bluuebunny/crossref_metadata_2025 huggingface dataset:
Shortening of an existing generic online health‐related quality of life instrument for dogs
Authors: Reid J. , Wiseman‐Orr L. , Scott M.
Published: October 2017

Objective

Development, initial validation and reliability testing of a shortened version of a web‐based questionnaire instrument to measure generic health‐related quality of life in companion dogs, to facilitate smartphone and online use.

Materials and Methods

The original 46 items were reduced using expert judgment and factor analysis. Items were removed on the basis of item loadings and communalities on factors identified through factor analysis of responses from owners of healthy and unwell dogs, intrafactor item correlations, readability of items in the UK, USA and Australia and ability of individual items to discriminate between healthy and unwell dogs. Validity was assessed through factor analysis and a field trial using a “known groups” approach. Test–retest reliability was assessed using intraclass correlation coefficients.

Results

The new instrument comprises 22 items, each of which was rated by dog owners using a 7‐point Likert scale. Factor analysis revealed a structure with four health‐related quality of life domains (energetic/enthusiastic, happy/content, active/comfortable, and calm/relaxed) accounting for 72% of the variability in the data compared with 64% for the original instrument. The field test involving 153 healthy and unwell dogs demonstrated good discriminative properties and high intraclass correlation coefficients.

Clinical Significance

The 22‐item shortened form is superior to the original instrument and can be accessed via a mobile phone app. This is likely to increase the acceptability to dog owners as a routine wellness measure in health care packages and as a therapeutic monitoring tool.
Videourodynamic factors predictive of successful onabotulinumtoxinA urethral sphincter injection for neurogenic or non‐neurogenic detrusor underactivity
Authors: Jiang Yuan‐Hong , Jhang Jia‐Fong , Chen Sheng‐Fu , Kuo Hann‐Chorng
Published: October 2017

Objective

The aim of the present study was to analyze treatment outcomes and identify videourodynamic factors predictive of successful urethral onabotulinumtoxinA treatment of neurogenic and non‐neurogenic detrusor underactivity (DU).

Methods

Patients with DU refractory to medical treatment were treated with injections totaling 100 U onabotulinumtoxinA into the urethral sphincter. Treatment outcomes were assessed 1 month after treatment using the Global Response Assessment. The videourodynamic parameters evaluated included bladder neck status during voiding, bladder sensation, detrusor pressure, maximum flow rate, and post‐void residual volume. Treatment outcome was analyzed by patient and baseline videourodynamic characteristics.

Results

In all, 60 patients (27 with non‐neurogenic and 33 with neurogenic DU) were included in the study and received urethral sphincter injections of 100 U onabotulinumtoxinA in total. Good outcomes were reported in 36 (60%) patients (20 [74.1%] with non‐neurogenic and 16 [48.5%] with neurogenic DU). Treatment outcome was significantly better in patients with non‐neurogenic than neurogenic DU (P = .039). However, good treatment outcome was not related to age, gender, or any videourodynamic variables, except for an open bladder neck during voiding vs non‐opening bladder neck (94.3% vs. 12.0%; P < .0001). The duration of the therapeutic effect was similar between patients with non‐neurogenic and neurogenic DU (mean [± SD] 7.37 ± 3.69 vs. 7.69 ± 3.18 months, respectively; P = .788). In all, 12 patients reported de novo urinary incontinence after urethral onabotulinumtoxinA injection, 4 of whom developed stress urinary incontinence and 8 who had exacerbated urgency urinary incontinence.

Conclusion

Urethral sphincter injection of onabotulinumtoxinA is effective in 60% of patients with DU. Careful videourodynamic interpretation of bladder neck opening enables urologists to select appropriate candidates for onabotulinumtoxinA treatment.
Pregnant Metaphors and Surrogate Meanings: Bringing the Ethnography of Pregnancy and Surrogacy into Conversation in Israel and Beyond
Authors: Ivry Tsipy , Teman Elly
Published: October 2017

This article explores the way that surrogacy and normal pregnancy share cultural assumptions about pregnancy. Through a juxtaposition of our ethnographic studies of two groups of Jewish–Israeli women—women who have undergone “normal,” low‐risk pregnancies and women who have given birth as gestational surrogates—we argue that surrogacy and pregnancy emerge as potent metaphors for one another. Both pregnant women and surrogates divided their bodies into two separate realms: fetus and maternal pregnant body. Both trivialized the effect of gestational influence on fetal health, making the fetus seem detached from gestational capacities of the mother. We argue for closer scrutiny of the way local cultural priorities and experiences of pregnancy shape surrogacy and for bringing the scholarship on pregnancy and on surrogacy into deeper conversation.
Phosphorylation coexists with O‐GlcNAcylation in a plant virus protein and influences viral infection
Authors: Martínez‐Turiño Sandra , Pérez José De Jesús , Hervás Marta , Navajas Rosana , Ciordia Sergio , Udeshi Namrata D. , Shabanowitz Jeffrey , Hunt Donald F. , García Juan Antonio
Published: October 2017

Phosphorylation and O‐GlcNAcylation are two widespread post‐translational modifications (PTMs), often affecting the same eukaryotic target protein. Plum pox virus (PPV) is a member of the genus Potyvirus which infects a wide range of plant species. O‐GlcNAcylation of the capsid protein (CP) of PPV has been studied extensively, and some evidence of CP phosphorylation has also been reported. Here, we use proteomics analyses to demonstrate that PPV CP is phosphorylated in vivo at the N‐terminus and the beginning of the core region. In contrast with the ‘yin–yang’ mechanism that applies to some mammalian proteins, PPV CP phosphorylation affects residues different from those that are O‐GlcNAcylated (serines Ser‐25, Ser‐81, Ser‐101 and Ser‐118). Our findings show that PPV CP can be concurrently phosphorylated and O‐GlcNAcylated at nearby residues. However, an analysis using a differential proteomics strategy based on iTRAQ (isobaric tags for relative and absolute quantitation) showed a significant enhancement of phosphorylation at Ser‐25 in virions recovered from O‐GlcNAcylation‐deficient plants, suggesting that crosstalk between O‐GlcNAcylation and phosphorylation in PPV CP takes place. Although the preclusion of phosphorylation at the four identified phosphotarget sites only had a limited impact on viral infection, the mimicking of phosphorylation prevents PPV infection in Prunus persica and weakens infection in Nicotiana benthamiana and other herbaceous hosts, prompting the emergence of potentially compensatory second mutations. We postulate that the joint action of phosphorylation and O‐GlcNAcylation in the N‐proximal segment of CP allows a fine‐tuning of protein stability, providing the amount of CP required in each step of viral infection.
Percutaneous transapical approach and transcatheter closure for ventricular tachycardia ablation
Authors: Vurgun Veysel Kutay , Altin Ali Timucin , Kilickap Mustafa , Candemir Basar , Akyurek Omer
Published: October 2017

In patients with mechanical aortic and mitral valve prosthesis, left ventricular endocardial ablation via retrograde transaortic or antegrade transmitral approach carry high risk of catheter entrapment and death. In such cases, ablation can be performed via ventricular transseptal or transapical approach. Transapical approach, with the ease of catheter maneuverability and better endocardial contact, may be performed surgically or percutaneously. In this case report, we describe a patient with both aortic and mitral mechanical prosthesis who underwent ventricular tachycardia ablation via percutaneous transapical endocardial approach with the use of closure device.
Real Definitions
Authors: Correia Fabrice
Published: October 2017

I offer and defend an account of real definitions. I put forward two versions of the account, one formulated in terms of the notion of generalised identity and of a suitable notion of grounding (RD1), and the other one formulated in terms of the former notion and of a suitable notion of comparative joint‐carvingness (RD2). Given a plausible assumption, (RD1) and (RD2) turn out to be equivalent. I give a sketch of a unified account of the three notions involved in (RD1) and (RD2) from which the assumption can be derived.
Ideology in a Desert Landscape*
Authors: Torza Alessandro
Published: October 2017

On one influential view, metaphysical fundamentality can be understood in terms of joint‐carving. Ted Sider has recently argued that (i) some first order quantifier is joint‐carving, and (ii) modal notions are not joint‐carving. After vindicating the theoretical indispensability of quantification against recent criticism, I will defend a logical result due to Arnold Koslow which implies that (i) and (ii) are incompatible. I will therefore consider an alternative understanding of Sider's metaphysics to the effect that (i) some first order quantifier is joint‐carving, and (iii) intensional notions are not joint‐carving. Another result due to Koslow entails that (i) and (iii) are also incompatible. I will argue that this second result is inconclusive. Nevertheless, (iii) is incompatible with another tenet of Sider's metaphysics, namely that (iv) ‘being joint‐carving’ is itself joint‐carving. In order to resolve the inconsistency, I will tentatively argue that condition (iv) should be renounced.
How to Be a Substantivalist Without Getting Shifty About It*
Authors: Perry Zee R.
Published: October 2017

According to substantivalism, spacetime points and regions are real entities whose existence is not dependent on matter. In this paper, I motivate and defend a version of substantivalism which takes the totality of spacetime as fundamental, and show how this position avoids certain problem cases, in particular the objection from static Leibniz shifts, and better conforms to how we think about space in physics. I argue that, even though the static Leibniz shifts do not show ordinary substantivalism is committed to in‐principle undetectable physical structure (pace Dasgupta (2015a)), they do indicate something problematic about the modal profile of space‐time and its constituents. While the problem is modal, the solution cannot be solely a matter of revising the substantivalist's modal claims. Rather, I argue, the substantivalist must revise her background ontology of space‐time. I show how this can be done by developing substantivalist theory that rejects this picture in favor of an alternative ontology of space‐time in the spirit of priority monism.
Morphodynamic evolution and stratal architecture of translating tidal point bars: Inferences from the northern Venice Lagoon (Italy)
Authors: Ghinassi Massimiliano , D'alpaos Andrea , Gasparotto Andrea , Carniello Luca , Brivio Lara , Finotello Alvise , Roner Marcella , Franceschinis Erica , Realdon Nicola , Howes Nick , Cantelli Alessandro
Published: October 2017

The widespread distribution of tidal creeks and channels that undertake meandering behaviour in modern coasts contrasts with their limited documentation in the fossil record, where point‐bar elements arising from the interaction between a mix of both fluvial and tidal currents are mainly documented. The sedimentary products of tidal channel‐bend evolution are relatively poorly known, and few studies have focused previously on specific facies models for tidal point bars present in modern settings. This study improves understanding of tidal channel meander bends through a multi‐disciplinary approach that combines analyses of historical aerial photographs, measurements of in‐channel flow velocity, high‐resolution facies analyses of sedimentary cores and three‐dimensional architectural modelling. The studied channel bend (12 to 15 m wide and 2 to 3 m deep) drains a salt marsh area located in the north‐eastern sector of the microtidal Venice Lagoon, Italy. Historical photographs show that, during the past 77 years, the bend has translated seaward ca 15 m. Results show that the channel bend formed on a non‐vegetated mud flat that was progressively colonized by vegetation. Seaward translation occurred under aggradational conditions, with an overall migration rate of 0·2 to 0·3 m year−1, and was promoted by the occurrence of cohesive, poorly erodible outer bank deposits. Ebb currents are dominant, and translation of the channel bend promotes erosion and deposition along the landward and seaward side of the bar, respectively. Tidal currents show a clear asymmetry in terms of velocity distribution, and their offset pattern provides a peculiar grain‐size distribution within the bar. During the flood stage, sand sedimentation occurs in the upper part of the bar, where the maximum flow velocity occurs. During the ebb stage, the bar experiences the secondary helical flow that accumulates sand at the toe of the bar. Lateral stacking of flood and ebb deposits has caused the formation of localized coarsening‐upward and fining‐upward sedimentary packages, respectively.
Using climate to relate water discharge and area in modern and ancient catchments
Authors: Eide Christian Haug , Müller Reidar , Helland‐Hansen William
Published: October 2017

Models relating sediment supply to catchment properties are important in order to use the geological record to deduce landscape evolution and interplay between tectonics and climate. Water discharge (Qw) is an important factor in the widely used ‘BQART’ model, which relates sediment load to a set of measurable catchment parameters. Although many of the factors in this equation may be independently estimated with some degree of certainty in ancient systems, water discharge (Qw) certainly cannot. An analysis of a world database of modern catchments with 1255 entries shows that the commonly applied equation relating catchment area (A) to water discharge (Qw = 0·075A0·8) does not predict water discharge from catchment area well in many cases (R2 = 0·5 and an error spanning about three orders of magnitude). This is because the method does not incorporate the effect of arid and wet climate on river water discharge. The inclusion of climate data into such estimations is an opportunity to refine these estimates, because generalized estimates of palaeoclimate can often be deduced on the basis of sedimentological data such as palaeosol types, mineralogy and palaeohydraulics. This paper investigates how the relationship between catchment area and river discharge varies with four runoff categories (arid, semi‐arid, humid and wet), which are recognizable in the geological record, and modifies the coefficient and exponent of the above‐mentioned equation according to these classes. This modified model yields improved results in relating discharge to catchment area (R2 = 0·95 and error spanning one order of magnitude) when core, outcrop or regional palaeoclimate reconstruction data are available in non‐arid systems. Arid systems have an inherently variable water discharge, and catchment area is less important as a control due to downstream losses. The model here is sufficient for many geological applications and makes it possible to include variations in catchment humidity in mass‐flux estimates in ancient settings.
Iron deficiency among blood donors: experience from the Danish Blood Donor Study and from the Copenhagen ferritin monitoring scheme
Authors: Rigas A. S. , Pedersen O. B. , Magnussen K. , Erikstrup C. , Ullum H.
Published: October 2017

Blood components collected from blood donors are an invaluable part of modern‐day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood donors is not reflected in a reduced self‐perceived mental and physical health.

In general, the high proportion of iron‐deficient donors can be alleviated either by extending the inter‐donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels.
Maternal control of embryogenesis by MPK6 and its upstream MKK4/MKK5 in Arabidopsis
Authors: Zhang Mengmeng , Wu Hongjiao , Su Jianbin , Wang Huachun , Zhu Qiankun , Liu Yidong , Xu Juan , Lukowitz Wolfgang , Zhang Shuqun
Published: October 2017

In flowering plants, developing embryos reside in maternal sporophytes. It is known that maternal generation influences the development of next‐generation embryos; however, little is known about the signaling components in the process. Previously, we demonstrated that Arabidopsis mitogen‐activated protein kinase 6 (MPK6) and MPK3 play critical roles in plant reproduction. In addition, we noticed that a large fraction of seeds from mpk6 single‐mutant plants showed a wrinkled seed coat or a burst‐out embryo phenotype. Here, we report that these seed phenotypes can be traced back to defective embryogenesis. The defective embryos have shorter suspensors and reduced growth along the longitudinal axis. Furthermore, the cotyledons fail to bend over to progress to the bent‐cotyledon stage. As a result of the uneven circumference along the axis, the seed coat wrinkles to develop raisin‐like morphology after dehydration. In more severe cases, the embryo can be pushed out from the micropylar end, resulting in the burst‐out embryo seed phenotype. Genetic analyses demonstrated that the defective embryogenesis of the mpk6 mutant is a maternal effect. Heterozygous or homozygous mpk6 embryos have defects only in mpk6 homozygous maternal plants, but not in wild‐type or heterozygous maternal plants. The loss of function of MKK4/MKK5 also results in the same phenotypes, suggesting that MKK4/MKK5 might act upstream of MPK6 in this pathway. The maternal‐mediated embryo defects are associated with changes in auxin activity maxima and PIN localization. In summary, this research demonstrates that the Arabidopsis MKK4/MKK5–MPK6 cascade is an important player in the maternal control of embryogenesis.
Improved properties of the MEMS-type ion-sorption micropump
Authors: Grzebyk Tomasz , Górecka-Drzazga Anna , Dziuban Jan A.
Published: October 2017

In this paper, the authors demonstrate how to improve the properties of a recently elaborated microelectromechanical system (MEMS) ion-sorption micropump in order to generate high and ultrahigh vacuum inside MEMS and miniature nanoelectronics devices. This research goal has been achieved by applying mechanisms leading to an increase of the efficiency of a gas ionization process. One of the cathodes of the micropump was covered with different nanomaterials, which have either good field emission properties (carbon nanotubes) or high secondary emission coefficient (nanoporous silicon and magnesium oxide nanopowder). In this way, the number of primary or secondary electrons which collide with gas particles was multiplied. For all of the modified structures a significant increase of a discharge current inside the micropump was observed. In the case of electrodes covered with MgO, it increased about 1000 times. The use of these cathodes may allow to obtain ultrahigh vacuum inside hermetically sealed MEMS structure.
A two-microphone method for the determination of the mode amplitude distribution in high-frequency ducted broadband sound fields
Authors: Joseph P. F
Published: October 2017

This paper describes a measurement technique that allows the modal amplitude distribution to be determined in ducts with mean flow and reflections. The method is based only on measurements of the acoustic pressure two-point coherence at the duct wall. The technique is primarily applicable to broadband sound fields in the high frequency limit and whose mode amplitudes are mutually incoherent. The central assumption underlying the technique is that the relative mode amplitude distribution is independent of frequency. The two-microphone method proposed in this paper is also used to determine the transmitted sound power and far field pressure directivity.
Particulars of a transmitted acoustic signal at the shelf of decreasing depth
Authors: Dolgikh Grigory I. , Budrin Sergey S. , Dolgikh Stanislav G. , Ovcharenko Vladimir V. , Chupin Vladimir A. , Yakovenko Sergey V.
Published: October 2017

The paper analyzes the experimental data obtained in a comprehensive experiment aimed at identifying the regularities of transmitted hydroacoustic signal transformations at the shelf of decreasing depth. The 33 Hz harmonic hydroacoustic signals were generated at the shelf of the Sea of Japan by a low-frequency source. Distribution of the transmitted energy at vertical sounding from the surface to the bottom was studied at different shelf points with Bruel & Kjaer 8104 hydrophone. At the shore, the transformed seismo-acoustic signals were received by a 52.5 m shore laser strainmeter. The experiments showed that about 22% of the transmitted energy was transformed into the energy of hydroacoustic waves propagating in the water. About 72% of hydroacoustic wave energy, in turn, was transformed into the energy of R-waves, which were registered by the shore laser strainmeter. Other regularities of hydroacoustic signals distribution with 33 Hz frequency over the V-shaped shelf are identified.
Functional ultrasound imaging of brain activity in human newborns
Authors: Demene Charlie , Baranger Jérome , Bernal Miguel , Delanoe Catherine , Auvin Stéphane , Biran Valérie , Alison Marianne , Mairesse Jérome , Harribaud Elisabeth , Pernot Mathieu , Tanter Mickael , Baud Olivier
Published: October 2017

Functional ultrasound imaging with high spatiotemporal resolution monitors brain function in babies.
An analysis of IL-36 signature genes and individuals with
IL1RL2
knockout mutations validates IL-36 as a psoriasis therapeutic target
Authors: Mahil Satveer K. , Catapano Marika , Di Meglio Paola , Dand Nick , Ahlfors Helena , Carr Ian M. , Smith Catherine H. , Trembath Richard C. , Peakman Mark , Wright John , Ciccarelli Francesca D. , Barker Jonathan N. , Capon Francesca
Published: October 2017

IL-36 receptor (IL-36R) blockade ameliorates psoriatic inflammation and should be well tolerated, because IL-36R knockout mutations are benign.
Quinolone Resistance Reversion by Targeting the SOS Response
Authors: Recacha E. , Machuca J. , Díaz de Alba P. , Ramos-Güelfo M. , Docobo-Pérez F. , Rodriguez-Beltrán J. , Blázquez J. , Pascual A. , Rodríguez-Martínez J. M.
Published: October 2017

Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of
Escherichia coli
representing multiple levels of quinolone resistance.
E. coli
mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate
in vivo
impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog
10
CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the
in vivo
efficacy of ciprofloxacin was significantly enhanced (Δlog
10
CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of
E. coli
phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the
in vivo
efficacy.

IMPORTANCE
The rapid rise of antibiotic resistance in bacterial pathogens is now considered a major global health crisis. New strategies are needed to block the development of resistance and to extend the life of antibiotics. The SOS response is a promising target for developing therapeutics to reduce the acquisition of antibiotic resistance and enhance the bactericidal activity of antimicrobial agents such as quinolones. Significant questions remain regarding its impact as a strategy for the reversion or resensitization of antibiotic-resistant bacteria. To address this question, we have generated
E. coli
mutants that exhibited a spectrum of SOS activity, ranging from a natural SOS response to a hypoinducible or constitutively suppressed response. We tested the effects of these mutations on quinolone resistance reversion under therapeutic concentrations in a set of isogenic strains carrying different combinations of chromosome- and plasmid-mediated quinolone resistance mechanisms with susceptible, low-level quinolone resistant, resistant, and highly resistant phenotypes. Our comprehensive analysis opens up a new strategy for reversing drug resistance by targeting the SOS response.
An Engineered Synthetic Pathway for Discovering Nonnatural Nonribosomal Peptides in
Escherichia coli
Authors: Cleto Sara , Lu Timothy K.
Published: October 2017

Peptides that are synthesized independently of the ribosome in plants, fungi, and bacteria can have clinically relevant anticancer, antihemochromatosis, and antiviral activities, among many other. Despite their natural origin, discovering new natural products is challenging, and there is a need to expand the chemical diversity that is accessible. In this work, we created a novel, compressed synthetic pathway for the heterologous expression and diversification of nonribosomal peptides (NRPs) based on homologs of siderophore pathways from
Escherichia coli
and
Vibrio cholerae
. To enhance the likelihood of successful molecule production, we established a selective pressure via the iron-chelating properties of siderophores. By supplementing cells containing our synthetic pathway with different precursors that are incorporated into the pathway independently of NRP enzymes, we generated over 20 predesigned, novel, and structurally diverse NRPs. This engineering approach, where phylogenetically related genes from different organisms are integrated and supplemented with novel precursors, should enable heterologous expression and molecular diversification of NRPs.

IMPORTANCE
Nonribosomal peptides (NRPs) constitute a source of bioactive molecules with potential therapeutic applications. However, discovering novel NRPs by rational engineering of biosynthetic pathways remains challenging. Here, we show that a synthetic compressed pathway in which we replaced biosynthetic genes with their ancestral homologs and orthologs enabled successful heterologous NRP expression. Polyamines added exogenously were incorporated into nascent NRPs, and molecular production was pressured by growing the host under conditions that make such NRPs beneficial for survival. This multilayered approach resulted in the assembly of over 20 distinct and novel molecules. We envision this strategy being used to enable the production of NRPs from heterologous pathways.
Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolites
Authors: Reddivari Lavanya , Veeramachaneni D. N. Rao , Walters William A. , Lozupone Catherine , Palmer Jennifer , Hewage M. K. Kurundu , Bhatnagar Rohil , Amir Amnon , Kennett Mary J. , Knight Rob , Vanamala Jairam K. P.
Published: October 2017

Emerging evidence suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA, an environmental endocrine disruptor, can transfer across the placenta and accumulate in fetal gut and liver. However, underlying mechanisms for BPA-induced colonic and liver inflammation are not fully elucidated. In this report, we show how perinatal BPA exposure in rabbits alters gut microbiota and their metabolite profiles, which leads to colonic and liver inflammation as well as to increased gut permeability as measured by elevated serum lipopolysaccharide (LPS) levels in the offspring. Also, perinatal BPA exposure leads to reduced levels of gut bacterial diversity and bacterial metabolites (short-chain fatty acids [SCFA]) and elevated gut permeability—three common early biomarkers of inflammation-promoted chronic diseases. In addition, we showed that SCFA ameliorated BPA-induced intestinal permeability
in vitro
. Thus, our study results suggest that correcting environmental toxicant-induced bacterial dysbiosis early in life may reduce the risk of chronic diseases later in life.
FulminantBacillus cereussepticaemia with multiple organ ischaemic/haemorrhagic complications in a patient undergoing chemotherapy for acute myelogenous leukaemia
Authors: Hori Yusuke S , Kodera Satoshi , Nagai Yurie , Suzuki Yoshio
Published: October 2017

Bacillus cereusis a Gram-positive spore-forming rod widely found in the environment and is thought to be a frequent source of contamination. This micro-organism is reportedly a significant pathogenic agent among immunocompromised individuals. Furthermore, multiple cases of fulminant septicaemia have been reported among individuals receiving chemotherapy for acute myelogenous leukaemia. In some cases,B. cereussepticaemia was associated with multiple haemorrhages. We, herein, describe a patient with an extremely acute course ofB. cereussepticaemia characterised by haemorrhage and infarction of multiple organs, which led to his death. Our findings suggest that delayed treatment ofB. cereusin patients with haematologic malignancies undergoing chemotherapy may result in extremely poor outcomes; thus, immediate empirical treatment with vancomycin should be considered.
Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis
Authors: Liu Xiaoqian , Machado Gustavo C , Eyles Jillian P , Ravi Varshini , Hunter David J
Published: October 2017

Objective

To investigate the efficacy and safety of dietary supplements for patients with osteoarthritis.

Design

An intervention systematic review with random effects meta-analysis and meta-regression.

Data sources

MEDLINE, EMBASE, Cochrane Register of Controlled Trials, Allied and Complementary Medicine and Cumulative Index to Nursing and Allied Health Literature were searched from inception to April 2017.

Study eligibility criteria

Randomised controlled trials comparing oral supplements with placebo for hand, hip or knee osteoarthritis.

Results

Of 20 supplements investigated in 69 eligible studies, 7 (collagen hydrolysate, passion fruit peel extract,Curcuma longaextract,Boswellia serrataextract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size >0.80) and clinically important effects for pain reduction at short term. Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance. Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term. No supplements were identified with clinically important effects on pain reduction at long term. Similar results were found for physical function. Chondroitin demonstrated statistically significant, but not clinically important structural improvement (effect size −0.30, –0.42 to −0.17). There were no differences between supplements and placebo for safety outcomes, except for diacerein. The Grading of Recommendations Assessment, Development and Evaluation suggested a wide range of quality evidence from very low to high.

Conclusions

The overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low. Some supplements with a limited number of studies and participants suggested large treatment effects, while widely used supplements such as glucosamine and chondroitin were either ineffective or showed small and arguably clinically unimportant treatment effects. Supplements had no clinically important effects on pain and function at medium-term and long-term follow-ups.
Association between MRI-defined osteoarthritis, pain, function and strength 3–10 years following knee joint injury in youth sport
Authors: Whittaker Jackie L , Toomey Clodagh M , Woodhouse Linda J , Jaremko Jacob L , Nettel-Aguirre Alberto , Emery Carolyn A
Published: October 2017

Background

Youth and young adults who participate in sport have an increased risk of knee injury and subsequent osteoarthritis. Improved understanding of the relationship between structural and clinical outcomes postinjury could inform targeted osteoarthritis prevention interventions. This secondary analysis examines the association between MRI-defined osteoarthritis and self-reported and functional outcomes, 3–10 years following youth sport-related knee injury in comparison to healthy controls.

Methods

Participants included a subsample (n=146) of the Alberta Youth Prevention of Early Osteoarthritis cohort: specifically, 73 individuals with 3–10years history of sport-related intra-articular knee injury and 73 age-matched, sex-matched and sport-matched controls with completed MRI studies. Outcomes included: MRI-defined osteoarthritis, radiographic osteoarthritis, Knee Injury and Osteoarthritis Outcome Score, Intermittent and Constant Osteoarthritis Pain, knee extensor/flexor strength, triple-hop and Y-balance test. Descriptive statistics and univariate logistic regression were used to compare those with and without MRI-defined osteoarthritis. Associations between MRI-defined osteoarthritis and each outcome were assessed using multivariable linear regression considering the influence of injury history, sex, body mass index and time since injury.

Results

Participant median age was 23 years (range 15–27), and 63% were female. MRI-defined osteoarthritis varied by injury history, injury type and surgical history and was not isolated to participants with ACL and/or meniscal injuries. Those with a previous knee injury had 10-fold (95% CI 2.3 to 42.8) greater odds of MRI-defined osteoarthritis than uninjured participants. MRI-defined osteoarthritis was independently significantly associated with quality of life, but not symptoms, strength or function.

MRI-detected structural changes 3– 10 years following youth sport-related knee injury may not dictate clinical symptomatology, strength or function but may influence quality of life.
Stair ascending–descending exercise accelerates the decrease in postprandial hyperglycemia more efficiently than bicycle exercise
Authors: Takaishi Tetsuo , Hayashi Tatsuya
Published: October 2017

Objective

Stair climbing–descending exercise (ST-EX) is a convenient method to increase exercise intensity. We compared the acute effect of ST-EX on lowering postprandial hyperglycemia with that of constant bicycle exercise (BI-EX) performed at the same heart rate (HR).

Research design and methods

Seven people with type 2 diabetes and seven with impaired glucose tolerance volunteered for this study. The step rate for ST-EX and work rate for BI-EX were individually determined to correspond to high-moderate to low-vigorous intensity (HR ~130 beats per minute). For the ST-EX trial, the subjects performed 16 repetitions of walking down one flight of stairs followed by climbing up to the starting point (~8 min in duration) 90 min after consuming a test meal. For the BI-EX trial, the subjects performed a constant pedaling exercise for the same duration at the same time after the meal.

Results

The reduction in blood glucose (BG) level between 90 and 105 min after a meal was significantly greater for ST-EX (–4.0±0.7mmol/L) than for BI-EX (–2.7±0.9mmol/L). The net reduction in BG between 90 and 105 min was also significantly greater for ST-EX (–3.2±0.7mmol/L) than for BI-EX (–2.0±0.6mmol/L). Serum insulin levels did not differ between the groups. Oxygen consumption for ST-EX was higher than that for BI-EX, but the blood lactate level and respiratory exchange ratio (RER) for ST-EX were lower than those for BI-EX.

Conclusions

Compared with BI-EX performed at the same HR, ST-EX more rapidly decreased postprandial BG level with lower blood lactate and RER responses. A short bout of ST-EX may be clinically useful to acutely ameliorate BG levels after meals.
Statin use and risk of developing diabetes: results from the Diabetes Prevention Program
Authors: Crandall Jill P , Mather Kieren , Rajpathak Swapnil N , Goldberg Ronald B , Watson Karol , Foo Sandra , Ratner Robert , Barrett-Connor Elizabeth , Temprosa Marinella
Published: October 2017

Objective

Several clinical trials of cardiovascular disease prevention with statins have reported increased risk of type 2 diabetes (T2DM) with statin therapy. However, participants in these studies were at relatively low risk for diabetes. Further, diabetes was often based on self-report and was not the primary outcome. It is unknown whether statins similarly modify diabetes risk in higher risk populations.

Research design and methods

During the Diabetes Prevention Program Outcomes Study (n=3234), the long-term follow-up to a randomized clinical trial of interventions to prevent T2DM, incident diabetes was assessed by annual 75 g oral glucose tolerance testing and semiannual fasting glucose. Lipid profile was measured annually, with statin treatment determined by a participant’s own physician outside of the protocol. Statin use was assessed at baseline and semiannual visits.

Results

At 10 years, the cumulative incidence of statin initiation prior to diabetes diagnosis was 33%–37% among the randomized treatment groups (p=0.36). Statin use was associated with greater diabetes risk irrespective of treatment group, with pooled HR (95% CI) for incident diabetes of 1.36 (1.17 to 1.58). This risk was not materially altered by adjustment for baseline diabetes risk factors and potential confounders related to indications for statin therapy.

Conclusions

In this population at high risk for diabetes, we observed significantly higher rates of diabetes with statin therapy in all three treatment groups. Confounding by indication for statin use does not appear to explain this relationship. The effect of statins to increase diabetes risk appears to extend to populations at high risk for diabetes.

Trial registration number

NCT00038727; Results.
Pilot study for the registry of complications in rheumatic diseases from the German Society of Surgery (DGORh): evaluation of methods and data from the first 1000 patients
Authors: Kostuj Tanja , Rehart Stefan , Matta-Hurtado Ronald , Biehl Christoph , Willburger Roland E , Schmidt Klaus
Published: October 2017

Objective

Most patients suffering with rheumatic diseases who undergo surgical treatment are receiving immune-modulating therapy. To determine whether these medications affect their outcomes a national registry was established in Germany by the German Society of Surgery (DGORh). Data from the first 1000 patients were used in a pilot study to identify relevant corisk factors and to determine whether such a registry is suitable for developing accurate and relevant recommendations.

Design and participants

Data were collected from patients undergoing surgical treatments with their written consent. A second consent form was used, if complications occurred. During this pilot study, in order to obtain a quicker overview, risk factors were considered only in patients with complications. Only descriptive statistical analysis was employed in this pilot study due to limited number of observed complications and inhomogeneous data regarding the surgery and the medications the patients received. Analytical statistics will be performed to confirm the results in a future outcome study.

Results

Complications occurred in 26 patients and were distributed equally among the different types of surgeries. Twenty one of these patients were receiving immune-modulating therapy at the time, while five were not. Infections were observed in 2.3% of patients receiving and in 5.1% not receiving immunosuppression.

Conclusions

Due to the low number of cases, inhomogeneity in the diseases and the treatments received by the patients in this pilot study, it is not possible to develop standardised best-practice recommendations to optimise their care. Based on this observation we conclude that in order to be suitable to develop accurate and relevant recommendations a national registry must include the most important and relevant variables that impact the care and outcomes of these patients.
Post-abortion care with misoprostol – equally effective, safe and accepted when administered by midwives compared to physicians: a randomised controlled equivalence trial in a low-resource setting in Kenya
Authors: Makenzius Marlene , Oguttu Monica , Klingberg-Allvin Marie , Gemzell-Danielsson Kristina , Odero Theresa M A , Faxelid Elisabeth
Published: October 2017

Objective

To assess the effectiveness of midwives administering misoprostol to women with incomplete abortion seeking post-abortion care (PAC), compared with physicians.

Design

A multicentre randomised controlled equivalence trial. The study was not masked.

Settings

Gynaecological departments in two hospitals in a low-resource setting, Kenya.

Population

Women (n=1094) with incomplete abortion in the first trimester, seeking PAC between 1 June 2013 to 31 May 2016. Participants were randomly assigned to receive treatment from midwives or physicians. 409 and 401 women in the midwife and physician groups, respectively, were included in the per-protocol analysis.

Interventions

600 µg misoprostol orally, and contraceptive counselling by a physician or midwife.

Main outcome measures

Complete abortion not needing surgical intervention within 7–10 days. The main outcome was analysed on the per-protocol population with a generalised estimating equation model. The predefined equivalence range was –4% to 4%. Secondary outcomes were analysed descriptively.

Results

The proportion of complete abortion was 94.8% (768/810): 390 (95.4%) in the midwife group and 378 (94.3%) in the physician group. The proportion of incomplete abortion was 5.2% (42/810), similarly distributed between midwives and physicians. The model-based risk difference for midwives versus physicians was 1.0% (–4.1 to 2.2). Most women felt safe (97%; 779/799), and 93% (748/801) perceived the treatment as expected/easier than expected. After contraceptive counselling the uptake of a contraceptive method after 7–10 days occurred in 76% (613/810). No serious adverse events were recorded.

Conclusions

Treatment of incomplete abortion with misoprostol provided by midwives is equally effective, safe and accepted by women as when administered by physicians in a low-resource setting. Systematically provided contraceptive counselling in PAC is effective to mitigate unmet need for contraception.

Trial registration number

NCT01865136; Results.
Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza in 2015–2016: a hospital-based test-negative case–control study in Lithuania
Authors: Kuliese Monika , Jancoriene Ligita , Grimalauskaite Rita , Zablockiene Birute , Damuleviciene Gyte , Velyvyte Daiva , Lesauskaite Vita , Ambrozaitis Arvydas , Mickiene Aukse , Gefenaite Giedre
Published: October 2017

Objective

A case–control study was conducted to assess seasonal influenza vaccine effectiveness (SIVE) during the 2015–2016 influenza season.

Methods

A study was performed in three departments in Lithuania between 1 December 2015 and 1 May 2016. Data on demographic and clinical characteristics including influenza vaccination status were collected from the patients recommended to receive the seasonal influenza vaccine. Influenza virus infection was confirmed by multiplex reverse transcription polymerase chain reaction (RT-PCR) .

Results

Ninety-one (56.4%) of the 163 included subjects were ≥65 years old. Fifteen (9.2%) subjects were vaccinated against influenza at least 2 weeks before the onset of influenza symptoms, 12 of them were ≥65 years old. Of the 72 (44.2%) influenza virus positive cases, 65 (39.9%) were confirmed with influenza A (including 50 cases of influenza A(H1N1)pdm09), eight (4.9%) were confirmed with influenza B and one was a co-infection. Unadjusted SIVE against any influenza, influenza type A and influenza A(H1N1)pdm09 was 57% (95% CI −41% to 87%), 52% (95% CI −57% to 85%) and 70% (95% CI −43% to 94%) respectively.

Conclusion

Although SIVE estimates were not statistically significant the point estimates suggest moderate effectiveness against influenza type A.
Organisational and extraorganisational determinants of volume of service delivery by English community pharmacies: a cross-sectional survey and secondary data analysis
Authors: Hann Mark , Schafheutle Ellen I , Bradley Fay , Elvey Rebecca , Wagner Andrew , Halsall Devina , Hassell Karen , Jacobs Sally
Published: October 2017

Objectives

This study aimed to identify the organisational and extraorganisational factors associated with existing variation in the volume of services delivered by community pharmacies.

Design and setting

Linear and ordered logistic regression of linked national data from secondary sources—community pharmacy activity, socioeconomic and health need datasets—and primary data from a questionnaire survey of community pharmacies in nine diverse geographical areas in England.

Outcome measures

Annual dispensing volume; annual volume of medicines use reviews (MURs).

Results

National dataset (n=10 454 pharmacies): greater dispensing volume was significantly associated with pharmacy ownership type (large chains>independents>supermarkets), greater deprivation, higher local prevalence of cardiovascular disease and depression, older people (aged >75 years) and infants (aged 0–4 years) but lower prevalence of mental health conditions. Greater volume of MURs was significantly associated with pharmacy ownership type (large chains/supermarkets>>independents), greater dispensing volume, and lower disease prevalence.

Survey dataset (n=285 pharmacies; response=34.6%): greater dispensing volume was significantly associated with staffing, skill-mix, organisational culture, years open and greater deprivation. Greater MUR volume was significantly associated with pharmacy ownership type (large chains/supermarkets>>independents), greater dispensing volume, weekly opening hours and lower asthma prevalence.

Conclusions

Organisational and extraorganisational factors were found to impact differently on dispensing volume and MUR activity, the latter being driven more by corporate ownership than population need. While levels of staffing and skill-mix were associated with dispensing volume, they did not influence MUR activity. Despite recent changes to the contractual framework, the existing fee-for-service reimbursement may therefore not be the most appropriate for the delivery of cognitive (rather than supply) services, still appearing to incentivise quantity over the quality (in terms of appropriate targeting) of services delivered. Future research should focus on the development of quality measures that could be incorporated into community pharmacy reimbursement mechanisms.