bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering of Bacteriophages Y2::
dpoL1-C
and Y2::
luxAB
for Efficient Control and Rapid Detection of the Fire Blight Pathogen, Erwinia amylovora
Authors: Born Yannick , Fieseler Lars , Thöny Valentin , Leimer Nadja , Duffy Brion , Loessner Martin J.
Published: April 2017

Erwinia amylovora
is the causative agent of fire blight, a devastating plant disease affecting members of the
Rosaceae
. Alternatives to antibiotics for control of fire blight symptoms and outbreaks are highly desirable, due to increasing drug resistance and tight regulatory restrictions. Moreover, the available diagnostic methods either lack sensitivity, lack speed, or are unable to discriminate between live and dead bacteria. Owing to their extreme biological specificity, bacteriophages are promising alternatives for both aims. In this study, the virulent broad-host-range
E. amylovora
virus Y2 was engineered to enhance its killing activity and for use as a luciferase reporter phage, respectively. Toward these aims, a depolymerase gene of
E. amylovora
virus L1 (
dpoL1-C
) or a bacterial
luxAB
fusion was introduced into the genome of Y2 by homologous recombination. The genes were placed downstream of the major capsid protein
orf68
, under the control of the native promoter. The modifications did not affect viability of infectivity of the recombinant viruses. Phage Y2::
dpoL1-C
demonstrated synergistic activity between the depolymerase degrading the exopolysaccharide capsule and phage infection, which greatly enhanced bacterial killing. It also significantly reduced the ability of
E. amylovora
to colonize the surface of detached flowers. The reporter phage Y2::
luxAB
transduced bacterial luciferase into host cells and induced synthesis of large amounts of a LuxAB luciferase fusion. After the addition of aldehyde substrate, bioluminescence could be readily monitored, and this enabled rapid and specific detection of low numbers of viable bacteria, without enrichment, both
in vitro
and in plant material.

IMPORTANCE
Fire blight, caused by
Erwinia amylovora
, is the major threat to global pome fruit production, with high economic losses every year. Bacteriophages represent promising alternatives to not only control the disease, but also for rapid diagnostics. To enhance biocontrol efficacy, we combined the desired properties of two phages, Y2 (broad host range) and L1 (depolymerase for capsule degradation) in a single recombinant phage. This phage showed enhanced biocontrol and could reduce
E. amylovora
on flowers. Phage Y2 was also genetically engineered into a luciferase reporter phage, which transduces bacterial bioluminescence into infected cells and allows detection of low numbers of viable target bacteria. The combination of speed, sensitivity, and specificity is superior to previously used diagnostic methods. In conclusion, genetic engineering could improve the properties of phage Y2 toward better killing efficacy and sensitive detection of
E. amylovora
cells.
Acid Evolution of Escherichia coli K-12 Eliminates Amino Acid Decarboxylases and Reregulates Catabolism
Authors: He Amanda , Penix Stephanie R. , Basting Preston J. , Griffith Jessie M. , Creamer Kaitlin E. , Camperchioli Dominic , Clark Michelle W. , Gonzales Alexandra S. , Chávez Erazo Jorge Sebastian , George Nadja S. , Bhagwat Arvind A. , Slonczewski Joan L.
Published: April 2017

Acid-adapted strains of
Escherichia coli
K-12 W3110 were obtained by serial culture in medium buffered at pH 4.6 (M. M. Harden, A. He, K. Creamer, M. W. Clark, I. Hamdallah, K. A. Martinez, R. L. Kresslein, S. P. Bush, and J. L. Slonczewski, Appl Environ Microbiol 81:1932–1941, 2015,
https://doi.org/10.1128/AEM.03494-14
). Revised genomic analysis of these strains revealed insertion sequence (IS)-driven insertions and deletions that knocked out regulators CadC (acid induction of lysine decarboxylase), GadX (acid induction of glutamate decarboxylase), and FNR (anaerobic regulator). Each acid-evolved strain showed loss of one or more amino acid decarboxylase systems, which normally help neutralize external acid (pH 5 to 6) and increase survival in extreme acid (pH 2). Strains from populations B11, H9, and F11 had an IS
5
insertion or IS-mediated deletion in
cadC
, while population B11 had a point mutation affecting the arginine activator
adiY
. The
cadC
and
adiY
mutants failed to neutralize acid in the presence of exogenous lysine or arginine. In strain B11-1, reversion of an
rpoC
(RNA polymerase) mutation partly restored arginine-dependent neutralization. All eight strains showed deletion or downregulation of the Gad acid fitness island. Strains with the Gad deletion lost the ability to produce GABA (gamma-aminobutyric acid) and failed to survive extreme acid. Transcriptome sequencing (RNA-seq) of strain B11-1 showed upregulated genes for catabolism of diverse substrates but downregulated acid stress genes (the biofilm regulator
ariR
,
yhiM
, and Gad). Other strains showed downregulation of H
2
consumption mediated by hydrogenases (
hya
and
hyb
) which release acid. Strains F9-2 and F9-3 had a deletion of
fnr
and showed downregulation of FNR-dependent genes (
dmsABC
,
frdABCD
,
hybABO
,
nikABCDE
, and
nrfAC
). Overall, strains that had evolved in buffered acid showed loss or downregulation of systems that neutralize unbuffered acid and showed altered regulation of catabolism.

IMPORTANCE
Experimental evolution of an enteric bacterium under a narrow buffered range of acid pH leads to loss of genes that enhance fitness above or below the buffered pH range, including loss of enzymes that may raise external pH in the absence of buffer. Prominent modes of evolutionary change involve IS-mediated insertions and deletions that knock out key regulators. Over generations of acid stress, catabolism undergoes reregulation in ways that differ for each evolving strain.
Pumilacidin-Like Lipopeptides Derived from Marine Bacterium Bacillus sp. Strain 176 Suppress the Motility of Vibrio alginolyticus
Authors: Xiu Pengyuan , Liu Rui , Zhang Dechao , Sun Chaomin
Published: April 2017

Bacterial motility is a crucial factor during the invasion and colonization processes of pathogens, which makes it an attractive therapeutic drug target. Here, we isolated a marine bacterium (
Vibrio alginolyticus
strain 178) from a seamount in the tropical West Pacific that exhibits vigorous motility on agar plates and severe pathogenicity to zebrafish. We found that
V. alginolyticus
178 motility was significantly suppressed by another marine bacterium,
Bacillus
sp. strain 176, isolated from the same niche. We isolated, purified, and characterized two different cyclic lipopeptides (CLPs) from
Bacillus
sp. 176 using high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. The two related CLPs have a pumilacidin-like structure and were both effective inhibitors of
V. alginolyticus
178 motility. The CLPs differ by only one methylene group in their fatty acid chains. In addition to motility suppression, the CLPs also induced cell aggregation in the medium and reduced adherence of
V. alginolyticus
178 to glass substrates. Notably, upon CLP treatment, the expression levels of two
V. alginolyticus
flagellar assembly genes (
flgA
and
flgP
) dropped dramatically. Moreover, the CLPs inhibited biofilm formation in several other strains of pathogenic bacteria without inducing cell death. This study indicates that CLPs from
Bacillus
sp. 176 show promise as antimicrobial lead compounds targeting bacterial motility and biofilm formation with a low potential for eliciting antibiotic resistance.

IMPORTANCE
Pathogenic bacteria often require motility to establish infections and subsequently spread within host organisms. Thus, motility is an attractive therapeutic target for the development of novel antibiotics. We found that cyclic lipopeptides (CLPs) produced by marine bacterium
Bacillus
sp. strain 176 dramatically suppress the motility of the pathogenic bacterium
Vibrio alginolyticus
strain 178, reduce biofilm formation, and promote cellular aggregation without inducing cell death. These findings suggest that CLPs hold great promise as potential drug candidates targeting bacterial motility and biofilm formation with a low overall potential for triggering antibiotic resistance.
Nitrous Oxide Reduction by an Obligate Aerobic Bacterium, Gemmatimonas aurantiaca Strain T-27
Authors: Park Doyoung , Kim Hayeon , Yoon Sukhwan
Published: April 2017

N
2
O-reducing organisms with nitrous oxide reductases (NosZ) are known as the only biological sink of N
2
O in the environment. Among the most abundant
nosZ
genes found in the environment are
nosZ
genes affiliated with the understudied
Gemmatimonadetes
phylum. In this study, a unique regulatory mechanism of N
2
O reduction in
Gemmatimonas aurantiaca
strain T-27, an isolate affiliated with the
Gemmatimonadetes
phylum, was examined. Strain T-27 was incubated with N
2
O and/or O
2
as the electron acceptor. Significant N
2
O reduction was observed only when O
2
was initially present. When batch cultures of strain T-27 were amended with O
2
and N
2
O, N
2
O reduction commenced after O
2
was depleted. In a long-term incubation with the addition of N
2
O upon depletion, the N
2
O reduction rate decreased over time and came to an eventual stop. Spiking of the culture with O
2
resulted in the resuscitation of N
2
O reduction activity, supporting the hypothesis that N
2
O reduction by strain T-27 required the transient presence of O
2
. The highest level of
nosZ
transcription (8.97
nosZ
transcripts/
recA
transcript) was observed immediately after O
2
depletion, and transcription decreased ∼25-fold within 85 h, supporting the observed phenotype. The observed difference between responses of strain T-27 cultures amended with and without N
2
O to O
2
starvation suggested that N
2
O helped sustain the viability of strain T-27 during temporary anoxia, although N
2
O reduction was not coupled to growth. The findings in this study suggest that obligate aerobic microorganisms with
nosZ
genes may utilize N
2
O as a temporary surrogate for O
2
to survive periodic anoxia.

IMPORTANCE
Emission of N
2
O, a potent greenhouse gas and ozone depletion agent, from the soil environment is largely determined by microbial sources and sinks. N
2
O reduction by organisms with N
2
O reductases (NosZ) is the only known biological sink of N
2
O at environmentally relevant concentrations (up to ∼1,000 parts per million by volume [ppmv]). Although a large fraction of
nosZ
genes recovered from soil is affiliated with
nosZ
found in the genomes of the obligate aerobic phylum
Gemmatimonadetes
, N
2
O reduction has not yet been confirmed in any of these organisms. This study demonstrates that N
2
O is reduced by an obligate aerobic bacterium,
Gemmatimonas aurantiaca
strain T-27, and suggests a novel regulation mechanism for N
2
O reduction in this organism, which may also be applicable to other obligate aerobic organisms possessing
nosZ
genes. We expect that these findings will significantly advance the understanding of N
2
O dynamics in environments with frequent transitions between oxic and anoxic conditions.
Microbiota in Exhaled Breath Condensate and the Lung
Authors: Glendinning Laura , Wright Steven , Tennant Peter , Gill Andrew C. , Collie David , McLachlan Gerry
Published: April 2017

The lung microbiota is commonly sampled using relatively invasive bronchoscopic procedures. Exhaled breath condensate (EBC) collection potentially offers a less invasive alternative for lung microbiota sampling. We compared lung microbiota samples retrieved by protected specimen brushings (PSB) and exhaled breath condensate collection. We also sought to assess whether aerosolized antibiotic treatment would influence the lung microbiota and whether this change could be detected in EBC. EBC was collected from 6 conscious sheep and then from the same anesthetized sheep during mechanical ventilation. Following the latter EBC collection, PSB samples were collected from separate sites within each sheep lung. On the subsequent day, each sheep was then treated with nebulized colistimethate sodium. Two days after nebulization, EBC and PSB samples were again collected. Bacterial DNA was quantified using 16S rRNA gene quantitative PCR. The V2-V3 region of the 16S rRNA gene was amplified by PCR and sequenced using Illumina MiSeq. Quality control and operational taxonomic unit (OTU) clustering were performed with mothur. The EBC samples contained significantly less bacterial DNA than the PSB samples. The EBC samples from anesthetized animals clustered separately by their bacterial community compositions in comparison to the PSB samples, and 37 bacterial OTUs were identified as differentially abundant between the two sample types. Despite only low concentrations of colistin being detected in bronchoalveolar lavage fluid, PSB samples were found to differ by their bacterial compositions before and after colistimethate sodium treatment. Our findings indicate that microbiota in EBC samples and PSB samples are not equivalent.

IMPORTANCE
Sampling of the lung microbiota usually necessitates performing bronchoscopic procedures that involve a hospital visit for human participants and the use of trained staff. The inconvenience and perceived discomfort of participating in this kind of research may deter healthy volunteers and may not be a safe option for patients with advanced lung disease. This study set out to evaluate a less invasive method for collecting lung microbiota samples by comparing samples taken via protected specimen brushings (PSB) to those taken via exhaled breath condensate (EBC) collection. We found that there was less bacterial DNA in EBC samples compared with that in PSB samples and that there were differences between the bacterial communities in the two sample types. We conclude that while EBC and PSB samples do not produce equivalent microbiota samples, the study of the EBC microbiota may still be of interest.
Holotrichia oblita Midgut Proteins That Bind to Bacillus thuringiensis Cry8-Like Toxin and Assembly of the H. oblita Midgut Tissue Transcriptome
Authors: Jiang Jian , Huang Ying , Shu Changlong , Soberón Mario , Bravo Alejandra , Liu Chunqing , Song Fuping , Lai Jinsheng , Zhang Jie
Published: April 2017

The
Bacillus thuringiensis
strain HBF-18 (CGMCC 2070), containing two
cry
genes (
cry8
-like and
cry8Ga
), is toxic to
Holotrichia oblita
larvae. Both Cry8-like and Cry8Ga proteins are active against this insect pest, and Cry8-like is more toxic. To analyze the characteristics of the binding of Cry8-like and Cry8Ga proteins to brush border membrane vesicles (BBMVs) in
H. oblita
larvae, binding assays were conducted with a fluorescent DyLight488-labeled Cry8-like toxin. The results of saturation binding assays demonstrated that Cry8-like bound specifically to binding sites on BBMVs from
H. oblita
, and heterologous competition assays revealed that Cry8Ga shared binding sites with Cry8-like. Furthermore, Cry8-like-binding proteins in the midgut from
H. oblita
larvae were identified by pulldown assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, the
H. oblita
midgut transcriptome was assembled by high-throughput RNA sequencing and used for identification of Cry8-like-binding proteins. Eight Cry8-like-binding proteins were obtained from pulldown assays conducted with BBMVs. The LC-MS/MS data for these proteins were successfully matched with the
H. oblita
transcriptome, and BLASTX results identified five proteins as serine protease, transferrin-like, uncharacterized protein LOC658236 of
Tribolium castaneum
, ATPase catalytic subunit, and actin. These identified Cry8-like-binding proteins were different from those confirmed previously as receptors for Cry1A proteins in lepidopteran insect species, such as aminopeptidase, alkaline phosphatase, and cadherin.

IMPORTANCE
Holotrichia oblita
is one of the main soil-dwelling pests in China. The larvae damage the roots of crops, resulting in significant yield reductions and economic losses.
H. oblita
is difficult to control, principally due to its soil-dwelling habits. In recent years, some Cry8 toxins from
Bacillus thuringiensis
were shown to be active against this pest. Study of the mechanism of action of these Cry8 toxins is needed for their effective use in the control of
H. oblita
and for their future utilization in transgenic plants. Our work provides important basic data and promotes understanding of the insecticidal mechanism of Cry8 proteins against
H. oblita
larvae.
Engineering Streptomyces coelicolor Carbonyl Reductase for Efficient Atorvastatin Precursor Synthesis
Authors: Li Min , Zhang Zhi-Jun , Kong Xu-Dong , Yu Hui-Lei , Zhou Jiahai , Xu Jian-He
Published: April 2017

Streptomyces coelicolorCR1 (ScCR1) has been shown to be a promising biocatalyst for the synthesis of an atorvastatin precursor, ethyl-(S)-4-chloro-3-hydroxybutyrate [(S)-CHBE]. However, limitations ofScCR1 observed for practical application include low activity and poor stability. In this work, protein engineering was employed to improve the catalytic efficiency and stability ofScCR1. First, the crystal structure ofScCR1 complexed with NADH and cosubstrate 2-propanol was solved, and the specific activity ofScCR1 was increased from 38.8 U/mg to 168 U/mg (ScCR1I158V/P168S) by structure-guided engineering. Second, directed evolution was performed to improve the stability usingScCR1I158V/P168Sas a template, affording a triple mutant,ScCR1A60T/I158V/P168S, whose thermostability (T5015, defined as the temperature at which 50% of initial enzyme activity is lost following a heat treatment for 15 min) and substrate tolerance (C5015, defined as the concentration at which 50% of initial enzyme activity is lost following incubation for 15 min) were 6.2°C and 4.7-fold higher than those of the wild-type enzyme. Interestingly, the specific activity of the triple mutant was further increased to 260 U/mg. Protein modeling and docking analysis shed light on the origin of the improved activity and stability. In the asymmetric reduction of ethyl-4-chloro-3-oxobutyrate (COBE) on a 300-ml scale, 100 g/liter COBE could be completely converted by only 2 g/liter of lyophilizedScCR1A60T/I158V/P168Swithin 9 h, affording an excellent enantiomeric excess (ee) of >99% and a space-time yield of 255 g liter−1day−1. These results suggest high efficiency of the protein engineering strategy and good potential of the resulting variant for efficient synthesis of the atorvastatin precursor.

IMPORTANCEApplication of the carbonyl reductaseScCR1 in asymmetrically synthesizing (S)-CHBE, a key precursor for the blockbuster drug Lipitor, from COBE has been hindered by its low catalytic activity and poor thermostability and substrate tolerance. In this work, protein engineering was employed to improve the catalytic efficiency and stability ofScCR1. The catalytic efficiency, thermostability, and substrate tolerance ofScCR1 were significantly improved by structure-guided engineering and directed evolution. The engineeredScCR1 may serve as a promising biocatalyst for the biosynthesis of (S)-CHBE, and the protein engineering strategy adopted in this work would serve as a useful approach for future engineering of other reductases toward potential application in organic synthesis.
Earned print media in advancing tobacco control in Himachal Pradesh, India: a descriptive study
Authors: Sharma Renu , Shewade Hemant Deepak , Gopalan Balasubramaniam , Badrel Ramesh Kumar , Rana Jugdeep Singh
Published: April 2017

Background

The Union-Bloomberg Initiative tobacco control projects were implemented in Himachal Pradesh (a hilly state in North India) from 2007 to 2014. The project focused on the establishment of an administrative framework; increasing the capacity of stakeholders; enforcement of legislation; coalition and networking with multiple stakeholders; awareness generation with focus on earned media and monitoring and evaluation with policy-focussed research. This study aimed to systematically analyse all earned print news items related to the projects.

Methods

In this cross-sectional descriptive study, quantitative content analysis of earned print news items was carried out using predetermined codes related to areas of tobacco control policies. We also carried out a cost description of the hypothetical value of this earned media. The area of the news item in cm2was multiplied by the average rate of space for the paid news item in that particular newspaper.

Results

There were 6348 news items: the numbers steadily increased with time. Focus on Monitoring tobacco use, Protecting people from tobacco smoke, Offering help to quit, Warning about dangers of tobacco, Enforcing a ban on tobacco advertising and promotion, Raising tax on tobacco products was seen in 24, 17, 9, 23, 22 and 3% of news items, respectively. Press releases were highest at 44% and report by correspondents at 24%. Further, 55, 23 and 21% news items focused on smoking, smokeless and both forms of tobacco use, respectively. Sixty-six per cent and 34% news items, respectively, were focused on youth and women. The news items had a hypothetical value of US$1503 628.3, which was three times more than the funds spent on all project activities.

Conclusions

In the absence of funding for paid media, the project strategically used earned media to promote tobacco control policies in the state.
Governing the mixed health workforce: learning from Asian experiences
Authors: Sheikh Kabir , Josyula Lakshmi K , Zhang Xiulan , Bigdeli Maryam , Ahmed Syed Masud
Published: April 2017

Examination of the composition of the health workforce in many low and middle-income countries (LMICs) reveals deep-seated heterogeneity that manifests in multiple ways: varying levels of official legitimacy and informality of practice; wide gradation in type of employment and behaviour (public to private) and diverse, sometimes overlapping, systems of knowledge and variably specialised cadres of providers. Coordinating this mixed workforce necessitates an approach to governance that is responsive to the opportunities and challenges presented by this diversity. This article discusses some of these opportunities and challenges for LMICs in general, and illustrates them through three case studies from different Asian country settings.
Relationship between uric acid and technique failure in patients on continuous ambulatory peritoneal dialysis: a long-term observational cohort study
Authors: Hsieh Yao-Peng , Chang Chia-Chu , Kor Chew-Teng , Yang Yu , Wen Yao-Ko , Chiu Ping-Fang , Lin Chi-Chen
Published: April 2017

Objectives

Uric acid (UA) is the product of purine or nucleotide metabolism via the pathway of xanthine oxidase or xanthine dehydrogenase. Although epidemiological studies assessing the role of UA in cardiovascular disease or mortality have produced inconsistent results, the correlation between UA and technique failure in patients on continuous ambulatory peritoneal dialysis (CAPD) remains to be assessed.

Design

A retrospective cohort study.

Setting

Patients starting CAPD between 2001 and 2009 in a single centre in Taiwan.

Participants

A total of 371 patients on CAPD.

Primary outcome measures

All-cause and peritonitis-related technique failure.

Results

A cohort of 371 participants (43.9% male) was enrolled in the study with a mean age of 55.7±15.9 years at the start of CAPD. During the study period, technique failure occurred in 41 (34.4%) patients in the hyperuricaemia group compared with 49 (19.4%) in the normouricaemia group (p=0.003). In the multivariate Cox regression models, hyperuricaemia at baseline was significantly associated with both a higher risk of technique failure (HR 1.24; 95% CI 1.09 to 1.42, p=0.001) and peritonitis-related technique failure (HR 1.29; 95% CI 1.07 to 1.57, p=0.008).

Conclusions

UA was shown to be associated with all-cause and peritonitis-related technique failure in our study. Patients on CAPD with hyperuricaemia should be closely monitored and strategies of increasing survival on CAPD should be taken.
What are the risks and benefits of temporarily discontinuing medications to prevent acute kidney injury? A systematic review and meta-analysis
Authors: Whiting Penny , Morden Andrew , Tomlinson Laurie A , Caskey Fergus , Blakeman Thomas , Tomson Charles , Stone Tracey , Richards Alison , Savović Jelena , Horwood Jeremy
Published: April 2017

Objectives

To summarise evidence on temporary discontinuation of medications to prevent acute kidney injury (AKI).

Design

Systematic review and meta-analysis of randomised and non-randomised studies.

Participants

Adults taking diuretics, ACE inhibitors (ACEI), angiotensin receptor blockers (ARB), direct renin inhibitors, non-steroidal anti-inflammatories, metformin or sulfonylureas, experiencing intercurrent illnesses, radiological or surgical procedures.

Interventions

Temporary discontinuation of any of the medications of interest.

Primary and secondary outcome measures

Risk of AKI. Secondary outcome measures were estimated glomerular filtration rate and creatinine post-AKI, urea, systolic and diastolic blood pressure, death, clinical outcomes and biomarkers.

Results

6 studies were included (1663 participants), 3 randomised controlled trials (RCTs) and 3 prospective cohort studies. The mean age ranged from 65 to 73 years, and the proportion of women ranged from 31% to 52%. All studies were in hospital settings; 5 evaluated discontinuation of medication prior to coronary angiography and 1 prior to cardiac surgery. 5 studies evaluated discontinuation of ACEI and ARBs and 1 small cohort study looked at discontinuation of non-steroidal anti-inflammatory drugs. No studies evaluated discontinuation of medication in the community following an acute intercurrent illness. There was an increased risk of AKI of around 15% in those in whom medication was continued compared with those in whom it was discontinued (relative risk (RR) 1.17, 95% CI 0.99 to 1.38; 5 studies). When only results from RCTs were pooled, the increase in risk was almost 50% (RR 1.48, 95% CI 0.84 to 2.60; 3 RCTs), but the CI was wider. There was no difference between groups for any secondary outcomes.

Conclusions

There is low-quality evidence that withdrawal of ACEI/ARBs prior to coronary angiography and cardiac surgery may reduce the incidence of AKI. There is no evidence of the impact of drug cessation interventions on AKI incidence during intercurrent illness in primary or secondary care.

Trial registration number

PROSPERO CRD42015023210.
Epidemiology of rubella infection in Cameroon: a 7-year experience of measles and rubella case-based surveillance, 2008–2014
Authors: Nimpa Mengouo Marcellin , Ndze Valantine Ngum , Baonga Frangy , Kobela Marie , Wiysonge Charles Shey
Published: April 2017

Objective

The aim of this study was to estimate the proportion of rubella disease in a measles case-based surveillance in Cameroon prior to rubella vaccine introduction into the national immunisation programme.

Design

This was a cross-sectional study for rubella infection in Cameroon for the period 2008 to 2014.

Setting

Patients suspected with measles from the 10 regions of Cameroon were recruited according to the WHO measles case definition and were tested for rubella IgM antibodies accompanied with the case report/investigation forms.

Participants

All persons with rash and fever within 14 days of onset of rash according to the standard WHO African Regional Office (WHO/AFRO) case definition for a suspected measles case.

Outcome measures

Descriptive analyses and simple logistic regressions were performed. OR were estimated.

Results

A total of 9907 serum samples from people with fever and rash were received in the laboratory from 2008 to 2014. A total of 7489 (75.59%) measles-negative samples were tested for rubella; 699 (9.3%) were positive for rubella IgM antibodies. Logistic regression analysis was done using IgM antibodies detection as the outcome variable. Age, sex and setting were explanatory variables. Logistic regression analysis revealed that, comparing the proportion of rubella IgM seropositivity status by age, the association to a positive rubella IgM increased with age from 1 to 4 years (OR 7.11; 95% CI 4.35 to 12.41; p<0.0001), through 5 to 9 years (OR 13.07; 95% CI 7.93 to 22.93; p<0.001), to 10 to 14 years of age (OR 13.86; 95% CI 8.06 to 25.12; p<0.001). Persons aged ≥15 years were also more likely to have rubella infection than children under one (OR 3.69; 95% CI 1.85 to 7.48; p=0.0001). There were also significant associations with sex, with males being less associated to a positive rubella serology than females (OR 1.33; 95% CI 1.14 to 1.56; p=0.0001). No statistically significant difference in proportion of rubella cases was observed between urban and rural populations (OR 1.11; 95% CI 0.94 to 1.31; p=0.208).

Conclusions

This study reveals that rubella virus circulates in Cameroon, with important number of cases in children under 15 years. This finding supports the planned introduction of rubella-containing vaccines into the Expanded Program on Immunization.
Long-term use benefits of personal frequency-modulated systems for speech in noise perception in patients with stroke with auditory processing deficits: a non-randomised controlled trial study
Authors: Koohi Nehzat , Vickers Deborah , Warren Jason , Werring David , Bamiou Doris-Eva
Published: April 2017

Objectives

Approximately one in five stroke survivors suffer from difficulties with speech reception in noise, despite normal audiometry. These deficits are treatable with personal frequency-modulated systems (FMs). This study aimed to evaluate long-term benefits in speech reception in noise, after daily 10-week use of personal FMs, in non-aphasic patients with stroke with auditory processing deficits.

Design

This was a prospective non-randomised controlled trial study. Patients were allocated to an intervention care group or standard care subjects group according to their willingness to use the intervention or not.

Setting

Tertiary care setting.

Participants

Nine non-aphasic subjects with ischaemic stroke, normal/near-normal audiometry and auditory processing deficits and with reported difficulties understanding speech in background noise were recruited in the subacute stroke stage (3–12 months after stroke).

Interventions

Four patients (intervention care subjects) used the FMs in their daily life over 10 weeks. Five patients (standard care subjects) received standard care.

Primary outcome measures

All subjects were tested at baseline (visit 1) and 10 weeks later (visit 2) on a sentences in noise test with the FMs (aided) and without the FMs (unaided).

Results

Speech reception thresholds showed clinically and statistically significant improvements in intervention but not in standard care subjects at 10 weeks in aided and unaided conditions.

Conclusions

10-week use of FMs by adult patients with stroke may lead to benefits in unaided speech in noise perception. Our findings may indicate auditory plasticity type changes and require further investigation.

Trial registration number

Pre-results;NCT02889107.
Social prescribing: less rhetoric and more reality. A systematic review of the evidence
Authors: Bickerdike Liz , Booth Alison , Wilson Paul M , Farley Kate , Wright Kath
Published: April 2017

Objectives

Social prescribing is a way of linking patients in primary care with sources of support within the community to help improve their health and well-being. Social prescribing programmes are being widely promoted and adopted in the UK National Health Service and so we conducted a systematic review to assess the evidence for their effectiveness.

Setting/data sources

Nine databases were searched from 2000 to January 2016 for studies conducted in the UK. Relevant reports and guidelines, websites and reference lists of retrieved articles were scanned to identify additional studies. All the searches were restricted to English language only.

Participants

Systematic reviews and any published evaluation of programmes where patient referral was made from a primary care setting to a link worker or facilitator of social prescribing were eligible for inclusion. Risk of bias for included studies was undertaken independently by two reviewers and a narrative synthesis was performed.

Primary and secondary outcome measures

Primary outcomes of interest were any measures of health and well-being and/or usage of health services.

Results

We included a total of 15 evaluations of social prescribing programmes. Most were small scale and limited by poor design and reporting. All were rated as a having a high risk of bias. Common design issues included a lack of comparative controls, short follow-up durations, a lack of standardised and validated measuring tools, missing data and a failure to consider potential confounding factors. Despite clear methodological shortcomings, most evaluations presented positive conclusions.

Conclusions

Social prescribing is being widely advocated and implemented but current evidence fails to provide sufficient detail to judge either success or value for money. If social prescribing is to realise its potential, future evaluations must be comparative by design and consider when, by whom, for whom, how well and at what cost.

Trial registration number

PROSPERO Registration: CRD42015023501.
What is the care pathway of patients who undergo thyroid surgery in France and its potential pitfalls? A national cohort
Authors: Mathonnet Muriel , Cuerq Anne , Tresallet Christophe , Thalabard Jean-Christophe , Fery-Lemonnier Elisabeth , Russ Gilles , Leenhardt Laurence , Bigorgne Claude , Tuppin Philippe , Millat Bertrand , Fagot-Campagna Anne
Published: April 2017

Context

The rate of thyroid cancer is increasing in France, as well as concerns about overdiagnosis and treatment.

Objectives

To examine the care pathway of patients who undergo thyroid surgery in France and detect potential pitfalls.

Design

A large observational study based on medical reimbursements, 2009–2011.

Setting

Data from the Sniiram (National Health Insurance Information System).

Patients

Patients with thyroid surgery in 2010, classified into 4 groups: thyroid cancer, benign nodule, goitre or multiple nodules, other (hyperthyroidism, head–neck cancer).

Main outcome measures

Medical investigations during, prior and after thyroidectomy.

Results

A total of 35 367 patients underwent surgery (mean age 51 years, 80% women): 17% had a reported diagnosis of thyroid cancer, 20% benign nodule, 38% goitre or multiple nodules and 25% another diagnosis. The ratio of thyroidectomies with cancer over thyroidectomies with benign nodule was 0.8 and varied across regions. In the year preceding surgery, 82% of patients had an investigation by thyroid ultrasonography, 21% thyroid scintigraphy, 34% fine-needle aspiration cytology, 40% serum calcitonin assay and 54% serum calcium assay. In the following year, all patients with total thyroidectomy and 44% of patients with partial thyroidectomy and a diagnosis of benign nodule were taking thyroid hormone therapy. 100 patients had been reoperated for a compressive haematoma and 63 died during the first month, half of whom had been operated for cancer. Mean rates of recurrent laryngeal nerve injury and hypocalcaemia (requiring blood tests plus treatments within 4–12 months) were estimated at 1.5% and 3.4%, respectively, and were higher in the cancer group (2.3% and 5.7%).

Conclusions

This almost nationwide study demonstrates the suboptimal management of patients prior to thyroidectomy in France. It suggests overdiagnosis and potential harms to patients, and calls for a review of the relevance of thyroidectomy, particularly with regard to microcancers.
Secular trends in the incidence of dementia in high-income countries: a protocol of a systematic review and a planned meta-analysis
Authors: Roehr Susanne , Pabst Alexander , Luck Tobias , Riedel-Heller Steffi G
Published: April 2017

Introduction

A global dementia epidemic is projected for the year 2050 with an ever-rising number of individuals living with the syndrome worldwide. However, increasingly, studies are emerging from high-income countries (HIC) that show a positive trend towards a possible decrease in dementia occurrence. Therefore, we aim to systematically summarise evidence regarding secular trends in the incidence of dementia in HIC.

Methods and analysis

We will conduct a systematic review of the literature on secular trends in dementia incidence in HIC according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statements. To do so, we will search the databases MEDLINE (PubMed interface), EMBASE (Ovid interface) and Web of Science (Web of Science interface), as well as the grey literature on unpublished studies. To be eligible, studies must have been published in English or German since 1990 and provide sufficient information on prespecified eligibility criteria regarding outcome measurement and methodological approach. Study selection, data extraction and risk of bias assessment will be performed independently by 2 reviewers. Disagreement will be resolved by discussion and/or the involvement of a third researcher. Data abstraction will include study and participant characteristics, outcomes and methodological aspects. Results will be described and discussed regarding methodology. Depending on the number of studies found and the heterogeneity between the studies, we plan to combine outcome data through meta-analysis in order to get pooled incidence measures.

Ethics and dissemination

No primary data will be collected; thus, ethical approval is not required. The results will be disseminated through a peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD42016043232.
Long-term effect of smartphone-delivered Interval Walking Training on physical activity in patients with type 2 diabetes: protocol for a parallel group single-blinded randomised controlled trial
Authors: Valentiner Laura Staun , Ried-Larsen Mathias , Karstoft Kristian , Brinkløv Cecilie Fau , Brøns Charlotte , Nielsen Rasmus Oestergaard , Christensen Robin , Nielsen Jens Steen , Vaag Allan Arthur , Pedersen Bente Klarlund , Langberg Henning
Published: April 2017

Introduction

Physical activity is a cornerstone in type 2 diabetes (T2D) rehabilitation. Effective long-term and low-cost strategies to keep these patients' physically active are needed. However, maintaining physical activity behaviour is difficult once formalised interventions end. Structured exercise training supported by mobile technology and remote feedback is potentially an effective strategy. The objective of the trial is to investigate whether mobile health support using the InterWalk application for smartphones is effective in increasing physical activity levels in persons with T2D over time compared with standard care. We investigate whether Interval Walking Training using the InterWalk application is superior to Danish municipality-based rehabilitation in increasing moderate-and-vigorous physical activity levels in patients with T2D across 52 weeks. Secondary, we hypothesise that a motivational programme added from end of intervention to 52 weeks further increases level of physical activity in everyday life in patients with T2D.

Methods and analysis

The trial is a parallel-group, open-labelled, randomised controlled trial with long-term follow-up at 52 week including patients with T2D. The primary outcome is change in moderate-and-vigorous physical activity. The key secondary outcome includes motivation for physical activity behaviour change. Other secondary outcomes are VO2-peak, strength in the lower extremities. Exclusion criterion is medical contraindication to exercise. We include up to 246 patients and randomly allocate them into a control (standard group) or an experimental group (8–12 weeks of IWT supported by the smartphone-based InterWalk application) in a 1:2 fashion. After intervention, the experimental group is randomly allocated into two follow-up conditions with unsupervised IWT with or without motivational support until 52-week follow-up. The intention-to-treat principle is applied.

Ethics and dissemination

The local regional Research Ethics Committee in Denmark (H-1-2014-074) and the Danish Data Protection Agency (j.nr. 2014-54-0897) have approved the trial. Positive, negative or inconclusive results will be disseminated in scientific journals and conferences.

Trial registration number

NCT02341690.
Prevalence-based, disease-specific estimate of the social cost of smoking in Singapore
Authors: Cher Boon Piang , Chen Cynthia , Yoong Joanne
Published: April 2017

Objective

To estimate the cost of smoking in Singapore in 2014 from the societal perspective.

Methods

A prevalence-based, disease-specific approach was undertaken to estimate the smoking-attributable costs. These include direct and indirect costs of inpatient treatment, premature mortality, loss of productivity due to medical leaves and smoking breaks.

Results

In 2014, the social cost of smoking in Singapore was conservatively estimated to be at least US$479.8 million, ∼0.2% of the 2014 gross domestic product. Most of this cost was attributable to productivity losses (US$464.9 million) and largely concentrated in the male population (US$434.9 million). Direct healthcare costs amounted to US$14.9 million where ischaemic heart disease and lung cancer had the highest cost burden.

Conclusions

The social cost of smoking is smaller in Singapore than in other Asian countries. However, there is still cause for concern. A recently observed increase in smoking prevalence, particularly among adolescent men, is likely to result in rising total cost. Most significantly, our results suggest that a large share of the overall cost burden lies outside the healthcare system or may not be highly salient to the relevant decision makers. This is partly because of the nature of such costs (indirect or intangible costs such as productivity losses are often not salient) or data limitations (a potentially significant fraction of direct healthcare expenditure may be in private primary care where costs are not systematically captured and reported). The case of Singapore thus illustrates that even in countries perceived as success stories, strong multisectoral anti-tobacco strategies and a supporting research agenda continue to be needed.
External validation and extension of a diagnostic model for obstructive coronary artery disease: a cross-sectional predictive evaluation in 4888 patients of the Austrian Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort
Authors: Edlinger Michael , Wanitschek Maria , Dörler Jakob , Ulmer Hanno , Alber Hannes F , Steyerberg Ewout W
Published: April 2017

Objective

To externally validate and extend a recently proposed prediction model to diagnose obstructive coronary artery disease (CAD), with the ultimate aim to better select patients for coronary angiography.

Design

Analysis of individual baseline data of a prospective cardiology cohort.

Setting

Single-centre secondary and tertiary cardiology clinic.

Participants

4888 patients with suspected CAD, without known previous CAD or other heart diseases, who underwent an elective coronary angiography between 2004 and 2008 as part of the prospective Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort. Relevant data were recorded as in routine clinical practice.

Main outcome measures

The probability of obstructive CAD, defined as a stenosis of minimally 50% diameter in at least one of the main coronary arteries, estimated with the predictors age, sex, type of chest pain, diabetes status, hypertension, dyslipidaemia, smoking status and laboratory data. Missing predictor data were multiply imputed. Performance of the suggested models was evaluated according to discrimination (area under the receiver operating characteristic curve, depicted by the c statistic) and calibration. Logistic regression modelling was applied for model updating.

Results

Among the 4888 participants (38% women and 62% men), 2127 (44%) had an obstructive CAD. The previously proposed model had a c statistic of 0.69 (95% CI 0.67 to 0.70), which was lower than the expected c statistic while correcting for case mix (c=0.80). Regarding calibration, there was overprediction of risk for high-risk patients. All logistic regression coefficients were smaller than expected, especially for the predictor ‘chest pain’. Extension of the model with high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and C reactive protein led to better discrimination (c=0.72, 95% CI 0.71 to 0.74, p<0.001 for improvement).

Conclusions

The proposed prediction model has a moderate performance to diagnose obstructive CAD in an unselected patient group with suspected CAD referred for elective CA. A small, but significant improvement was attained by including easily available and measurable cardiovascular risk factors.
Employment status and psychological distress in a population-based cross-sectional study in Sweden: the impact of migration
Authors: Sidorchuk Anna , Engström Karin , Johnson Charisse M , Kayser Leeoza Naima , Möller Jette
Published: April 2017

Objectives

Unemployment and temporary employment are known to impact psychological health. However, the extent to which the effect is altered by migration-related and sociodemographic determinants is less clear. The purpose of this study was to investigate whether the association between employment status and psychological distress differs between immigrants and Swedish-born and to what extent, the association is modified by gender and reason for immigration.

Design

Cross-sectional survey study.

Participants and setting

Data from public health surveys undertaken in 2002, 2006 and 2010 from random samples of Stockholm County residents, Sweden, were used to analyse a weighted sample of 51 118 individuals aged 18–64 (43 444 Swedish-born, 4055 non-refugees, 3619 refugees). According to their activity in the labour market, the participants were categorised into permanently/self-employed, temporarily employed and unemployed.

Outcomes measures

Associations between self-reported employment and psychological distress measured by a 12-item version of the General Health Questionnaire were explored across individuals with different migration status and reasons for immigration using logistic regression and pairwise comparisons. The analyses were stratified by gender and adjusted for age, socioeconomic characteristics and survey year.

Results

Unemployment was associated with elevated likelihood of psychological distress across the study population, regardless of migration status and gender. Fully adjusted models revealed nearly a 3-fold higher odds of distress in unemployed Swedish-born (OR 3.05, 95% CI 2.66 to 3.51), non-refugees (OR 3.51, 95% CI 2.44 to 5.05) and refugees (OR 2.91, 95% CI 2.20 to 3.85) when compared with permanently/self-employed. Temporary employment also increased the likelihood of distress, particularly among refugees and Swedish-born.

Conclusions

The effect of unemployment on increased likelihood of poor psychological well-being overcomes gender-specific and migration-specific differences and is equally pronounced for Swedish-born, non-refugees and refugees. Exclusion from the labour market appears to be a major determinant of psychological health inequalities in contemporary Sweden.