and yet their
in vivo
role in LPS-mediated sepsis has remained unexplored. LPS can be released from lysed bacteria as “free” LPS aggregates or actively secreted by live bacteria as a component of outer membrane vesicles (OMVs). Here, we report that GBPs control inflammation and sepsis in mice injected with either free LPS or purified OMVs derived from Gram-negative
Escherichia coli
. In agreement with our observations from
in vivo
experiments, we demonstrate that macrophages lacking GBP2 expression fail to induce pyroptotic cell death and proinflammatory interleukin-1β (IL-1β) and IL-18 secretion when exposed to OMVs. We propose that in order to activate caspase-11
in vivo
, GBPs control the processing of bacterium-derived OMVs by macrophages as well as the processing of circulating free LPS by as-yet-undetermined cell types.

IMPORTANCE
The bacterial cell wall component LPS is a strong inducer of inflammation and is responsible for much of the toxicity of Gram-negative bacteria. Bacteria shed some of their cell wall and its associated LPS in the form of outer membrane vesicles (OMVs). Recent work demonstrated that secreted OMVs deliver LPS into the host cell cytosol by an unknown mechanism, resulting in the activation of the proinflammatory LPS sensor caspase-11. Here, we show that activation of cytosolic caspase-11 by OMVs requires additional host factors, the so-called guanylate binding proteins (GBPs). The discovery of GBPs as regulators of OMV-mediated inflammation paves the way toward a mechanistic understanding of the host response toward bacterial OMVs and may lead to effective strategies to ameliorate inflammation induced by bacterial infections.
Neuroimaging and endocrine disorders in paediatric optic nerve hypoplasia
Authors: Qian Xiaoxiao , Fouzdar Jain Samksha , Morgan Linda A , Kruse Travis , Cabrera Monina , Suh Donny W
Published: October 2017

Purpose

Optic nerve hypoplasia (ONH) is one of the leading causes of blindness among children. The purpose of this retrospective study is to determine the risk factors and association between brain MRI findings, pituitary abnormalities and endocrine disorders with the presence of ONH.

Methods

A retrospective review of patients seen at paediatric ophthalmology clinics from January 2006 to December 2016 at Children’s Hospital and Medical Center and the University of Nebraska Medical Center was performed. All patients with a documented diagnosis of ONH or septo-optic dysplasia were identified. MRI and endocrinology results were analysed by masked examiners.

Results

Out of 77 patients, overall incidence of abnormal pituitary on MRI was 35.1% and the incidence of endocrine abnormalities was 37.7%. Of the 57 patients with bilateral ONH, 23 (40.4%) had an abnormal pituitary while 4 of the 20 patients (20.0%) with unilateral ONH had an abnormal pituitary on MRI. The sensitivity and specific of brain MRI as signs of endocrinopathy are 67.9% and 83.3%, respectively.

Conclusion

This study has determined that abnormal MRI findings do not have the sensitivity to predict endocrinopathy, nor does a normal MRI rule out possible endocrine abnormalities. When patients with ONH present with normal neurological examinations, normal endocrine workup and normal developmental milestones, a MRI of the brain may be deferred until new indications arise. Regardless of the MRI status, children with ONH should have a comprehensive endocrine evaluation and continue to have routine endocrine follow-up.
Modifiable factors associated with patient-reported pain during and after screening colonoscopy
Authors: Bugajski Marek , Wieszczy Paulina , Hoff Geir , Rupinski Maciej , Regula Jaroslaw , Kaminski Michal Filip
Published: October 2017

Objective

Pain associated with colonoscopy is a major burden for patients. We investigated modifiable factors associated with patient-reported pain during and after colonoscopy.

Design

This cross-sectional analysis included database records from 23 centres participating in a population-based colonoscopy screening programme in Poland. Colonoscopies were performed under three sedation modalities: none, benzodiazepine-opioid sedation or propofol sedation. We used Gastronet (a validated tool) to assess patients’ pain during and after colonoscopy; pain was scored on a four-point scale (no, little, moderate or severe pain), with moderate to severe defined as painful. We used multivariate logistic regression models to estimate ORs for painful colonoscopy and calculated risk-adjusted ratios of painful colonoscopies per endoscopist and compared it to the mean rate.

Results

Of 35 216 screening colonoscopies in 2014 and 2015 included in our study, 22 725 (64.5%) patients returned valid Gastronet questionnaires. The proportion of examinations described as causing pain during (after) the procedure was 22.5% (14.2%) for unsedated, 19.9% (13.5%) for benzodiazepine-opioid sedation and 2.5% (7.5%) for propofol sedation. Propofol sedation, higher case volume of endoscopists, newest endoscope generation and adequate bowel preparation were significantly associated with lower odds of painful colonoscopy. Pain scores after colonoscopy showed similar associations. Adjusted pain rates during and after colonoscopy varied 11 and over 23-fold, respectively, between endoscopists.

Conclusion

We identified several independent, modifiable factors associated with pain during and after colonoscopy, of which individual endoscopist was the most important. Dedicated training should be considered to decrease variability among endoscopists.
Health system and law enforcement synergies for injury surveillance, control and prevention: a scoping review
Authors: Jacoby Sara F , Kollar Laura M Mercer , Ridgeway Greg , Sumner Steven A
Published: October 2017

Background

Healthcare providers and law enforcement (LE) officers are among the most common first responders to injuring events. Despite frequent interface between the health system (HS) and LE sectors, the published evidence that supports their collaboration in injury surveillance, control and prevention has not been comprehensively reviewed.

Methods

We conducted a scoping review of literature published from 1990 to 2016 that focused on local and regional HS and LE collaborations in injury surveillance, control and prevention. Our aim was to describe what is known and what remains unexplored about these cross-sector efforts.

Results

128 articles were included in the final review. These were categorised by their focus on either surveillance activities or partnerships in injury control and prevention programmes. The majority of surveillance articles focused on road traffic injuries. Conversely, articles describing partnerships and programme evaluations primarily targeted the prevention of interpersonal violence.

Discussion

This review yielded two major findings: overall, the combination of HS and LE injury data added value to surveillance systems, especially as HS data augmented LE data; and HS and LE partnerships have been developed to improve injury control and prevention. However, there are few studies that have evaluated the impact and sustainability of these partnerships.

Conclusions

The current evidence to support HS and LE collaboration in injury surveillance and control and prevention programmes is heterogeneous. Notable gaps suggest ample opportunity for further research and programme evaluation across all types of injury.
Coeliac disease and the liver: spectrum of liver histology, serology and treatment response at a tertiary referral centre
Authors: Majumdar Kaushik , Sakhuja Puja , Puri Amarender Singh , Gaur Kavita , Haider Aiman , Gondal Ranjana
Published: October 2017

Background

Coeliac disease (CD) is a gluten-sensitive enteropathy diagnosed on the basis of ESPGHAN criteria and clinical response to gluten-free diet (GFD). Histological abnormalities on liver biopsy have been noted in CD but have seldom been described.

Aims

To assess the histological spectrum of ‘coeliac hepatitis’ and possibility of reversal of such features after a GFD.

Methods

Twenty-five patients with concomitant CD and hepatic derangement were analysed for clinical profile, laboratory investigations and duodenal and liver biopsy. A histological comparison of pre- and post-GFD duodenal and liver biopsies was carried out, wherever possible.

Results

Fifteen patients presenting with CD subsequently developed abnormal liver function tests; 10 patients presenting with liver disease were found to have tissue positive transglutaminase in 70% and antigliadin antibodies in 60%. Serological markers for autoimmune liver disease (AILD) were positive in eight patients. Liver histology ranged from mild reactive hepatitis, chronic hepatitis, steatosis to cirrhosis. Liver biopsies after a GFD were available in six cases, of which five showed a decrease in steatosis, portal and lobular inflammation and fibrosis score.

Conclusion

Coeliac hepatitis could be a distinct entity and the patients may present with either CD or secondary hepatic derangement. Evaluation for the presence of CD is recommended for patients presenting with AILD, unexplained transaminasaemia or anaemia. This is one of the very few studies demonstrating the continuum of liver histological changes in ‘coeliac hepatitis’. Trial of a GFD may result in clinicopathological improvement of ‘coeliac hepatitis’.
Infectious and non-infectious complications in primary immunodeficiency disorders: an autopsy study from North India
Authors: Gupta Kirti , Rawat Amit , Agrawal Parimal , Jindal Ankur , Nada Ritambhra , Saikia Biman , Chan Koon Wing , Lau Yu Lung , Minz Ranjana Walker , Singh Surjit
Published: October 2017

Background

Primary immunodeficiency disorders (PID) include a wide spectrum of inherited disorders characterised by functional abnormalities of one or more components of the immune system. Recent updates from the genomic data have contributed significantly to its better understanding with identification of new entities. Diagnosis is always challenging due to their variable clinical presentation. With the evolution of molecular diagnosis, many of these children are being diagnosed early and offered appropriate therapy. However, in developing countries, early diagnosis is still not being made: as a result these patients succumb to their disease. Autopsy data on PID is notably lacking in the literature with histopathological evaluation of PID being limited to rare case reports.

Objective

To analyse the clinical, immunologic (including mutational) and morphologic features at autopsy in 10 proven and suspected cases of primary immunodeficiency disorders diagnosed at our Institute over the past decade.

Methods

Study includes a detailed clinico-pathological analysis of 10 proven and suspected cases of primary immunodeficiency disorders.

Results

A varied spectrum of infectious and non-infectious complications were identified in these cases of which fungal infections were found to be more frequent compared with viral or bacterial infections. Rare and novel morphological findings, like granulomatous involvement of the heart in a patient with chronic granulomatous disease, systemic amyloidosis in a teenage girl with X-linked agammaglobulinemia, are highlighted which is distinctly lacking in the literature.

Conclusions

The present study is perhaps the first autopsy series on PID. Even in the molecular era, such analysis is still important, as correlation of pathological features with clinical symptoms provides clues for a timely diagnosis and appropriate therapeutic intervention.
Understanding bias in relationships between the food environment and diet quality: the Coronary Artery Risk Development in Young Adults (CARDIA) study
Authors: Rummo Pasquale E , Guilkey David K , Ng Shu Wen , Meyer Katie A , Popkin Barry M , Reis Jared P , Shikany James M , Gordon-Larsen Penny
Published: October 2017

Background

The relationship between food environment exposures and diet behaviours is unclear, possibly because the majority of studies ignore potential residual confounding.

Methods

We used 20 years (1985–1986, 1992–1993 2005–2006) of data from the Coronary Artery Risk Development in Young Adults (CARDIA) study across four US cities (Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; Oakland, California) and instrumental variables (IV) regression to obtain causal estimates of longitudinal associations between the percentage of neighbourhood food outlets (per total food outlets within 1 km network distance of respondent residence) and ana prioridiet quality score, with higher scores indicating higher diet quality. To assess the presence and magnitude of bias related to residual confounding, we compared results from causal models (IV regression) to non-causal models, including ordinary least squares regression, which does not account for residual confounding at all and fixed-effects regression, which only controls for time-invariant unmeasured characteristics.

Results

The mean diet quality score across follow-up was 63.4 (SD=12.7). A 10% increase in fast food restaurants (relative to full-service restaurants) was associated with a lower diet quality score over time using IV regression (β=−1.01, 95% CI −1.99 to –0.04); estimates were attenuated using non-causal models. The percentage of neighbourhood convenience and grocery stores (relative to supermarkets) was not associated with diet quality in any model, but estimates from non-causal models were similarly attenuated compared with causal models.

Conclusion

Ignoring residual confounding may generate biased estimated effects of neighbourhood food outlets on diet outcomes and may have contributed to weak findings in the food environment literature.
Multifocal necrotising leucoencephalopathy following Salmonella infection in an immunocompetent patient
Authors: O’Gara Michael A , Dharia Sonali , Hilton David , Gutowski Nicholas J
Published: October 2017

Multifocal necrotising leucoencephalopathy is a rare disorder affecting the central nervous system. It is characterised pathologically by microscopic areas of necrosis with pontine predilection but also involvement of extrapontine regions, including the cerebellum, medulla and cerebral hemispheres. It usually occurs on the background of immunosuppression. Here we describe an immunocompetent patient with a recent history of Salmonella infection who presented with subacute neurological deterioration. At postmortem, she had evidence of multifocal necrotising leucoencephalopathy.
Diverse phenotype of hypokalaemic periodic paralysis within a family
Authors: Chalissery Albi Jose , Munteanu Tudor , Langan Yvonne , Brett Francesca , Redmond Janice
Published: October 2017

Hypokalaemic periodic paralysis typically presents with intermittent mild-to-moderate weakness lasting hours to days. We report a case with an uncommon phenotype of late-onset myopathy without episodic paralytic attacks. Initial work-up including muscle biopsy was inconclusive. A subsequent review of the right deltoid biopsy, long exercise testing and repeated family history was helpful, followed by appropriate genetic testing. We identified a heterozygous pathogenic mutation in calcium ion channel (CACNA1S:c.1583G>A p.Arg528His) causing hypokalaemic periodic paralysis. Myopathy can present without episodic paralysis and the frequency of paralytic episodes does not correlate well with the development and progression of a fixed myopathy. Our report also highlights the intrafamilial phenotypic variation of hypokalaemic periodic paralysis secondary to a CACNA1S gene mutation.
Potential deaths averted in USA by replacing cigarettes with e-cigarettes
Authors: Levy David T , Borland Ron , Lindblom Eric N , Goniewicz Maciej L , Meza Rafael , Holford Theodore R , Yuan Zhe , Luo Yuying , O’Connor Richard J , Niaura Raymond , Abrams David B
Published: October 2017

Introduction

US tobacco control policies to reduce cigarette use have been effective, but their impact has been relatively slow. This study considers a strategy of switching cigarette smokers to e-cigarette use (‘vaping’) in the USA to accelerate tobacco control progress.

Methods

A Status Quo Scenario, developed to project smoking rates and health outcomes in the absence of vaping, is compared with Substitution models, whereby cigarette use is largely replaced by vaping over a 10-year period. We test an Optimistic and a Pessimistic Scenario, differing in terms of the relative harms of e-cigarettes compared with cigarettes and the impact on overall initiation, cessation and switching. Projected mortality outcomes by age and sex under the Status Quo and E-Cigarette Substitution Scenarios are compared from 2016 to 2100 to determine public health impacts.

Findings

Compared with the Status Quo, replacement of cigarette by e-cigarette use over a 10-year period yields 6.6 million fewer premature deaths with 86.7 million fewer life years lost in the Optimistic Scenario. Under the Pessimistic Scenario, 1.6 million premature deaths are averted with 20.8 million fewer life years lost. The largest gains are among younger cohorts, with a 0.5 gain in average life expectancy projected for the age 15 years cohort in 2016.

Conclusions

The tobacco control community has been divided regarding the role of e-cigarettes in tobacco control. Our projections show that a strategy of replacing cigarette smoking with vaping would yield substantial life year gains, even under pessimistic assumptions regarding cessation, initiation and relative harm.
Designer pets discussed in House of Lords
Authors: Waddell Amy
Published: October 2017

Amy Waddell, BVA head of media and public affairs, outlines the current debate around animal welfare and ‘designer’ breeds in the House of Lords.
Surveillance in Scotland and Northern Ireland – how do you engage?
Authors: Atkin Hayley
Published: October 2017

Hayley Atkin, BVA policy officer, encourages vets in Scotland and Northern Ireland to help BVA understand how they engage with veterinary surveillance.
Cardiac actin changes in the actomyosin interface have different effects on myosin duty ratio
Authors: Liu Haidun , Henein Mary , Anillo Maria , Dawson John F.
Published: October 2017

Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disease (CD) that commonly causes an increased size of cardiomyocytes in the left ventricle. The proteins myosin and actin interact in the myocardium to produce contraction through the actomyosin ATPase cycle. The duty ratio (r) of myosin is the proportion of the actomyosin ATPase cycle that myosin is bound to actin and does work. A common hypothesis is that HCM mutations increase contraction in cardiac sarcomeres; however, the available data are not clear on this connection. Based on previous work with human α-cardiac actin (ACTC), we hypothesize that HCM-linked ACTC variants with alterations near the myosin binding site have an increased r, producing more force. Myosin duty ratios using human ACTC variant proteins were calculated with myosin ATPase activity and in-vitro motility data. We found no consistent changes in the duty ratio of the ACTC variants, suggesting that other factors are involved in the development of HCM when ACTC variants are present.
Fire-mediated patterns of habitat use by male moose (Alcesalces) in Alaska
Authors: Brown C.L. , Kielland K. , Euskirchen E.S. , Brinkman T.J. , Ruess R.W. , Kellie K.A.
Published: October 2017

Fire severity is an important control over regeneration of deciduous species and can influence the overall quality of habitat for herbivores, such as moose (Alces alces (Linnaeus, 1758)), but the relationships between availability and duration of biomass production and moose habitat use are largely unknown. We evaluate the relative influence of a regenerating burn, paying particular attention to fire severity, on winter forage production and duration, offtake, nutritional quality, and seasonal moose habitat use. We used data from 14 GPS collared male moose in the 20-year-old Hajdukovich Creek Burn (HCB) in interior Alaska, USA, to generate seasonal dynamic Brownian bridge movement models. Within HCB, moose selected for low-severity sites more than high- and moderate-severity sites during the winter. Over the past decade, willow (species of the genus Salix L.) biomass production in low-severity sites has doubled and is likely influencing winter habitat selection patterns. In summer, moose selected for high-severity sites where there is a more abundant understory layer (e.g., stem densities) providing both forage and cover. The initial pulse of biomass production in high-severity sites, as well as the delay in growth and maturation of vegetation in low-severity sites, indicate that differing distributions of wildfire severity can create a dynamic mosaic of habitat patches that may extend the value of burns over time for moose.
Mathieu functions for fermions generated in magnetar’s corona
Authors: Dariescu Marina-Aura , Dariescu Ciprian
Published: October 2017

This work deals with the behavior of fermions in a configuration supposed to exist in magnetar’s corona. For a static magnetic induction parallel to a time-harmonic electric field, the solution to the U(1)-gauge invariant Dirac equation is expressed in terms of Laguerre polynomials and Mathieu’s functions of complex parameter. Using the Fourier series valid before the branching point, we are computing the conserved current density components.