bluuebunny/crossref_metadata_2025 huggingface dataset:
A rice PHD‐finger protein OsTITANIA, is a growth regulator that functions through elevating expression of transporter genes for multiple metals
Authors: Tanaka Nobuhiro , Uraguchi Shimpei , Kajikawa Masataka , Saito Akihiro , Ohmori Yoshihiro , Fujiwara Toru
Published: September 2018

Essential metal absorption for plant growth is mediated predominantly by metal‐specific transporters, with expression that responds to the environmental or cellular conditions of specific metals. Differing from metal‐specific regulation, we describe a constitutively expressed transcription factor that regulates the transport of several metals in rice. We characterized the rice mutant LOW CADMIUM 5 (LC5), which exhibited reduced growth and accumulation of essential metals (e.g., copper [Cu], zinc [Zn] and manganese [Mn]) in shoots. LC5 was dwarf and developed less tillers than the wild type, but the structure of vasculature was apparently normal. Molecular genetic analysis revealed that the causal gene of LC5 is an ortholog of the transcriptional regulator Arabidopsis thaliana TITANIA (TTA), known as a transcriptional regulator. Expression analyses demonstrated that the OsTTA gene encodes a nucleus‐localized protein containing a plant homeodomain‐finger (PHD‐finger) domain and is expressed ubiquitously in rice plants. RNA sequencing and quantitative PCR analyses revealed that the mRNA accumulation of transporter genes for essential metals, including iron (Fe), Zn, or Mn, were substantially lower in LC5 roots than in the wild type. Unlike known transcription factors of metal transport regulation, OsTTA transcript accumulation was not affected by metal availability. In addition, the growth defect of LC5 was partially rescued by Fe, Zn, or Mn supplementation, respectively. Taken together, OsTTA is a constitutively expressed regulator of multiple metal transporter genes responsible for essential metals delivery to shoots for their normal growth.
Membrane physical state and stress regulation in Synechocystis: fluidizing alcohols repress fatty acid desaturation
Authors: Mironov Kirill S. , Shumskaya Maria , Sidorov Roman A. , Trofimova Marina S. , Los Dmitry A.
Published: September 2018

Cyanobacteria are prokaryotic photosynthetic organisms widely used in biotechnology, photosynthesis and abiotic stress research. There are several cyanobacterial strains modified to produce biofuels, but the influence of alcohols on cyanobacterial cell physiology is poorly understood. Here, we conducted a systematic study of the effects of nine primary aliphatic alcohols and an aromatic benzyl alcohol on both membrane physical state and the expression of genes for fatty acid desaturases (FADs) in a model cyanobacterium Synechocystis sp. strain PCC 6803. Hexan‐1‐ol was found to have the most membrane fluidizing action among all alcohols studied, with its efficiency correlating with both duration of treatment and alcohol concentration. A prolonged exposure to alcohol results in a continuous loss of unsaturated fatty acids (FAs) followed by cell death, an undesired challenge that should be considered in cyanobacterial biotechnology. We suggest that membrane fluidization is the key component in alcohol stress causing inactivation of FADs and resulting in a lethal depletion of unsaturated FAs. Due to the most pronounced effects of alcohol‐ and heat‐induced membrane fluidization on desB encoding a terminal ω3‐FAD, we propose to call desB a ‘viscosity gene’ in analogy to heat‐induced ‘fluidity gene’ hspA.
Ascites formation accompanied by portal vein thrombosis after porcine islet xenotransplantation via the portal vein in Rhesus macaque (Macaca mulatta)
Authors: Kim Jong‐Min , Shin Jun‐Seop , Han Sungyoung , Min Byoung‐Hoon , Jeong Won Young , Lee Ga Eul , Kim Min Sun , Kwon Seeun , Chung Hyunwoo , Kang Hee Jung , Park Chung‐Gyu
Published: September 2018

Pig‐to‐nonhuman primate (NHP) islet transplantation has been widely conducted as a preclinical xenotransplantation model prior to human clinical trial. Portal vein thrombosis is one of the complications associated with islet infusion through the portal vein into the liver. Here, we briefly report severe case of ascites formation accompanied by portal vein thrombi after pig‐to‐NHP islet xenotransplantation in a rhesus monkey. Meticulous prophylactic treatment such as continuous heparin infusion should be implemented to prevent portal vein thrombi in pig‐to‐NHP islet transplantation models.
Opioid Addicted Pregnancies: A Public Health Issue
Authors: Anderson James F. , Reinsmith-Jones Kelley , Dyson Laronistine , Langsam Adam H.
Published: September 2018

While the opioid crisis in the US has been widely publicized, what has not been given equal attention is the increasing number of pregnant women addicted to various prescribed and illegal opioids which has paralleled the current opioid epidemic. Instead of viewing the matter as a criminal justice issue, many experts believe that the issue is a public health problem because of the sheer number of people who are impacted nationwide, as well as the negative health consequences that affect the mothers and infants. We argue that opioid addicted pregnant women is not a criminal justice issue, but rather, a public health epidemic that requires healthcare approaches rather than punitive criminal justice strategies.
Reviewer Acknowledgements
Authors: Young James
Published: September 2018

Reviewer AcknowledgementsInternational Journal of Social Science Studies (IJSSS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether IJSSS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 6, Number 9 António Calha, Polytechnic Institute of Portalegre, PortugalBashar Malkawi, "University of Sharjah, College of Law, UAEBegoña Montero-Fleta, Universitat Politécnica de València, SpainE.Ozan Aksoz, Anadolu University, TurkeyEmanuele Achino, C. D. T. O., ItalyFroilan Mobo, Philippine Merchant Marine Academy, PhilippinesJohn Boulard Forkuor , Kwame Nkrumah University of Science and Technology (KNUST), GhanaK.O. Aramide, The Polytechnic Ibadan, NigeriaLaura Diaconu Maxim, "Alexandru Ioan Cuza University" of Iasi, RomaniaMei-Ling Lin, National Open University, TaiwanMickey Langlais, University of Nebraska – Kearney, USAQingzhi Huan, Peking University, ChinaShariq aziz butt, Superior University Lahore, PakistanYaghoob Foroutan , The University of Waikato, New Zealand
Sodium and potassium conductances in principal neurons of the mouse piriform cortex: a quantitative description
Authors: Ikeda Kaori , Suzuki Norimitsu , Bekkers John M.
Published: September 2018

Key points

The primary olfactory (or piriform) cortex is a promising model system for understanding how the cerebral cortex processes sensory information, although an investigation of the piriform cortex is hindered by a lack of detailed information about the intrinsic electrical properties of its component neurons.

In the present study, we quantify the properties of voltage‐dependent sodium currents and voltage‐ and calcium‐dependent potassium currents in two important classes of excitatory neurons in the main input layer of the piriform cortex.

We identify several classes of these currents and show that their properties are similar to those found in better‐studied cortical regions.

Our detailed quantitative descriptions of these currents will be valuable to computational neuroscientists who aim to build models that explain how the piriform cortex encodes odours.

The primary olfactory cortex (or piriform cortex, PC) is an anatomically simple palaeocortex that is increasingly used as a model system for investigating cortical sensory processing. However, little information is available on the intrinsic electrical conductances in neurons of the PC, hampering efforts to build realistic computational models of this cortex. In the present study, we used nucleated macropatches and whole‐cell recordings to rigorously quantify the biophysical properties of voltage‐gated sodium (NaV), voltage‐gated potassium (KV) and calcium‐activated potassium (KCa) conductances in two major classes of glutamatergic neurons in layer 2 of the PC, semilunar (SL) cells and superficial pyramidal (SP) cells. We found that SL and SP cells both express a fast‐inactivating NaV current, two types of KV current (A‐type and delayed rectifier‐type) and three types of KCa current (fast‐, medium‐ and slow‐afterhyperpolarization currents). The kinetic and voltage‐dependent properties of the NaV and KV conductances were, with some exceptions, identical in SL and SP cells and similar to those found in neocortical pyramidal neurons. The KCa conductances were also similar across the different types of neurons. Our results are summarized in a series of empirical equations that should prove useful to computational neuroscientists seeking to model the PC. More broadly, our findings indicate that, at the level of single‐cell electrical properties, this palaeocortex is not so different from the neocortex, vindicating efforts to use the PC as a model of cortical sensory processing in general.
Social Media and Digital Breakage on the Sports Beat
Authors: Lowes Mark , Robillard Christopher
Published: September 2018

This scholarly commentary draws on existing sport communication literature in an exploration of social media’s role in, and impact on, sport journalism practices and the production of sport news. Of particular concern is the emergence of a form of citizen sport journalism that usurps the traditional role of sport journalists as gatekeepers of the relationship between the sports world and its multitude of audiences. It is argued that social media are providing audiences with more opportunities to create the type of mediated discourses they want to experience by eliminating the scarcity of time and space that once privileged the gatekeeping status of sport journalists. Consequently, sport reporters are becoming social-media content creators and curators while competing against spectator sport-news content creators. Whereas these changes might have a negative connotation, the authors conclude that sport coverage in digital culture offers more opportunities for journalists to step outside the confines of traditional sport journalism work routines and news-production practices.
Corporate Social Responsibility in Professional Team Sports Organizations: An Integrative Review
Authors: Walzel Stefan , Robertson Jonathan , Anagnostopoulos Christos
Published: September 2018

Professional team sports organizations (PTSOs) are highly influential in our society. They can both positively and negatively shape the public discourse around responsible norms of behavior. The purpose of this article is to describe and critically review the literature on PTSOs’ corporate social responsibility (CSR) to develop a comprehensive understanding of current and future research directions in the field. Our analysis reviewed articles on CSR within PTSOs and identified publication year; geographical dispersion; journal type; sports contexts; social issues investigated; research approaches and methods; and how CSR was conceptualized, defined, and theoretically supported. The findings indicate that CSR within PTSOs has primarily been investigated in community programs, using qualitative research methods and pragmatically conceptualizing CSR on the basis of return on investments to the organization in European and North American contexts. Our discussion provides a critical review of the literature before outlining avenues for future research and practice.
The Effects of a 12-Week Combined Exercise Training Program on Arterial Stiffness, Vasoactive Substances, Inflammatory Markers, Metabolic Profile, and Body Composition in Obese Adolescent Girls
Authors: Wong Alexei , Sanchez-Gonzalez Marcos A. , Son Won-Mok , Kwak Yi-Sub , Park Song-Young
Published: September 2018

Purpose: Childhood and adolescent obesity is a major international public health crisis. It is crucial to prevent the negative effects of obesity at an early age by implementing appropriate lifestyle interventions, such as exercise training. We evaluated the effects of a combined resistance and aerobic exercise training (CET) regimen on arterial stiffness, vasoactive substances, inflammatory markers, metabolic profile, and body composition in obese adolescent girls. Methods: A total of 30 obese adolescent girls were randomly assigned to a CET (n = 15) or a control group (n = 15). The CET group trained for 3 days per week. Plasma nitric oxide, endothelin-1, C-reactive protein, arterial stiffness, glucose, insulin, the adiponectin/leptin ratio, and body fat were measured before and after 12 weeks. Results: There were significant increases (P < .05) in nitric oxide (4.0 μM) and adiponectin/leptin ratio (0.33); and decreases (P < .05) in arterial stiffness (−1.0 m/s), C-reactive protein (−0.5 mg/L), glucose (−1.2 mmol/L), insulin (−17.1 μU/mL), and body fat (−3.6%) following CET compared with control. There were no significant changes in endothelin-1 after CET or control. Conclusions: The findings of this study indicate that CET improves arterial stiffness, nitric oxide, and inflammatory and metabolic markers in obese adolescent girls. CET may have important health implications for the prevention of atherosclerosis at an early age.
Does Wearing a Portable Metabolic Unit Affect Youth’s Physical Activity or Enjoyment During Physically Active Games or Video Games?
Authors: Clevenger Kimberly A. , Pfeiffer Karin A. , Howe Cheryl A.
Published: September 2018

Portable metabolic units (PMUs) are used to assess energy expenditure, with the assumption that physical activity level and enjoyment are unaffected due to the light weight and small size. Purpose: To assess differences in physical activity level and enjoyment while wearing and not wearing a PMU. Method: Youth (8–17 y; N = 73) played children’s games or active video games while wearing and not wearing a PMU (crossover design). Participants wore an accelerometer and heart rate monitor and responded to questions about enjoyment on a facial affective scale. A repeated-measures analysis of variance was used to determine if accelerometer measures, heart rate, or enjoyment differed between conditions overall and by sex and weight status. Results: Steps per minute were lower while wearing the PMU than not wearing the PMU (40 vs 44, P = .03). There was an interaction between PMU condition and weight status for enjoyment (P = .01), with overweight participants reporting less enjoyment when wearing the PMU compared with not wearing the PMU (72 vs 75 out of 100). Heart rate, vector magnitude, and counts per minute were not different. Conclusion: There may be psychosocial effects of wearing the PMU, specifically in overweight participants. Activity level was minimally affected, but the practical significance for research is still unknown.
Phosphodiesterase EdpX1 Promotes Xanthomonas oryzae pv. oryzae Virulence, Exopolysaccharide Production, and Biofilm Formation
Authors: Xue Dingrong , Tian Fang , Yang Fenghuan , Chen Huamin , Yuan Xiaochen , Yang Ching-Hong , Chen Yihua , Wang Qi , He Chenyang
Published: September 2018

Bacteria utilize c-di-GMP as a second messenger to regulate various biological functions. The synthesis and degradation of c-di-GMP are catalyzed by GGDEF domains and an EAL or HD-GYP domain, respectively. Multiple genes encoding these domains are often found in one bacterial strain. For example, in the genome of
X. oryzae
pv. oryzae PXO99
A
, 26 genes encoding proteins containing these domains were identified. Therefore, to fully appreciate the complexity and specificity of c-di-GMP signaling in
X. oryzae
pv. oryzae, the enzymatic activities and regulatory functions of each GGDEF, EAL, and HD-GYP domain protein need to be elucidated. In this study, we showed that the EAL domain protein EdpX1 is a major PDE to regulate diverse virulence phenotypes through the c-di-GMP signaling pathway.
Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology
Authors: Lakhundi Sahreena , Zhang Kunyan
Published: September 2018

Staphylococcus aureus, a major human pathogen, has a collection of virulence factors and the ability to acquire resistance to most antibiotics. This ability is further augmented by constant emergence of new clones, makingS. aureusa “superbug.” Clinical use of methicillin has led to the appearance of methicillin-resistantS. aureus(MRSA).
Acupressure for Respiratory Allergic Diseases: A Systematic Review of Randomised Controlled Trials
Authors: Liang Yaqun , Lenon George Binh , Yang Angela Wei Hong
Published: September 2018

Objective

To evaluate the effects and safety of acupressure for the management of respiratory allergic diseases by systematically reviewing randomised controlled trials (RCTs).

Methods

A total of 13 electronic English and Chinese databases were searched until July 2017. Two authors extracted data and evaluated risk of bias independently. Review Manager V.5.3 was employed for data analysis.

Results

The literature search identified 186 papers, of which only four of met the inclusion criteria: two for allergic rhinitis (AR) and two for asthma. High and unclear risk of bias existed across all the included studies. The findings demonstrated that acupressure greater effects on the relief of nasal symptoms of AR compared with 1% ephedrine nasal drop plus thermal therapy. With either Western medicine or Chinese herbal medicine as a cointervention, one study indicated that acupressure plus salbutamol was led to a significantly greater improvement of pulmonary function for patients with asthma compared with salbutamol only. However, the remaining two studies indentified no significant differences in any outcome measures between the two groups.

Conclusions

No reliable conclusions regarding the effects of acupressure on AR and asthma could be drawn by this review due to the small number of available trials with significant heterogeneity of study design and high/unclear risk of bias. Further, more rigorously designed RCTs are needed. Acupressure seems safe for symptomatic relief of AR and asthma, although larger studies are required to be able to robustly confirm its safety.

Trial registration number

ACTRN12617001106325; Pre-results.
Venous thromboembolism leading to diagnosis of de novo malignancy in an organ transplant recipient
Authors: Mitchell Natalie , Connell Alana , Kurth Benjamin
Published: September 2018

We report the case of a patient with remote orthotopic liver transplant who was ultimately diagnosed with Merkel cell carcinoma following admission for initial venous thromboembolism. Additionally, we review pertinent literature related to the risk of skin cancer in solid organ transplant recipients and discuss the importance of yearly skin exams in this patient population.
Recurrent gallstone ileus in a patient with ileostomy successfully treated by removal of impacted gallstone via the stoma
Authors: Korsager Leise Elisabeth Hviid , Qvist Niels , Bjørn Niels
Published: September 2018

A 75-year-old man with a permanent ileostomy presented with recurrent gallstone ileus that was treated successfully with removal of the stones via the stoma.
Effect of halo-type frontal cockpit protection on overtaking
Authors: Rosalie Simon M , Malone James M
Published: September 2018

In 2018, the Fédération Internationale de l’Automobile introduced the halo frontal cockpit protection system into Formula 1. While extensive testing was conducted to confirm that the halo protects the driver from contact, the halo’s effect on the driver during overtaking was not tested prior to its introduction. Here, we describe the effect of a halo-type structure on the neck muscle activity of one of the authors, a national-level amateur racing driver, during on-track simulations designed to practise overtaking. We found that the halo-type structure caused an increase in the rates of fatigue and workloads of sternocleidomastoid and cervical erector spinae. The results suggest that the driver adopted a forward and right laterally flexed head position, presumably to clear the central pillar from his visible field. This has the potential to increase compressive loading of the cervical spine and affect the ability to use visual cues during steering manoeuvres.
Neuroblastoma with flat genomic profile: a question of representativity?
Authors: Valind Anders , Öra Ingrid , Mertens Fredrik , Gisselsson David
Published: September 2018

Neuroblastoma is one of the most common paediatric malignancies. Detection of somatic genetic alterations in this tumour is instrumental for its risk stratification and treatment. On the other hand, an absence of detected chromosomal imbalances in neuroblastoma biopsies is difficult to interpret because it is unclear whether this situation truly reflects the tumour genome or if it is due to suboptimal sampling. We here present a neuroblastoma in the left adrenal of a newborn. The tumour was subjected to single-nucleotide polymorphism array analysis of five tumour regions with >80% tumour cells in histological mirror sections. This revealed no aberrations compared with a normal reference sample from the patient. Whole exome sequencing identified two single-nucleotide variants present in most tumour regions, corroborating that the tumour resulted from monoclonal expansion. Our data provide proof-of-principle that rare cases of neuroblastoma can have a normal whole genome copy number and allelic profile.
Neuromyelitis optica spectrum disorder presenting in an octogenarian
Authors: Campbell Amy , Ogundipe Olayinka Ayodele
Published: September 2018

This case describes an 81-year-old woman with a history of Sjögren’s syndrome presenting with recurrent falls and poor balance. She subsequently developed new and rapidly evolving neurology including hyperaesthesia, spastic paraplegia and sphincteric dysfunction. Following serial clinical reviews and detailed investigations, MRI (brainstem and cervicothoracic spine) and a seropositive result for aquaporin 4 IgG, a diagnosis of neuromyelitis optica spectrum disorder (NMOSD) was made. This case describes the clinical course of this index patient with an unusual late age of onset. The report also includes a discussion on NMOSD. We review aspects of terminology, brief epidemiology, pathogenesis, notable autoimmune associations, variance in clinical presentation and current diagnostic criteria. We also review the importance of distinguishing NMOSD from multiple sclerosis in view of the significant implications for treatment and prognosis.
Long-term survival in a patient with pulmonary spindle cell carcinoma treated with traditional Chinese medicine
Authors: Li Wenyuan , Chen Maoyan , Zhao Yuanhong
Published: September 2018

Spindle cell carcinoma (SCC) is a rare pulmonary malignancy, accounting for only 0.2%–0.3% of all lung cancers. Therefore, the prognosis and treatment of pulmonary SCC is unclear. There are only 13 reported cases in literature, only three of which had a survival of more than 11 months. Here we reported a long-term survival of a patient with pulmonary SCC who underwent treatment with traditional Chinese medicine. At the most recent follow-up in July 2018, her survival after diagnosis is 48 months and she continues to do well. To our knowledge, this is the longest survival of late stage SCC with the largest tumour burden.
Adjuvant conundrum in central mucoepidermoid carcinoma of the mandible: case presentation and literature review
Authors: Singh Maneesh , Nangia Sapna , Cudahy Terence , Mir Ruquaya
Published: September 2018

The cornerstone modality of treatment of central mucoepidermoid carcinoma (CMEC) of the mandible is surgery, optimally, an en bloc resection with/without segmental or hemimandibulectomy. Notwithstanding the documentation of a survival benefit in few case reports with the addition of postoperative radiotherapy in carefully selected high-risk patients, there does not exist a clearly defined consensus regarding the role of adjuvant radiotherapy. We report the case of a 49-year-old man who presented with right lower jaw swelling which on imaging was found to be a multiloculated lesion causing bony expansion and cortical destruction of the mandible and was diagnosed with CMEC after radiological and histopathological criteria were met. He underwent right hemimandibulectomy and histopathology showed squamous and mucinous cells with positive mucicarmine staining and characteristic immunohistochemistry markers confirming the diagnosis of CMEC. He subsequently underwent adjuvant radiotherapy and is disease free 5 years since treatment completion.
Chronic ocular hypertension in rabbits induced by limbal buckling
Authors: Wang Qilin , Wang Juanjuan , Lin Xingyan , Lui Kwok Ho , Chang Suiting , Zhou Rouxi , Lam Dennis Shun-Chiu
Published: September 2018

Aim

To establish a rabbit model of chronic ocular hypertension (OHT) by limbal buckling.

Methods

Eighteen New Zealand White rabbits were involved and divided into three groups. A latex encircling band of 20, 25 or 35 mm was implanted behind the limbus in the right eye of each animal. The intraocular pressure (IOP) was monitored for 8 weeks, after which optic nerve damage was evaluated by fundus photography, optical coherence tomography (OCT) retrograde labelling and histology. Meanwhile, the anterior chamber angle (ACA) was examined by OCT and gonioscopy.

Results

OHT was induced in all animals after surgery. The IOP peaked at 38.0±3.7, 32.0±3.9 and 24.1±6.5 mm Hg in groups 1, 2 and 3, respectively, and remained elevated for 22, 25 and 39 days on average, respectively. The elevated IOPs showed good consistency within 2 weeks, although the durations of high IOP varied moderately. The area ratio between the optic cup and disc (cup to disc area) was increased in 73% of the treated eyes, and the average changes were 0.10±0.13, 0.11±0.08 and 0.09±0.02 in groups 1, 2 and 3, respectively. The depth of the optic cup was also increased in the treated eyes, and the density of the retinal ganglion cells was reduced. Additionally, the ACA showed a dynamic change with IOP after the latter was reduced by paracentesis.

Conclusion

Limbal buckling provides an effective method of producing chronic OHT and glaucomatous optic neuropathy in rabbits.
Hepatic fat and glucose tolerance in women with recent gestational diabetes
Authors: Mehmood Sadia , Margolis Myles , Ye Chang , Maple-Brown Louise , Hanley Anthony J , Connelly Philip W , Sermer Mathew , Zinman Bernard , Retnakaran Ravi
Published: September 2018

Objective

Women with a history of gestational diabetes mellitus (GDM) have an elevated risk of ultimately developing pre-diabetes and diabetes later in life. They also have an increased prevalence of fatty liver, but recent studies have reported conflicting findings on whether hepatic fat affects their risk of pre-diabetes/diabetes. Thus, we sought to evaluate the associations of liver fat with glucose homeostasis and determinants thereof in women with and without recent gestational dysglycemia.

Methods

Two hundred and fifty-seven women underwent an antepartum oral glucose tolerance test (OGTT), which diagnosed 97 with GDM, 40 with gestational impaired glucose tolerance (GIGT), and 120 with normal glucose tolerance (NGT). At a mean of 4.8 years post partum, they underwent an OGTT (which revealed that 52 had progressed to pre-diabetes/diabetes) and hepatic ultrasound, on which liver fat was graded as none (n=164), mild (n=66), or moderate (n=27).

Results

Liver fat was more prevalent in women with previous GDM than in those with GIGT or NGT (p=0.009) and in women with current pre-diabetes/diabetes than in those without (p=0.0003). As the severity of liver fat increased, there was a progressive worsening of insulin sensitivity and beta-cell function, coupled with rising fasting and 2-hour glucose (all p<0.0001). On multiple linear regression analyses, moderate liver fat was independently associated with lower insulin sensitivity (p=0.0002) and higher 2-hour glucose (p=0.009). Moreover, moderate liver fat emerged as an independent predictor of pre-diabetes/diabetes (OR=3.66, 95% CI 1.1 to 12.5).

Conclusion

The higher prevalence of liver fat in women with previous GDM is associated with their increased risk of pre-diabetes/diabetes.
Institutionalising an evidence-informed approach to guideline development: progress and challenges at the World Health Organization
Authors: Gopinathan Unni , Hoffman Steven J
Published: September 2018

This study explored experiences, perceptions and views among World Health Organization (WHO) staff about the changes, progress and challenges brought by the guideline development reforms initiated in 2007. Thirty-five semistructured interviews were conducted with senior WHO staff. Sixteen of the interviewees had in-depth experience with WHO’s formal guideline development process. Thematic analysis was conducted to identify key themes in the qualitative data, and these were interpreted in the context of the existing literature on WHO’s guideline development processes. First, the reforms were seen to have transformed and improved the quality of WHO’s guidelines. Second, independent evaluation and feedback by the Guidelines Review Committee (GRC) was described to have strengthened the legitimacy of WHO’s recommendations. Third, WHO guideline development processes are not yet designed to systematically make use of all types of research evidence needed to inform decisions about health systems and public health interventions. For example, several interviewees expressed dissatisfaction with the insufficient attention paid to qualitative evidence and evidence from programme experience, and how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process evaluates the quality of evidence from non-randomised study designs, while others believed that GRADE was just not properly understood or applied. Fourth, some staff advocated for a more centralised quality assurance process covering all outputs from WHO’s departments and scientific advisory committees, especially to eliminate strategic efforts aimed at bypassing the GRC’s requirements. Overall, the ‘culture change’ senior WHO staff called for over 10 years ago appears to have gradually spread throughout the organisation. However, at least two major challenges remain: (1) ensuring that all issued advice benefits from independent evaluation, monitoring and feedback for quality and (2) designing guideline development processes to better acquire, assess, adapt and apply the full range of evidence that can inform recommendations on health systems and public health interventions.
Effectiveness of service models and organisational structures supporting tuberculosis identification and management in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review
Authors: Heuvelings Charlotte C , Greve Patrick F , de Vries Sophia G , Jelle Visser Benjamin , Bélard Sabine , Janssen Saskia , Cremers Anne L , Spijker René , Shaw Elizabeth , Hill Ruaraidh A , Zumla Alimuddin , Sandgren Andreas , van der Werf Marieke J , Grobusch Martin Peter
Published: September 2018

Objective

To determine which service models and organisational structures are effective and cost-effective for delivering tuberculosis (TB) services to hard-to-reach populations.

Design

Embase and MEDLINE (1990–2017) were searched in order to update and extend the 2011 systematic review commissioned by National Institute for Health and Care Excellence (NICE), discussing interventions targeting service models and organisational structures for the identification and management of TB in hard-to-reach populations. The NICE and Cochrane Collaboration standards were followed.

Setting

European Union, European Economic Area, European Union candidate countries and Organisation for Economic Co-operation and Development countries.

Participants

Hard-to-reach populations, including migrants, homeless people, drug users, prisoners, sex workers, people living with HIV and children within vulnerable and hard-to-reach populations.

Primary and secondary outcome measures

Effectiveness and cost-effectiveness of the interventions.

Results

From the 19 720 citations found, five new studies were identified, in addition to the six discussed in the NICE review. Community health workers from the same migrant community, street teams and peers improved TB screening uptake by providing health education, promoting TB screening and organising contact tracing. Mobile TB clinics, specialised TB clinics and improved cooperation between healthcare services can be effective at identifying and treating active TB cases and are likely to be cost-effective. No difference in treatment outcome was detected when directly observed therapy was delivered at a health clinic or at a convenient location in the community.

Conclusions

Although evidence is limited due to the lack of high-quality studies, interventions using peers and community health workers, mobile TB services, specialised TB clinics and improved cooperation between health services can be effective to control TB in hard-to-reach populations. Future studies should evaluate the (cost-)effectiveness of interventions on TB identification and management in hard-to-reach populations and countries should be urged to publish the outcomes of their TB control systems.

PROSPERO registration number

CRD42015017865.
Incidence and characteristics of ventilator-associated pneumonia in a regional non-tertiary Australian intensive care unit: protocol for a retrospective clinical audit study
Authors: Watson Kirsty , Heales Luke J , Fernando Jeremy , Reoch Josephine , Tan Elise , Smith Karen , Austin David , Divanoglou Anestis
Published: September 2018

Introduction

Ventilator-associated pneumonia (VAP) is a medical complication associated with prolonged mechanical ventilation. Most studies looking at VAP originate from major, tertiary intensive care units (ICUs). Our understanding of VAP in regional hospitals is limited. Given that patient characteristics often differ between metropolitan and regional centres, it is important to investigate VAP in a regional non-tertiary ICU. This project will establish and report the incidence, case characteristics and outcomes including mortality and length of stay related to VAP in a regional non-tertiary Australian ICU. Furthermore, it will compare the incidence of VAP in accordance with consultant diagnosed cases in the medical record, and by a post hoc screening of all cases against a list of previously published diagnostic criteria.

Methods and analysis

This retrospective clinical audit study will screen medical records from the period 1 January 2013 to 31 December 2016. All cases requiring mechanical ventilation for ≥72 hours will be screened against previously reported diagnostic criteria for VAP. At the same time, their medical records will be screened for a documented diagnosis of VAP.

Ethics and dissemination

This study has been granted ethical approval from the Central Queensland Hospital and Health Service (CQHHS) Human Research Ethics Committee (HREC/17/QCQ/11) and the Central Queensland University Human Research Ethics Committee (H17/05-102). This study will be submitted for publication in a peer-reviewed scientific journal and presented at internal workshops (within Queensland Health) and national and/or international scientific conferences.
Systematic review of high-cost patients’ characteristics and healthcare utilisation
Authors: Wammes Joost Johan Godert , van der Wees Philip J , Tanke Marit A C , Westert Gert P , Jeurissen Patrick P T
Published: September 2018

Objectives

To investigate the characteristics and healthcare utilisation of high-cost patients and to compare high-cost patients across payers and countries.

Design

Systematic review.

Data sources

PubMed and Embase databases were searched until 30 October 2017.

Eligibility criteria and outcomes

Our final search was built on three themes: ‘high-cost’, ‘patients’, and ‘cost’ and ‘cost analysis’. We included articles that reported characteristics and utilisation of the top-X% (eg, top-5% and top-10%) patients of costs of a given population. Analyses were limited to studies that covered a broad range of services, across the continuum of care. Andersen’s behavioural model was used to categorise characteristics and determinants into predisposing, enabling and need characteristics.

Results

The studies pointed to a high prevalence of multiple (chronic) conditions to explain high-cost patients’ utilisation. Besides, we found a high prevalence of mental illness across all studies and a prevalence higher than 30% in US Medicaid and total population studies. Furthermore, we found that high costs were associated with increasing age but that still more than halve of high-cost patients were younger than 65 years. High costs were associated with higher incomes in the USA but with lower incomes elsewhere. Preventable spending was estimated at maximally 10% of spending. The top-10%, top-5% and top-1% high-cost patients accounted for respectively 68%, 55% and 24% of costs within a given year. Spending persistency varied between 24% and 48%. Finally, we found that no more than 30% of high-cost patients are in their last year of life.

Conclusions

High-cost patients make up the sickest and most complex populations, and their high utilisation is primarily explained by high levels of chronic and mental illness. High-cost patients are diverse populations and vary across payer types and countries. Tailored interventions are needed to meet the needs of high-cost patients and to avoid waste of scarce resources.
Protocol for a randomised controlled trial of interventions to promote adoption and maintenance of physical activity in adults with mental illness
Authors: Chapman Justin J , Suetani Shuichi , Siskind Dan , Kisely Steve , Breakspear Michael , Byrne Jacqueline H , Patterson Sue
Published: September 2018

Introduction

Physical activity (PA) has diverse benefits for physical and mental health and can reduce symptoms of mental illness. Adults with mental illness face practical, psychosocial and socioeconomic barriers to adopting and maintaining PA, and it is unclear how to effectively promote PA in this group. Supervised exercise interventions provide high support but may not promote autonomous motivation, which is important for PA maintenance. The aim of this study is to compare the effectiveness of two interventions to promote PA in adults with mental illness.

Methods and analysis

This is a randomised controlled trial of two interventions to promote PA: (1) supervised exercise and gym membership and (2) motivational discussions and self-monitoring of PA using fitness trackers. The intervention duration is 16 weeks, including 8 weeks of weekly supervised group sessions, and 8 weeks of access to the gym or fitness tracker unsupervised. Participants are community-dwelling adults recruited from outpatient clinics of public mental health services. The primary outcome is PA adoption assessed using GENEActiv accelerometers worn continuously over 8 weeks. Secondary outcomes measured at baseline, postintervention (8 weeks) and follow-up (16 weeks), include exercise motivation, psychological distress and self-reported PA assessed using self-administered questionnaires and indicators of physical health measured by a researcher blinded to allocation (blood pressure, weight, waist circumference, 6 min walk test). Participant experiences will be assessed using qualitative focus groups with analysis informed by a theoretical model of behaviour (COM-B).

Ethics and dissemination

Ethics approval has been obtained from the Royal Brisbane and Women’s Hospital (HREC/17/QRBW/302). We plan to submit a manuscript on protocol development from pilot work, and a manuscript of the results to a peer-reviewed journal. Results will be presented at conferences, community and consumer forums and hospital grand rounds.

Trial registration number

ACTRN12617001017314; Pre-results.
Optimisation of hyperemesis gravidarum management through an emergency department setting
Authors: Skalley Graham , Denny John , Allen Eve , Rao Shwetha
Published: September 2018

Hyperemesis gravidarum is a common condition characterised by severe nausea and vomiting. The referral process from the emergency department (ED) to obstetrics and gynaecology (O&G) can lead to treatment delays before the gynaecology team review the patient, resulting in unnecessary prolonged inpatient stays in O&G. This quality improvement project created a clinical pathway which optimised care of patients presenting with hyperemesis gravidarum in the ED at the Princess Royal University Hospital using a treatment protocol. Two audits were carried out to assess improvements in patient care and reduction in admissions to O&G. Overall, admissions to O&G were reduced by 68.7% (cycle 1) and 70.5% (cycle 2) compared with admission rates before the proforma, saving the trust an estimated £265 700 and 235 bed days over a year.
Assessors’ and trainees’ perceptions of workplace-based assessments in histopathology
Authors: Brierley Daniel J , Farthing Paula M , Zijlstra-Shaw Sandra
Published: September 2018

Aim

Workplace-based assessments (WBAs) are an integral part of specialist medical and dental training in the UK. Histopathology represents a very different training environment to the surgical specialities so it is important to know that the current WBAs are fit for purpose. A literature search revealed very little evidence regarding the perception of WBAs in histopathology. The aim of this study was therefore to assess the current perception of WBAs in histopathology by assessors and trainees.

Methods

A questionnaire was sent to all histopathology assessors and trainees on the Royal College of Pathologists database. Data were analysed using basic descriptive statistics. Free text comments were analysed by thematic analysis.

Results

The questionnaire was completed by 242/2175 assessors (response rate 11.1%) and 91/519 trainees (response rate 17.5%). There was no significantly different perception of WBAs between trainers and trainees (p>0.05). Key findings included respondents stating that they strongly disagreed or disagreed WBAs identify diagnostic competence (68% of trainees; 62% of assessors), identify trainees in difficulty (69% of trainees; 64% of assessors) or accurately reflect trainee progress (62% of trainees; 59% of assessors). Analysis of free text comments identified three main issues related to WBAs: their utilisation, purpose and design.

Conclusion

There was an overall negative perception of WBAs, particularly their perceived regulatory nature. It appears that the current WBAs do not always meet the criteria of a useful test in that they are perceived as being applied variably, produce results with questionable validity and have little apparent educational value.
X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence for an association
Authors: Koutsis Georgios , Breza Marianthi , Velonakis Georgios , Tzartos John , Kasselimis Dimitrios , Kartanou Chrisoula , Karavasilis Efstratios , Tzanetakos Dimitrios , Anagnostouli Maria , Andreadou Elisavet , Evangelopoulos Maria-Eleftheria , Kilidireas Constantinos , Potagas Constantin , Panas Marios , Karadima Georgia
Published: September 2018

Objective

X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary neuropathy caused by mutations in GJB1 coding for connexin-32, a gap junction protein expressed in Schwann cells, but also found in oligodendrocytes. Four patients with CMTX developing central nervous system (CNS) demyelination compatible with multiple sclerosis (MS) have been individually published. We presently sought to systematically investigate the relationship between CMTX and MS.

Methods

Over 20 years, 70 consecutive patients (36 men) with GJB1 mutations were identified at our Neurogenetics Unit, Athens, Greece, and assessed for clinical features suggestive of MS. Additionally, 18 patients with CMTX without CNS symptoms and 18 matched controls underwent brain MRI to investigate incidental findings. Serum from patients with CMTX and MS was tested for CNS immunoreactivity.

Results

We identified three patients with CMTX who developed clinical features suggestive of inflammatory CNS demyelination fulfilling MS diagnostic criteria. The resulting 20-year MS incidence (4.3%) differed significantly from the highest background 20-year MS incidence ever reported from Greece (p=0.00039). The search for incidental brain MRI findings identified two CMTX cases (11%) with lesions suggestive of focal demyelination compared with 0 control. Moreover, 10 cases in the CMTX cohort had hyperintensity in the splenium of the corpus callosum compared with 0 control (p=0.0002). No specific CNS-reactive humoral factors were identified in patients with CMTX and MS.

Conclusions

We have demonstrated a higher than expected frequency of MS in patients with CMTX and identified incidental focal demyelinating lesions on brain MRI in patients with CMTX without CNS symptoms. This provides circumstantial evidence for GJB1 mutations acting as a possible MS risk factor.
Ixekizumab is efficacious when used alone or when added to conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor inhibitors
Authors: Nash Peter , Behrens Frank , Orbai Ana-Maria , Rathmann Suchitrita S , Adams David H , Benichou Olivier , Deodhar Atul
Published: September 2018

Objective

To conduct subset analyses of SPIRIT-P2 (NCT02349295) to investigate the efficacy and safety of ixekizumab versus placebo in three subgroups of patients with active psoriatic arthritis (PsA) according to the concomitant conventional synthetic disease-modifying antirheumatic drug (cDMARD) received: any background cDMARDs (including methotrexate), background methotrexate only, or none.

Methods

Patients were randomised to receive placebo, ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W). Efficacy and safety were assessed when patients were subdivided according to cDMARD use at baseline. Efficacy was evaluated versus placebo at week 24 by the American College of Rheumatology criteria (ACR20/50), achievement of minimal disease activity (MDA) state, Disease Activity Index for PsA (DAPSA), 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire-Disability Index and the 36-item Short-Form health survey physical functioning domain.

Results

Regardless of background cDMARD status, ACR20, ACR50 and MDA response rates were significantly higher than placebo with IXEQ4W or IXEQ2W treatment. Similarly, significant improvements were observed relative to placebo for DAS28-CRP and DAPSA across subgroups. Physical function also significantly improved relative to placebo with IXEQ4W treatment regardless of background cDMARD status and with IXEQ2W alone. Percentages of reported treatment-emergent adverse events (AEs), serious AEs (including serious infections) and discontinuations due to AEs in each subgroup were comparable to the overall SPIRIT-P2 population.

Conclusion

Ixekizumab was efficacious in patients with active PsA and previous tumour necrosis factor inhibitor (TNFi) inadequate response or TNFi intolerance treated with ixekizumab alone or when added to cDMARDs with subgroup safety profiles that were consistent with that observed in the overall SPIRIT-P2 population.