bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination Effects of Antimicrobial Peptides
Authors: Yu Guozhi , Baeder Desiree Y. , Regoes Roland R. , Rolff Jens
Published: January 2016

Antimicrobial peptides (AMPs) are ancient and conserved across the tree of life. Their efficacy over evolutionary time has been largely attributed to their mechanisms of killing. Yet, the understanding of their pharmacodynamics both
in vivo
and
in vitro
is very limited. This is, however, crucial for applications of AMPs as drugs and also informs the understanding of the action of AMPs in natural immune systems. Here, we selected six different AMPs from different organisms to test their individual and combined effects
in vitro
. We analyzed their pharmacodynamics based on the Hill function and evaluated the interaction of combinations of two and three AMPs. Interactions of AMPs in our study were mostly synergistic, and three-AMP combinations displayed stronger synergism than two-AMP combinations. This suggests synergism to be a common phenomenon in AMP interaction. Additionally, AMPs displayed a sharp increase in killing within a narrow dose range, contrasting with those of antibiotics. We suggest that our results could lead a way toward better evaluation of AMP application in practice and shed some light on the evolutionary consequences of antimicrobial peptide interactions within the immune system of organisms.
Combinatorial Pharmacodynamics of Ceftolozane-Tazobactam against Genotypically Defined β-Lactamase-Producing Escherichia coli: Insights into the Pharmacokinetics/Pharmacodynamics of β-Lactam–β-Lactamase Inhibitor Combinations
Authors: Soon Rachel L. , Lenhard Justin R. , Bulman Zackery P. , Holden Patricia N. , Kelchlin Pamela , Steenbergen Judith N. , Friedrich Lawrence V. , Forrest Alan , Tsuji Brian T.
Published: January 2016

Despite a dearth of new agents currently being developed to combat multidrug-resistant Gram-negative pathogens, the combination of ceftolozane and tazobactam was recently approved by the Food and Drug Administration to treat complicated intra-abdominal and urinary tract infections. To characterize the activity of the combination product, time-kill studies were conducted against 4 strains of
Escherichia coli
that differed in the type of β-lactamase they expressed. The four investigational strains included 2805 (no β-lactamase), 2890 (AmpC β-lactamase), 2842 (CMY-10 β-lactamase), and 2807 (CTX-M-15 β-lactamase), with MICs to ceftolozane of 0.25, 4, 8, and >128 mg/liter with no tazobactam, and MICs of 0.25, 1, 4, and 8 mg/liter with 4 mg/liter tazobactam, respectively. All four strains were exposed to a 6 by 5 array of ceftolozane (0, 1, 4, 16, 64, and 256 mg/liter) and tazobactam (0, 1, 4, 16, and 64 mg/liter) over 48 h using starting inocula of 10
6
and 10
8
CFU/ml. While ceftolozane-tazobactam achieved bactericidal activity against all 4 strains, the concentrations of ceftolozane and tazobactam required for a ≥3-log reduction varied between the two starting inocula and the 4 strains. At both inocula, the Hill plots (
R
2
> 0.882) of ceftolozane revealed significantly higher 50% effective concentrations (EC
50
s) at tazobactam concentrations of ≤4 mg/liter than those at concentrations of ≥16 mg/liter (
P
< 0.01). Moreover, the EC
50
s at 10
8
CFU/ml were 2.81 to 66.5 times greater than the EC
50
s at 10
6
CFU/ml (median, 10.7-fold increase;
P
= 0.002). These promising results indicate that ceftolozane-tazobactam achieves bactericidal activity against a wide range of β-lactamase-producing
E. coli
strains.
In Vitro
Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens
Authors: Biedenbach D. J. , Bouchillon S. K. , Hackel M. , Miller L. A. , Scangarella-Oman N. E. , Jakielaszek C. , Sahm D. F.
Published: January 2016

Gepotidacin inhibits bacterial DNA replication through a mode different from that of fluoroquinolones. Gepotidacin and comparators were tested by broth and agar dilution against clinical isolates. The
in vitro
activities of gepotidacin were comparable against methicillin-susceptible and -resistant
Staphylococcus aureus
(MSSA and MRSA, respectively) isolates (MIC
90
, 0.5 μg/ml). The gepotidacin MIC
90
s were as follows (in micrograms per milliliter) for the indicated bacteria:
Streptococcus pyogenes
, 0.25;
Escherichia coli
, 2;
Moraxella catarrhalis
, ≤0.06;
Streptococcus pneumoniae
(0.25),
Haemophilus influenzae
, 1;
Clostridium perfringens
, 0.5; and
Shigella
spp., 1, including levofloxacin-resistant subsets. Gepotidacin warrants further investigation for clinical development.
Survival Strategies of the Plant-Associated Bacterium Enterobacter sp. Strain EG16 under Cadmium Stress
Authors: Chen Yanmei , Chao Yuanqing , Li Yaying , Lin Qingqi , Bai Jun , Tang Lu , Wang Shizhong , Ying Rongrong , Qiu Rongliang
Published: January 2016

Plant-associated bacteria are of great interest because of their potential use in phytoremediation. However, their ability to survive and promote plant growth in metal-polluted soils remains unclear. In this study, a soilborne Cd-resistant bacterium was isolated and identified as
Enterobacter
sp. strain EG16. It tolerates high external Cd concentrations (Cd
2+
MIC, >250 mg liter
−1
) and is able to produce siderophores and the plant hormone indole-3-acetic acid (IAA), both of which contribute to plant growth promotion. Surface biosorption in this strain accounted for 31% of the total Cd accumulated. The potential presence of cadmium sulfide, shown by energy-dispersive X-ray (EDX) analysis, suggested intracellular Cd binding as a Cd response mechanism of the isolate. Cd exposure resulted in global regulation at the transcriptomic level, with the bacterium switching to an energy-conserving mode by inhibiting energy-consuming processes while increasing the production of stress-related proteins. The stress response system included increased import of sulfur and iron, which become deficient under Cd stress, and the redirection of sulfur metabolism to the maintenance of intracellular glutathione levels in response to Cd toxicity. Increased production of siderophores, responding to Cd-induced Fe deficiency, not only is involved in the Cd stress response systems of EG16 but may also play an important role in promoting plant growth as well as alleviating the Cd-induced inhibition of IAA production. The newly isolated strain EG16 may be a suitable candidate for microbially assisted phytoremediation due to its high resistance to Cd and its Cd-induced siderophore production, which is likely to contribute to plant growth promotion.
Effects of Cover Crop Species and Season on Population Dynamics of Escherichia coli and Listeria innocua in Soil
Authors: Reed-Jones Neiunna L. , Marine Sasha Cahn , Everts Kathryne L. , Micallef Shirley A.
Published: January 2016

Cover crops provide several ecosystem services, but their impact on enteric bacterial survival remains unexplored. The influence of cover cropping on foodborne pathogen indicator bacteria was assessed in five cover crop/green manure systems: cereal rye, hairy vetch, crimson clover, hairy vetch-rye and crimson clover-rye mixtures, and bare ground. Cover crop plots were inoculated with
Escherichia coli
and
Listeria innocua
in the fall of 2013 and 2014 and tilled into the soil in the spring to form green manure. Soil samples were collected and the bacteria enumerated. Time was a factor for all bacterial populations studied in all fields (
P
< 0.001).
E. coli
levels declined when soil temperatures dipped to <5°C and were detected only sporadically the following spring.
L. innocua
diminished somewhat but persisted, independently of season. In an organic field, the cover crop was a factor for
E. coli
in year 1 (
P
= 0.004) and for
L. innocua
in year 2 (
P
= 0.011). In year 1,
E. coli
levels were highest in the rye and hairy vetch-rye plots. In year 2,
L. innocua
levels were higher in hairy vetch-rye (
P
= 0.01) and hairy vetch (
P
= 0.03) plots than in the rye plot. Bacterial populations grew (
P
< 0.05) or remained the same 4 weeks after green manure incorporation, although initial reductions in
L. innocua
numbers were observed after tilling (
P
< 0.05). Green manure type was a factor only for
L. innocua
abundance in a transitional field (
P
< 0.05). Overall, the impacts of cover crops/green manures on bacterial population dynamics in soil varied, being influenced by bacterial species, time from inoculation, soil temperature, rainfall, and tillage; this reveals the need for long-term studies.
Robustness of the Process of Nucleoid Exclusion of Protein Aggregates in Escherichia coli
Authors: Neeli-Venkata Ramakanth , Martikainen Antti , Gupta Abhishekh , Gonçalves Nadia , Fonseca Jose , Ribeiro Andre S.
Published: January 2016

Escherichia coli
segregates protein aggregates to the poles by nucleoid exclusion. Combined with cell divisions, this generates heterogeneous aggregate distributions in subsequent cell generations. We studied the robustness of this process with differing medium richness and antibiotics stress, which affect nucleoid size, using multimodal, time-lapse microscopy of live cells expressing both a fluorescently tagged chaperone (IbpA), which identifies
in vivo
the location of aggregates, and HupA-mCherry, a fluorescent variant of a nucleoid-associated protein. We find that the relative sizes of the nucleoid's major and minor axes change widely, in a positively correlated fashion, with medium richness and antibiotic stress. The aggregate's distribution along the major cell axis also changes between conditions and in agreement with the nucleoid exclusion phenomenon. Consequently, the fraction of aggregates at the midcell region prior to cell division differs between conditions, which will affect the degree of asymmetries in the partitioning of aggregates between cells of future generations. Finally, from the location of the peak of anisotropy in the aggregate displacement distribution, the nucleoid relative size, and the spatiotemporal aggregate distribution, we find that the exclusion of detectable aggregates from midcell is most pronounced in cells with mid-sized nucleoids, which are most common under optimal conditions. We conclude that the aggregate management mechanisms of
E. coli
are significantly robust but are not immune to stresses due to the tangible effect that these have on nucleoid size.

IMPORTANCE
Escherichia coli
segregates protein aggregates to the poles by nucleoid exclusion. From live single-cell microscopy studies of the robustness of this process to various stresses known to affect nucleoid size, we find that nucleoid size and aggregate preferential locations change concordantly between conditions. Also, the degree of influence of the nucleoid on aggregate positioning differs between conditions, causing aggregate numbers at midcell to differ in cell division events, which will affect the degree of asymmetries in the partitioning of aggregates between cells of future generations. Finally, we find that aggregate segregation to the cell poles is most pronounced in cells with mid-sized nucleoids. We conclude that the energy-free process of the midcell exclusion of aggregates partially loses effectiveness under stressful conditions.
The Activity of Escherichia coli Chaperone SurA Is Regulated by Conformational Changes Involving a Parvulin Domain
Authors: Soltes Garner R. , Schwalm Jaclyn , Ricci Dante P. , Silhavy Thomas J.
Published: January 2016

The periplasmic chaperone SurA is critical for the biogenesis of outer membrane proteins (OMPs) and, thus, the maintenance of membrane integrity in
Escherichia coli
. The activity of this modular chaperone has been attributed to a core chaperone module, with only minor importance assigned to the two SurA peptidyl-prolyl isomerase (PPIase) domains. In this work, we used synthetic phenotypes and covalent tethering to demonstrate that the activity of SurA is regulated by its PPIase domains and, furthermore, that its activity is correlated with the conformational state of the chaperone. When combined with mutations in the β-barrel assembly machine (BAM), SurA mutations resulting in deletion of the second parvulin domain (P2) inhibit OMP assembly, suggesting that P2 is involved in the regulation of SurA. The first parvulin domain (P1) potentiates this autoinhibition, as mutations that covalently tether the P1 domain to the core chaperone module severely impair OMP assembly. Furthermore, these inhibitory mutations negate the suppression of and biochemically stabilize the protein specified by a well-characterized gain-of-function mutation in P1, demonstrating that SurA cycles between distinct conformational and functional states during the OMP assembly process.

IMPORTANCE
This work reveals the reversible autoinhibition of the SurA chaperone imposed by a heretofore underappreciated parvulin domain. Many β-barrel-associated outer membrane (OM) virulence factors, including the P-pilus and type I fimbriae, rely on SurA for proper assembly; thus, a mechanistic understanding of SurA function and inhibition may facilitate antibiotic intervention against Gram-negative pathogens, such as uropathogenic
Escherichia coli
,
E. coli
O157:H7,
Shigella
, and
Salmonella
. In addition, SurA is important for the assembly of critical OM biogenesis factors, such as the lipopolysaccharide (LPS) transport machine, suggesting that specific targeting of SurA may provide a useful means to subvert the OM barrier.
Interplay of CodY and ScoC in the Regulation of Major Extracellular Protease Genes of Bacillus subtilis
Authors: Barbieri Giulia , Albertini Alessandra M. , Ferrari Eugenio , Sonenshein Abraham L. , Belitsky Boris R.
Published: January 2016

AprE and NprE are two major extracellular proteases in
Bacillus subtilis
whose expression is directly regulated by several pleiotropic transcriptional factors, including AbrB, DegU, ScoC, and SinR. In cells growing in a rich, complex medium, the
aprE
and
nprE
genes are strongly expressed only during the post-exponential growth phase; mutations in genes encoding the known regulators affect the level of post-exponential-phase gene expression but do not permit high-level expression during the exponential growth phase. Using DNA-binding assays and expression and mutational analyses, we have shown that the genes for both exoproteases are also under strong, direct, negative control by the global transcriptional regulator CodY. However, because CodY also represses
scoC
, little or no derepression of
aprE
and
nprE
was seen in a
codY
null mutant due to overexpression of
scoC
. Thus, CodY is also an indirect positive regulator of these genes by limiting the synthesis of a second repressor. In addition, in cells growing under conditions that activate CodY, a
scoC
null mutation had little effect on
aprE
or
nprE
expression; full effects of
scoC
or
codY
null mutations could be seen only in the absence of the other regulator. However, even the
codY scoC
double mutant did not show high levels of
aprE
and
nprE
gene expression during exponential growth phase in a rich, complex medium. Only a third mutation, in
abrB
, allowed such expression. Thus, three repressors can contribute to reducing exoprotease gene expression during growth in the presence of excess nutrients.

IMPORTANCE
The major
Bacillus subtilis
exoproteases, AprE and NprE, are important metabolic enzymes whose genes are subject to complex regulation by multiple transcription factors. We show here that expression of the
aprE
and
nprE
genes is also controlled, both directly and indirectly, by CodY, a global transcriptional regulator that responds to the intracellular pools of amino acids. Direct CodY-mediated repression explains a long-standing puzzle, that is, why exoproteases are not produced when cells are growing exponentially in a medium containing abundant quantities of proteins or their degradation products. Indirect regulation of
aprE
and
nprE
through CodY-mediated repression of the
scoC
gene, encoding another pleiotropic repressor, serves to maintain a significant level of repression of exoprotease genes when CodY loses activity.
Proteomic Analyses of Chlorhexidine Tolerance Mechanisms in Delftia acidovorans Biofilms
Authors: Rema Tara , Medihala Prabhakara , Lawrence John R. , Vidovic Sinisa , Leppard Gary G. , Reid Marcia , Korber Darren R.
Published: January 2016

Delftia acidovorans
has been associated with a number of serious infections, including bacteremia, empyema, bacterial endocarditis, and ocular and urinary tract infections. It has also been linked with a variety of surface-associated nosocomial infections. Biofilm-forming antimicrobial-resistant
D. acidovorans
strains have also been isolated, including ones displaying resistance to the common broad-spectrum agent chlorhexidine. The mechanisms of chlorhexidine resistance in
D. acidovorans
are not known; hence, a chlorhexidine-susceptible mutant of the tolerant wild-type strain was obtained using transposon mutagenesis, and the proteome and ultrastructural changes of both strains were compared under chlorhexidine challenge.
Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine
Authors: Theriot Casey M. , Bowman Alison A. , Young Vincent B.
Published: January 2016

Antibiotics alter the gastrointestinal microbiota, allowing for
Clostridium difficile
infection, which is a significant public health problem. Changes in the structure of the gut microbiota alter the metabolome, specifically the production of secondary bile acids. Specific bile acids are able to initiate
C. difficile
spore germination and also inhibit
C. difficile
growth
in vitro
, although no study to date has defined physiologically relevant bile acids in the gastrointestinal tract. In this study, we define the bile acids
C. difficile
spores encounter in the small and large intestines before and after various antibiotic treatments. Antibiotics that alter the gut microbiota and deplete secondary bile acid production allow
C. difficile
colonization, representing a mechanism of colonization resistance. Multiple secondary bile acids in the large intestine were able to inhibit
C. difficile
spore germination and growth at physiological concentrations and represent new targets to combat
C. difficile
in the large intestine.
Omental torsion, a rare cause of acute abdomen
Authors: Joshi Shivani , Cuthbert Gary Andrew , Kerwat Rajab
Published: January 2016

Omental torsion is a rare cause of acute abdominal pain. We report a case of omental torsion in a 7-year-old girl, who presented with right iliac fossa pain. The patient underwent an open appendicectomy, during which a normal appendix was identified and a diagnosis of omental torsion was made. The affected segment of omentum was resected along with the appendix. The patient made an uncomplicated recovery and was discharged on day 1 postoperatively. A normal appendix in the presence of omental torsion is found in 0.1% of all appendicectomies in children. We suggest routine visualisation of the omentum in the presence of a normal appendix during appendicectomy.
Nivolumab causing painless thyroiditis in a patient with adenocarcinoma of the lung
Authors: Verma Isha , Modi Anar , Tripathi Hemantkumar , Agrawal Abhinav
Published: January 2016

Thyroiditis is characterised by transient hyperthyroidism, followed sometimes by hypothyroidism, and then recovery. We report a case of painless drug-induced thyroiditis—in a patient with no history of any thyroid disorder—treated with Nivolumab (an IgG4 monoclonal antibody against Programmed Death Receptor 1). The purpose of this case report is to increase awareness among clinicians regarding this possible adverse effect from Nivolumab, and discuss the possible pathophysiology and management strategies in such patients.
Marital status and risk of dementia: a nationwide population-based prospective study from Sweden
Authors: Sundström Anna , Westerlund Olle , Kotyrlo Elena
Published: January 2016

Objectives

To examine the association between marital status and dementia in a cohort of young-old (50–64) and middle-old (65–74) adults, and also whether this may differ by gender.

Design

Prospective population-based study with follow-up time of up to 10 years.

Setting

Swedish national register-based study.

Participants

2 288 489 individuals, aged 50–74 years, without prior dementia diagnosis at baseline. Dementia was identified using the Swedish National Patient Register and the Cause of Death Register.

Outcome measures

The influence of marital status on dementia was analysed using Cox proportional hazards models, adjusted stepwise for multiple covariates (model 1: adjusted for age and gender; and model 2: additionally adjusted for having adult children, education, income and prior cardiovascular disease).

Results

During follow-up, 31 572 individuals in the study were identified as demented. Cox regression showed each non-married subcategory to be associated with a significantly higher risk of dementia than the married group, with the highest risk observed among people in the young-old age group, especially among those who were divorced or single (HRs 1.79 vs 1.71, fully adjusted model). Analyses stratified by gender showed gender differences in the young-old group, with indications of divorced men having a higher relative risk compared with divorced women (HRs 2.1 vs 1.7, only-age adjusted model). However, in the fully adjusted model, these differences were attenuated and there was no longer any significant difference between male and female participants.

Conclusions

Our results suggest that those living alone as non-marrieds may be at risk for early-onset and late-onset dementia. Although more research is needed to understand the underlying mechanism by which marital status is associated with dementia, this suggests that social relationships should be taken seriously as a risk factor for dementia and that social-based interventions may provide an opportunity to reduce the overall dementia risk.
A protocol for a randomised clinical trial of the effect of providing feedback on inhaler technique and adherence from an electronic device in patients with poorly controlled severe asthma
Authors: Sulaiman Imran , Mac Hale Elaine , Holmes Martin , Hughes Cian , D'Arcy Shona , Taylor Terrence , Rapcan Viliam , Doyle Frank , Breathnach Aoife , Seheult Jansen , Murphy Desmond , Hunt Eoin , Lane Stephen J , Sahadevan Abhilash , Crispino Gloria , Diette Greg , Killane Isabelle , Reilly Richard B , Costello Richard W
Published: January 2016

Introduction

In clinical practice, it is difficult to distinguish between patients with refractory asthma from those with poorly controlled asthma, where symptoms persist due to poor adherence, inadequate inhaler technique or comorbid diseases. We designed an audio recording device which, when attached to an inhaler, objectively identifies the time and technique of inhaler use, thereby assessing both aspects of adherence. This study will test the hypothesis that feedback on these two aspects of adherence when passed on to patients improves adherence and helps clinicians distinguish refractory from difficult-to-control asthma.

Methods

This is a single, blind, prospective, randomised, clinical trial performed at 5 research centres. Patients with partially controlled or uncontrolled severe asthma who have also had at least one severe asthma exacerbation in the prior year are eligible to participate. The effect of two types of nurse-delivered education interventions to promote adherence and inhaler technique will be assessed. The active group will receive feedback on their inhaler technique and adherence from the new device over a 3-month period. The control group will also receive training in inhaler technique and strategies to promote adherence, but no feedback from the device. The primary outcome is the difference in actual adherence, a measure that incorporates time and technique of inhaler use between groups at the end of the third month. Secondary outcomes include the number of patients who remain refractory despite good adherence, and differences in the components of adherence after the intervention. Data will be analysed on an intention-to-treat and a per-protocol basis. The sample size is 220 subjects (110 in each group), and loss to follow-up is estimated at 10% which will allow results to show a 10% difference (0.8 power) in adherence between group means with a type I error probability of 0.05.

Trial registration number

NCT01529697; Pre-results.
ESCAPS study protocol: a feasibility randomised controlled trial of ‘Early electrical stimulation to the wrist extensors and wrist flexors to prevent the post-stroke complications of pain and contractures in the paretic arm’
Authors: Fletcher-Smith Joanna C , Walker Dawn-Marie , Sprigg Nikola , James Marilyn , Walker Marion F , Allatt Kate , Mehta Rajnikant , Pandyan Anand D
Published: January 2016

Introduction

Approximately 70% of patients with stroke experience impaired arm function, which is persistent and disabling for an estimated 40%. Loss of function reduces independence in daily activities and impacts on quality of life. Muscles in those who do not recover functional movement in the stroke affected arm are at risk of atrophy and contractures, which can be established as early as 6 weeks following stroke. Pain is also common. This study aims to evaluate the feasibility of a randomised controlled trial to test the efficacy and cost-effectiveness of delivering early intensive electrical stimulation (ES) to prevent post-stroke complications in the paretic upper limb.

Methods and analysis

This is a feasibility randomised controlled trial (n=40) with embedded qualitative studies (patient/carer interviews and therapist focus groups) and feasibility economic evaluation. Patients will be recruited from the Stroke Unit at the Nottingham University Hospitals National Health Service (NHS) Trust within 72 h after stroke. Participants will be randomised to receive usual care or usual care and early ES to the wrist flexors and extensors for 30 min twice a day, 5 days a week for 3 months. The initial treatment(s) will be delivered by an occupational therapist or physiotherapist who will then train the patient and/or their nominated carer to self-manage subsequent treatments.

Ethics and dissemination

This study has been granted ethical approval by the National Research Ethics Service, East Midlands Nottingham1 Research Ethics Committee (ref: 15/EM/0006). To our knowledge, this is the first study of its kind of the early application (within 72 h post-stroke) of ES to both the wrist extensors and wrist flexors of stroke survivors with upper limb impairment. The results will inform the design of a definitive randomised controlled trial. Dissemination will include 2 peer-reviewed journal publications and presentations at national conferences.

Trial registration number

ISRCTN1648908; Pre-results. Clinicaltrials.gov ID:NCT02324634.
Protocol for the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) Million Persons Project pilot
Authors: Lu Jiapeng , Xuan Si , Downing Nicholas S , Wu Chaoqun , Li Li , Krumholz Harlan M , Jiang Lixin
Published: January 2016

Introduction

Collection of high-quality data from large populations is considered essential to generate knowledge that is critical to an era of precision medicine. Cardiovascular disease (CVD) is a leading cause of mortality in China and is a suitable focus of an initiative to discover factors that would improve our ability to assess and modify individual risk.

Methods and analysis

The pilot phase of China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) Million Persons Project is being conducted during 2014–2015 in four provinces across China to demonstrate the feasibility of a population-based assessment. It is designed to screen 0.4 million community-dwelling residents aged 40–75 years with measurements of blood pressure, height and weight, a lipid blood test, and a questionnaire on cardiovascular-related health status. Participants identified at high risk of CVD receive further health assessments, including ECG, ultrasound scan, blood and urine analysis, and a questionnaire on lifestyle and medical history. Collection of blood and urine samples is used to establish a biobank. High-risk subjects are also counselled with suggestions regarding potential lifestyle changes. In addition, high-risk subjects are followed-up either in a return clinic visit or by telephone interview, with measurement of blood pressure, weight, ECG, and a questionnaire on survival status, hospitalisations and lifestyle. The first 0.1 million participants screened were used to conduct a preliminary analysis, with information on baseline characteristics, health-related behaviours, anthropometric variables, medical history, and prevalence of high-risk subjects.

Ethics and dissemination

The central ethics committee at the China National Center for Cardiovascular Disease (NCCD) approved the pilot. Written informed consent is obtained from all participants on entry into the project. Findings will be disseminated in future peer-reviewed papers and will inform strategies aimed at developing precise methods of assessing and modifying risk.

Trial registration number

NCT02536456.
Fatal river drowning: the identification of research gaps through a systematic literature review
Authors: Peden Amy E , Franklin Richard C , Leggat Peter A
Published: January 2016

Introduction

Drowning is a leading cause of unintentional death. Rivers are a common location for drowning. Unlike other location-specific prevention efforts (home swimming pools and beaches), little is known about prevention targeting river drowning deaths.

Methods

A systematic literature review was undertaken using English language papers published between 1980 and 2014, exploring gaps in the literature, with a focus on epidemiology, risk factors and prevention strategies for river drowning.

Results

Twenty-nine papers were deemed relevant to the study design including 21 (72.4%) on epidemiology, 18 (62.1%) on risk factors and 10 (34.5%) that proposed strategies for prevention. Risk factors identified included age, falls into water, swimming, using watercraft, sex and alcohol.

Discussion

Gaps were identified in the published literature. These included a lack of an agreed definition for rivers, rates for fatal river drowning (however, crude rates were calculated for 12 papers, ranging from 0.20 to 1.89 per 100 000 people per annum), and consensus around risk factors, especially age. There was only one paper that explored a prevention programme; the remaining nine outlined proposed prevention activities. There is a need for studies into exposure patterns for rivers and an agreed definition (with consistent coding).

Conclusions

This systematic review has identified that river drowning deaths are an issue in many regions and countries around the world. Further work to address gaps in the published research to date would benefit prevention efforts.
Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ hybridisation (FISH) analyses
Authors: Kawai Toshiaki , Tominaga Susumu , Hiroi Sadayuki , Ogata Sho , Nakanishi Kuniaki , Kawahara Kunimitsu , Sonobe Hiroshi , Hiroshima Kenzo
Published: January 2016

Aims

Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7–9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging.

Methods

To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma-associated markers (CEA, BerEP4, MOC31, ER (estrogen receptor), PgR, TTF-1, Claudin-4, Pax8), and malignant-related and benign-related markers (epithelial membrane antigen (EMA), desmin, GLUT-1, CD146 and IMP3), and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F=18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs and 23 RMHs.

Results

Seventeen of the mesotheliomas (four PMM from women) were classified as diffuse, while five were localised. Calretinin was 91% positive in PMM, but negative in PPSC (specificity, 100%). BerEP4, Claudin-4 and PAX8 were all 100% positive in PPSC (specificities, 100%, 95% and 95%, respectively, for excluding PMM). For distinguishing PMM and RMH, sensitivity for EMA in mesothelioma was 68%, while for IMP3 and GLUT-1 it was 64% and 50%, respectively, all with high specificities. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 PMMs, but in 0/11 RMHs.

Conclusions

Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PPSC. EMA, in combination with IMP3 and desmin, is useful, and homozygous deletion of 9p21 may be helpful, for differentiating PMM from RMH.
Pulmonary toxoplasmosis in immunocompromised patients with interstitial pneumonia: a single-centre prospective study assessing PCR-based diagnosis
Authors: Desoubeaux Guillaume , Cabanne Églantine , Franck-Martel Claire , Gombert Martin , Gyan Emmanuel , Lissandre Séverine , Renaud Marc , Monjanel Hélène , Dartigeas Caroline , Bailly Éric , Van Langendonck Nathalie , Chandenier Jacques
Published: January 2016

Aims

Pulmonary toxoplasmosis has become a very rare parasitic infection since the advent of highly active antiretroviral therapies. It is generally diagnosed by the direct microscopic observation ofToxoplasma gondiitachyzoites in bronchoalveolar lavage fluid (BALF). The aim of this study was to assess possible improvements in diagnostic performance associated with the use of real-time PCR.

Methods

This prospective study was carried out on BALFs obtained from immunocompromised patients over a 2-year period. We systematically compared the results of conventional staining with those of molecular detection.

Results

Two cases of pulmonary toxoplasmosis were diagnosed for a total of 336 samples. PCR did not detect any additional cases and was more time-consuming than conventional staining.

Conclusions

Conventional staining is a reliable technique and is probably the most appropriate method for experienced microbiology laboratories, whereasT. gondii-specific PCR may be useful for laboratories with less experience in parasitology.

Trial registration number

2015_030, May 27th 2015.
Oxyntic gastric atrophy inHelicobacter pylorigastritis is distinct from autoimmune gastritis
Authors: Venerito Marino , Varbanova Mariya , Röhl Friedrich-Wilhelm , Reinhold Dirk , Frauenschläger Katrin , Jechorek Doerthe , Weigt Jochen , Link Alexander , Malfertheiner Peter
Published: January 2016

Aim

To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence ofHelicobacter pyloriinfection.

Methods

Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology andH. pyloritesting. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies againstH. pyloriand cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology.

Results

Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or pastH. pyloriinfection and AIG were present in 14/34 and 22/34 patients, respectively.H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared withH. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% ofH. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited forH. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively).

Conclusions

H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA inH. pylorigastritis.
Sarcoma of the breast: an update on a rare entity
Authors: Lim Sue Zann , Ong Kong Wee , Tan Benita Kiat Tee , Selvarajan Sathiyamoorthy , Tan Puay Hoon
Published: January 2016

Breast sarcoma is a rare condition. It consists of a heterogeneous group of non-epithelial tumours arising from the mesenchymal tissue of the breast. It has a distinctly different natural history, treatment response and prognosis as compared with carcinoma of the breast. A different diagnostic approach and treatment strategy have to be defined for this group of tumours. Due to its rarity, the current understanding on breast sarcoma is limited and is mostly based on small retrospective case series or case reports. Hence, the management generally follows the algorithms derived from randomised control trials of soft tissue sarcomas in the extremities and chest wall. Through this review, we discuss the results of major retrospective studies on breast sarcomas including data on epidemiology, aetiology, diagnostic approach, treatment strategies and outcomes of this challenging and potentially aggressive condition.
Incubation of lake whitefish (Coregonus clupeaformis) embryos in cooling water discharge and the impacts of fluctuating thermal regimes on development
Authors: Thome Christopher , Mitz Charles , Somers Christopher M. , Manzon Richard G. , Boreham Douglas R. , Wilson Joanna Y.
Published: January 2016

Thermal discharges released from industrial cooling water systems represent a potential environmental risk to fish species that spawn in nearshore waters. We investigated the impacts of in situ incubation of lake whitefish (Coregonus clupeaformis) embryos in the vicinity of a nuclear generating station. Over 3 consecutive years, fertilized embryos were deployed in Lake Huron using custom-built incubation chambers coupled with data loggers to monitor water temperature. Temperatures at sites in the vicinity of the thermal discharge were significantly elevated compared with reference locations, with mean winter temperatures up to 3 °C warmer. Temperatures were also more variable at these sites, with a significantly greater daily temperature range and rate of change. Embryos developing at discharge sites were significantly larger with smaller yolks than those from the reference stations, suggesting an advanced growth. This increased growth was supported by thermal data, with discharge sites predicted to be more than 10% advanced based on growth rate modelling. These temperature changes and increase in development rate are below thresholds for embryonic mortality but could potentially impact posthatch larval survival.
What does “First Nation deep roots in the forests” mean? Identification of principles and objectives for promoting forest-based development
Authors: Beaudoin Jean-Michel , Bouthillier Luc , Bulkan Janette , Nelson Harry , Trosper Ronald , Wyatt Stephen
Published: January 2016

We often hear about the resistance of First Nation (FN) communities to the industrial model of forestry, but we hear less about what they wish to achieve. Translating FN perspectives into concepts that are understood by the mainstream society can help inform current and future forest policies. Such translation can support initiatives that seek ways to increase FN participation in the forest sector. This paper documents one process of translation. It identifies the principles and objectives for forest-based development of the Essipit Innu First Nation in Quebec, Canada, reflective of the deep roots that anchor the Essipit to their territory. Based on participatory research carried out between January and July 2013, we identify 34 objectives folded into three core FN principles: Nutshimiu–Aitun (identity–territoriality), Mishkutunam (sharing–exchange), and Pakassitishun (responsibility–autonomy). Our analysis shows that the economic aims of the dominant forestry model are too narrow for FN communities. This paper contributes to expanding FN engagement in forestry through management and economic approaches that are better adapted to their culture and values.
Influence of hemlock woolly adelgid infestation on the physiological and reflectance characteristics of eastern hemlock
Authors: Williams Justin P. , Hanavan Ryan P. , Rock Barrett N. , Minocha Subhash C. , Linder Ernst
Published: January 2016

The hemlock woolly adelgid (HWA) (Adelges tsugae Annand) is an invasive insect in the eastern United States. Since its initial detection in Richmond, Virginia, in 1951, HWA has spread to half of the eastern hemlock (Tsuga canadensis (L.) Carr.) natural range. Detection of early infestation symptoms via remote sensing requires the knowledge of the changes in reflectance resulting from physiological changes in the host as inflicted by the insect and the selection of equipment with the appropriate sensor characteristics. Laboratory-based reflectance measurements of infested and non-infested hemlock foliage collected from four sites in southern New Hampshire and Maine occurred biweekly over 6 months in 2012 and weekly over 5 weeks in 2013. Vegetation indices (red edge inflection point (REIP), normalized difference vegetation index (NDVI), moisture stress index (MSI), and near infrared (NIR) 3/1 ratio) were associated with concurrent chlorophyll and moisture content data. Infested first-year foliage contained greater concentrations of chlorophyll and moisture, resulting in reduced visible spectral reflectance, greater REIP and NDVI values, and lower MSI and NIR 3/1 values than non-infested foliage. Furthermore, fluorescence measurements indicated greater photosystem function during the early stages of infestation, suggesting a possible compensatory response by hemlock to infestation. Significant differences in reflectance between infested and non-infested foliage were observed in late June and July in the weeks immediately following HWA settlement on new growth. Implementing these observations during remote sensing mission planning may increase the likelihood of detecting early HWA infestation symptoms at landscape scales.
Central charge for the Schwarzschild black hole
Authors: Ropotenko K.
Published: January 2016

Proceeding in exactly the same way as in the derivation of the temperature of a dual CFT for the extremal black hole in the Kerr/CFT correspondence, it is found that the temperature of a chiral, dual CFT for the Schwarzschild black hole is [Formula: see text]. Comparing Cardy’s formula with the Bekenstein–Hawking entropy and using [Formula: see text], it is found that the central charge for the Schwarzschild black hole is of the form [Formula: see text], where [Formula: see text] is the intrinsic angular momentum of the black hole, [Formula: see text]. It is shown that the central charge for any four-dimensional (4D) extremal black hole is of the same form. The possible universality of this form is briefly discussed.
General relativity for N properties
Authors: Delbourgo Robert , Stack Paul D.
Published: January 2016

We determine the coefficients of the terms multiplying the gauge fields, gravitational field and cosmological term in a scheme whereby properties are characterized by N anticommuting scalar Grassmann variables. We do this for general N, using analytical methods; this obviates the need for our algebraic computing package which can become quite unwieldy as N is increased.
Carbon nanotube-based supercapacitors using low cost collectors
Authors: Amirhoseiny Maryam , Zandi Majid , Mosayyebi Abolghasem , Khademian Mehrzad
Published: January 2016

In this work, electrochemical double layer supercapacitors were fabricated using multiwalled carbon nanotube (MWCNT) composite microfilm as electrode. To improve the electrochemical properties, MWCNTs were functionalized with −COOH by acid treatments. CNT/PVA films have been deposited on different current collectors by spin coating to drastically enhance the electrode performance. Electrode fabrication involved various stages preparing of the CNT composite, and coating of the CNT/PVA paste on different substrates which also served as current collector. Al, Ni and graphite were used and compared as current collectors. The surface morphology of the fabricated electrodes was investigated with scanning electrode microscopy (SEM). Overall cell performance was evaluated with a multi-channel potentiostat/galvanostat analyzer. Each supercapacitor cell was subjected to charge–discharge cycling study at different current rates from 0.2[Formula: see text]Ag[Formula: see text] to 1[Formula: see text]Ag[Formula: see text]. The results showed that graphite-based electrodes offer advantages of significantly higher conductivity and superior capacitive behavior compared to thin film electrodes formed on Ni and Al current collectors. The specific capacitance of graphite based electrode is found to be 29[Formula: see text]Fg[Formula: see text].
Qualitative Upper and Lower Approximations of Complex Nonlinear Chaotic and Nonchaotic Models
Authors: Dohnal Mirko , Doubravsky Karel
Published: January 2016

Soft sciences, e.g. economics, ecology, sociology and their various integrations, are often used to develop e.g. forecasting models and optimization constraints. However, highly nonlinear, vague, partially inconsistent and multidimensional systems are prohibitively difficult to study at the quantitative level. Different types of quantitative simplifications are therefore used, e.g. linearization. The resulting models are oversimplified and therefore inapplicable results are often obtained. There are just three values used to quantify qualitative variables and their derivatives: plus/increasing; zero/constant; negative/decreasing. It means that a set of scenarios, i.e. the qualitative solution, is discrete. A qualitative model can be simplified by ignoring some of its equations. The simplified model is less restrictive and gives more scenarios. This set of scenarios is the model’s upper approximation. An additional equation makes the model more complex and the resulting set of fewer scenarios is the lower approximation. A qualitative model of dumped oscillations, upper and lower approximations of well-known Lorenz model and a vaguely known five-dimensional bankruptcy model are presented in detail. The upper approximation of the Lorenz set of differential equations has 213 and its lower approximation has 189 scenarios. No a priori knowledge of qualitative models theory is required.
Strong Li–Yorke Chaos for Time-Varying Discrete Dynamical Systems with A-Coupled-Expansion
Authors: Shao Hua , Shi Yuming , Zhu Hao
Published: January 2016

This paper is concerned with strong Li–Yorke chaos induced by [Formula: see text]-coupled-expansion for time-varying (i.e. nonautonomous) discrete systems in metric spaces. Some criteria of chaos in the strong sense of Li–Yorke are established via strict coupled-expansions for irreducible transition matrices in bounded and closed subsets of complete metric spaces and in compact subsets of metric spaces, respectively, where their conditions are weaker than those in the existing literature. One example is provided for illustration.
A New Reliable Numerical Method for Computing Chaotic Solutions of Dynamical Systems: The Chen Attractor Case
Authors: Lozi René , Pchelintsev Alexander N.
Published: January 2016

This paper describes a new reliable numerical method for computing chaotic solutions of dynamical systems and, in special cases, is applied to Chen strange attractor. The numerical precision of the computation is finely mastered. We introduce a modification of the method of power series for the construction of approximate solutions of the Chen system together with forward/backward control of the precision. As a test for the method, we obtained the region of convergence of series and researched the behavior of the trajectories on this attractor. The results of a numerical experiment are presented.