bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural polyreactive IgA antibodies coat the intestinal microbiota
Authors: Bunker Jeffrey J. , Erickson Steven A. , Flynn Theodore M. , Henry Carole , Koval Jason C. , Meisel Marlies , Jabri Bana , Antonopoulos Dionysios A. , Wilson Patrick C. , Bendelac Albert
Published: September 2017

Programmed recognition of microbiota

Increasingly, we recognize that the gut is a specialized organ for maintaining microbial symbioses alongside nutritional functions. The gut produces large quantities of immunoglobulin A (IgA), which adheres to the surface of gut microbes. Bunker
et al.
discovered that antibodies produced by naïve small intestinal plasma cells are recirculated and enriched within Peyer's patches, independently of exogenous antigen and T cell help. The resulting polyreactive IgAs are released into the gut lumen and bind to microbial surface glycans, thus innately recognizing the gut microbiota. Polyreactive IgAs appear to be a product of the coevolution of host and microbiota to maintain symbiotic homeostasis.

Science
, this issue p.
eaan6619
Engineering a highly elastic human protein–based sealant for surgical applications
Authors: Annabi Nasim , Zhang Yi-Nan , Assmann Alexander , Sani Ehsan Shirzaei , Cheng George , Lassaletta Antonio D. , Vegh Andrea , Dehghani Bijan , Ruiz-Esparza Guillermo U. , Wang Xichi , Gangadharan Sidhu , Weiss Anthony S. , Khademhosseini Ali
Published: October 2017

A highly elastic and adhesive photocrosslinkable surgical sealant using a modified human protein controls liquid leakages without the need for suturing.
An anti–glypican 3/CD3 bispecific T cell–redirecting antibody for treatment of solid tumors
Authors: Ishiguro Takahiro , Sano Yuji , Komatsu Shun-ichiro , Kamata-Sakurai Mika , Kaneko Akihisa , Kinoshita Yasuko , Shiraiwa Hirotake , Azuma Yumiko , Tsunenari Toshiaki , Kayukawa Yoko , Sonobe Yukiko , Ono Natsuki , Sakata Kiyoaki , Fujii Toshihiko , Miyazaki Yoko , Noguchi Mizuho , Endo Mika , Harada Asako , Frings Werner , Fujii Etsuko , Nanba Eitaro , Narita Atsushi , Sakamoto Akihisa , Wakabayashi Tetsuya , Konishi Hiroko , Segawa Hiroaki , Igawa Tomoyuki , Tsushima Takashi , Mutoh Hironori , Nishito Yukari , Takahashi Mina , Stewart Lorraine , ElGabry Ehab , Kawabe Yoshiki , Ishigai Masaki , Chiba Shuichi , Aoki Masahiro , Hattori Kunihiro , Nezu Junichi
Published: October 2017

An anti–glypican 3/CD3 bispecific T cell–redirecting antibody (ERY974) is a promising therapeutic agent for solid tumors.
Linker proteins restore basement membrane and correct
LAMA2
-related muscular dystrophy in mice
Authors: Reinhard Judith R. , Lin Shuo , McKee Karen K. , Meinen Sarina , Crosson Stephanie C. , Sury Maurizio , Hobbs Samantha , Maier Geraldine , Yurchenco Peter D. , Rüegg Markus A.
Published: September 2017

Transgenic expression of two small linker proteins restores muscle function and prolongs life span in a mouse model of
LAMA2
-related muscular dystrophy.
Strengthening brittle bones
Authors: Shoemaker Ashley H.
Published: September 2017

Decreased
WNT1
signaling weakens bones but is partially reversed by blocking the
WNT1
inhibitory regulator sclerostin.
First Draft Genome Sequence of a Clinical Strain of Nocardia cerradoensis
Authors: Carrasco Gema , Monzón Sara , Jiménez Pilar , Cuesta Isabel , Bartolomé-Alvarez Joaquín , Valdezate Sylvia
Published: September 2017

This paper reports the first draft genome sequence for a strain of
Nocardia cerradoensis
obtained from an immunocompetent patient with a knee infection. The 8.2-Mb genome has 8,329 coding sequences, including intrinsic resistance genes, biosynthetic gene clusters for polyketide synthase and nonribosomal peptide synthase, virulence genes, and prophages.
Draft Genome Sequences of Three Novel Low-Abundance Species Strains Isolated from Kefir Grain
Authors: Kim Yongkyu , Blasche Sonja , Patil Kiran R.
Published: September 2017

We report here the genome sequences of three novel bacterial species strains—
Bacillus kefirresidentii
Opo,
Rothia kefirresidentii
KRP, and
Streptococcus kefirresidentii
YK—isolated from kefir grains collected in Germany. The draft genomes of these isolates were remarkably dissimilar (average nucleotide identities, 77.80%, 89.01%, and 92.10%, respectively) to those of the previously sequenced strains.
Complete Draft Genome Sequence of Escherichia coli K802
Authors: Kleiner-Grote Gabriele R. M. , Wibberg Daniel , Winkler Anika , Kalinowski Jörn , Friehs Karl
Published: September 2017

Escherichia coli
K802 is an old strain used for cloning experiments, as well as for the production of recombinant proteins. To understand the genomic background of
E. coli
K802 better, we present here its complete draft genome sequence.
First Nearly Complete Genome Sequence of
Feline immunodeficiency virus
from Brazil
Authors: Taniwaki Sueli A. , Araújo João P. , Brandão Paulo E.
Published: September 2017

Feline immunodeficiency virus
(FIV) has worldwide distribution; nevertheless, only a few FIV genomes from domestic cats are available. This is the first report of a nearly complete genome of FIV from a Brazilian cat (8,967 nucleotides [nt]), including the entire coding region and the 3′ untranslated region.
Draft Genome Sequence of Lactobacillus salivarius L28 Isolated from Ground Beef
Authors: Ayala Diana I. , Cook Peter W. , Campos David L. , Brashears Mindy M. , den Bakker Henk , Nightingale Kendra K.
Published: September 2017

In this report, we describe the draft genome sequence of a newly discovered probiotic strain,
Lactobacillus salivarius
L28.
L. salivarius
L28 demonstrates antagonistic effects against human foodborne pathogens, including
Escherichia coli
O157:H7,
Salmonella
spp., and
Listeria monocytogenes
, in coculture experiments and food matrices.
Draft Genome Sequences of the Avirulent Coxiella burnetii Dugway 7D77-80 and Dugway 7E65-68 Strains Isolated from Rodents in Dugway, Utah
Authors: Beare Paul A. , Jeffrey Brendan M. , Martens Craig A. , Heinzen Robert A.
Published: September 2017

Here, we present the draft genome sequences of theCoxiella burnetiiDugway 7D77-80 and Dugway 7E65-68 strains, which were isolated from rodents in Dugway, UT, in the 1950s. The strains reside in a distinct genomic group ofC. burnetiiand are considered avirulent despite having the largest genomes of theCoxiellagenus.
Draft Genome Sequence of Bacillus velezensis 3A-25B, a Strain with Biocontrol Activity against Fungal and Oomycete Root Plant Phytopathogens, Isolated from Grassland Soil
Authors: Martínez-Raudales Inés , De La Cruz-Rodríguez Yumiko , Vega-Arreguín Julio , Alvarado-Gutiérrez Alejandro , Fraire-Mayorga Atzin , Alvarado-Rodríguez Miguel , Balderas-Hernández Victor , Gómez-Soto José Manuel , Fraire-Velázquez Saúl
Published: September 2017

Here, we present the draft genome of
Bacillus velezensis
3A-25B, which totaled 4.01 Mb with 36 contigs, 3,948 genes, and a GC content of 46.34%. This strain, which demonstrates biocontrol activity against root rot causal phytopathogens in horticultural crops and friendly interactions in roots of pepper plantlets, was obtained from grassland soil in Zacatecas Province, Mexico.
Draft Genome Sequence of the Type Strain Pseudomonas jessenii DSM 17150
Authors: Furmanczyk Ewa M. , Kaminski Michal A. , Dziembowski Andrzej , Lipinski Leszek , Sobczak Adam
Published: September 2017

We present the draft genome sequence of
Pseudomonas jessenii
type strain DSM 17150. The assembly consists of 13 contigs, contains 6,537,206 bp, and has a GC content of 59.7%.
Draft Genome Sequence of Streptomyces olivochromogenes NBRC 3561, a Bioactive Peptide-Producing Actinobacterium
Authors: Dohra Hideo , Miyake Yuto , Kodani Shinya
Published: September 2017

Recently, we found that
Streptomyces olivochromogenes
NBRC 3561 produced a bioactive peptide, so we sequenced its genome to clarify its biosynthesis. We report here the draft genome sequence of
S. olivochromogenes
NBRC 3561, in which 40 potential secondary metabolite gene clusters were predicted by antiSMASH.
Complete Genome Sequences of Human Immunodeficiency Type 1 Viruses Genetically Engineered To Be Tropic for Rhesus Macaques
Authors: Nomaguchi Masako , Doi Naoya , Koma Takaaki , Adachi Akio
Published: September 2017

We have constructed two human immunodeficiency type 1 (HIV-1) derivatives, CXCR4 tropic and CCR5 tropic, that replicate in rhesus macaques. They are genetically engineered to be resistant to macaque restriction factors against HIV-1, including TRIM5α, APOBEC3, and tetherin proteins. The two HIV-1 variants described here are fundamental clones aiming for rhesus infection studies of HIV-1.
Draft Genome Sequence of
Xenophilus
sp., a Novel Bacterium Isolated from the Skin of a Southern Leopard Frog (
Rana sphenocephala
) in Florida, USA
Authors: Lebert Brittany M. , Sanford Samantha A. , Reisinger Levi M. , Forsman Anna M. , Savage Anna E.
Published: September 2017

We report here the draft genome sequence of a novel
Xenophilus
species cultured from the skin of a southern leopard frog (
Rana sphenocephala
). Compared to previously sequenced bacterial genomes, our novel isolate showed the most significant homology with
Xenophilus azovorans
. The assembled genome is 3,978,285 bp, with 3,704 predicted genes and one predicted plasmid.
Draft Genome Sequence of
Pseudomonas
sp. Strain DrBHI1 (Phylum
Proteobacteria
)
Authors: Wilson Alexandria K. , Watral Virginia G. , Kent Michael L. , Sharpton Thomas J. , Gaulke Christopher A.
Published: September 2017

Here, we report the draft genome sequence of
Pseudomonas
sp. strain DrBHI1. The total assembly length is 5,649,751 bp in 146 contigs. This strain was isolated from zebrafish (
Danio rerio
) feces.
Time-Resolved Transposon Insertion Sequencing Reveals Genome-Wide Fitness Dynamics during Infection
Authors: Yang Guanhua , Billings Gabriel , Hubbard Troy P. , Park Joseph S. , Yin Leung Ka , Liu Qin , Davis Brigid M. , Zhang Yuanxing , Wang Qiyao , Waldor Matthew K.
Published: October 2017

Transposon insertion sequencing (TIS) is a powerful high-throughput genetic technique that is transforming functional genomics in prokaryotes, because it enables genome-wide mapping of the determinants of fitness. However, current approaches for analyzing TIS data assume that selective pressures are constant over time and thus do not yield information regarding changes in the genetic requirements for growth in dynamic environments (e.g., during infection). Here, we describe structured analysis of TIS data collected as a time series, termed pattern analysis of conditional essentiality (PACE). From a temporal series of TIS data, PACE derives a quantitative assessment of each mutant’s fitness over the course of an experiment and identifies mutants with related fitness profiles. In so doing, PACE circumvents major limitations of existing methodologies, specifically the need for artificial effect size thresholds and enumeration of bacterial population expansion. We used PACE to analyze TIS samples ofEdwardsiella piscicida(a fish pathogen) collected over a 2-week infection period from a natural host (the flatfish turbot). PACE uncovered more genes that affectE. piscicida’s fitnessin vivothan were detected using a cutoff at a terminal sampling point, and it identified subpopulations of mutants with distinct fitness profiles, one of which informed the design of new live vaccine candidates. Overall, PACE enables efficient mining of time series TIS data and enhances the power and sensitivity of TIS-based analyses.

IMPORTANCETransposon insertion sequencing (TIS) enables genome-wide mapping of the genetic determinants of fitness, typically based on observations at a single sampling point. Here, we move beyond analysis of endpoint TIS data to create a framework for analysis of time series TIS data, termed pattern analysis of conditional essentiality (PACE). We applied PACE to identify genes that contribute to colonization of a natural host by the fish pathogenEdwardsiella piscicida.PACE uncovered more genes that affectE. piscicida’s fitnessin vivothan were detected using a terminal sampling point, and its clustering of mutants with related fitness profiles informed design of new live vaccine candidates. PACE yields insights into patterns of fitness dynamics and circumvents major limitations of existing methodologies. Finally, the PACE method should be applicable to additional “omic” time series data, including screens based on clustered regularly interspaced short palindromic repeats with Cas9 (CRISPR/Cas9).
U.S. Regulatory Considerations for Development of Live Biotherapeutic Products as Drugs
Authors: Dreher-Lesnick Sheila M. , Stibitz Scott , Carlson, Jr. Paul E.
Published: October 2017

Interest in the use of bacteria-containing products for the treatment or prevention of disease has increased in recent years. Bacterial preparations for human consumption are commercially available in the form of dietary supplements and typically contain strains with a history of use in food fermentation. Advances in our understanding of the role of the microbiota in health and disease are likely to lead to development of products containing more novel bacterial species, along with genetic modification of strains to provide specific functions. By law, any substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans meets the definition of a drug, and an Investigational New Drug (IND) application for clinical investigation must be filed with the FDA. This article is meant to provide information about the IND submission process and additional considerations with regard to chemistry, manufacturing, and controls information for live biotherapeutic products.
Management of extensive external apical root resorption leading to root perforation
Authors: Ghafoor Robia , Tabassum Sadia , Hameed Muhammad Hasan
Published: October 2017

Resorption is both a physiological and pathological process which results in loss of hard tissues of the tooth, i.e , cementum and dentine and the surrounding bone. External resorption is much more common than internal resorption and can occur when tooth is luxated or avulsed. If remained unchecked, resorption can eventually lead to loss of the tooth. Timely management of the affected tooth can slow down the resorptive lesion and increase the prognosis of the survival of the tooth. This case report describes the surgical management of extensive external root resorption leading to perforation of apical one-third of the root area which was managed through root canal along with periapical surgery and bone grafting. A 6-month follow-up showed arrest of the resorptive defect and progressive healing as evident on the cone-beam computed tomography.
Chyluria in non-filarial endemic areas: an internist’s perspective
Authors: Tan Yuyang
Published: October 2017

A 60-year-old Chinese woman presented with intermittent, painless, gross haematuria and subsequently complained of persistent milky urine. The diagnosis of chyluria was confirmed after cystoscopy demonstrated ureteric milky fluid discharge which had elevated levels of triglycerides. The patient did not travel to filarial endemic areas and her serum circulating filarial antigen was negative. Intravenous pyelography with CT of the abdomen did not reveal any masses or obstruction. It was determined that her chyluria was non-parasitic in origin and her symptoms improved with a low fat, high-protein diet. However, her chyluria recurred 1 year later, resulting in hypoalbuminaemia and proteinuria. Her symptoms resolved and her albumin levels normalised with adherence to dietary modifications.
Glucose-lowering effects and safety of DS-8500a, a G protein-coupled receptor 119 agonist, in Japanese patients with type 2 diabetes: results of a randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase II study
Authors: Inagaki Nobuya , Chou Hubert S , Tsukiyama Shuji , Washio Takuo , Shiosakai Kazuhito , Nakatsuka Yasuhiko , Taguchi Takashi
Published: September 2017

Objective

DS-8500a is a novel G protein-coupled receptor 119 agonist being developed for the treatment of type 2 diabetes. The study objective was to assess the efficacy and safety of DS-8500a in Japanese patients with type 2 diabetes.

Research design and methods

In this double-blind, parallel-group, phase II study, 99 Japanese patients with type 2 diabetes were randomized to receive placebo, or DS-8500a 10 mg or 75 mg once daily for 28 days. The primary efficacy endpoint was change in the 24-hour weighted mean glucose (WMG) from baseline (day −1) to day 28. Other endpoints included changes in fasting plasma glucose, postprandial glucose, lipids, and safety.

Results

The 24-hour WMG decreased significantly after 28 days of treatment in the 10 mg and 75 mg groups with placebo-subtracted least squares mean differences (95% CI) of −0.74 (−1.29 to –0.19) mmol/L and −1.05 (−1.59 to –0.50) mmol/L, respectively. Reductions in 24-hour WMG in both DS-8500a groups were observed on day 14 and were greater on day 28 than on day 14. The reductions in fasting plasma glucose and 2-hour postprandial glucose were significantly greater in the 75 mg DS-8500a group versus placebo. Total cholesterol, low-density lipoprotein cholesterol, and triglycerides decreased significantly; high-density lipoprotein cholesterol increased significantly in the 75 mg group versus placebo. Both doses of DS-8500a were well tolerated without significant treatment-related adverse events, hypoglycemia, or discontinuations due to adverse events.

Conclusions

DS-8500a significantly improved glycemic control and lipids and was well tolerated over 28 days of administration in Japanese patients with type 2 diabetes.

Trial registration number

NCT02222350; Post-results.
Is the sustainable development goal target for financial risk protection in health realistic?
Authors: Verguet Stéphane , Woldemariam Addis Tamire , Durrett Warren N , Norheim Ole F , Kruk Margaret E
Published: September 2017

Background

Setting Millennium Development Goals and Sustainable Development Goals for health has largely focused on defining specific targets of mortality and morbidity reduction over given time periods. Yet, less attention has been devoted to setting targets for the systemic determinants of health delivery, such as access and financial risk protection (FRP)—prevention of medical impoverishment. We examined candidate targets for FRP among low and middle-income countries by 2040.

Methods

We used a data set on estimates of incidence of catastrophic health expenditure (CHE)—medical expenditure exceeding 40% of household capacity to pay—among 110 countries over 1995–2007, augmented by estimates of the percentage of out-of-pocket expenditure out of total health expenditure (OOPEXP), the share of health expenditure as a percentage of gross domestic product (HEXGDP) and the gross domestic product per capita (GDPC). Using a simple model and 2040 estimates for OOPEXP, HEXGDPand GDPCfrom the World Bank, the International Monetary Fund and the Institute for Health Metrics and Evaluation, we projected CHE incidence by 2040 for four country income groups.

Results

We predicted that the 2040 incidence of CHE among households would be: 2.13% (Uncertainty interval: 0.60-6.87) among low-income countries, 1.15% (0.32–3.81) among lower-middle-income countries and 0.65% (0.18–2.21) among upper-middle-income countries. By 2040, the probability of achieving CHE <1.00% would be: 0.1 for low-income countries, 0.4 for lower-middle-income countries and 0.7 for upper-middle-income countries; for CHE <0.50% , it would be 0 for low-income countries, 0.1 for lower-middle-income countries and 0.3 for upper-middle-income countries.

Conclusions

Historical trends of CHE rates can help define post-2015 targets for FRP. The projected achievements suggest that elimination of medical impoverishment will not be achieved by 2040 and that countries must urgently enact dramatic changes in policy to ensure FRP to their populations.
Introducing visual participatory methods to develop local knowledge on HIV in rural South Africa
Authors: Brooks Chloe , D’Ambruoso Lucia , Kazimierczak Karolina , Ngobeni Sizzy , Twine Rhian , Tollman Stephen , Kahn Kathleen , Byass Peter
Published: September 2017

Introduction

South Africa is a country faced with complex health and social inequalities, in which HIV/AIDS has had devastating impacts. The study aimed to gain insights into the perspectives of rural communities on HIV-related mortality.

Methods

A participatory action research (PAR) process, inclusive of a visual participatory method (Photovoice), was initiated to elicit and organise local knowledge and to identify priorities for action in a rural subdistrict underpinned by the Agincourt Health and Socio-Demographic Surveillance System (HDSS). We convened three village-based discussion groups, presented HDSS data on HIV-related mortality, elicited subjective perspectives on HIV/AIDS, systematised these into collective accounts and identified priorities for action. Framework analysis was performed on narrative and visual data, and practice theory was used to interpret the findings.

Findings

A range of social and health systems factors were identified as causes and contributors of HIV mortality. These included alcohol use/abuse, gender inequalities, stigma around disclosure of HIV status, problems with informal care, poor sanitation, harmful traditional practices, delays in treatment, problems with medications and problematic staff–patient relationships. To address these issues, developing youth facilities in communities, improving employment opportunities, timely treatment and extending community outreach for health education and health promotion were identified.

Discussion

Addressing social practices of blame, stigma and mistrust around HIV-related mortality may be a useful focus for policy and planning. Research that engages communities and authorities to coproduce evidence can capture these practices, improve communication and build trust.

Conclusion

Actions to reduce HIV should go beyond individual agency and structural forces to focus on how social practices embody these elements. Initiating PAR inclusive of visual methods can build shared understandings of disease burdens in social and health systems contexts. This can develop shared accountability and improve staff–patient relationships, which, over time, may address the issues identified, here related to stigma and blame.
Use of IMMPACT domains in clinical trials of acupuncture for chronic pain: a protocol for a methodological survey
Authors: Mazzei Lauren Giustti , Bergamaschi Cristiane de Cássia , Silva Marcus Tolentino , Lopes Luciane Cruz
Published: September 2017

Introduction

Pain is one of the most common and most debilitating complaints among patients. It affects the individual, their relationship with friends and family, their ability to function at work, and their sociability. Acupuncture is one of the therapeutic resources for managing chronic pain. Given the variability of outcome measures in controlled randomised clinical trials on non-oncologicchronic pain (CRCT-NOCP), the Initiative in Methods, Measurements and Pain Assessment in Clinical Trials (IMMPACT) recommends six domains to be covered in evaluating the effectiveness of treatments for chronic pain.

Objective

To check whether the methodological quality of outcome reporting in published trials has used IMMPACT recommendations in measuring CRCT-NOCP outcomes when acupuncture was used as a treatment.

Method

This is a methodological study. We will systematically search for eligible studies in specific databases with a defined strategy. We will use the MeSHterms of ‘acupuncture’, ‘chronic pain’ and similar terms, without restrictions on idiom. Eligible studies will include those which are randomised and chose NOCP patients to be treated with acupuncture or control (sham acupuncture or no acupuncture), recruited after September 2004, with ≥100 patients. The measured outcomes are to be the presence of outcome domains recommended by IMMPACT, domains reported by the patient or clinician, tools used to measure such domains, as well as other features of the studies. We shall conduct a regression analysis to explore factors which can be associated with the presence of outcome domains according to IMMPACT recommendations.

Ethics and dissemination

This survey will be submitted for presentation at congresses and for publication in a scientific journal. The findings obtained in this study will allow us to measure the quality of the evidence and provide greater transparency in decisions regarding the use of acupuncture as a viable alternative to managing chronic pain.
The potential clinical benefits of medicines optimisation through comprehensive geriatric assessment, carried out by secondary care geriatricians, in a general practice care setting in North Staffordshire, UK: a feasibility study
Authors: Lea Simon Christian , Watts Keira Louise , Davis Nathan Ashley , Panayiotou Barnabas , Bankart Michael John , Arora Amit , Chambers Ruth
Published: September 2017

Objectives

To evaluate the feasibility and potential clinical benefits of medicines optimisation through comprehensive geriatric assessment (CGA) of frail patients with multiple conditions, by secondary care geriatricians in a general practice care setting.

Methods

Seven general practitioner (GP) practices in one region of Stoke-on-Trent volunteered to take part. GPs selected patients (n=186) who were local permanent residents, at least 65 years old and on eight or more medications per day. Patients were sent a written invitation outlining the assessment purpose/format. Prior to patient assessments, primary care staff prepared packs detailing patient medical history, recent consultations, current medications, recent laboratory tests and social circumstances. One hour was allocated for the CGA per patient, with one of three geriatricians, to enable sufficient time to explore all relevant aspects. Assessment comprised a full history, thorough clinical examination, assessment of balance and mobility, mental function and information on home environment and support arrangements. After consultation, geriatricians made recommendations regarding further assessments, investigations or medication changes. Geriatricians entered their main findings and recommendations onto a standard template.

Results

In total, 687 recommendations for changes in patients’ medication regimens were made for 169 (91%) patients. In 17 (9%) patients there was no recommendation to alter medications. This resulted in an average of four alterations in medication per patient. The predominant changes to medications were to stop medications (34%) or to reduce the dosage (24%). Starting a new medication represented 18% of all the medication changes. Adherence rates to geriatrician medication recommendations were 72% at 6 months and 65% at 12 months.

Conclusions

CGA of older patients with complex needs, by geriatricians in a general practice care setting, is feasible. Our study demonstrated constructive collaboration between GPs and geriatricians from secondary care, suggesting further studies and clinical trials are feasible and have scope to yield beneficial outcomes.
Non-adherence to immunosuppressants following renal transplantation: a protocol for a systematic review
Authors: Hucker Abigail , Bunn Frances , Carpenter Lewis , Lawrence Christopher , Farrington Ken , Sharma Shivani
Published: September 2017

Introduction

Adherence to immunosuppressant medication is essential for renal transplant recipients. This review aims to summarise what is known about non-adherence, with a view to providing comprehensive evidence to inform strategies aimed at advancing adherent behaviour.

Methods and analysis

A systematic review of quantitative studies that report adherence to immunosuppressants in adult (over 18 years) renal transplant recipients. The review will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines; study quality will be assessed using the Downs and Black checklist. Systematic searches will be completed across relevant databases. Two reviewers will independently extract data using a predefined data extraction form. We will summarise the operationalisation of adherence across studies and use narrative synthesis to identify factors associated with non-adherence. A meta-analysis will be conducted if there is sufficient homogeneity, and available data, across studies to estimate the prevalence of non-adherence in renal transplant recipients. Heterogeneity will be assessed using the I2test. Survival analysis will be conducted to estimate hazard ratios to explore the impact of non-adherence on graft survival, graft failure and patient survival.

Ethics and dissemination

Findings will be published in a peer-reviewed journal and disseminated at conferences for professionals and researchers. Review outcomes will help support clinical practice by highlighting the extent of non-adherence among adults, and in doing so, signpost the need for suitable intervention.

Trial registration number

PROSPERO registration number (CRD42016038751).
Protocol for the Northern babies longitudinal study: predicting postpartum depression and improving parent–infant interaction with The Newborn Behavioral Observation
Authors: Høifødt Ragnhild Sørensen , Nordahl Dag , Pfuhl Gerit , Landsem Inger Pauline , Thimm Jens C , Ilstad Linn Kathrin K , Wang Catharina Elisabeth Arfwedson
Published: September 2017

Introduction

Postpartum depression (PPD) is a prevalent disorder. Studying the factors related to PPD will help to identify families at risk and provide preventive interventions. This can in turn improve the developmental trajectories for the children. Several previous studies have investigated risk factors for PPD. However, few studies have focused on cognitive vulnerability factors. The first aim of the present study is to explore a range of protective and risk factors, including cognitive factors, for PPD, parent–infant interactions and child development. The second aim of the study is to evaluate the effectiveness of The Newborn Behavioral Observation (NBO) as a universal preventive intervention delivered in routine practice. The NBO is a brief relationship-enhancing intervention that may reduce depressive symptomatology in mothers.

Methods

The study is a longitudinal observational study with an intervention. The observational study uses a prospective cohort design, whereas the intervention study has a non-randomised cluster-controlled design comparing a group receiving NBO with a group receiving standard care. The intervention group will receive three NBO sessions within the first 4 weeks postdelivery. Between 2015 and 2018, approximately 200 families will be recruited in the municipality of Tromsø, Norway. Parents are recruited during pregnancy, and assessments will be performed during gestational weeks 16–22, 24–30 and 31, and at 6 weeks, 4 months and 6 months postdelivery. Predictor variables include several cognitive vulnerability factors including early maladaptive schemas, implicit attitudes and cognitive processing of emotionally valenced infant facial information.

Ethics and dissemination

The Regional Committee for Medical and Health Research Ethics in Northern Norway has approved the project. The research team has collaboration with local health services and can assist participants who need more extensive follow-up. Results from the project will be disseminated in international and national peer-reviewed journals, and at courses and conferences.

Trials registration number

NCT02538497; Pre-results.
Adiposity measures and arterial stiffness in primary care: the MARK prospective observational study
Authors: Gomez-Sanchez Leticia , Garcia-Ortiz Luis , Patino-Alonso Maria C , Recio-Rodriguez Jose I , Rigo Fernando , Martí Ruth , Agudo-Conde Cristina , Rodriguez-Sanchez Emiliano , Maderuelo-Fernandez Jose A , Ramos Rafel , Gomez-Marcos Manuel A
Published: September 2017

Background

The cardiovascular risk of obesity is potentially increased by arterial stiffness.

Objective

To assess the relationship of adiposity measures with arterial stiffness in Caucasian adults with intermediate cardiovascular risk.

Setting

Six Spanish health centres.

Participants

We enrolled 2354 adults (age range, 35–74 years; mean age, 61.4±7.7 years, 61.9% male).

Methods

This is a cross-sectional study that analyses data from the baseline visit of the improving interMediAte RisK management (MARK) study. The main outcome variables were body mass index (BMI), waist-to-height ratio (WHtR), Clínica Universidad de Navarra-body adiposity estimation (CUN-BAE) body fat percentage and body roundness index (BRI). Vascular function was assessed by the cardio-ankle vascular index (CAVI) with the VaSera device; brachial-ankle pulse wave velocity (baPWV) was determined using a validated equation.

Results

The mean adiposity measures were a BMI of 29.2±4.4, WHtR of 0.61±0.07, CUN-BAE of 35.7±1.7 and BRI of 5.8±1.7. The mean stiffness measures were a CAVI of 8.8±1.2 and baPWV of 14.9±2.5. In multiple linear regression analyses, all adiposity measures were negatively associated with CAVI and baPWV (p<0.01 for all) after adjustment for possible factors of confusion. The proportion of CAVI variability via the adiposity measures were 5.5% for BMI, 5.8% for CUN-BAE, 3.8% for WHtR and 3.7% for BRI. These were higher among diabetic, obese, younger (≤62 years) and non-hypertensive subjects who had similar activity and sedentary profiles.

Conclusions

Adiposity measures are negatively associated with arterial stiffness measures. The percentage of variation in CAVI explained by its relation to the different measures of adiposity ranges from 5.8% (CUN-BAE) to 3.7% (BRI). In the case of baPWV, it oscillates between 0.7% (CUN-BAE and BMI) and 0.1% (WHtR).

Trial registration number

NCT01428934.
New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey
Authors: Iba Toshiaki , Nisio Marcello Di , Levy Jerrold H , Kitamura Naoya , Thachil Jecko
Published: September 2017

Objective

Recent clinical studies have shown that anticoagulant therapy might be effective only in specific at-risk subgroups of patients with sepsis and coagulation dysfunction. The definition of sepsis was recently modified, and as such, old scoring systems may no longer be appropriate for the diagnosis of sepsis-associated coagulopathy. The aim of this study was to evaluate prognostic factors in patients diagnosed with sepsis and coagulopathy according to the new sepsis definition and assess their accuracy in comparison with existing models.

Design

Retrospective analysis of the nationwide survey for recombinant human soluble thrombomodulin.

Setting

General emergency and critical care centres in secondary and tertiary care hospitals.

Participants

We evaluated the prognostic value of the newly proposed diagnostic criteria for sepsis-induced coagulopathy (SIC). A total of 1498 Japanese patients with sepsis and coagulopathy complications who were treated with recombinant thrombomodulin were analysed in this study.

Main outcome measures

The platelet count, prothrombin time (PT) ratio, fibrinogen/fibrin degradation products, systemic inflammatory response syndrome score and Sequential Organ Failure Assessment (SOFA) score obtained just before the start of treatment were examined in relation to the 28-day mortality rate.

Results

The platelet count, PT ratio and total SOFA were independent predictors of a fatal outcome in a logistic regression model. A SIC score was defined using the three above-mentioned variables with a positivity threshold of 4 points or more. The SIC score predicted higher 28-day mortality rate compared with the current Japanese Association for Acute Medicine-disseminated intravascular coagulation score (38.4%vs34.7%).

Conclusion

The SIC score is based on readily available parameters, is easy to calculate and has a high predictive value for 28-day mortality. Future studies are warranted to evaluate whether the SIC score may guide the decision to initiate anticoagulant therapy.
Associations of caesarean delivery and the occurrence of neurodevelopmental disorders, asthma or obesity in childhood based on Taiwan birth cohort study
Authors: Chen Ginden , Chiang Wan-Lin , Shu Bih-Ching , Guo Yue Leon , Chiou Shu-Ti , Chiang Tung-liang
Published: September 2017

Objectives

Whether birth by caesarean section (CS) increases the occurrence of neurodevelopmental disorders, asthma or obesity in childhood is controversial. We tried to demonstrate the association between children born by CS and the occurrence of the above three diseases at the age of 5.5 years.

Methods

The database of the Taiwan Birth Cohort Study which was designed to assess the developmental trajectories of 24 200 children born in 2005 was used in this study. Associations between children born by CS and these three diseases were evaluated before and after controlling for gestational age (GA) at birth, children’s characteristics and disease-related predisposing factors.

Results

Children born by CS had significant increases in neurodevelopmental disorders (20%), asthma (14%) and obesity (18%) compared with children born by vaginal delivery. The association between neurodevelopmental disorders and CS was attenuated after controlling for GA at birth (OR 1.15; 95% CI 0.98 to 1.34). Occurrence of neurodevelopmental disorders steadily declined with increasing GA up to ≤40–42 weeks. CS and childhood asthma were not significantly associated after controlling for parental history of asthma and GA at birth. Obesity in childhood remained significantly associated with CS (OR 1.13; 95% CI 1.04 to 1.24) after controlling for GA and disease-related factors.

Conclusions

Our results implied that the association between CS birth and children’s neurodevelopmental disorders was significantly influenced by GA. CS birth was weakly associated with childhood asthma since parental asthma and preterm births are stronger predisposing factors. The association between CS birth and childhood obesity was robust after controlling for disease-related factors.
Randomised controlled trial of bariatric surgery versus a community weight loss programme for the sustained treatment of idiopathic intracranial hypertension: the Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) protocol
Authors: Ottridge Ryan , Mollan Susan P , Botfield Hannah , Frew Emma , Ives Natalie J , Matthews Tim , Mitchell James , Rick Caroline , Singhal Rishi , Woolley Rebecca , Sinclair Alexandra J
Published: September 2017

Introduction

Effective treatments are lacking for idiopathic intracranial hypertension (IIH), a condition characterised by raised intracranial pressure (ICP) and papilloedema, and found primarily in obese women. Weight loss and lowering body mass index (BMI) have been shown to lower ICP and improve symptoms in IIH; however, weight loss is typically not maintained, meaning IIH symptoms return. The Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) will assess whether bariatric surgery is an effective long-term treatment for patients with IIH with a BMI over 35 kg/m2. The National Institute for Health and Care Excellence recommends bariatric surgery in people with a BMI over 35 kg/m2and a qualifying comorbidity; currently IIH does not qualify as a comorbidity.

Methods and analysis

IIH:WT is a multicentre, open-label, randomised controlled clinical trial of 64 participants with active IIH and a BMI over 35 kg/m2. Participants will be randomised in a 1:1 ratio to bariatric surgery or a dietary weight loss programme and followed up for 5 years. The primary outcome measure is ICP at 12 months. Secondary outcome measures include ICP at 24 and 60 months, and IIH symptoms, visual function, papilloedema, headache, quality of life and cost-effectiveness at 12, 24 and 60 months.

Trial registration number

IIH:WT is registered asISRCTN40152829and on ClinicalTrials.gov asNCT02124486and is in the pre-results stage.
Efficacy and safety of instantaneous wave-free ratio in patients undergoing coronary revascularisation: protocol for a systematic review
Authors: Kwong Joey S.W. , Li Sheyu , Gu Wan-Jie , Chen Hao , Zhang Chao , Zeng Xian-Tao , Yu Cheuk-Man
Published: September 2017

Introduction

Effective selection of coronary lesions for revascularisation is pivotal in the management of symptoms and adverse outcomes in patients with coronary artery disease. Recently, instantaneous ‘wave-free’ ratio (iFR) has been proposed as a new diagnostic index for assessing the severity of coronary stenoses without the need of pharmacological vasodilation. Evidence of the effectiveness of iFR-guided revascularisation is emerging and a systematic review is warranted.

Methods and analysis

This is a protocol for a systematic review of randomised controlled trials and controlled observational studies. Electronic sources including MEDLINE via Ovid, Embase, Cochrane databases and ClinicalTrials.gov will be searched for potentially eligible studies investigating the effects of iFR-guided strategy in patients undergoing coronary revascularisation. Studies will be selected against transparent eligibility criteria and data will be extracted using a prestandardised data collection form by two independent authors. Risk of bias in included studies and overall quality of evidence will be assessed using validated methodological tools. Meta-analysis will be performed using the Review Manager software. Our systematic review will be performed according to the guidance from the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Ethics and dissemination

Ethics approval is not required. Results of the systematic review will be disseminated as conference proceedings and peer-reviewed journal publication.

Trial registration number

This protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42017065460.
Canada-DONATE study protocol: a prospective national observational study of the medical management of deceased organ donors
Authors: D’Aragon Frederick , Dhanani Sonny , Lamontagne Francois , Cook Deborah J , Burns Karen , Akhtar Aemal , Chassé Michaël , Frenette Anne-Julie , Keenan Sean , Lize Jean-Francois , Kutsogiannis Demetrios J , Kramer Andreas , Hand Lori E , Arseneau Erika , Masse Marie-Helene , Ribic Christine , Ball Ian , Baker Andrew , Boyd Gordon , Rochwerg Bram , Healey Andrew , Hanna Steven , Guyatt Gordon H , Meade Maureen O
Published: September 2017

Introduction

Research on the management of deceased organ donors aims to improve the number and quality of transplants and recipient outcomes. In Canada, this research is challenged by regionalisation of donation services within provinces and the geographical, clinical and administrative separation of donation from transplantation services. This study aims to build a national platform for future clinical trials in donor management. Objectives are to engage collaborators at donation hospitals and organ donation organisations (ODOs) across Canada, describe current practices, evaluate the effectiveness of donation-specific interventions and assess the feasibility of future clinical trials.

Methods and analysis

This ongoing prospective observational study of the medical management of deceased organ donors will enrol more than 650 consented potential donors from adult intensive care units at 33 hospital sites across Canada, each participating for 12 months. ODOs ensure enrolment of consecutive eligible participants. Research staff record detailed data about participants, therapies, organ assessments, death declaration procedures and adverse clinical exposures from the time of donation consent to organ recovery. ODOs provide reasons that organs are declined, dates and places of transplantation, and recipient age and sex.

Descriptive analyses will summarise current practices. Effectiveness analyses will examine donation-specific interventions with respect to the number of transplants, using multilevel regression models to account for clustering by donor, hospitals and ODOs. Feasibility analyses will focus on acceptance of the research consent model; participation of academic and community hospitals as well as ODOs; and accessibility of recipient data.

Ethics and dissemination

This study uses a waiver of research consent. Hospitals will receive reports on local practices benchmarked to (1) national practices and (2) national donor management guidelines. We will report findings to donation and transplant collaborators (ie, clinicians, researchers, ODOs) and publish in peer-reviewed journals.

Trial registration number

NCT03114436.
Spatiotemporal characteristics of motor actions by blind long jump athletes
Authors: Torralba Miguel Angel , Padullés José María , Losada Jose Luis , López Jose Luis
Published: September 2017

Background

Blind people depend on spatial and temporal representations to perform activities of daily living and compete in sport.

Objective

The aim of this study is to determine the spatiotemporal characteristics of long jumps performed by blind athletes and compare findings with those reported for sighted athletes.

Methods

We analysed a sample of 12 male athletes competing in the F11 Long Jump Finals at the Paralympic Games in London 2012. Performances were recorded using four high-speed cameras, and speeds were measured using a radar speed gun. The images were processed using validated image analysis software.

Results

The long jump run-up is shorter in blind athletes than in sighted athletes. We observed statistically significant differences for body centre of mass velocity and an increase in speed over the last three strides prior to take-off, contrasting with reports for sighted athletes and athletes with less severe visual impairment, who maintain or reduce their speed during the last stride. Stride length for the last three strides was the only spatial characteristic that was not significantly associated with effective jump distance. Blind long jumpers extend rather than shorten their last stride. Contact time with the take-off board is longer than that reported for sighted athletes.

Conclusion

The actions of blind long jumpers, unlike those without disabilities, do not vary their leg actions during the final runway approach for optimal placement on the take-off board.
Introducing the National Institute for Sports Medicine in Hungary: a complex sports medical healthcare and screening system
Authors: Laki Judit , Soós Ágnes , Jákó Péter , Tállay András , Perjés Ábel , Szabó Anita Megyeriné
Published: September 2017

The Hungarian National Institute for Sports Medicine (NISM) was founded in 1952 to provide medical coverage for national teams, screening and periodic health evaluation (PHE) for all Hungarian athletes. The system of ‘all in one and ASAP’ evolved by now to a specific state-funded healthcare provider with complex sports medical and sport-related services available for athletes. The NISM created a countrywide network to make health clearance available for all athletes close to their place of residency. This centralised system guarantees the uniformity and financial independence of the network, as it is directly financed by the government and free for every competitive athlete. Thus, it leaves no chance for conflict of interest in evaluating athletes’ eligibility. In 2013, NISM established an online registry for preparticipation screening and PHE. This made the registry available for sports physicians and certain data for both sports physicians and athletes themselves. Furthermore, NISM created a nationwide, centrally coordinated, out of turn care with central coordination for elite athletes nationwide. Outpatient and inpatient clinics of NISM provide sports-specific care. Most of the minimally invasive techniques used at the Department of Sports Surgery are applied only here in the country. The medical staff of NISM has special experience in Sports Medicine and sport-related conditions. All tasks are managed within the same system, within institutional frames by professionals at Sports Medicine, which guarantees institutional expertise, competence and responsibility. Our aim is to introduce the complex system, the services and the recent achievements of the Hungarian NISM.