bluuebunny/crossref_metadata_2025 huggingface dataset:
A Nonsense Mutation in Mycobacterium marinum That Is Suppressible by a Novel Mechanism
Authors: Williams Emily A. , Mba Medie Felix , Bosserman Rachel E. , Johnson Benjamin K. , Reyna Cristal , Ferrell Micah J. , Champion Matthew M. , Abramovitch Robert B. , Champion Patricia A.
Published: October 2016

Mycobacterial pathogens use the ESAT-6 system 1 (Esx-1) exporter to promote virulence. Previously, we used gene disruption and complementation to conclude that the
MMAR_0039
gene in
Mycobacterium marinum
is required to promote Esx-1 export. Here we applied molecular genetics, proteomics, and whole-genome sequencing to demonstrate that the
MMAR_0039
gene is not required for Esx-1 secretion or virulence. These findings suggest that we initially observed an indirect mechanism of genetic complementation. We identified a spontaneous nonsense mutation in a known Esx-1-associated gene which causes a loss of Esx-1 activity. We show that the Esx-1 function was restored by nonsense suppression. Moreover, we identified a polar mutation in the
ppsC
gene which reduced cellular impermeability but did not impact cytotoxicity in macrophages. Our studies reveal insight into Esx-1 export, nonsense suppression, and cell envelope lipid biogenesis.
Tricellular Tight Junction Protein Tricellulin Is Targeted by the Enteropathogenic Escherichia coli Effector EspG1, Leading to Epithelial Barrier Disruption
Authors: Morampudi Vijay , Graef Franziska A. , Stahl Martin , Dalwadi Udit , Conlin Victoria S. , Huang Tina , Vallance Bruce A. , Yu Hong B. , Jacobson Kevan
Published: October 2016

Enteropathogenic
Escherichia coli
(EPEC)-induced diarrhea is often associated with disruption of intestinal epithelial tight junctions. Although studies have shown alterations in the expression and localization of bicellular tight junction proteins during EPEC infections, little is known about whether tricellular tight junction proteins (tTJs) are affected. Using Caco-2 cell monolayers, we investigated if EPEC is capable of targeting the tTJ protein tricellulin. Our results demonstrated that at 4 h postinfection, EPEC induced a significant reduction in tricellulin levels, accompanied by a significant loss of transepithelial resistance (TEER) and a corresponding increase in paracellular permeability. Conversely, cells overexpressing tricellulin were highly resistant to EPEC-induced barrier disruption. Confocal microscopy revealed the distribution of tricellulin into the plasma membrane of infected epithelial cells and confirmed the localization of EPEC aggregates in close proximity to tTJs. Moreover, infections with EPEC strains lacking genes encoding specific type III secreted effector proteins demonstrated a crucial role for the effector EspG1 in modulating tricellulin expression. Complementation studies suggest that the EspG-induced depletion of tricellulin is microtubule dependent. Overall, our results show that EPEC-induced epithelial barrier dysfunction is mediated in part by EspG1-induced microtubule-dependent depletion of tricellulin.
Null Mutations of Group A Streptococcus Orphan Kinase RocA: Selection in Mouse Infection and Comparison with CovS Mutations in Alteration of
In Vitro
and
In Vivo
Protease SpeB Expression and Virulence
Authors: Feng Wenchao , Minor Dylan , Liu Mengyao , Li Jinquan , Ishaq Suzanne L. , Yeoman Carl , Lei Benfang
Published: October 2016

Group A
Streptococcus
(GAS) acquires mutations of the virulence regulator CovRS in human and mouse infections, and these mutations result in the upregulation of virulence genes and the downregulation of the protease SpeB. To identify
in vivo
mutants with novel phenotypes, GAS isolates from infected mice were screened by enzymatic assays for SpeB and the platelet-activating factor acetylhydrolase Sse, and a new type of variant that had enhanced Sse expression and normal levels of SpeB production was identified (the variants had a phenotype referred to as enhanced Sse activity [Sse
A+
] and normal SpeB activity [SpeB
A+
]). Sse
A+
SpeB
A+
variants had transcript levels of CovRS-controlled virulence genes comparable to those of a
covS
mutant but had no
covRS
mutations. Genome resequencing of an Sse
A+
SpeB
A+
isolate identified a C605A nonsense mutation in orphan kinase gene
rocA
, and 6 other Sse
A+
SpeB
A+
isolates also had nonsense mutations or small indels in
rocA
. RocA and CovS mutants had similar levels of enhancement of the expression of CovRS-controlled virulence genes at the exponential growth phase; however, mutations of RocA but not mutations of CovS did not result in the downregulation of
speB
transcription at stationary growth phase or in subcutaneous infection of mice. GAS with RocA and CovS mutations caused greater enhancement of the expression of
hasA
than
spyCEP
in mouse skin infection than wild-type GAS did. RocA mutants ranked between wild-type GAS and CovS mutants in skin invasion, inhibition of neutrophil recruitment, and virulence in subcutaneous infection of mice. Thus, GAS RocA mutants can be selected in subcutaneous infections in mice and exhibit gene expression patterns and virulences distinct from those of CovS mutants. The findings provide novel information for understanding GAS fitness mutations
in vivo
, virulence gene regulation,
in vivo
gene expression, and virulence.
Suppressor Mutations LinkinggpsBwith the First Committed Step of Peptidoglycan Biosynthesis in Listeria monocytogenes
Authors: Rismondo Jeanine , Bender Jennifer K. , Halbedel Sven
Published: October 2016

The cell division protein GpsB is a regulator of the penicillin binding protein A1 (PBP A1) in the Gram-positive human pathogenListeria monocytogenes. Penicillin binding proteins mediate the last two steps of peptidoglycan biosynthesis as they polymerize and cross-link peptidoglycan strands, the main components of the bacterial cell wall. It is not known what other processes are controlled by GpsB.L. monocytogenesgpsBmutants are unable to grow at 42°C, but we observed that spontaneous suppressors correcting this defect arise on agar plates with high frequency. We here describe a first set ofgpsBsuppressors that mapped to theclpCandmurZgenes. While ClpC is the ATPase component of the Clp protease, MurZ is a paralogue of the listerial UDP–N-acetylglucosamine (UDP-GlcNAc) 1-carboxyvinyltransferase MurA. Both enzymes catalyze the enolpyruvyl transfer from phosphoenolpyruvate to UDP-GlcNAc, representing the first committed step of peptidoglycan biosynthesis. We confirmed that clean deletion of theclpCormurZgene suppressed the ΔgpsBphenotype. It turned out that the absence of either gene leads to accumulation of MurA, and we show that artificial overexpression of MurA alone was sufficient for suppression. Inactivation of other UDP-GlcNAc-consuming pathways also suppressed the heat-sensitive growth of the ΔgpsBmutant, suggesting that an increased influx of precursor molecules into peptidoglycan biosynthesis can compensate for the lack of GpsB. Our results support a model according to which PBP A1 becomes misregulated and thus toxic in the absence of GpsB due to unproductive consumption of cell wall precursor molecules.

IMPORTANCEThe late cell division protein GpsB is important for cell wall biosynthesis in Gram-positive bacteria. GpsB of the human pathogenL. monocytogenesinteracts with one of the key enzymes of this pathway, penicillin binding protein A1 (PBP A1), and influences its activity. PBP A1 catalyzes the last two steps of cell wall biosynthesis, but it is unknown how GpsB controls PBP A1. We observed that aL. monocytogenesgpsBmutant forms spontaneous suppressors and have mapped their mutations to genes mediating and influencing the first step of cell wall biosynthesis, likely stimulating the influx of metabolites into this pathway. We assume that GpsB is important to ensure productive incorporation of cell wall precursors into the peptidoglycan sacculus by PBP A1.
Genes Required for Bacillus anthracis Secondary Cell Wall Polysaccharide Synthesis
Authors: Oh So-Young , Lunderberg J. Mark , Chateau Alice , Schneewind Olaf , Missiakas Dominique
Published: October 2016

The secondary cell wall polysaccharide (SCWP) is thought to be essential for vegetative growth and surface (S)-layer assembly in
Bacillus anthracis
; however, the genetic determinants for the assembly of its trisaccharide repeat structure are not known. Here, we report that WpaA (BAS0847) and WpaB (BAS5274) share features with membrane proteins involved in the assembly of O-antigen lipopolysaccharide in Gram-negative bacteria and propose that WpaA and WpaB contribute to the assembly of the SCWP in
B. anthracis
. Vegetative forms of the
B. anthracis wpaA
mutant displayed increased lengths of cell chains, a cell separation defect that was attributed to mislocalization of the S-layer-associated murein hydrolases BslO, BslS, and BslT. The
wpaB
mutant was defective in vegetative replication during early logarithmic growth and formed smaller colonies. Deletion of both genes,
wpaA
and
wpaB
, did not yield viable bacilli, and when depleted of both
wpaA
and
wpaB
,
B. anthracis
could not maintain cell shape, support vegetative growth, or assemble SCWP. We propose that WpaA and WpaB fulfill overlapping glycosyltransferase functions of either polymerizing repeat units or transferring SCWP polymers to linkage units prior to LCP-mediated anchoring of the polysaccharide to peptidoglycan.

IMPORTANCE
The secondary cell wall polysaccharide (SCWP) is essential for
Bacillus anthracis
growth, cell shape, and division. SCWP is comprised of trisaccharide repeats (→4)-β-ManNAc-(1→4)-β-GlcNAc-(1→6)-α-GlcNAc-(1→) with α-Gal and β-Gal substitutions; however, the genetic determinants and enzymes for SCWP synthesis are not known. Here, we identify WpaA and WpaB and report that depletion of these factors affects vegetative growth, cell shape, and S-layer assembly. We hypothesize that WpaA and WpaB are involved in the assembly of SCWP prior to transfer of this polymer onto peptidoglycan.
Inflammation—a Critical Appreciation of the Role of Myeloid Cells
Authors: Iqbal Asif J. , Fisher Edward A. , Greaves David R.
Published: October 2016

What is inflammation’s big idea? In this brief overview of the role of myeloid cells in inflammation, we will critically discuss what drives the initiation, amplification, and resolution of inflammation in different anatomical sites in response to different pathological stimuli. It can be argued that we have a good understanding of the basic principles that underlie myeloid cell activation and the mobilization of innate immune cells to sites of injury and infection in acute inflammation. The challenge now for inflammation biologists is to understand how resolution of this normal physiological response goes wrong in hyperacute and chronic inflammation. A better understanding of how inflammation is regulated will allow us to develop new anti-inflammatory drugs that will reduce the burden of inflammatory disease without compromising the patient’s immune defenses against infectious disease. Ideally such drugs should encourage a return to homeostasis and enhance tissue repair processes.
Regulatory Issues Associated with Preharvest Food Safety: European Union Perspective
Authors: Alban Lis
Published: October 2016

Free movement of safe and wholesome food is an essential aspect of any society. This article contains an updated description of the regulatory issues associated with preharvest food safety within the European Union.
Salmonella
,
Campylobacter
,
Trichinella
, antimicrobial resistance, and bovine spongiform encephalopathy are dealt with in detail. Moreover,
Cysticercus bovis
/
Taenia saginata
,
Toxoplasma
,
Yersinia
, verotoxigenic/shigatoxigenic
Escherichia coli
,
Listeria
, and foodborne viruses are briefly covered. The article describes how the focus in the European Union is changing to involve a supply chain view with a focus on cost-effectiveness. The precautionary principle—as well as the use of private standards as an instrument to ensure compliance—is dealt with. In addition, actions in the pipeline are presented and discussed.
Diagnosing haemophagocytic syndrome
Authors: Sen Ethan S , Steward Colin G , Ramanan Athimalaipet V
Published: October 2016

Haemophagocytic syndrome, or haemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory disorder characterised by uncontrolled activation of the immune system. It can result from mutations in multiple genes involved in cytotoxicity or occur secondary to a range of infections, malignancies or autoimmune rheumatic diseases. In the latter case, it is also known as macrophage activation syndrome (MAS). Characteristic features are persistent fever, hepatosplenomegaly, petechial/purpuric rash, progressive cytopenias, coagulopathy, transaminitis, raised C reactive protein, falling erythrocyte sedimentation rate, hypertriglyceridaemia, hypofibrinogenaemia and extreme hyperferritinaemia often associated with multi-organ impairment. Distinguishing HLH from systemic sepsis can present a major challenge. Criteria for diagnosis and classification of HLH and MAS are available and a serum ferritin >10 000 µg/L is strongly supportive of HLH. Without early recognition and appropriate treatment, HLH is almost universally fatal. However, with prompt referral and advancements in treatment over the past two decades, outcomes have greatly improved.
Persistent urinary incontinence after a robot-assisted artificial urinary sphincter procedure: lessons learnt from two cases
Authors: Hervé François , Lumen Nicolaas , Goessaert An-Sofie , Everaert Karel
Published: October 2016

This case report describes 2 cases of persistent urinary incontinence in the beginning of the learning curve of robot-assisted bladder neck implantation of an artificial urinary sphincter (RA-AUS) in men at risk for erosion due to neurological lesions. Among a series of 4 RA-AUS, 2 patients still experienced urinary incontinence after surgery. A complete urological workup was strictly normal and did not show any device malfunction. However, during an AUS revision in these two patients, exploration revealed that the cuff was not tight enough. This issue was resolved by placing smaller cuffs. After re-do surgery, one of the two patients no longer had urinary incontinence, while the second patient was lost to follow-up. Insufficient tightness of the cuff could be explained by an inability of the surgeon to feel the force while pulling the cuff around the urethra due to the absence of haptic sensation in robotic surgery.
Visual disturbance with systemic symptoms: old lessons revisited
Authors: Hume Megan E , Fernandes Peter M , MacLean Kirsty , McRorie Euan , Davenport Richard
Published: October 2016

We describe a retired physician who presented with visual disturbance and systemic symptoms. The presence of general malaise, headache and scalp tenderness, with raised inflammatory markers, suggested that giant cell arteritis (GCA) was the likely diagnosis. Rapid response to initial steroid therapy and histological evidence of inflammation in the temporal artery supported this diagnosis. The character of these visual symptoms was, however, atypical for GCA. The patient, who had heart valve disease, subsequently deteriorated and developed further symptoms warranting investigation of bacterial endocarditis. Retinal emboli are a recognised complication of endocarditis, which could account for these visual symptoms. Moreover, interpretation of the temporal artery biopsy is limited in the context of existing steroid therapy. Our patient was consequently diagnosed with bacterial endocarditis. This case reminds us to consider the wider differential diagnoses for headache, visual disturbance and systemic symptoms, where echocardiogram and blood cultures may be crucial to reach the diagnosis.
Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial
Authors: Violato M , Dakin H , Chakravarthy U , Reeves B C , Peto T , Hogg R E , Harding S P , Scott L J , Taylor J , Cappel-Porter H , Mills N , O'Reilly D , Rogers C A , Wordsworth S
Published: October 2016

Objectives

To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals.

Design

A model-based cost-effectiveness analysis with a 4-week time horizon, based on a ‘virtual’ non-inferiority randomised trial designed to emulate a parallel group design.

Setting

A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics.

Participants

Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes.

Interventions

The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions.

Main outcome measures

Correct classification of whether further treatment is needed, compared with a reference standard.

Results

The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI −£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference −1.0%; 95% CI −4.5% to 2.5%).

Conclusions

In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the 2 care pathways are significant in economic terms.

Trial registration number

ISRCTN07479761; Pre-results.
Experiences and explanations of mental ill health in a group of devout Christians from the ethnic majority population in secular Sweden: a qualitative study
Authors: Lilja Aina , DeMarinis Valerie , Lehti Arja , Forssén Annika
Published: October 2016

Objective

To explore existential meaning-making in an ethnic-majority subgroup with mental ill health and to increase knowledge about the importance of gaining access to such information in mental healthcare.

Design

Qualitative study using in-depth interviews and systematic text condensation analysis.

Participants

17 devote Christians with an ethnic-Swedish background, 12 women and 5 men, 30–73 years old, from different congregations across Sweden, having sought medical care for mental ill health of any kind.

Setting

The secular Swedish society.

Results

A living, although asymmetric, relationship with God often was seen as the most important relationship, giving hope and support when ill, but creating feelings of abandonment and fear if perceived as threatened. Symptoms were interpreted through an existential framework influenced by their view of God. A perceived judging God increased feelings of guilt, sinfulness and shame. A perceived merciful God soothed symptoms and promoted recovery. Existential consequences, such as being unable to pray or participate in congregational rituals, caused feelings of ‘spiritual homelessness’. Participants gave biopsychosocial explanations of their mental ill health, consonant with and sometimes painfully conflicting with existential explanations, such as being attacked by demons. Three different patterns of interaction among biopsychosocial and existential dimensions in their explanatory systems of illness causation were identified: (a) comprehensive thinking and consensus; (b) division and parallel functions and (c) division and competitive functions.

Conclusions

Prevailing medical models for understanding mental ill health do not include the individual's existential experiences, which are important for identifying risk and protective factors as well as possible resources for recovery. The various expressions of existential meaning-making identified in this devout religious subgroup illustrate that existential information cannot be generalised, even within a small, seemingly homogenous group. The three identified patterns of interactions formed a typology that may be of use in clinical settings.
Impact of service redesign on the socioeconomic inequity in revascularisation rates for patients with acute myocardial infarction: a natural experiment and electronic record-linked cohort study
Authors: Evans Lloyd W , van Woerden Hugo , Davies Gareth R , Fone David
Published: October 2016

Aim

To investigate the impact of service redesign in the provision of revascularisation procedures on the historical socioeconomic inequity in revascularisation rates for patients with acute myocardial infarction (AMI).

Design

Natural experiment and retrospective cohort study using linked data sets in the Secure Anonymised Information Linkage databank.

Non-randomised intervention

An increase in the capacity of revascularisation procedures and service redesign in the provision of revascularisation in late 2011 to early 2012.

Setting

South Wales cardiac network, Census 2011 population 1 359 051 aged 35 years and over.

Participants

9128 participants admitted to an NHS hospital with a first AMI between 1 January 2010 and 30 June 2013, with 6-months follow-up.

Main outcome measure

Hazard ratios (HRs) for the time to revascularisation for deprivation quintiles, age, gender, comorbidities, rural–urban classification and revascularisation facilities of admitting hospital.

Results

In the preintervention period, there was a statistically significant decreased adjusted risk of revascularisation for participants in the most deprived quintile compared to the least deprived quintile (HR 0.80; 95% CI 0.69 to 0.92, p=0.002). In the postintervention period, the increase in revascularisation rates was statistically significant in all quintiles, and there was no longer any statistically significant difference in the adjusted revascularisation risk between the most and the least deprived quintile (HR 1.04; 95% CI 0.89 to 1.20, p<0.649). However, inequity persisted for those aged 75 years and over (HR 0.40; 95% CI 0.35 to 0.46, p<0.001) and women (HR 0.77; 95% CI 0.70 to 0.86, p<0.001).

Conclusions

Socioeconomic inequity of access to revascularisation was no longer apparent following redesign of revascularisation services in the south Wales cardiac network, although inequity persisted for women and those aged 75+ years. Increasing the capacity of revascularisation did not differentially benefit participants from the least deprived areas.
Desensitisation to cigarette package graphic health warnings: a cohort comparison between London and Singapore
Authors: Ratneswaran Culadeeban , Chisnall Ben , Li Mingyue , Tan Sarah , Douiri Abdel , Anantham Devanand , Steier Joerg
Published: October 2016

Objectives

We compared 2 sociocultural cohorts with different duration of exposure to graphic health warning labels (GHWL), to investigate a possible desensitisation to their use. We further studied how a differing awareness and emotional impact of smoking-associated risks could be used to prevent this.

Setting

Structured interviews of patients from the general respiratory department were undertaken between 2012 and 2013 in 2 tertiary hospitals in Singapore and London.

Participants

266 participants were studied, 163 Londoners (35% smokers, 54% male, age 52±18 years) and 103 Singaporeans (53% smokers, p=0.003; 78% male, p<0.001; age 58±15 years, p=0.012).

Main outcomes and measures

50 items assessed demographics, smoking history, knowledge and the deterring impact of smoking-associated risks. After showing 10 GHWL, the impact on emotional response, cognitive processing and intended smoking behaviour was recorded.

Results

Singaporeans scored lower than the Londoners across all label processing constructs, and this was consistent for the smoking and non-smoking groups. Londoners experienced more ‘disgust’ and felt GHWL were more effective at preventing initiation of, or quitting, smoking. Singaporeans had a lower awareness of lung cancer (82% vs 96%, p<0.001), despite ranking it as the most deterring consequence of smoking. Overall, ‘blindness’ was the least known potential risk (28%), despite being ranked as more deterring than ‘stroke’ and ‘oral cancer’ in all participants.

Conclusions

The length of exposure to GHWL impacts on the effectiveness. However, acknowledging the different levels of awareness and emotional impact of smoking-associated risks within different sociocultural cohorts could be used to maintain their impact.
Primary care interventions and current service innovations in modifying long-term outcomes after stroke: a protocol for a scoping review
Authors: Pindus Dominika M , Lim Lisa , Rundell A Viona , Hobbs Victoria , Aziz Noorazah Abd , Mullis Ricky , Mant Jonathan
Published: October 2016

Introduction

Interventions delivered by primary and/or community care have the potential to reach the majority of stroke survivors and carers and offer ongoing support. However, an integrative account emerging from the reviews of interventions addressing specific long-term outcomes after stroke is lacking. The aims of the proposed scoping review are to provide an overview of: (1) primary care and community healthcare interventions by generalist healthcare professionals to stroke survivors and/or their informal carers to address long-term outcomes after stroke, (2) the scope and characteristics of interventions which were successful in addressing long-term outcomes, and (3) developments in current clinical practice.

Methods and analysis

Studies that focused on adult community dwelling stroke survivors and informal carers were included. Academic electronic databases will be searched to identify reviews of randomised controlled trials (RCTs) and controlled trials, trials from the past 5 years; reviews of observational studies. Practice exemplars from grey literature will be identified through advanced Google search. Reports, guidelines and other documents of major health organisations, clinical professional bodies, and stroke charities in the UK and internationally will be included. Two reviewers will independently screen titles, abstracts and full texts for inclusion of published literature. One reviewer will screen search results from the grey literature and identify relevant documents for inclusion. Data synthesis will include analysis of the number, type of studies, year and country of publication, a summary of intervention components/service or practice, outcomes addressed, main results (an indicator of effectiveness) and a description of included interventions.

Ethics and dissemination

The review will help identify components of care and care pathways for primary care services for stroke. By comparing the results with stroke survivors' and carers' needs identified in the literature, the review will highlight potential gaps in research and practice relevant to long-term care after stroke.
Radiation-related anxiety among public health nurses in the Fukushima Prefecture after the accident at the Fukushima Daiichi Nuclear Power Station: a cross-sectional study
Authors: Yoshida Koji , Orita Makiko , Goto Aya , Kumagai Atsushi , Yasui Kiyotaka , Ohtsuru Akira , Hayashida Naomi , Kudo Takashi , Yamashita Shunichi , Takamura Noboru
Published: October 2016

Objective

In Japan, public health nurses (PHNs) play important roles in managing the health of local residents, especially after a disaster. In this study, we assessed radiation anxiety and the stress processing capacity of PHNs in the Fukushima Prefecture in Japan, after the accident at the Fukushima Daiichi Nuclear Power Station (FDNPS).

Methods

We conducted a questionnaire survey among the PHNs (n=430) in July of 2015 via postal mail. The questions included demographic factors (sex, age and employment position), knowledge about radiation, degree of anxiety about radiation at the time of the FDNPS accident (and at present), by asking them to answer questions about radiation and the Sense of Coherence-13 (SOC-13). We classified the low and high levels of anxiety by asking them to answer questions about radiation, and compared the anxiety-negative (−) group with the anxiety-positive (+) group.

Results

Of the PHNs, 269 (62.6%) were classified in the anxiety (−) group and 161 (37.4%) were in the anxiety (+) group. When the multivariate logistic regression analysis was conducted, the PHNs at the time of the accident (OR: 2.37, p=0.007), current general anxieties about radiation (OR: 3.56, p<0.001), current possession of materials to obtain knowledge about radiation (OR: 2.11, p=0.006) and knowledge of the childhood thyroid cancer increase after the Chernobyl accident (OR: 1.69, p=0.035) were significantly associated with anxiety after the FDNPS accident. The mean SOC-13 was 43.0±7.7, with no significant difference between the anxiety (−) group and anxiety (+) group (p=0.47).

Conclusions

Our study suggested that anxiety about radiation was associated with materials and knowledge about radiation in the PHNs in the Fukushima Prefecture 4 years after the FDNPS accident. It is important for PHNs to obtain knowledge and teaching materials about radiation, and radiation education programmes for PHNs must be established in areas that have nuclear facilities.
Prenatal sex selection and female infant mortality are more common in India after firstborn and second-born daughters
Authors: Gellatly Corry , Petrie Marion
Published: October 2016

Background

The Indian sex ratio has become highly male-biased in recent decades. This may be attributed to prenatal sex selection (PSS) and excess female infant mortality. However, the question of whether these factors are related has not been adequately studied. Here we examine whether increased use of PSS may offset excess female infant mortality, by reducing the number of ‘unwanted’ daughters being born.

Methods

We analyse the National Family Health Survey (NHFS) data sets for India, which contain nationally representative samples of birth histories for women aged 15–49, interviewed in 1992–1993, 1998–1999 and 2005–2006. We test for missing female births at the second and third birth order, by analysis of the frequencies of sibling sex combinations, and examine the mortality differential between male and female infants, controlling for household wealth and sex(es) of older siblings.

Results

PSS was used most in wealthier households at the second and third birth order, when the firstborn, or firstborn and second-born, siblings were female. Having preceding female siblings was a significant risk factor for female infant mortality, but was not correlated with household wealth.

Conclusions

PSS and female infant mortality increase with the presence of older female siblings, yet we find no evidence that increasing use of PSS prevents female infant mortality, because PSS and the proportion of female infant mortality attributable to having older sisters increased over the study period. Increased pressure on higher birth order females caused by the trend towards smaller family sizes may explain this.
Calcipotriol Inhibits Proliferation of Human Keratinocytes by Downregulating Stat1 and Stat3 Signaling
Authors: Liang Wenli , Lin Zigang , Zhang Li , Qin Xuan , Zhang Yuan , Sun Ledong
Published: October 2016

Psoriasis is an autoimmune disease, which is characterized by aberrantly high levels of inflammation, but the underlying pathogenic mechanisms are still not fully understood. Signal transducer and activator of transcription 1 (STAT1) and STAT3, and the downstream proteins suppressor of cytokine signaling 1 (SOCS1) and SOCS3, have been implicated in psoriasis disease progression. Calcipotriol, a synthetic derivative of vitamin D, has been used clinically to treat psoriasis, but the mechanism of action that underlies the beneficial effects of calcipotriol is still being explored. The objective of this study was to determine whether STAT1 and STAT3 signaling is involved in calcipotriol treatment. Using an in vitro immortal human keratinocyte cell line, HaCaT cells, as a psoriasis model, we examined the molecular signaling induced by calcipotriol treatment. We found that calcipotriol treatment or silencing of either STAT1 or STAT3 inhibited proliferation of HaCaT cells. Calcipotriol downregulated the expression of STAT1 and STAT3 at the messenger RNA (mRNA) and protein levels. The levels of phosphorylated STAT1 and STAT3 were also decreased, suggesting calcipotriol treatment inhibited STAT1 and STAT3 activation. Calcipotriol-mediated STAT inhibition was further substantiated by the downregulation of SOCS1 and SOCS3 at the mRNA and protein expression levels. Taken together, our results suggest a novel molecular mechanism for calcipotriol-mediated treatment effects in psoriasis.
Patterns of acute oncology admissions: an exploratory analysis of over 7000 patient episodes
Authors: Neville-Webbe Helen L , Wong Helen , Marshall Ernie
Published: October 2016

Background

Following the National Chemotherapy Advisory Group report, calling for better management of patients with cancer admitted acutely to hospital, Clatterbridge Cancer Centre, with Merseyside and Cheshire Cancer Network, implemented an acute oncology service (AOS) for the region's seven acute trusts.

Study design

We prospectively collected data on all referrals from March 2010 to December 2012, seen by the seven local teams within the cancer network.

Results

Over 7000 patient-episodes were analyzed. We found an AOS has the greatest impact on reducing hospital stay of patients admitted with complications of cancer treatment, compared with patients presenting with cancer symptoms, or those presenting with a new cancer as an emergency. Also an AOS significantly reduces the mortality rate of patients admitted with complications of cancer treatment, compared with patients presenting with cancer symptoms, either of a known cancer or those patients presenting with a new cancer as an emergency.

Conclusions

Our network establishment of an AOS has had a positive impact on the quality of care cancer patients receive, in addition to saving local trusts valuable bed days, due to the overall reduction in hospital stay. This study also highlights deficiencies in the cancer journeys of certain patients with cancer, such as patients who present with a new cancer as an emergency admission, or patients unable to be discharged due to a lack of community resources. Such analysis is important in highlighting where the AOS can concentrate resources and collaborate with other healthcare professionals, especially within the local community.
Diagnostic evaluation and treatment of a Chinese crocodile lizard (Shinisaurus crocodilurus) with seizures
Authors: Brady Sean , Harrison Tara , Williams Colette , Evola Maria , Wack Raymund F
Published: October 2016

An 11‐year‐old female Chinese crocodile lizard (Shinisaurus crocodilurus) with presumed seizures was examined. Complete blood count, plasma biochemistry and MRI did not identify a cause of seizures and thus cryptogenic epilepsy was diagnosed. Electroencephalogram (EEG) was performed on the affected lizard and a healthy conspecific, revealing a lack of normal background electrical activity in the affected individual compared with the normal individual. The patient was treated with oral phenobarbital and serum phenobarbital levels were routinely measured. Although phenobarbital was an effective antiepileptic drug, the patient's clinical condition worsened and the lizard was humanely euthanased after 70 days of therapy. Postmortem examination and histopathology did not identify a cause for the seizures. This is the first description of seizures, MRI, EEG and seizure treatment in a Chinese crocodile lizard.
CASSCF-based explicit ligand field models clarify the ground state electronic structures of transition metal phthalocyanines (MPc; M = Mn, Fe, Co, Ni, Cu, Zn)
Authors: Wallace Andrew J. , Williamson Bryce E. , Crittenden Deborah L.
Published: October 2016

Multireference electronic structure methods are used to assign ground state electronic configurations for a series of metallophthalocyanines. Ligand orbital occupancies remain constant across the period and are consistent with a formal 2– charge on the ligand. The d electron configurations of some metallophthalocyanines are straightforward and can be unambiguously assigned, (dxy)2(dxz,dyz)2,2( [Formula: see text])2([Formula: see text])n, with n = 2, 1, 0, respectively, for ZnPc, CuPc, and NiPc. Controversies over ground state electronic structure assignments for other metallophthalocyanines arise due to multiple complicating factors: accidental near-degeneracies, environmental effects, and different ligand field models used in interpreting experimental spectra. We demonstrate that explicit ligand field models provide more reliable and consistent interpretations of experimental data than implicit, parameterized alternatives. On this basis, we assign gas-phase electronic ground states for MnPc, (dxy)2(dxz,dyz)1,1([Formula: see text])1 and CoPc, (dxy)2(dxz,dyz)2,2([Formula: see text])1, and show that the ground state of FePc cannot be resolved to a single state, with two near-degenerate states that are likely spin-orbit coupled: (dxy)2(dxz,dyz)1,1( [Formula: see text])2 and (dxy)2(dxz,dyz)2,1([Formula: see text])1. Remaining differences between computational predictions and experimental observations are small and may be ascribed primarily to environmental effects but are also partly due to incomplete modelling of electron correlation.
Vacuum energy through Krein quantization approach
Authors: Pirmoradian R. , Tavakoli F.
Published: October 2016

In this paper, we consider a new version of indefinite metric field quantization called “Krein” quantization approach. Centering on the vacuum energy, fundamental subjects revolving around this concept will be discussed. In this approach, vacuum expectation value of the energy–momentum tensor can be defined properly and uniquely. Actually, no infinite term appears and the vacuum energy of the free field vanishes. These properties allow us to propose a discussion that creates an interesting link to the cosmological constant problem. Achieving this goal, however, necessitates consistency of the theory with conventional ones, so we have studied and made comparison with essential issues, such as unitarity of the theory, physical achievements of renormalizing process, and the trace anomaly subject.
Priming of a DNA metabarcoding approach for species identification and inventory in marine macrobenthic communities
Authors: Hollatz Claudia , Leite Barbara R. , Lobo Jorge , Froufe Hugo , Egas Conceição , Costa Filipe O.
Published: October 2016

In marine and estuarine benthic communities, the inventory and estimation of species richness are often hampered by the need for broad taxonomic expertise across several phyla. The use of DNA metabarcoding has emerged as a powerful tool for the fast assessment of species composition in a diversity of ecological communities. Here, we tested the amplification success of five primer sets targeting different COI-5P regions by 454 pyrosequencing to maximize the recovery of two simulated macrobenthic communities containing 21 species (SimCom1 and SimCom 2). Species identification was first performed against a compiled reference library of macrobenthic species. Reads with similarity results to reference sequences between 70% and 97% were then submitted to GenBank and BOLD to attempt the identification of concealed species in the bulk sample. The combination of at least three primer sets was able to recover more species than any primer set alone, achieving 85% of represented species in SimCom1 and 76% in SimCom2. Our approach was successful to detect low-frequency specimens, as well as concealed species, in the bulk sample, indicating the potential for the application of this approach on marine bioassessment and inventory, including the detection of “hidden” biodiversity that would hardly be possible based on morphology only.
The Role of Thalamus Versus Cortex in Epilepsy: Evidence from Human Ictal Centromedian Recordings in Patients Assessed for Deep Brain Stimulation
Authors: Martín-López David , Jiménez-Jiménez Diego , Cabañés-Martínez Lidia , Selway Richard P. , Valentín Antonio , Alarcón Gonzalo
Published: October 2016

Background: The onset of generalized seizures is a long debated subject in epilepsy. The relative roles of cortex and thalamus in initiating and maintaining the different seizure types are unclear. Objective: The purpose of the study is to estimate whether the cortex or the centromedian thalamic nucleus is leading in initiating and maintaining seizures in humans. Methods: We report human ictal recordings with simultaneous thalamic and cortical electrodes from three patients without anesthesia being assessed for deep brain stimulation (DBS). Patients 1 and 2 had idiopathic generalized epilepsy whereas patient 3 had frontal lobe epilepsy. Visual inspection was combined with nonlinear correlation analysis. Results: In patient 1, seizure onset was bilateral cortical and the belated onset of leading thalamic discharges was associated with an increase in rhythmicity of discharges, both in thalamus and cortex. In patient 2, we observed bilateral independent interictal discharges restricted to the thalamus. However, ictal onset was diffuse, with discharges larger in the cortex even though they were led by the thalamus. In patient 3, seizure onset was largely restricted to frontal structures, with belated lagging thalamic involvement. Conclusion: In human generalized seizures, the thalamus may become involved early or late in the seizure but, once it becomes involved, it leads the cortex. In contrast, in human frontal seizures the thalamus gets involved late in the seizure and, once it becomes involved, it lags behind the cortex. In addition, the centromedian nucleus of the thalamus is capable of autonomous epileptogenesis as suggested by the presence of independent focal unilateral epileptiform discharges restricted to thalamic structures. The thalamus may also be responsible for maintaining the rhythmicity of ictal discharges.
Coriandrum sativumSuppresses Aβ42-Induced ROS Increases, Glial Cell Proliferation, and ERK Activation
Authors: Liu Quan Feng , Jeong Haemin , Lee Jang Ho , Hong Yoon Ki , Oh Youngje , Kim Young-Mi , Suh Yoon Seok , Bang Semin , Yun Hye Sup , Lee Kyungho , Cho Sung Man , Lee Sung Bae , Jeon Songhee , Chin Young-Won , Koo Byung-Soo , Cho Kyoung Sang
Published: October 2016

Alzheimer’s disease (AD), the most common neurodegenerative disease, has a complex and widespread pathology that is characterized by the accumulation of amyloid [Formula: see text]-peptide (A[Formula: see text]) in the brain and various cellular abnormalities, including increased oxidative damage, an amplified inflammatory response, and altered mitogen-activated protein kinase signaling. Based on the complex etiology of AD, traditional medicinal plants with multiple effective components are alternative treatments for patients with AD. In the present study, we investigated the neuroprotective effects of an ethanol extract of Coriandrum sativum (C. sativum) leaves on A[Formula: see text] cytotoxicity and examined the molecular mechanisms underlying the beneficial effects. Although recent studies have shown the benefits of the inhalation of C. sativum oil in an animal model of AD, the detailed molecular mechanisms by which C. sativum exerts its neuroprotective effects are unclear. Here, we found that treatment with C. sativum extract increased the survival of both A[Formula: see text]-treated mammalian cells and [Formula: see text]42-expressing flies. Moreover, C. sativum extract intake suppressed [Formula: see text]-induced cell death in the larval imaginal disc and brain without affecting A[Formula: see text]42 expression and accumulation. Interestingly, the increases in reactive oxygen species levels and glial cell number in AD model flies were reduced by C. sativum extract intake. Additionally, C. sativum extract inhibited the epidermal growth factor receptor- and A[Formula: see text]-induced phosphorylation of extracellular signal-regulated kinase (ERK). The constitutively active form of ERK abolished the protective function of C. sativum extract against the [Formula: see text]-induced eye defect phenotype in Drosophila. Taken together, these results suggest that C. sativum leaves have antioxidant, anti-inflammatory, and ERK signaling inhibitory properties that are beneficial for patients with AD.
Tetrahydroxystilbene Glucoside Inhibits Excessive Autophagy and Improves Microvascular Endothelial Dysfunction in Prehypertensive Spontaneously Hypertensive Rats
Authors: Dong Qianqian , Xing Wenjuan , Fu Feng , Liu Zhenghua , Wang Jie , Liang Xiangyan , Zhou Xuanxuan , Yang Qian , Zhang Wei , Gao Feng , Wang Siwang , Zhang Haifeng
Published: October 2016

Autophagy exists in vascular endothelial cells, but the relationship between autophagy and blood vessel dysfunction in hypertension remains elusive. This study aimed to investigate role of autophagy in vascular endothelial dysfunction in prehypertension and hypertension and the underlying mechanisms involved. Furthermore, we sought to determine if and how tetrahydroxystilbene glucoside (TSG), a resveratrol analogue and active ingredient of Polygonum multiflorum Thunb used for its cardiovascular protective properties in traditional Chinese medicine, influences vascular endothelial function. Male spontaneously hypertensive rats (SHRs) aged 4 weeks (young) and 12 weeks (adult) were studied and the vascular function of isolated aorta and mesenteric artery was assessed in vitro. Compared with Wistar Kyoto rats (WKY), young and adult SHRs showed endothelial dysfunction of the aorta and mesenteric artery, along with decreased pAkt, pmTOR, and autophagic marker protein p62 and increased LC3 II/I in microvascular but not aortic tissues. TSG administration for 14 days significantly improved mesenteric vascular endothelial function, increased levels of pAkt and pmTOR, and decreased autophagy. Pretreatment of young SHRs with the mTOR inhibitor rapamycin blocked the antiautophagic and vasodilative effects of TSG. Moreover, TSG significantly activated Akt-mTOR signaling in HUVECs and reduced the autophagic levels in vitro, which were almost completely blocked by rapamycin. In summary, mesenteric endothelial dysfunction in prehypertensive SHRs was at least partly attributable to excessive autophagy in vascular tissues. TSG partly restored microvascular endothelial dysfunction through activating the Akt/mTOR pathway, which consequently suppressed autophagy, indicating that TSG could be potentially applied to protect vascular function against subclinical changes in prehypertension.
Strongly prime ideals and strongly zero-dimensional rings
Authors: Gottlieb Christian
Published: October 2016

A prime ideal [Formula: see text] is said to be strongly prime if whenever [Formula: see text] contains an intersection of ideals, [Formula: see text] contains one of the ideals in the intersection. A commutative ring with this property for every prime ideal is called strongly zero-dimensional. Some equivalent conditions are given and it is proved that a zero-dimensional ring is strongly zero-dimensional if and only if the ring is quasi-semi-local. A ring is called strongly [Formula: see text]-regular if in each ideal [Formula: see text], there is an element [Formula: see text] such that [Formula: see text] for all [Formula: see text]. Connections between the concepts strongly zero-dimensional and strongly [Formula: see text]-regular are considered.