bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine and dopamine oppositely modulate a hyperpolarization‐activated current Ih in chemosensory neurons of the rat carotid body in co‐culture
Authors: Zhang Min , Vollmer Cathy , Nurse Colin A.
Published: August 2017

Key points

Adenosine and dopamine (DA) are neuromodulators in the carotid body (CB) chemoafferent pathway, but their mechanisms of action are incompletely understood.

Using functional co‐cultures of rat CB chemoreceptor (type I) cells and sensory petrosal neurons (PNs), we show that adenosine enhanced a hyperpolarization‐activated cation current Ih in chemosensory PNs via A2a receptors, whereas DA had the opposite effect via D2 receptors.

Adenosine caused a depolarizing shift in the Ih activation curve and increased firing frequency, whereas DA caused a hyperpolarizing shift in the curve and decreased firing frequency.

Acute hypoxia and isohydric hypercapnia depolarized type I cells concomitant with increased excitation of adjacent PNs; the A2a receptor blocker SCH58261 inhibited both type I and PN responses during hypoxia, but only the PN response during isohydric hypercapnia.

We propose that adenosine and DA control firing frequency in chemosensory PNs via their opposing actions on Ih.

Adenosine and dopamine (DA) act as neurotransmitters or neuromodulators at the carotid body (CB) chemosensory synapse, but their mechanisms of action are not fully understood. Using a functional co‐culture model of rat CB chemoreceptor (type I) cell clusters and juxtaposed afferent petrosal neurons (PNs), we tested the hypothesis that adenosine and DA act postsynaptically to modulate a hyperpolarization‐activated, cyclic nucleotide‐gated (HCN) cation current (Ih). In whole‐cell recordings from hypoxia‐responsive PNs, cAMP mimetics enhanced Ih whereas the HCN blocker ZD7288 (2 μm) reversibly inhibited Ih. Adenosine caused a potentiation of Ih (EC50 ∼ 35 nm) that was sensitive to the A2a blocker SCH58261 (5 nm), and an ∼16 mV depolarizing shift in V½ for voltage dependence of Ih activation. By contrast, DA (10 μm) caused an inhibition of Ih that was sensitive to the D2 blocker sulpiride (1–10 μm), and an ∼11 mV hyperpolarizing shift in V½. Sulpiride potentiated Ih in neurons adjacent to, but not distant from, type I cell clusters. DA also decreased PN action potential frequency whereas adenosine had the opposite effect. During simultaneous paired recordings, SCH58261 inhibited both the presynaptic hypoxia‐induced receptor potential in type I cells and the postsynaptic PN response. By contrast, SCH58261 inhibited only the postsynaptic PN response induced by isohydric hypercapnia. Confocal immunofluorescence confirmed the localization of HCN4 subunits in tyrosine hydroxylase‐positive chemoafferent neurons in tissue sections of rat petrosal ganglia. These data suggest that adenosine and DA, acting through A2a and D2 receptors respectively, regulate PN excitability via their opposing actions on Ih.
Membrane localization of acetylated CNK1 mediates a positive feedback on RAF/ERK signaling
Authors: Fischer Adrian , Mühlhäuser Wignand W. D. , Warscheid Bettina , Radziwill Gerald
Published: August 2017

Acetylated scaffold protein CNK1 promotes ERK-dependent cell proliferation and migration in normal cells and in tumor cells.
HfSe
2
and ZrSe
2
: Two-dimensional semiconductors with native high-κ oxides
Authors: Mleczko Michal J. , Zhang Chaofan , Lee Hye Ryoung , Kuo Hsueh-Hui , Magyari-Köpe Blanka , Moore Robert G. , Shen Zhi-Xun , Fisher Ian R. , Nishi Yoshio , Pop Eric
Published: August 2017

Atomically thin two-dimensional semiconductors feature silicon-like band gaps and native high-κ metal oxides.
3D imaging of optically cleared tissue using a simplified CLARITY method and on-chip microscopy
Authors: Zhang Yibo , Shin Yoonjung , Sung Kevin , Yang Sam , Chen Harrison , Wang Hongda , Teng Da , Rivenson Yair , Kulkarni Rajan P. , Ozcan Aydogan
Published: August 2017

Using lens-free holographic microscopy, we demonstrated 3D imaging in optically cleared tissue over a thickness of 0.2 mm.
Response of Methylocystis sp. Strain SC2 to Salt Stress: Physiology, Global Transcriptome, and Amino Acid Profiles
Authors: Han Dongfei , Link Hannes , Liesack Werner
Published: August 2017

Soil microorganisms have to rapidly respond to salt-induced osmotic stress. Type II methanotrophs of the genus
Methylocystis
are widely distributed in upland soils but are known to have a low salt tolerance. Here, we tested the ability of
Methylocystis
sp. strain SC2 to adapt to increased salinity. When exposed to 0.75% NaCl, methane oxidation was completely inhibited for 2.25 h and fully recovered within 6 h. Growth was inhibited for 23.5 h and then fully recovered. Its transcriptome was profiled after 0 min (control), 45 min (early response), and 14 h (late response) of stress exposure. Physiological and transcriptomic stress responses corresponded well. Salt stress induced the differential expression of 301 genes, with sigma factor σ
32
being a major controller of the transcriptional stress response. The transcript levels of nearly all the genes involved in oxidizing CH
4
to CO
2
remained unaffected, while gene expression involved in energy-yielding reactions (
nuoA-N
) recovered concomitantly with methane oxidation from salt stress shock. Glutamate acted as an osmoprotectant. Its accumulation in late stress response corresponded to increased production of glutamate dehydrogenase 1. Chromosomal genes whose products (stress-induced protein, DNA-binding protein from starved cells, and CsbD family protein) are known to confer stress tolerance showed increased expression. On plasmid pBSC2-1, genes encoding type IV secretion system and single-strand DNA-binding protein were upregulated in late response, suggesting stress-induced activation of the plasmid-borne conjugation machinery. Collectively, our results show that
Methylocystis
sp. strain SC2 is able to adapt to salt stress, but only within a narrow range of salinities.

IMPORTANCE
Besides the oxic interface of methanogenic environments,
Methylocystis
spp. are widely distributed in upland soils, where they may contribute to the oxidation of atmospheric methane. However, little is known about their ability to cope with changes in soil salinity. Growth and methane oxidation of
Methylocystis
sp. strain SC2 were not affected by the presence of 0.5% NaCl, while 1% NaCl completely inhibited its activity. This places strain SC2 into the low-salt-tolerance range reported for other
Methylocystis
species. Our results show that, albeit in a narrow range, strain SC2 is able to respond and adapt to salinity changes. It possesses various stress response mechanisms, which allow resumption of growth within 24 h when exposed to 0.75% NaCl. Presumably, these mechanisms allow
Methylocystis
spp., such as strain SC2, to thrive in upland soils and to adapt to certain fluctuations in soil salinity.
Syntrophomonas wolfei Uses an NADH-Dependent, Ferredoxin-Independent [FeFe]-Hydrogenase To Reoxidize NADH
Authors: Losey Nathaniel A. , Mus Florence , Peters John W. , Le Huynh M. , McInerney Michael J.
Published: August 2017

Syntrophomonas wolfeisyntrophically oxidizes short-chain fatty acids (four to eight carbons in length) when grown in coculture with a hydrogen- and/or formate-using methanogen. The oxidation of 3-hydroxybutyryl-coenzyme A (CoA), formed during butyrate metabolism, results in the production of NADH. The enzyme systems involved in NADH reoxidation inS. wolfeiare not well understood. The genome ofS. wolfeicontains a multimeric [FeFe]-hydrogenase that may be a mechanism for NADH reoxidation. TheS. wolfeigenes for the multimeric [FeFe]-hydrogenase (hyd1ABC; SWOL_RS05165, SWOL_RS05170, SWOL_RS05175) and [FeFe]-hydrogenase maturation proteins (SWOL_RS05180, SWOL_RS05190, SWOL_RS01625) were coexpressed inEscherichia coli, and the recombinant Hyd1ABC was purified and characterized. The purified recombinant Hyd1ABC was a heterotrimer with an αβγ configuration and a molecular mass of 115 kDa. Hyd1ABC contained 29.2 ± 1.49 mol of Fe and 0.7 mol of flavin mononucleotide (FMN) per mole enzyme. The purified, recombinant Hyd1ABC reduced NAD+and oxidized NADH without the presence of ferredoxin. The HydB subunit of theS. wolfeimultimeric [FeFe]-hydrogenase lacks two iron-sulfur centers that are present in known confurcating NADH- and ferredoxin-dependent [FeFe]-hydrogenases. Hyd1ABC is a NADH-dependent hydrogenase that produces hydrogen from NADH without the need of reduced ferredoxin, which differs from confurcating [FeFe]-hydrogenases. Hyd1ABC provides a mechanism by whichS. wolfeican reoxidize NADH produced during syntrophic butyrate oxidation when low hydrogen partial pressures are maintained by a hydrogen-consuming microorganism.

IMPORTANCEOur work provides mechanistic understanding of the obligate metabolic coupling that occurs between hydrogen-producing fatty and aromatic acid-degrading microorganisms and their hydrogen-consuming partners in the process called syntrophy (feeding together). The multimeric [FeFe]-hydrogenase used NADH without the involvement of reduced ferredoxin. The multimeric [FeFe]-hydrogenase would produce hydrogen from NADH only when hydrogen concentrations were low. Hydrogen production from NADH bySyntrophomonas wolfeiwould likely cease before any detectable amount of cell growth occurred. Thus, continual hydrogen production requires the presence of a hydrogen-consuming partner to keep hydrogen concentrations low and explains, in part, the obligate requirement thatS. wolfeihas for a hydrogen-consuming partner organism during growth on butyrate. We have successfully expressed genes encoding a multimeric [FeFe]-hydrogenase inE. coli, demonstrating that such an approach can be advantageous to characterize complex redox proteins from difficult-to-culture microorganisms.
Functional Analysis of Genes Comprising the Locus of Heat Resistance in Escherichia coli
Authors: Mercer Ryan , Nguyen Oanh , Ou Qixing , McMullen Lynn , Gänzle Michael G.
Published: August 2017

The locus of heat resistance (LHR) is a 15- to 19-kb genomic island conferring exceptional heat resistance to organisms in the family
Enterobacteriaceae
, including pathogenic strains of
Salmonella enterica
and
Escherichia coli
. The complement of LHR-comprising genes that is necessary for heat resistance and the stress-induced or growth-phase-induced expression of LHR-comprising genes are unknown. This study determined the contribution of the seven LHR-comprising genes
yfdX1
GI
,
yfdX2
,
hdeD
GI
,
orf11
,
trx
GI
,
kefB
, and
psiE
GI
by comparing the heat resistances of
E. coli
strains harboring plasmid-encoded derivatives of the different LHRs in these genes. (Genes carry a subscript “GI” [genomic island] if an ortholog of the same gene is present in genomes of
E. coli
.) LHR-encoded heat shock proteins sHSP20, ClpK
GI
, and sHSP
GI
are not sufficient for the heat resistance phenotype; YfdX1, YfdX2, and HdeD are necessary to complement the LHR heat shock proteins and to impart a high level of resistance. Deletion of
trx
GI
,
kefB
, and
psiE
GI
from plasmid-encoded copies of the LHR did not significantly affect heat resistance. The effect of the growth phase and the NaCl concentration on expression from the putative LHR promoter p2 was determined by quantitative reverse transcription-PCR and by a plasmid-encoded p2:GFP promoter fusion. The expression levels of exponential- and stationary-phase
E. coli
cells were not significantly different, but the addition of 1% NaCl significantly increased LHR expression. Remarkably, LHR expression in
E. coli
was dependent on a chromosomal copy of
evgA
. In conclusion, this study improved our understanding of the genes required for exceptional heat resistance in
E. coli
and factors that increase their expression in food.

IMPORTANCE
The locus of heat resistance (LHR) is a genomic island conferring exceptional heat resistance to several foodborne pathogens. The exceptional level of heat resistance provided by the LHR questions the control of pathogens by current food processing and preparation techniques. The function of LHR-comprising genes and their regulation, however, remain largely unknown. This study defines a core complement of LHR-encoded proteins that are necessary for heat resistance and demonstrates that regulation of the LHR in
E. coli
requires a chromosomal copy of the gene encoding EvgA. This study provides insight into the function of a transmissible genomic island that allows otherwise heat-sensitive enteric bacteria, including pathogens, to lead a thermoduric lifestyle and thus contributes to the detection and control of heat-resistant enteric bacteria in food.
An Intramolecular Salt Bridge in Bacillus thuringiensis Cry4Ba Toxin Is Involved in the Stability of Helix α-3, Which Is Needed for Oligomerization and Insecticidal Activity
Authors: Pacheco Sabino , Gómez Isabel , Sánchez Jorge , García-Gómez Blanca-Ines , Soberón Mario , Bravo Alejandra
Published: August 2017

Bacillus thuringiensis
three-domain Cry toxins kill insects by forming pores in the apical membrane of larval midgut cells. Oligomerization of the toxin is an important step for pore formation. Domain I helix α-3 participates in toxin oligomerization. Here we identify an intramolecular salt bridge within helix α-3 of Cry4Ba (D111-K115) that is conserved in many members of the family of three-domain Cry toxins. Single point mutations such as D111K or K115D resulted in proteins severely affected in toxicity. These mutants were also altered in oligomerization, and the mutant K115D was more sensitive to protease digestion. The double point mutant with reversed charges, D111K-K115D, recovered both oligomerization and toxicity, suggesting that this salt bridge is highly important for conservation of the structure of helix α-3 and necessary to promote the correct oligomerization of the toxin.

IMPORTANCE
Domain I has been shown to be involved in oligomerization through helix α-3 in different Cry toxins, and mutations affecting oligomerization also elicit changes in toxicity. The three-dimensional structure of the Cry4Ba toxin reveals an intramolecular salt bridge in helix α-3 of domain I. Mutations that disrupt this salt bridge resulted in changes in Cry4Ba oligomerization and toxicity, while a double point reciprocal mutation that restored the salt bridge resulted in recovery of toxin oligomerization and toxicity. These data highlight the role of oligomer formation as a key step in Cry4Ba toxicity.
Comparison of a ‘two-bag system’ versus conventional treatment protocol (‘one-bag system’) in the management of diabetic ketoacidosis
Authors: Munir Iqbal , Fargo Ramiz , Garrison Roger , Yang Almira , Cheng Andy , Kang Ilho , Motabar Ali , Xu Karen , Loo Lawrence K , Kim Daniel I
Published: August 2017

Objective

We compared the conventional ‘one-bag protocol’ of management of diabetic ketoacidosis (DKA) with the ‘two-bag protocol’ which utilizes two bags of fluids, one containing saline and supplemental electrolytes and the other containing the same solution with the addition of 10% dextrose.

Research design and methods

A retrospective chart review and analysis was done on adult patients admitted for DKA to the Riverside University Health System Medical Center from 2008 to 2015. There were 249 cases of DKA managed by the one-bag system and 134 cases managed by the two-bag system.

Results

The baseline patient characteristics were similar in both groups. The anion gap closed in 13.56 hours in the one-bag group versus 10.94 hours in the two-bag group (p value <0.0002). None of the individual factors significantly influenced the anion gap closure time; only the two-bag system favored earlier closure of the anion gap. Plasma glucose levels improved to <250 mg/dL earlier with two-bag protocol (9.14 vs 7.82 hours, p=0.0241). The incidence of hypoglycemic events was significantly less frequent with the two-bag protocol compared with the standard one-bag system (1.49% vs 8.43%, p=0.0064). Neither the time to improve serum HCO3level >18 mg/dL nor the hospital length of stay differed between the two groups.

Conclusions

Our study indicates that the two-bag protocol closes the anion gap earlier than the one-bag protocol in adult patients with DKA. Blood glucose levels improved faster with the two-bag protocol compared with the one-bag protocol with fewer associated episodes of hypoglycemia. Prospective studies are needed to evaluate the clinical significance of these findings.
Presentation, pathology and prognosis of renal disease in type 2 diabetes
Authors: Tan Jasmine , Zwi L Jonathan , Collins John F , Marshall Mark R , Cundy Tim
Published: August 2017

Objective

Non-diabetic renal disease (NDRD) is common in patients with type 2 diabetes (T2D), but the relationship between its presentation and prognosis is unknown.

Research design and methods

In a retrospective cohort study, we compared renal and patient survival among 263 patients with T2D who had native renal biopsies between 2002 and 2008 from three Auckland hospitals in New Zealand. The presence of diabetic nephropathy (DN), NDRD or mixed (DN and NDRD) was determined from biopsy. We examined clinical associations according to NDRD etiologies and mode of presentation—acute (defined by acute kidney injury (AKI)) or non-acute. Patients were followed until end-stage renal disease, death or December 2015. Survival was compared using Log-rank test.

Results

94 (36%) patients had DN, 72 (27%) had NDRD, and 97 (37%) had mixed pathologies. Obesity-related focal segmental glomerulosclerosis was the most common NDRD (46%) in patients with non-acute presentations, whereas interstitial nephritis or immune-complex glomerulonephritides were the most prevalent in those with acute presentations (60%). DN was commonly associated with AKI (p<0.001). The prevalence of DN increased with diabetes duration (p<0.001), but NDRD was still found in 55% of subjects with ≥14 years T2D. NDRD was strongly associated with the absence of retinopathy (p<0.001).

Renal survival was best in the NDRD group (p<0.001). Among those with DN, renal prognosis was worse in those with more advanced DN lesions and those with an acute presentation (p<0.001). The proportion of all-cause mortality was similar in all three groups, but overall survival was poorest in the DN group (p=0.025).

Conclusions

Renal disease in patients with T2D is heterogeneous. The renal prognosis differs markedly according to histopathological diagnosis and mode of presentation.
Does foreign aid crowd out government investments? Evidence from rural health centres in Rwanda
Authors: Lu Chunling , Cook Benjamin , Desmond Chris
Published: August 2017

Background

Rural healthcare facilities in low-income countries play a major role in providing primary care to rural populations. We examined the link of foreign aid with government investments and medical service provision in rural health centres in Rwanda.

Methods

Using the District Health System Strengthening Tool, a web-based database built by the Ministry of Health in Rwanda, we constructed two composite indices representing provision of (1) child and maternal care and (2) HIV, tuberculosis (TB) and malaria services in 330 rural health centres between 2009 and 2011. Financing variables in a healthcare centre included received funds from various sources, including foreign donors and government. We used multilevel random-effects model in regression analyses and examined the robustness of results to a range of alternative specification, including scale of dependent variables, estimation methods and timing of aid effects.

Findings

Both government and foreign donors increased their direct investments in the 330 rural healthcare centres during the period. Foreign aid was positively associated with government investments (0.13, 95% CI 0.06 to 0.19) in rural health centres. Aid in the previous year was positively associated with service provision for child and maternal health (0.008, 95% CI 0.002 to 0.014) and service provision for HIV, TB and malaria (0.014, 95% CI 0.004 to 0.022) in the current year. The results are robust when using fixed-effects models.

Conclusions

These findings suggest that foreign aid did not crowd out government investments in the rural healthcare centres. Foreign aid programmes, conducted in addition to government investments, could benefit rural residents in low-income countries through increased service provision in rural healthcare facilities.
Long-term outcomes after acute myocardial infarction in countries with different socioeconomic environments: an international prospective cohort study
Authors: Kämpfer Judith , Yagensky Andriy , Zdrojewski Tomasz , Windecker Stephan , Meier Bernhard , Pavelko Mykhailo , Sichkaruk Iryna , Kasprzyk Piotr , Gruchala Marzin , Giacomini Mikael , Räber Lukas , Saner Hugo
Published: August 2017

Background

Hospital-based data on the impact of socioeconomic environment on long-term survival after myocardial infarction (MI) are lacking. We compared outcome and quality of secondary prevention in patients after MI living in three different socioeconomic environments including patients from three tertiary-care teaching hospitals with similar service population size in Switzerland, Poland and Ukraine.

Methods

This is a prospective cohort study of patients with a first MI in three different tertiary-care teaching hospitals in Bern (Switzerland), Gdansk (Poland) and Lutsk (Ukraine) during the acute phase in the year 2010 and follow-up of these patients with a questionnaire and, if necessary, telephone interviews 3.5 years after the acute event. The study cohort comprises all consecutive patients hospitalised in every one of the three study centres during the year 2010 for a first MI in the age ≤75 years who survived ≥30 days.

Results

The proportion of patients with ST-segment elevation myocardial infarction (STEMI) was high in Gdansk (Poland) (80%) and in Lutsk (Ukraine) (74%), while the ratio of STEMIs to non-STEMIs was nearly 50:50 in Bern (Switzerland) (50.6% STEMIs). Percutaneous coronary intervention (PCI) was the first choice therapy both in Bern (Switzerland) (100%) and in Gdansk (Poland) (92%), while it was not performed at all in Lutsk (Ukraine). We found substantial differences in treatment and also in secondary prevention interventions including cardiac rehabilitation. All-cause mortality at 3.5 year follow-up was 4.6% in Bern (Switzerland), 8.5% in Gdansk (Poland) and 14.6% in Lutsk (Ukraine).

Conclusion

Substantial differences in treatment and secondary prevention measures according to low-income, middle-income and high-income socioeconomic situation are associated with a threefold difference in mortality 3.5 years after the acute event. Countries with low socioeconomic environment should increase efforts and be supported to improve care including secondary prevention in particular for MI patients. A greater number of PCIs per million inhabitants itself does not guarantee lower mortality scores.
Diagnostic barriers for somatic symptom disorders in primary care: study protocol for a mixed methods study in Germany
Authors: Heinbokel Christina , Lehmann Marco , Pohontsch Nadine Janis , Zimmermann Thomas , Althaus Astrid , Scherer Martin , Löwe Bernd
Published: August 2017

Introduction

Somatoform or somatic symptom disorders ((S)SD) are common and have a negative impact on the patients’ health-related quality of life, healthcare use and costs. In primary care, which is central to the management of (S)SD, diagnosis and treatment tend to be delayed. There is a significant lack of evidence regarding the barriers in the diagnostic process of (S)SD in primary care and how interventions should be tailored to address them. The aim of this study is to analyse the diagnostic process in primary care that results in the diagnosis or non-diagnosis of a (S)SD.

Methods and analysis

This mixed methods study will investigate the topic with qualitative methods, subsequently proceeding to a quantitative phase where the initial results will be validated and/or generalised. First, focus groups will explore meanings and patterns, inconsistencies and conflicts in general practitioners’ (GPs) thoughts and behaviours when diagnosing (S)SD. Second, the results of these focus groups will be used to develop interview guidelines for subsequent face-to-face interviews. Patients and their treating GPs will be interviewed separately on how they experience the history of illness, the diagnostic process and treatment. Third, based on the results of the first two study parts, a questionnaire will be derived and a nationwide survey among German GPs will be conducted, quantifying the barriers and difficulties identified before.

Ethics and dissemination

Ethics approval was obtained from the Ethics Committee of the Hamburg Medical Association, Germany (approval number PV4763). The results of this study will be disseminated through conference presentation and publications in peer-reviewed journals.

Trial registration number

The study is registered in the German Clinical Trial Register (DRKS), DRKS-ID DRKS00009736.
Gender differences in infant survival: a secondary data analysis in rural North India
Authors: Chowdhury Ranadip , Taneja Sunita , Mazumder Sarmila , Bhandari Nita , Strand Tor A
Published: August 2017

Objective

To examine gender differences in infant survival on the first day of life, in the first week of life, and in the neonatal and post-neonatal periods by socio-demographic and economic variables.

Design

Secondary data analysis was performed on data from a cluster randomised trial on the effect of implementation of the Integrated Management of Neonatal and Childhood Illness programme, India.

Settings

The study setting was Palwal and Faridabad, districts of Haryana, a state in North India.

Measures

Multiple logistic regression models taking the cluster design into account were used to estimate gender differences in mortality in different periods of infancy.

Results

A total of 60 480 infants were included in these analyses. Of 4060 infant deaths, 2054 were female (7.2% of all females born) and 2006 were male (6.3% of all males born). The death rate was significantly higher in females in the post-neonatal period but not during the neonatal period. The odds of death at 29–180 days and at 181–365 days were 1.4 (95% CI 1.3 to 1.6) and 1.7 (95% CI: 1.4 to 2.0) higher in females compared with males, respectively. This increase was seen across all socio-demographic and economic strata.

Conclusion

Gender differences during the post-neonatal period are a major threat to the survival and health of female infants in India. Programmes need to identify measures that can specifically reduce female mortality.

Trial registration

Clinical trialsNCT00474981
Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions: protocol for a phase II single-arm trial
Authors: Ebben Harm P , Nederhoed Johanna H , Lely Rutger J , Wisselink Willem , Yeung Kakkhee
Published: August 2017

Introduction

Acute peripheral arterial occlusions can be treated with intra-arterial catheter-directed thrombolysis as an alternative to surgical thromboembolectomy. Although less invasive, this treatment is time-consuming and carries a significant risk of haemorrhagic complications. Contrast-enhanced ultrasound using microbubbles could accelerate dissolution of thrombi by thrombolytic medications due to mechanical effects caused by oscillation; this could allow for lower dosages of thrombolytics and faster thrombolysis, thereby reducing the risk of haemorrhagic complications. In this study, the safety and practical applicability of this treatment will be investigated.

Methods and analysis

A single-arm phase II trial will be performed in 20 patients with acute peripheral arterial occlusions eligible for thrombolytic treatment. Low-dose catheter-directed thrombolysis with urokinase will be used. The investigated treatment will be performed during the first hour of thrombolysis, consisting of intravenous infusion of 4 Luminity phials (6 mL in total, diluted with saline 0.9% to 40 mL total) of microbubbles with the use of local ultrasound at the site of occlusion. Primary end points are the incidence of complications and technical feasibility. Secondary end points are angiographic and clinical success, duration of thrombolytic infusion, treatment-related mortality, amputations, additional interventions and quality of life.

Ethics and dissemination

Ethical approval for this study was obtained in 2015 from the Medical Ethics Committee of the VU University Medical Center, Amsterdam, the Netherlands. A statement of consent for this study was given by the Dutch national competent authority. Data will be presented at national and international conferences and published in a peer-reviewed journal.

Trial registration numbers

Dutch National Trial Registry: NTR4731; European Clinical Trials Database of the European Medicines Agency: 2014-003469-10; Pre-results.
Facilitation roles and characteristics associated with research use by healthcare professionals: a scoping review
Authors: Cranley Lisa A , Cummings Greta G , Profetto-McGrath Joanne , Toth Ferenc , Estabrooks Carole A
Published: August 2017

Background

Implementing research findings into practice is a complex process that is not well understood. Facilitation has been described as a key component of getting research findings into practice. The literature on facilitation as a practice innovation is growing. This review aimed to identify facilitator roles and to describe characteristics of facilitation that may be associated with successful research use by healthcare professionals.

Methods

We searched 10 electronic databases up to December 2016 and used predefined criteria to select articles. We included conceptual papers and empirical studies that described facilitator roles, facilitation processes or interventions, and that focused on healthcare professionals and research use. We used content and thematic analysis to summarise data. Rogers’ five main attributes of an innovation guided our synthesis of facilitation characteristics.

Results

Of the 38 488 articles identified from our online and manual search, we included 195 predominantly research studies. We identified nine facilitator roles: opinion leaders, coaches, champions, research facilitators, clinical/practice facilitators, outreach facilitators, linking agents, knowledge brokers and external-internal facilitators. Fifteen facilitation characteristics were associated with research use, which we grouped into five categories using Rogers’ innovation attributes: relative advantage, compatibility, complexity, trialability and observability.

Conclusions

We found a diverse and broad literature on the concept of facilitation that can expand our current thinking about facilitation as an innovation and its potential to support an integrated, collaborative approach to improving healthcare delivery.
The role of rehabilitation measures in reintegration of children with brain tumours or leukaemia and their families after completion of cancer treatment: a study protocol
Authors: Peikert Mona Leandra , Inhestern Laura , Bergelt Corinna
Published: August 2017

Introduction

For ill children as well as for their parents and siblings, childhood cancer poses a major challenge. Little is known about the reintegration into daily life of childhood cancer survivors and their families. The aim of this prospective observational study is to further the understanding of the role of rehabilitation measures in the reintegration process of childhood leukaemia or brain tumour survivors and their family members after the end of cancer treatment.

Methods and analysis

This prospective observational study consists of three study arms: a quantitative study in cooperation with three German paediatric oncological study registries (study arm 1), a quantitative study in cooperation with a rehabilitation clinic that offers a family-oriented paediatric oncological rehabilitation programme (study arm 2) and a qualitative study at 12-month follow-up including families from the study arms 1 and 2 (study arm 3). In study arm 1, children, parents and siblings are surveyed after treatment (baseline), 4–6 months after baseline measurement and at 12-month follow-up. In study arm 2, data are collected at the beginning and at the end of the rehabilitation measure and at 12-month follow-up. Families are assessed with standardised questionnaires on quality of life, emotional and behavioural symptoms, depression, anxiety, fear of progression, coping and family functioning. Furthermore, self-developed items on rehabilitation aims and reintegration into daily life are used. Where applicable, users and non-users of rehabilitation measures will be compared regarding the outcome parameters. Longitudinal data will be analysed by means of multivariate analysis strategies. Reference values will be used for comparisons if applicable. Qualitative data will be analysed using thematic analysis.

Ethics and dissemination

This study has been approved by the medical ethics committee of the Medical Chamber of Hamburg. Data will be published in peer-reviewed journals and presented at conferences.
The benefits of hardware removal in patients with pain or discomfort after fracture healing of the ankle: a systematic review protocol
Authors: Thune Alexandra , Hagelberg Mårten , Nåsell Hans , Sköldenberg Olof
Published: August 2017

Introduction

For any orthopaedic surgeon working with trauma; ankle fractures are one of the most common injuries treated. The treatment of ankle fractures can be conservative, using external fixation, but more commonly the fractures are treated with open reduction and internal fixation. Residual pain and discomfort are common in patients after surgical treatment of fractures of the ankle. Sometimes it is difficult to determine whether the pain or discomfort is due to the implants left in situ or the primary injury itself. In many cases, the decision is made to remove the implants. Extraction of internal fixation material from the ankle is a common procedure in many orthopaedic clinics. There are no evidence-based guidelines or consensus regarding the effect of hardware removal from the ankle. The aim of this protocol is to describe the method that will be used to collect, describe and analyse the current evidence regarding hardware removal after fracture healing of the ankle.

Methods and analysis

We will conduct a systematic review of studies that were published after 1967 regarding the benefits of hardware removal in patients with pain or discomfort after fracture healing of the ankle. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We will make a predefined search strategy and use it in several databases. We will include both randomised controlled trials (RCTs) and non-RCT studies. We will use descriptive statistics to summarise the studies collected. If more than one RCT is collected then a meta-analysis will be conducted. The quality of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation guidelines.

Ethics and dissemination

No ethics approval is required as no primary data will be collected. Once complete, the results will be made available by peer-reviewed publication.

Trial registration number

PROSPERO registration number CRD42016039186
Equipping community pharmacy workers as agents for health behaviour change: developing and testing a theory-based smoking cessation intervention
Authors: Steed Liz , Sohanpal Ratna , James Wai-Yee , Rivas Carol , Jumbe Sandra , Chater Angel , Todd Adam , Edwards Elizabeth , Macneil Virginia , Macfarlane Fraser , Greenhalgh Trisha , Griffiths Chris , Eldridge Sandra , Taylor Stephanie , Walton Robert
Published: August 2017

Objective

To develop a complex intervention for community pharmacy staff to promote uptake of smoking cessation services and to increase quit rates.

Design

Following the Medical Research Council framework, we used a mixed-methods approach to develop, pilot and then refine the intervention.

Methods

Phase I: We used information from qualitative studies in pharmacies, systematic literature reviews and the Capability, Opportunity, Motivation—Behaviour framework to inform design of the initial version of the intervention.Phase II: We then tested the acceptability of this intervention with smoking cessation advisers and assessed fidelity using actors who visited pharmacies posing as smokers, in a pilot study.Phase III: We reviewed the content and associated theory underpinning our intervention, taking account of the results of the earlier studies and a realist analysis of published literature. We then confirmed a logic model describing the intended operation of the intervention and used this model to refine the intervention and associated materials.

Setting

Eight community pharmacies in three inner east London boroughs.

Participants

12 Stop Smoking Advisers.

Intervention

Two, 150 min, skills-based training sessions focused on communication and behaviour change skills with between session practice.

Results

The pilot study confirmed acceptability of the intervention and showed preliminary evidence of benefit; however, organisational barriers tended to limit effective operation. The pilot data and realist review pointed to additional use of Diffusion of Innovations Theory to seat the intervention in the wider organisational context.

Conclusions

We have developed and refined an intervention to promote smoking cessation services in community pharmacies, which we now plan to evaluate in a randomised controlled trial.

Trial registration number

UKCRN ID 18446, Pilot.
A cross-sectional study of travel patterns of older adults in the USA during 2015: implications for mobility and traffic safety
Authors: Shen Sijun , Koech Wilson , Feng Jing , Rice Thomas M , Zhu Motao
Published: August 2017

Background

With an ever increasing population of older adults (65+ years) in the USA, a better understanding of this population’s travel patterns is needed to improve travel mobility and transportation safety.

Objective

In this study, we described the travel patterns of older adults in the USA during 2015.

Methods

Travel patterns of older adults (65–74 and 75+ years) were compared with younger adults (25–64 years) by frequency and proportion of daily trips. The daily trips of various age groups were estimated using the 2015 American Time Use Survey.

Results

The percentage of daily travellers was 88% for adults (25–64 years), 75% for adults (65–74 years) and 68% for adults (75+ years). While the percentage of privately owned vehicle (POV) drivers and average time of driving POVs decreased, the percentage of POV passengers increased as adults aged. Females were less likely to drive POVs and had decreased average daily driving time, but they were more likely to ride in POVs as passengers and had longer average daily riding times than their male counterparts across all age groups. Older adults were more likely to travel in the mornings and early afternoons (from 8:00 to 15:59) while younger adults were more likely to travel in the late afternoons and early evenings (from 16:00 to 19:59).

Conclusions

POV use is the predominant mode of transit in the USA. As adults age, the percentages of daily travellers and POV drivers decrease. This pattern is more apparent among females than males. This study delineated travel patterns of older adults using a 2015 national survey, and the findings facilitate traffic systems designers and policy-makers to develop and implement initiatives to accommodate older adults’ mobility needs and improve traffic safety.
What is the prevalence of and associations with forced labour experiences among male migrants from Dolakha, Nepal? Findings from a cross-sectional study of returnee migrants
Authors: Mak Joelle , Abramsky Tanya , Sijapati Bandita , Kiss Ligia , Zimmerman Cathy
Published: August 2017

Objectives

Growing numbers of people are migrating outside their country for work, and many experience precarious conditions, which have been linked to poor physical and mental health. While international dialogue on human trafficking, forced labour and slavery increases, prevalence data of such experiences remain limited.

Methods

Men from Dolakha, Nepal, who had ever migrated outside of Nepal for work were interviewed on their experiences, from predeparture to return (n=194). Forced labour was assessed among those who returned within the past 10 years (n=140) using the International Labour Organization's forced labour dimensions: (1)unfree recruitment; (2)work and life under duress; and (3)impossibility to leave employer. Forced labour is positive if any one of the dimensions is positive.

Results

Participants had worked in India (34%), Malaysia (34%) and the Gulf Cooperation Council countries (29%), working in factories (29%), as labourers/porters (15%) or in skilled employment (12%). Among more recent returnees (n=140), 44% experiencedunfree recruitment, 71%work and life under duressand 14%impossibility to leave employer. Overall, 73% experienced forced labour during their most recent labour migration.

Forced labour was more prevalent among those who had taken loans for their migration (PR 1.23) and slightly less prevalent among those who had migrated more than once (PR 0.87); however the proportion of those who experienced forced labour was still high (67%). Age, destination and duration of stay were associated with only certain dimensions of forced labour.

Conclusion

Forced labour experiences were common during recruitment and at destination. Migrant workers need better advice on assessing agencies and brokers, and on accessing services at destinations. As labour migration from Nepal is not likely to reduce in the near future, interventions and policies at both source and destinations need to better address the challenges migrants face so they can achieve safer outcomes.
Exploring newly qualified doctors' workplace stressors: an interview study from Australia
Authors: Tallentire Victoria R , Smith Samantha E , Facey Adam D , Rotstein Laila
Published: August 2017

Purpose

Postgraduate year 1 (PGY1) doctors suffer from high levels of psychological distress, yet the contributory factors are poorly understood. This study used an existing model of workplace stress to explore the elements most pertinent to PGY1 doctors. In turn, the data were used to amend and refine the conceptual model to better reflect the unique experiences of PGY1 doctors.

Method

Focus groups were undertaken with PGY1 doctors working at four different health services in Victoria, Australia. Transcripts were coded using Michie's model of workplace stress as the initial coding template. Remaining text was coded inductively and the supplementary codes were used to modify and amplify Michie's framework.

Results

There were 37 participants in total. Key themes included stressors intrinsic to the job, such as work overload and long hours, as well as those related to the context of work such as lack of role clarity and relationships with colleagues. The main modification to Michie's framework was the addition of the theme of uncertainty. This concept related to most of the pre-existing themes in complex ways, culminating in an overall sense of anxiety.

Conclusions

Michie's model of workplace stress can be effectively used to explore the stressors experienced by PGY1 doctors. Pervasive uncertainty may help to explain the high levels of psychological morbidity in this group. While some uncertainty will always remain, the medical education community must seek ways to improve role clarity and promote mutual respect.
Effectiveness of rehabilitation after a total hip arthroplasty: a protocol for an observational study for the comparison of usual care in the Netherlands versus Germany
Authors: Seeber Gesine H , Wijnen Annet , Lazovic Djordje , Bulstra Sjoerd K , Dietz Günter , van Lingen Christiaan P , Stevens Martin
Published: August 2017

Introduction

Osteoarthritis is the most common joint disorder worldwide. Total hip arthroplasty (THA) is considered one of the most effective treatments for end-stage hip osteoarthritis. The number of THAs is expected to increase dramatically in the coming decades. Usual postoperative rehabilitation after primary THA differs between the German and the Dutch system. In the Netherlands, patients undergo fast-track surgery and are discharged into their home environment within a few days without receiving any aftercare. In Germany, patients stay in the hospital for about 12 days before being transferred to a rehabilitation centre for a period of 3 weeks. The superficially more cost-effective Dutch system of usual care after THA is judged critically in both countries due to suboptimal rehabilitation outcomes. The aim of this study is therefore to compare the Dutch with the German usual care rehabilitation after primary THA. It is hypothesised that the German procedure is more effective in terms of functional outcomes and patient satisfaction than the Dutch procedure and that in the long run the German approach is more cost-effective than the Dutch system.

Methods and analysis

Medical effectiveness will be assessed at four different time points by means of patient self-reported questionnaires and functional tests. Assessments include the Hip disability and Osteoarthritis Outcome Score, Patient Acceptable Symptom State, Short Form 36, EuroQol 5 Dimensions 3 Level Questionnaire, Timed Up & Go Test and Five Times Sit-to-Stand Test. Additionally, long-term economic aspects in both countries will be assessed from a societal perspective, to get a first impression on whether cutting costs for rehabilitation, as practised in the Netherlands, really disburdens the healthcare system efficiently.

Ethics and dissemination

The study is approved by the Institutional Review Boards of both University Medical Center Groningen (METc2015/483) and Hannover Medical School (no 2874-2015) and will be conducted according to the principles of the Declaration of Helsinki (64th, 2013). The results of the study will be published in international peer-reviewed scientific journals. Patient data will be presented anonymously in any publication or scientific journal.

Trial registration number

DRKS00011345; Pre-results.
Transformation of mortality in a remote Australian Aboriginal community: a retrospective observational study
Authors: Hoy Wendy E , Mott Susan Anne , McLeod Beverly June
Published: August 2017

Objectives

To describe trends in ages and causes of death in a remote-living Australian Aboriginal group over a recent 50-year period.

Design

A retrospective observational study, from 1960 to 2010, of deaths and people starting dialysis, using data from local clinic, parish, dialysis and birthweight registers.

Setting

A remote island community in the Top End of Australia’s Northern Territory, where a Catholic mission was established in 1911. The estimated Aboriginal population was about 800 in 1960 and 2260 in 2011.

Participants

All Aboriginal residents of this community whose deaths had been recorded.

Outcome measures

Annual frequencies and rates of terminal events (deaths and dialysis starts) by age group and cause of death.

Results

Against a background of high rates of low birth weight, 223 deaths in infants and children and 934 deaths in adults (age>15 years) were recorded; 88% were of natural causes. Most deaths in the 1960s were in infants and children. However, over time these fell dramatically, across the birthweight spectrum, while adult deaths progressively increased. The leading causes of adult natural deaths were chronic lung disease, cardiovascular disease and, more recently, renal failure, and rates were increased twofold in those of low birth weight. However, rates of natural adult deaths have been falling briskly since 1986, most markedly among people of age ≥45 years. The population is increasing and its age structure is maturing.

Conclusions

The changes in death profiles, the expression of the Barker hypothesis and the ongoing increases in adult life expectancy reflect epidemiological and health transitions of astonishing rapidity. These probably flow from advances in public health policy and healthcare delivery, as well as improved inter-sectoral services, which are all to be celebrated. Other remote communities in Australia are experiencing the same phenomena, and similar events are well advanced in many developing countries.