bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of glomerular filtration rate estimating equations derived from different reference methods on staging and long term mortality risks of chronic kidney disease in a Southeast Asian cohort
Authors: Yamwong Sukit , Kitiyakara Chagriya , Vathesatogkit Prin , Saranburut Krittika , Chittamma Anchalee , Cheepudomwit Sayan , Vanavanan Somlak , Akrawichien Tawatchai , Sritara Piyamitr
Published: October 2015

Aim

There are limited data on the risks of chronic kidney disease (CKD) in Southeast Asian populations. Several GFR estimating equations have been developed in diverse Asian populations, but they produce markedly discrepant results. We investigated the impact of Asian equations on the mortality risk of CKD in a Thai cohort during long term follow‐up, and explored the differences between equations grouped according to the reference GFR methods used to develop them.

Methods

Employees of the Electricity Generating Authority of Thailand (n = 3430) were enrolled in a health survey and followed up for 22 years. The risks for all‐cause mortality for each GFR stage classified by CKD‐EPI or different Asian equations were assessed by using Cox proportional hazard models.

Results

Equations derived from DTPA clearance (Chinese MDRD, Thai GFR, Singapore CKD‐EPI) produced higher GFR, whereas equations from inulin clearance (Japanese CKD‐EPI, Taiwan MDRD or Taiwan CKD‐EPI) produced lower GFR compared to CKD‐EPI. (Average ΔGFR: inulin, –14.9 vs. DTPA +5.80 mL/min per 1.73 m2, P < 0.001). CKD prevalence varied widely (0.7 to 24 %) with inulin‐based equations being higher than DTPA‐based. GFR stage concordance was over 80% for equations using similar reference method compared to less than 40% between inulin and DTPA‐based equations. Low GFR (<45) was an independent mortality risk factor when DTPA‐based equations were used, but not when inulin‐based equations were used.

Conclusion

Chronic kidney disease prevalence and prognosis in Thais varied widely depending on the equation used. Differences in the reference GFR methods could be an important cause for the discrepancies between Asian equations.
MicroRNA‐211 causes ganglion cell dysplasia in congenital intestinal atresia via down‐regulation of glial‐derived neurotrophic factor
Authors: Xia Z.‐q. , Ding D.‐k. , Zhang N. , Wang J.‐x. , Yang H.‐y. , Zhang D.
Published: October 2015

Background

MicroRNAs (miRNAs) are known to be involved in normal brain functions and nervous system diseases. Some evidence have pointed to the dysregulation of miRNAs in congenital intestinal atresia. In this study, we investigated the differential expression of miRNAs and the posttranscriptional regulation of glial‐derived neurotrophic factor (GDNF) by endogenous miRNA in congenital intestinal atresia.

Methods

Quantitative real‐time PCR and a Western blot were performed to determine the regulation of miRNA and GDNF in patients with congenital intestinal atresia. The results were verified in rat model of intestinal atresia and bone marrow derived stem cell BMSCs‐derived into intestinal ganglion cells. The effects of miRNA and GDNF on the cell proliferation and apoptosis of isolated intestinal ganglion cells were detected with an 3‐(4,5‐dimethylthiazol)‐2,5‐diphenyl tetrazolium (MTT) assay and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively.

Key Results

Only miR‐211 was greatly up‐regulated in the patients with congenital intestinal atresia. The other miRNAs examined showed no change. Overexpression of miR‐211 suppressed the differentiation of BMSCs into intestinal ganglion cells. In retinal ganglion cells (RGC‐5 cells), miR‐211 regulated the expression of GDNF. The MTT and TUNEL assays revealed that miR‐211 overexpression suppressed the cell proliferation of isolated intestinal ganglion cells and that GDNF overexpression reversed the effect of pre‐miR‐211 on cell proliferation and apoptosis.

Conclusions & Inferences

Our results indicate that overexpression of miR‐211 suppresses the differentiation of BMSCs into intestinal ganglion cells by directly down‐regulating the expression of GDNF. The findings elucidate the role of miRNA in congenital intestinal atresia.
Higher survival drives the success of nitrogen‐fixing trees through succession in Costa Rican rainforests
Authors: Menge Duncan N. L. , Chazdon Robin L.
Published: October 2015

Trees capable of symbiotic nitrogen (N) fixation (‘N fixers’) are abundant in many tropical forests. In temperate forests, it is well known that N fixers specialize in early‐successional niches, but in tropical forests, successional trends of N‐fixing species are poorly understood.

We used a long‐term census study (1997–2013) of regenerating lowland wet tropical forests in Costa Rica to document successional patterns of N fixers vs non‐fixers, and used an individual‐based model to determine the demographic drivers of these trends.

N fixers increased in relative basal area during succession. In the youngest forests, N fixers grew 2.5 times faster, recruited at a similar rate and were 15 times less likely to die as non‐fixers. As succession proceeded, the growth and survival disparities decreased, whereas N fixer recruitment decreased relative to non‐fixers. According to our individual‐based model, high survival was the dominant driver of the increase in basal area of N fixers.

Our data suggest that N fixers are successful throughout secondary succession in tropical rainforests of north‐east Costa Rica, and that attempts to understand this success should focus on tree survival.
Reduction of MDHAR activity in cherry tomato suppresses growth and yield and MDHAR activity is correlated with sugar levels under high light
Authors: Truffault Vincent , Gest Noé , Garchery Cécile , Florian Alexandra , Fernie Alisdair R. , Gautier Hélène , Stevens Rebecca G.
Published: October 2015

Ascorbate is oxidized into the radical monodehydroascorbate (MDHA) through ascorbate oxidase or peroxidase activity or non‐enzymatically by reactive oxygen species. Regeneration of ascorbate from MDHA is ensured by the enzyme MDHA reductase (MDHAR). Previous work has shown that growth processes and yield can be altered by modifying the activity of enzymes that recycle ascorbate; therefore, we have studied similar processes in cherry tomato (Solanum lycopersium L.) under‐ or overexpressing MDHAR. Physiological and metabolic characterization of these lines was carried out under different light conditions or by manipulating the source–sink ratio. Independently of the light regime, slower early growth of all organs was observed in MDHAR silenced lines, decreasing final fruit yield. Photosynthesis was altered as was the accumulation of hexoses and sucrose in a light‐dependent manner in plantlets. Sucrose accumulation was also repressed in young fruits and final yield of MDHAR silenced lines showed a stronger decrease under carbon limitation, and the phenotype was partially restored by reducing fruit load. Ascorbate and MDHA appear to be involved in control of growth and sugar metabolism in cherry tomato and the associated enzymes could be potential targets for yield improvement.
Therapeutic effects of dog visits in nursing homes for the elderly
Authors: Thodberg Karen , Sørensen Lisbeth Uhrskov , Christensen Janne Winther , Poulsen Pia Haun , Houbak Birthe , Damgaard Vibeke , Keseler Ingrid , Edwards David , Videbech Poul B.
Published: October 2015

Background

Previous studies have suggested that visiting dogs can have positive effects on elderly people in nursing homes. We wanted to study the effects of biweekly dog visits on sleep patterns and the psychiatric well‐being of elderly people.

Methods

A total of 100 residents (median age: 85.5 years; [79; 90]) from four nursing homes were randomly assigned to receive biweekly visits for 6 weeks from a person accompanied by either a dog, a robot seal (PARO), or a soft toy cat. Sleep patterns were measured using actigraphy technology before, during (the third and sixth week), and after the series of visits. The participants were weighed and scored on the Geriatric Depression Scale, the Gottfries‐Bråne‐Steen Scale, and the Mini‐Mental State Examination before and after the visit period.

Results

We found that sleep duration (min) increased in the third week when visitors were accompanied by a dog rather than the robot seal or soft toy cat (dog: 610 ± 127 min; seal: 498 ± 146 min; cat: 540 ± 163 min; F2,37 = 4.99; P = 0.01). No effects were found in the sixth week or after the visit period had ended. We found that visit type had no effect on weight (F2,88 = 0.13; P > 0.05), body mass index (F2,86 = 0.33; P > 0.05), Geriatric Depression Scale (F2,82 = 0.85; P > 0.05), Gottfries‐Bråne‐Steen Scale (F2,90 = 0.41; P > 0.05), or Mini‐Mental State Examination (F2,91 = 0.35; P > 0.05). Furthermore, we found a decrease in the Geriatric Depression Scale during the experimental period (S = −420; P < 0.05), whereas cognitive impairment worsened as shown by a decrease in Mini‐Mental State Examination score (S = −483; P < 0.05) and an increase in the Gottfries‐Bråne‐Steen Scale (t = 2.06; P < 0.05).

Conclusion

Visit type did not affect the long‐term mental state of the participants. The causal relationship between sleep duration and dog‐accompanied visits remains to be explored.
The effect of obesity on inflammatory cytokine and leptin production following acute mental stress
Authors: Caslin H. L. , Franco R. L. , Crabb E. B. , Huang C. J. , Bowen M. K. , Acevedo E. O.
Published: October 2015

Obesity may contribute to cardiovascular disease (CVD) risk by eliciting chronic systemic inflammation and impairing the immune response to additional stressors. There has been little assessment of the effect of obesity on psychological stress, an independent risk factor for CVD. Therefore, it was of interest to examine interleukin‐6, tumor necrosis factor‐α, interleukin‐1β (IL‐1β), interleukin‐1 receptor antagonist (IL‐1Ra), and leptin following an acute mental stress task in nonobese and obese males. Twenty college‐aged males (21.3 ± 0.56 years) volunteered to participate in a 20‐min Stroop color‐word and mirror‐tracing task. Subjects were recruited for obese (body mass index: BMI > 30) and nonobese (BMI < 25) groups, and blood samples were collected for enzyme‐linked immunosorbent assay analysis. The acute mental stress task elicited an increase in heart rate, catecholamines, and IL‐1β in all subjects. Additionally, acute mental stress increased cortisol concentrations in the nonobese group. There was a significant reduction in leptin in obese subjects 30 min posttask compared with a decrease in nonobese subjects 120 min posttask. Interestingly, the relationship between the percent change in leptin and IL‐1Ra at 120 min posttask in response to an acute mental stress task was only observed in nonobese individuals. This is the first study to suggest that adiposity in males may impact leptin and inflammatory signaling mechanisms following acute mental stress.
Tamoxifen as a new therapeutic tool for neutrophilic lung inflammation
Authors: Perez Barbara , Henriquez Claudio , Sarmiento Jose , Morales Natalia , Folch Hugo , Galesio Juan S. , Uberti Benjamin , Morán Gabriel
Published: October 2015

Background and objective

Neutrophilic asthma is an important disease subgroup, including patients with severe phenotypes and erratic responses to standard treatments.Tamoxifen (TX), a selective estrogen receptor modulator (SERM) used as treatment of human breast cancer, has been shown to induce early apoptosis of equine blood and bronchoalveolar lavage fluid (BALF) neutrophilsin vitro.Equine recurrent airway obstruction (RAO) is a naturally occurring neutrophilic condition, closely related with human asthma. Our purpose was to investigate the therapeutic potential of tamoxifen in horses with neutrophilic lung inflammation.

Methods

Twelve horses underwent acute lung inflammation through exposure to allergens known to causeRAO, after which they received treatment with either tamoxifen or dexamethasone. Outcome measures included evaluation of clinical signs,BALFcytology, and early apoptosis of blood andBALFneutrophils.

Results

Tamoxifen treatment decreasedBALFneutrophil counts (65.3 ± 19.38% before treatment; 7.6 ± 4.5% 2 days post‐treatment,; and 13.6 ± 9.3% 5 days post‐treatment). A similar decrease was observed with dexamethasone treatment (48.6 ± 5.88% before treatment; 11.5 ± 8.1% 2 days post‐treatment; 14.6 ± 10.3% 5 days post‐treatment). Clinical and endoscopic scores improved in both treatment groups.Tamoxifen treatment significantly increased early apoptosis of peripheral blood neutrophils at 5 days post‐treatment (27.04 ± 15.2%), and inBALFneutrophils at 2 and 5 days post‐treatment (42.11 ± 11.67% and 48.98 ± 2.6%, respectively).

Conclusion

Tamoxifen treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood andBALFneutrophils, reduction inBALFneutrophils and improvement in the animals' clinical status.
Undiagnosed airflow limitation is common in patients with coronary artery disease and associated with cardiac stress
Authors: Ko Fanny W.S. , Yan Bryan P. , Lam Yat‐yin , Chu Jojo H.Y. , Chan Ka‐pang , Hui David S.C.
Published: October 2015

Background and objective

Smoking is a common risk factor for coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). We evaluated the prevalence of undiagnosed COPD in patients with CAD and assessed the relationship between airflow obstruction and markers of cardiac stress.

Methods

We recruited prospectively consecutive patients aged >40 years without known history of chronic lung disease (e.g. asthma, COPD, bronchiectasis) who had undergone percutaneous coronary intervention (PCI) for obstructive CAD between August 2009 and October 2010. Spirometry was performed and serum ST2, a novel biomarker of cardiomyocyte stress and fibrosis, was measured by enzyme‐linked immunosorbent assay.

Results

Among 475 subjects (mean age 64 ± 9.7, range 42–85 years, 87.2% males, 58.5% current or ex‐smokers) who underwent spirometry, 51 (10.7%) had undiagnosed airflow obstruction with FEV1/FVC ratio <70%. Of these 51 subjects, 14 (2.9%), 23 (4.8%) and 14 (2.9%) had FEV1 ≥80, 50–80 and 30–50% predicted normal, respectively. ST2 level was measured in all the subjects with undiagnosed airflow obstruction and in 290 subjects with normal lung function. There was no significant difference in left ventricular ejection fraction on echocardiogram between subjects with and without airflow obstruction. Patients with severe airflow obstruction had a higher level of cardiac stress marker ST2 than those with mild and moderate airflow obstruction (rho = −0.214, P ≤ 0.001).

Conclusion

Undiagnosed airflow obstruction is common among patients with CAD who have undergone PCI. Severity of airflow limitation is associated with increasing cardiac stress.
Bayesian Hierarchical Modelling for Inferring Genetic Interactions in Yeast
Authors: Heydari Jonathan , Lawless Conor , Lydall David A. , Wilkinson Darren J.
Published: October 2015

Quantitative fitness analysis (QFA) is a high throughput experimental and computational methodology for measuring the growth of microbial populations. QFA screens can be used to compare the health of cell populations with and without a mutation in a query gene to infer genetic interaction strengths genomewide, examining thousands of separate genotypes. We introduce Bayesian hierarchical models of population growth rates and genetic interactions that better reflect QFA experimental design than current approaches. Our new approach models population dynamics and genetic interaction simultaneously, thereby avoiding passing information between models via a univariate fitness summary. Matching experimental structure more closely, Bayesian hierarchical approaches use data more efficiently and find new evidence for genes which interact with yeast telomeres within a published data set.
What Factors Influence the Decision to Share Suicidal Thoughts? A Multilevel Social Network Analysis of Disclosure Among Individuals with Serious Mental Illness
Authors: Fulginiti Anthony , Pahwa Rohini , Frey Laura M. , Rice Eric , Brekke John S.
Published: October 2015

Nondisclosure of suicidal thoughts limits suicide risk management. Consistent with disclosure models for other stigmatized statuses, understanding suicidal disclosure requires accounting for features of the discloser (individual factors) and the discloser–recipient relationship (relational factors). In a sample of 30 adults with schizophrenia, bipolar disorder, or major depressive disorder (Level 2) who nominated 436 social network members (Level 1), we examined disclosure patterns and identified individual and relational correlates of disclosure intent. Most individuals disclosed in the past (77%; n = 23) and all intended on disclosing (100%; n = 30). Disclosure was highly selective, with 14% (n = 62) of network members identified as prior confidants and 23% (n = 99) identified as intended confidants. Multilevel modeling indicated that relational factors were more central to disclosure than individual factors. Network members who were prior confidants and who provided social support were attractive targets for intended disclosure. Our findings suggest that “targeted” gatekeeper training may be a promising strategy and reveal relational characteristics to identify “high‐probability confidants.”
Hydrogen peroxide modulates synaptic transmission in ventral horn neurons of the rat spinal cord
Authors: Ohashi Masayuki , Hirano Toru , Watanabe Kei , Katsumi Keiichi , Ohashi Nobuko , Baba Hiroshi , Endo Naoto , Kohno Tatsuro
Published: October 2015

Key points

Excessive production of reactive oxygen species (ROS) is implicated in many central nervous system disorders; however, the physiological role of ROS in spinal ventral horn (VH) neurons remains poorly understood.

We investigated how pathological levels of H2O2, an abundant ROS, regulate synaptic transmission in VH neurons of rats using a whole‐cell patch clamp approach.

H2O2 increased the release of glutamate and GABA from presynaptic terminals.

The increase in glutamate release involved N‐type voltage‐gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inositol trisphosphate receptors (IP3Rs); the increase in GABA release, which inhibited glutamatergic transmission, involved IP3R.

Inhibiting N‐type VGCCs and RyRs attenuates excitotoxicity resulting from increased glutamatergic activity while preserving the neuroprotective effects of GABA, and may represent a novel strategy for treating H2O2‐induced motor neuron disorders resulting from trauma or ischaemia–reperfusion injury.

Excessive production of reactive oxygen species (ROS) is a critical component of the cellular and molecular pathophysiology of many central nervous system (CNS) disorders, including trauma, ischaemia–reperfusion injury, and neurodegenerative diseases. Hydrogen peroxide (H2O2), an abundant ROS, modulates synaptic transmission and contributes to neuronal damage in the CNS; however, the pathophysiological role of H2O2 in spinal cord ventral horn (VH) neurons remains poorly understood, despite reports that these neurons are highly vulnerable to oxidative stress and ischaemia. This was investigated in the present study using a whole‐cell patch clamp approach in rats. We found that exogenous application of H2O2 increased the release of glutamate from excitatory presynaptic terminals and γ‐aminobutyric acid (GABA) from inhibitory presynaptic terminals. The increase of glutamate release was induced in part by an increase in Ca2+ influx through N‐type voltage‐gated calcium channels (VGCCs) as well as by ryanodine receptor (RyR)‐ and inositol trisphosphate receptor‐mediated Ca2+ release from the endoplasmic reticulum (ER). In inhibitory presynaptic neurons, increased IP3R‐mediated Ca2+ release from the ER increased GABAergic transmission, which served to rescue VH neurons from excessive release of glutamate from presynaptic terminals. These findings indicate that inhibiting N‐type VGCCs or RyRs may attenuate excitotoxicity resulting from increased glutamatergic activity while preserving the neuroprotective effects of GABA, and may therefore represent a novel and targeted strategy for preventing and treating H2O2‐induced motor neuron disorders.
Understanding Communication and Collaboration in Social Product Development Through Social Network Analysis
Authors: Wu Dazhong , Rosen David W. , Panchal Jitesh H. , Schaefer Dirk
Published: October 2015

Social media have recently been introduced into the arena of collaborative design as a new means for seamlessly gathering, processing, and sharing product design-related information. As engineering design processes are becoming increasingly distributed and collaborative, it is crucial to understand the communication and collaboration mechanism of engineers participating in such dispersed engineering processes. In particular, mapping initially disconnected design individuals and teams into an explicit social network is challenging. The objective of this paper is to propose a generic framework for investigating communication and collaboration mechanisms in social media-supported engineering design environments. Specifically, we propose an approach for measuring tie strengths in the context of distributed and collaborative design. We transform an implicit design network into an explicit and formal social network based on specific indices of tie strengths. We visualize the process of transforming customer needs to functional requirements, to design parameters, and to process variables using social network analysis (SNA). Specifically, by utilizing a specific index for tie strengths, we can quantitatively measure tie strengths in a design network. Based on the tie strengths, we can map an implicit design network into an explicit social network. Further, using the typical measures (e.g., centrality and cluster coefficient) in SNA, we can analyze the social network at both actor and systems levels and detect design communities with common design interests. We demonstrate the applicability of the framework by means of two examples. The contribution in this paper is a systematic and formal approach that helps gain new insights into communication and collaboration mechanisms in distributed and collaborative design.
Bond Strength of Thermally Fused Vascular Tissue Varies With Apposition Force
Authors: Anderson Nicholas S. , Kramer Eric A. , Cezo James D. , Ferguson Virginia L. , Rentschler Mark E.
Published: October 2015

Surgical tissue fusion devices ligate blood vessels using thermal energy and coaptation pressure, while the molecular mechanisms underlying tissue fusion remain unclear. This study characterizes the influence of apposition force during fusion on bond strength, tissue temperature, and seal morphology. Porcine splenic arteries were thermally fused at varying apposition forces (10–500 N). Maximum bond strengths were attained at 40 N of apposition force. Bonds formed between 10 and 50 N contained laminated medial layers; those formed above 50 N contained only adventitia. These findings suggest that commercial fusion devices operate at greater than optimal apposition forces, and that constituents of the tunica media may alter the adhesive mechanics of the fusion mechanism.
Probabilistic Analysis of Stress Corrosion Crack Growth and Related Structural Reliability Considerations
Authors: Lee Dooyoul , Huang Yonggang , Achenbach Jan D.
Published: October 2015

The predetection evolution of stress corrosion cracking has been examined as a necessary preliminary to effective detection of such cracks. Anodic dissolution (AD) and hydrogen embrittlement (HE) have been considered to calculate the stress corrosion crack (SCC) growth in AA7050-T6 for a surface-breaking crack with blunt tip in an aqueous environment. Since these processes are not completely deterministic, several advanced statistical methods have been used to introduce probabilistic considerations. Based on the data from designed computer experiments, the computer code developed by the authors (Lee et al., 2015, “A Comprehensive Analysis of the Growth Rate of Stress Corrosion Cracks,” Proc. R. Soc. A, 471(2178), p. 20140703) to conduct deterministic stress corrosion crack growth analysis has been represented by metamodels using Gaussian process regression. Through sensitivity analysis, important variables which need to be calibrated have been identified. The dynamic Bayesian network (DBN) model and Monte Carlo simulation (MCS) have been utilized to quantify uncertainties. Statistical parameters of input variables have been obtained by a machine learning technique. The calibrated model has been validated using Bayesian hypothesis testing. Since the DBN model yields a probability of detection (POD) comparable to the probability based on binary validation data, the probabilistic model with calibrated parameters is expected to well represent the growth of a stress corrosion crack. The results also show that the reliability largely depends on the accuracy of flaw detection methods and on the critical crack length.
A Random Process Metamodel Approach for Time-Dependent Reliability
Authors: Drignei Dorin , Baseski Igor , Mourelatos Zissimos P. , Kosova Ervisa
Published: October 2015

A new metamodeling approach is proposed to characterize the output (response) random process of a dynamic system with random variables, excited by input random processes. The metamodel is then used to efficiently estimate the time-dependent reliability. The input random processes are decomposed using principal components, and a few simulations are used to estimate the distributions of the decomposition coefficients. A similar decomposition is performed on the output random process. A Kriging model is then built between the input and output decomposition coefficients and is used subsequently to quantify the output random process. The innovation of our approach is that the system input is not deterministic but random. We establish, therefore, a surrogate model between the input and output random processes. To achieve this goal, we use an integral expression of the total probability theorem to estimate the marginal distribution of the output decomposition coefficients. The integral is efficiently estimated using a Monte Carlo (MC) approach which simulates from a mixture of sampling distributions with equal mixing probabilities. The quantified output random process is finally used to estimate the time-dependent probability of failure. The proposed method is illustrated with a corroding beam example.
An Adaptive Bayesian Sequential Sampling Approach for Global Metamodeling
Authors: Liu Haitao , Xu Shengli , Ma Ying , Chen Xudong , Wang Xiaofang
Published: October 2015

Computer simulations have been increasingly used to study physical problems in various fields. To relieve computational budgets, the cheap-to-run metamodels, constructed from finite experiment points in the design space using the design of computer experiments (DOE), are employed to replace the costly simulation models. A key issue related to DOE is designing sequential computer experiments to achieve an accurate metamodel with as few points as possible. This article investigates the performance of current Bayesian sampling approaches and proposes an adaptive maximum entropy (AME) approach. In the proposed approach, the leave-one-out (LOO) cross-validation error estimates the error information in an easy way, the local space-filling exploration strategy avoids the clustering problem, and the search pattern from global to local improves the sampling efficiency. A comparison study of six examples with different types of initial points demonstrated that the AME approach is very promising for global metamodeling.
How some of the world's biggest dinosaurs got that way
Authors: Balter Michael
Published: October 2015

Fresh data reveal titanosaur growth stages, from egg to adult.
Comment on “Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism”
Authors: Wang Jimin
Published: October 2015

Li
et al
. (Reports, 30 January, p. 555) reported on a crystal structure for a translocator protein (TSPO) from
Rhodobacter sphaeroides
in which some of the electron density is modeled as a porphyrin. The analysis of the x-ray data discussed here suggests that this assignment is incorrect.
Pinched topography initiates the critical zone
Authors: Anderson Robert S.
Published: October 2015

Geophysical imaging provides a clearer picture of how rock turns into soil

[Also see Report by

St. Clair
et al.

]
Synthetic immunobiology boosts the IQ of T cells
Authors: Jensen Michael C.
Published: October 2015

Engineered chimeric antigen receptors show promise
Characterization of Staphylococcus caprae Clinical Isolates Involved in Human Bone and Joint Infections, Compared with Goat Mastitis Isolates
Authors: d'Ersu J. , Aubin G. G. , Mercier P. , Nicollet P. , Bémer P. , Corvec S.
Published: October 2015

Staphylococcus caprae
is an emerging microorganism in human bone and joint infections (BJI). The aim of this study is to describe the features of
S. caprae
isolates involved in BJI (H for human) compared with those of isolates recovered in goat mastitis (A for animal). Fourteen isolates of each origin were included. Identifications were performed using a Vitek 2 GP ID card,
tuf
gene sequencing, and matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) Vitek MS. Molecular typing was carried out using pulsed-field gel electrophoresis (PFGE) and DiversiLab technology. The crystal violet method was used to determine biofilm-forming ability. Virulence factors were searched by PCR. Vitek MS technology provides an accurate identification for the two types of isolates compared to that of gold-standard sequencing (sensitivity, 96.4%), whereas the Vitek 2 GP ID card was more effective for H isolates. Molecular typing methods revealed two distinct lineages corresponding to the origin despite few overlaps: H and A. In our experimental conditions, no significant difference was observed in biofilm production ability between H and A isolates. Nine isolates (5 H isolates and 4 A isolates) behaved as weak producers while one A isolate was a strong producer. Concerning virulence factors, the autolysin
atlC
and the serine aspartate adhesin (
sdrZ
) genes were detected in 24 isolates (86%), whereas the lipase gene was always detected, except in one H isolate (96%). The
ica
operon was present in 23 isolates (82%). Fibrinogen-binding (
fbe
) or collagen-binding (
cna
) genes were not detected by using primers designed for
Staphylococcus aureus
or
Staphylococcus epidermidis
, even in low stringency conditions. Although
S. caprae
probably remains underestimated in human infections, further studies are needed to better understand the evolution and the adaptation of this species to its host.
Sports: The Infectious Hazards
Authors: Minooee Arezou , Wang Jeff , Gupta Geeta K.
Published: October 2015

Although the medical complications of sports are usually traumatic in nature, infectious hazards also arise. While blood-borne pathogens such as HIV, hepatitis B, and hepatitis C, cause significant illness, the risk of acquiring these agents during sporting activities is minimal. Skin infections are more commonplace, arising from a variety of microbial agents including bacterial, fungal, and viral pathogens. Sports involving water contact can lead to enteric infections, eye infections, or disseminated infections such as leptospirosis. Mumps, measles, and influenza are vaccine-preventable diseases that have been transmitted during sporting events, both in players and in spectators. Prevention is the key to many of these infections. Players should be vaccinated and should not participate in sports if their infection can be spread by contact, airborne, or droplet transmission.
Structure, Function, and Assembly of Adhesive Organelles by Uropathogenic Bacteria
Authors: Chahales Peter , Thanassi David G.
Published: October 2015

Bacteria assemble a wide range of adhesive proteins, termed adhesins, to mediate binding to receptors and colonization of surfaces. For pathogenic bacteria, adhesins are critical for early stages of infection, allowing the bacteria to initiate contact with host cells, colonize different tissues, and establish a foothold within the host. The adhesins expressed by a pathogen are also critical for bacterial-bacterial interactions and the formation of bacterial communities, including biofilms. The ability to adhere to host tissues is particularly important for bacteria that colonize sites such as the urinary tract, where the flow of urine functions to maintain sterility by washing away non-adherent pathogens. Adhesins vary from monomeric proteins that are directly anchored to the bacterial surface to polymeric, hair-like fibers that extend out from the cell surface. These latter fibers are termed pili or fimbriae, and were among the first identified virulence factors of uropathogenicEscherichia coli. Studies since then have identified a range of both pilus and non-pilus adhesins that contribute to bacterial colonization of the urinary tract, and have revealed molecular details of the structures, assembly pathways, and functions of these adhesive organelles. In this review, we describe the different types of adhesins expressed by both Gram-negative and Gram-positive uropathogens, what is known about their structures, how they are assembled on the bacterial surface, and the functions of specific adhesins in the pathogenesis of urinary tract infections.
The medial tibial stress syndrome score: a new patient-reported outcome measure
Authors: Winters Marinus , Moen Maarten H , Zimmermann Wessel O , Lindeboom Robert , Weir Adam , Backx Frank JG , Bakker Eric WP
Published: October 2015

Background

At present, there is no validated patient-reported outcome measure (PROM) for patients with medial tibial stress syndrome (MTSS).

Aim

Our aim was to select and validate previously generated items and create a valid, reliable and responsive PROM for patients with MTSS: the MTSS score.

Methods

A prospective cohort study was performed in multiple sports medicine, physiotherapy and military facilities in the Netherlands. Participants with MTSS filled out the previously generated items for the MTSS score on 3 occasions. From previously generated items, we selected the best items. We assessed the MTSS score for its validity, reliability and responsiveness.

Results

The MTSS score was filled out by 133 participants with MTSS. Factor analysis showed the MTSS score to exhibit a single-factor structure with acceptable internal consistency (α=0.58) and good test–retest reliability (intraclass correlation coefficient=0.81). The MTSS score ranges from 0 to 10 points. The smallest detectable change in our sample was 0.69 at the group level and 4.80 at the individual level. Construct validity analysis showed significant moderate-to-large correlations (r=0.34–0.52, p<0.01). Responsiveness of the MTSS score was confirmed by a significant relation with the global perceived effect scale (β=−0.288, R2=0.21, p<0.001).

Conclusions

The MTSS score is a valid, reliable and responsive PROM to measure the severity of MTSS. It is designed to evaluate treatment outcomes in clinical studies.
Safety and immunogenicity of novel respiratory syncytial virus (RSV) vaccines based on the RSV viral proteins F, N and M2-1 encoded by simian adenovirus (PanAd3-RSV) and MVA (MVA-RSV); protocol for an open-label, dose-escalation, single-centre, phase 1 clinical trial in healthy adults
Authors: Green C A , Scarselli E , Voysey M , Capone S , Vitelli A , Nicosia A , Cortese R , Thompson A J , Sande C S , de Lara Catherine , Klenerman P , Pollard A J
Published: October 2015

Introduction

Respiratory syncytial virus (RSV) infection causes respiratory disease throughout life, with infants and the elderly at risk of severe disease and death. RSV001 is a phase 1 (first-in-man), open-label, dose-escalation, clinical trial of novel genetic viral-vectored vaccine candidates PanAd3-RSV and modified vaccinia virus Ankara (MVA)-RSV. The objective of RSV001 is to characterise the (primary objective) safety and (secondary objective) immunogenicity of these vaccines in healthy younger and older adults.

Methods and analysis

Heterologous and homologous ‘prime’/boost combinations of PanAd3-RSV and single-dose MVA-RSV are evaluated in healthy adults. 40 healthy adults aged 18–50 years test one of four combinations of intramuscular (IM) or intranasal (IN) PanAd3-RSV prime and IM PanAd3 or IM MVA-RSV boost vaccination, starting at a low dose for safety. The following year an additional 30 healthy adults aged 60–75 years test either a single dose of IM MVA-RSV, one of three combinations of IN or IM PanAd3-RSV prime and PanAd3-RSV or MVA-RSV boost vaccination used in younger volunteers, and a non-vaccinated control group. Study participants are self-selected volunteers who satisfy the eligibility criteria and are assigned to study groups by sequential allocation. Safety assessment includes the daily recording of solicited and unsolicited adverse events for 1 week after vaccination, as well as visit (nursing) observations and safety bloods obtained at all scheduled attendances. Laboratory measures of RSV-specific humoral and cellular immune responses after vaccination will address the secondary end points. All study procedures are performed at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK.

Ethics and dissemination

RSV001 has clinical trial authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) and ethics approval from NRES Berkshire (reference 13/SC/0023). All study procedures adhere to International Conference on Harmonisation (ICH) Good Clinical Practice guidelines. The results of the trial are to be published in peer-reviewed journals, conferences and academic forums.

Trial registration number

NCT01805921.
Prognosis of patients with dementia: results from a prospective nationwide registry linkage study in the Netherlands
Authors: van de Vorst Irene E , Vaartjes Ilonca , Geerlings Mirjam I , Bots Michael L , Koek Huiberdina L
Published: October 2015

Objective

To report mortality risks of dementia based on national hospital registry data, and to put these risks into perspective by comparing them with those in the general population and following cardiovascular diseases.

Design

Prospective cohort study from 1 January 2000 through 31 December 2010.

Setting

Hospital-based cohort.

Participants

A nationwide hospital-based cohort of 59 201 patients with clinical diagnosis of dementia (admitted to a hospital or visiting a day clinic) was constructed (38.7% men, 81.4 years (SD 7.0)).

Main outcomes and measures

1-year and 5-year age-specific and sex-specific mortality risks were reported for patients with dementia visiting a day clinic compared with the general population; for patients hospitalised with dementia compared with patients hospitalised for acute myocardial infarction (AMI), heart failure or stroke, these were presented as absolute and relative risks (RRs).

Results

1-year mortality was 38.3% in men and 30.5% in women. 5-year risk was 65.4% and 58.5%, respectively. Mortality risks were significantly higher in patients with dementia admitted to the hospital than in those visiting a day clinic (1-year RR 3.29, 95% CI 3.16 to 3.42; and 5-year RR 1.79, 95% CI 1.76 to 1.83). Compared with the general population, mortality risks were significantly higher among patients visiting a day clinic (1-year RR for women 2.99, 95% CI 2.84 to 3.14; and for men 3.94, 95% CI 3.74 to 4.16). 5-year RRs were somewhat lower, but still significant. Results were more pronounced at younger ages. Mortality risks among admitted patients were comparable or even exceeded those of cardiovascular diseases (1-year RR for women with dementia vs AMI 1.24, 95% CI 1.19 to 1.29; vs heart failure 1.05, 95% CI 1.02 to 1.08; vs stroke 1.07, 95% CI 1.04 to 1.10). 5-year RRs were comparable. For men, RRs were slightly higher.

Conclusions

Dementia has a poor prognosis as compared with other diseases and the general population. The risks among admitted patients even exceeded those following cardiovascular diseases.
Multimorbidity in primary care: protocol of a national cross-sectional study in Switzerland
Authors: Déruaz-Luyet Anouk , N'Goran A Alexandra , Tandjung Ryan , Frey Peter , Zeller Andreas , Haller Dagmar M , Rosemann Thomas , Burnand Bernard , Bodenmann Patrick , Senn Nicolas , Widmer Daniel , Herzig Lilli
Published: October 2015

Introduction

With the ageing of the population and the general improvement of care, an increasing number of people are living with multiple chronic health conditions or ‘multimorbidity’. Multimorbidity often implies multiple medical treatments. As a consequence, the risk of adverse events and the time spent by patients for their treatments increase exponentially. In many cases, treatment guidelines traditionally defined for single conditions are not easily applicable. Primary care for individuals with multimorbidity requires complex patient-centred care and good communication between the patient and the general practitioner (GP). This often includes prioritising among the different chronic conditions.

Methods and analysis

The main objectives of this study are to describe the burden related to multimorbidity (disease-related burden and burden of treatment) in primary care and to identify the factors influencing it. Other objectives include evaluating patients’ perception of treatment burden and quality of life, assessing factors influencing that perception, and investigating prioritisation in the management of multimorbidity from the perspectives of GPs and patients. For this cross-sectional study, patient enrolment will take place in GP's private practices across Switzerland. A convenient sample of 100 GPs will participate; overall, 1000 patients with at least three chronic health conditions will be enrolled. Data will be collected as paper-based questionnaires for GPs and delayed telephone interview questionnaires for patients. GPs will provide demographic and practice-related data. In addition, each GP will complete a paper-based questionnaire for each patient that they enrol. Each patient will complete a telephone interview questionnaire.

Ethics and dissemination

This study has been approved by the research ethics committee of Canton Vaud, Switzerland (Protocol 315/14). The results of the study will be reported in international peer-reviewed journals.
Vascular expression of annexin A2 in lupus nephritis
Authors: Salle V , Cordonnier C , Schmidt J , Mazière C , Smail A , Attencourt C , Mabille M P , Mazière J C , Makdassi R , Choukroun G , Diouf M , Duhaut P , Ducroix J P
Published: October 2015

Aims

To evaluate vascular expression of annexin A2 (ANXA2) and its subunit S100A10 in lupus nephritis (LN).

Methods

The present histological study included 14 patients with LN and 11 controls (patients with non-lupus kidney diseases). Kidney biopsies from patients with lupus were scored for lupus glomerulonephritis (according to the International Society of Nephrology/Renal Pathology Society 2003 classification) and vascular lesions (such as microthrombi and antiphospholipid syndrome nephropathy (APSN)). ANXA2 and S100A10 expression in glomerular and peritubular capillaries was evaluated by immunohistochemistry on tissue sections. The staining intensity score ranged from 0 (no expression) to 4 (intense expression).

Results

In patients with LN, the median age (range) at first kidney biopsy was 36 (18–49). Vascular lesions were observed in six patients (including two with APSN). We observed intense expression of ANXA2 in glomerular and peritubular capillaries while expression of S100A10 was weaker. However, one of the patients with APSN showed strong S100A10 expression. Patients with LN and controls differed significantly in terms of S100A10 expression in peritubular capillaries. We also observed a statistical difference between patients who had LN with renal vascular lesions and those without renal vascular lesions in terms of ANXA2 expression in peritubular capillaries.

Conclusions

The presence of vascular lesions in LN appears to be associated with significant differences in the vascular expression of ANXA2. Vascular expression of ANXA2 was somewhat higher in LN. Vascular expression of S100A10 was somewhat lower in LN (except one of the two patients with APSN). Further studies of ANXA2's putative value as a biomarker of active LN or of vascular lesions in LN are required.
Previous anxiety and depression as risk factors for early labour force exit
Authors: Rudolph Kara E , Eaton William W
Published: October 2015

Background

Individuals with a history of mental illness have lower earnings than individuals without. A possible reason is that those with prior anxiety or depression may be more likely to exit the labour force prior to retirement age, but evidence has been mixed and limited. Our objective was to compare risk of early labour force exit between employed adults with a history of depression or anxiety versus those without, separately for men and women.

Methods

We used data from the Baltimore Epidemiological Catchment Area Follow-up Cohort, which collected baseline data in 1981 and follow-up data 1993–1996 and 2004–2005. Cox proportional hazards models estimated the relative risk of labour force exit comparing those with versus without prior history of anxiety or depressive disorders.

Results

Women with prior anxiety or depression are at 37% increased risk of dropping out of the labour force as compared to women without, controlling for age, socioeconomic status, race and marital status (HR: 1.37, 95% CI 1.04 to 1.79). Men with prior anxiety or depression are 18% more likely to subsequently drop out of the labour force as compared to men without, controlling for the above confounders as well as veteran status, but this association is not statistically significant (HR: 1.18, 95% CI 0.72 to 1.27).

Conclusions

Prior anxiety or depression increases risk of early labour force exit for women. These findings may help explain previously reported lower earnings among female individuals with a history of mental illness and highlight the importance of considering anxiety and depressive disorders in policies supporting labour force participation.
Osseous associated cervical spondylomyelopathy at the C2‐C3 articular facet joint in 11 dogs
Authors: Cooper C. , Gutierrez‐Quintana R. , Penderis J. , Gonçalves R.
Published: October 2015

In dogs, vertebral canal stenosis at C2‐C3 due to articular facet joint degeneration is only sporadically identified. The authors’ aims were to review the clinical presentation, MRI characteristics, treatment and outcome of dogs presenting with this condition. Eleven cases were eligible for inclusion. Neurological examination revealed tetraparesis and proprioceptive ataxia in all 4 limbs in 3/11, proprioceptive tetra‐ataxia only in 4/11, pelvic limb proprioceptive ataxia in 2/11 and no gait abnormalities in 2/11 dogs. Cervical hyperaesthesia was present in 7/11 dogs. MRI revealed bilateral articular facet joint degeneration in 10/11 cases and unilateral degeneration in one. Surgery was performed in six cases and medical management elected in five. Long‐term follow‐up information was available for 11 animals. Four of the surgical cases are alive and have no neurological deficits, one was euthanased for an unrelated condition and one lost to follow‐up. Of the cases managed medically, three are alive showing no neurological deficits, one is alive still displaying neurological deficits and one euthanased for an unrelated condition whilst still ataxic. This study shows that both medical and surgical management can result in good outcomes in dogs with vertebral canal stenosis resulting from articular facet joint degeneration at the level of C2‐C3.
Building a career
Authors: McKintosh Darren
Published: October 2015

As veterinary graduates' expectations change, employers need to look at new ways to support, retain and develop them in their careers. Darren McKintosh, senior business support manager at Independent Vetcare, explains why the group set up its Graduate Academy and why he thinks it's important