bluuebunny/crossref_metadata_2025 huggingface dataset:
Short‐term low‐intensity blood flow restricted interval training improves both aerobic fitness and muscle strength
Authors: de Oliveira M. F. M. , Caputo F. , Corvino R. B. , Denadai B. S.
Published: September 2015

The present study aimed to analyze and compare the effects of four different interval‐training protocols on aerobic fitness and muscle strength. Thirty‐seven subjects (23.8 ± 4 years; 171.7 ± 9.5 cm; 70 ± 11 kg) were assigned to one of four groups: low‐intensity interval training with (BFR, n = 10) or without (LOW, n = 7) blood flow restriction, high‐intensity interval training (HIT, n = 10), and combined HIT and BFR (BFR + HIT, n = 10, every session performed 50% as BFR and 50% as HIT). Before and after 4 weeks training (3 days a week), the maximal oxygen uptake (VO2max), maximal power output (Pmax), onset blood lactate accumulation (OBLA), and muscle strength were measured for all subjects. All training groups were able to improve OBLA (BFR, 16%; HIT, 25%; HIT + BFR, 22%; LOW, 6%), with no difference between groups. However, VO2max and Pmax improved only for BFR (6%, 12%), HIT (9%, 15%) and HIT + BFR (6%, 11%), with no difference between groups. Muscle strength gains were only observed after BFR training (11%). This study demonstrates the advantage of short‐term low‐intensity interval BFR training as the single mode of training able to simultaneously improve aerobic fitness and muscular strength.
MR‐based in vivo follow‐up study of Achilles tendon volume and hydration state after ankle‐loading activity
Authors: Grosse U. , Syha R. , Gatidis S. , Grözinger G. , Martirosian P. , Partovi S. , Nikolaou K. , Robbin M. R. , Schick F. , Springer F.
Published: September 2015

The purpose of this study was to evaluate temporal alterations of the Achilles tendon volume and hydration state after cross‐country‐running. Achilles tendons of six untrained participants were examined on a 3T MR‐scanner before running, immediately afterwards, and in the following 24, 48, and 72 h. Using a 3D‐UTE sequence, caudal (CA) and cranial (CR) mid‐portion tendon areas were examined with off‐resonance saturation ratios (OSR) and T2* relaxation times. Tendon volume was measured with a self‐written Matlab‐based automated contour detection algorithm (AVAT) in submillimeter T2‐weighted MR images. A significant influence of running in caudal (P = 0.017) and cranial OSR values (P = 0.001), tendon volume (P = 0.024), and cranial T2* measurements (P = 0.046), but not in caudal T2* values (P = 0.298) were found. In detail, mean individual OSR and tendon volume measurements demonstrated a similar but inverted course in their values after exercise: initially, OSR values increased after running (and tendon volume decreased), while subsequently a decrease of OSR values (with an increase of tendon volume) could be observed. OSR and tendon volume measurements are able to detect a physiological response of tendons to a mechanical stimulus. After a transient decrease of free water in the Achilles tendon, an increase with a maximum free water content 48 h after ankle loading and a tendency toward normalization after 72 h was found.
Impact of prolonged sitting on vascular function in young girls
Authors: McManus Ali M. , Ainslie Philip N. , Green Daniel J. , Simair Ryan G. , Smith Kurt , Lewis Nia
Published: September 2015

New Findings

What is the central question of this study?

Children are spending more than 60% of their waking day sedentary. The consequences of excessive sedentary behaviour are not well understood in the child, but there is growing evidence that with increasing sedentary time, cardiovascular risk in childhood also increases.

What is the main finding and its importance?

Our findings show that a 3 h period of uninterrupted sitting causes a profound (33%) reduction in vascular function in young girls. Importantly, we also demonstrate that breaking up sitting with regular exercise breaks can prevent this.

Excessive sedentary behaviour has serious clinical and public health implications; however, the physiological changes that accompany prolonged sitting in the child are not completely understood. Herein, we examined the acute effect a prolonged period of sitting has upon superficial femoral artery function in 7‐ to 10‐year‐old girls and the impact of interrupting prolonged sitting with exercise breaks. Superficial femoral artery endothelium‐dependent flow‐mediated dilatation, total shear rate, anterograde and retrograde shear rates and oscillatory shear index were assessed before and after two experimental conditions: a 3 h uninterrupted period of sitting (SIT) and a 3 h period of sitting interrupted each hour with 10 min of moderate‐intensity exercise (EX). A mixed‐model analysis of variance was used to compare between‐condition and within‐condition main effects, controlling for the within‐subject nature of the experiment by including random effects for participant. Superficial femoral artery endothelium‐dependent flow‐mediated dilatation decreased significantly from pre‐ to post‐SIT (mean difference 2.2% flow‐mediated dilatation; 95% confidence interval = 0.60–2.94%, P < 0.001). This relative decline of 33% was abolished in the EX intervention. Shear rates were not significantly different within conditions. Our data demonstrate the effectiveness of short but regular exercise breaks in offsetting the detrimental effects of uninterrupted sitting in young girls.
Human skeletal muscle fibre contractile properties and proteomic profile: adaptations to 3 weeks of unilateral lower limb suspension and active recovery
Authors: Brocca Lorenza , Longa Emanuela , Cannavino Jessica , Seynnes Olivier , de Vito Giuseppe , McPhee Jamie , Narici Marco , Pellegrino Maria Antonietta , Bottinelli Roberto
Published: September 2015

Key points

It is generally assumed that muscle fibres go through atrophy following disuse with a loss of specific force and an increase in unloaded shortening velocity. However, the underlying mechanisms remain to be clarified.

Most studies have focused on events taking place during the development of disuse, whereas the subsequent recovery phase, which is equally important, has received little attention.

Our findings support the hypotheses that the specific force of muscle fibres decreased following unilateral lower limb suspension (ULLS) and returned to normal after 3 weeks of active recovery as a result of a loss and recovery of myosin and actin content.

Furthermore, muscle fibres went through extensive qualitative changes in muscle protein pattern following ULLS, and these were reversed by active recovery.

Resistance training was very effective in restoring both muscle mass and qualitative muscle changes, indicating that long‐term ULLS did not prevent the positive effect of exercise on human muscle.

Following disuse, muscle fibre function goes through adaptations such as a loss of specific force (PO/CSA) and an increase in unloaded shortening velocity, which could be a result of both quantitative changes (i.e. atrophy) and qualitative changes in protein pattern. The underlying mechanisms remain to be clarified. In addition, little is known about the recovery of muscle mass and strength following disuse. In the present study, we report an extensive dataset describing, in detail,the functional and protein content adaptations of skeletal muscle in response to both disuse and re‐training. Eight young healthy subjects were subjected to 3 weeks of unilateral lower limb suspension (ULLS), a widely used human model of disuse skeletal muscle atrophy. Needle biopsies samples were taken from the vastus lateralis muscle Pre‐ULLS, Post‐ULLS and after 3 weeks of recovery during which heavy resistance training was performed. After disuse, cross‐sectional area (CSA), PO/CSA and myosin concentration (MC) decreased in both type 1 and 2A skinned muscle fibres. After recovery, CSA and MC returned to levels comparable to those observed before disuse, whereas Po/CSA and unloaded shortening velocity reached a higher level. Myosin heavy chain isoform composition of muscle samples did not differ among the experimental groups. To study the mechanisms underlying such adaptations, a two‐dimensional proteomic analysis was performed. ULLS induced a reduction of myofibrillar, metabolic (glycolytic and oxidative) and anti‐oxidant defence system protein content. Resistance training was very effective in counteracting ULLS‐induced alterations, indicating that long‐term ULLS did not prevent the positive effect of exercise on human muscle.
Stability of Nonlinear Fractional-Order Time Varying Systems
Authors: Huang Sunhua , Zhang Runfan , Chen Diyi
Published: September 2015

This paper is concerned with the stability of nonlinear fractional-order time varying systems with Caputo derivative. By using Laplace transform, Mittag-Leffler function, and the Gronwall inequality, the sufficient condition that ensures local stability of fractional-order systems with fractional order α : 0<α≤1 and 1<α<2 is proposed, respectively. Moreover, the condition of the stability of fractional-order systems with a state-feedback controller is been put forward. Finally, a numerical example is presented to show the validity and feasibility of the proposed method.
Determination of Motion Equation of Rivet Head During Shaft Riveting Assembly Process for Wheel Hub Bearing Units
Authors: Qu Jie , Zhang Guojie
Published: September 2015

The shaft riveting assembly process is a very effective method for assembling lightweight, integrated, and highly reliable automobile wheel hub bearings. This paper proposes a method to determine the motion equation of a rivet head during the shaft riveting process based on a theoretical derivation, on-site test results, and structural equipment parameters. Based on the structure of the riveting machine, the motion equation of the rivet head is deduced through the combined application of a rectangular spatial coordinate system and the Euler angle method. In addition, the axial displacement and axial riveting force of the spindle were measured during the shaft riveting process using a newly developed on-site testing system. The axial velocity of the rivet head is determined using the spline function method based on the measured axial displacement–time curve. Subsequently, the motion equation of velocity and three-axis angular velocity of the rivet head can be obtained based on the deduced motion equation of the rivet head, test data, and structural equipment parameters. Finally, the motion equation of the rivet head is validated by simulating the shaft riveting process using the finite-element (FE) method, and then comparing the simulated axial riveting force and final geometric shape of the riveted hub shaft with the experimental ones. The result shows that the method proposed in this paper lays the foundation for the numerical simulation and optimization of the shaft riveting technology for a wheel hub bearing unit.
A Framework for Visualization-Driven Eco-Conscious Design Exploration
Authors: Ramanujan Devarajan , Bernstein William Z. , Benjamin William , Ramani Karthik , Elmqvist Niklas , Kulkarni Devadatta , Tew Jeffrey
Published: September 2015

A large portion of design activity involves applying previous design knowledge in order to solve new problems. Therefore, facilitating eco-conscious exploration of archived designs is needed for advancing sustainable product design. It is thus necessary to create integrated exploration tools that share common data representations for design and sustainability-related product metadata. This can allow designers to observe covariations in design data and develop engineering intuition with regards to environmental sustainability performance. In this work, we present a framework for relating sustainability and product metadata using taxonomy-based representations of lifecycle data. This facilitates simultaneous visualization of environmental indicators along with part similarities. To demonstrate this framework, we implement shapeSIFT, an interactive multidimensional visualization tool for eco-conscious design exploration. shapeSIFT uses a visual analytics-based approach to represent part metadata and environmental indicators. This facilitates query-based dynamic exploration of part repositories.
The effect of stimulus bandwidth on binaural loudness summation
Authors: Shao Zhiyue , Mo Fangshuo , Mao Dongxing
Published: September 2015

Binaural loudness summation is an important property of the human auditory system. This paper presents an experimental investigation of how binaural loudness summation varies with stimulus bandwidth. Loudness matches were obtained between dichotic stimuli, with interaural level differences (ILDs) of 2–12 dB, and diotic stimuli. The stimuli were noise bands with seven center frequencies and four bandwidths. Results showed that the loudness of dichotic stimuli increased nonlinearly with ILD, the increase being slightly less with broader bandwidths. There was a bandwidth-dependent difference between the listening tests results and the predictions of Moore and Glasberg's [(2007) J. Acoust. Soc. Am. 121, 1604–1612] loudness model. The size of the difference was, however, small. A characteristic function was derived describing how overall loudness depends on stimulus bandwidth and ILD.
Daily Physical Activity and Cognitive Function Variability in Older Adults
Authors: Phillips Christine B. , Edwards Jerri D. , Andel Ross , Kilpatrick Marcus
Published: September 2015

Physical activity (PA) is believed to preserve cognitive function in older adulthood, though little is known about these relationships within the context of daily life. The present microlongitudinal pilot study explored within- and between-person relationships between daily PA and cognitive function and also examined within-person effect sizes in a sample of community-dwelling older adults. Fifty-one healthy participants (mean age = 70.1 years) wore an accelerometer and completed a cognitive assessment battery for five days. There were no significant associations between cognitive task performance and participants’ daily or average PA over the study period. Effect size estimates indicated that PA explained 0–24% of within-person variability in cognitive function, depending on cognitive task and PA dose. Results indicate that PA may have near-term cognitive effects and should be explored as a possible strategy to enhance older adults’ ability to perform cognitively complex activities within the context of daily living.
Impact of Older Adults’ Neighborhood Perceptions on Walking Behavior
Authors: Maisel Jordana L.
Published: September 2015

Built environment features can have varying impacts on user behavior depending on the perceptions of the opportunities and obstacles that the environments create. This study systematically evaluated the relationship between neighborhood perceptions and the specific types of self-reported walking behavior for 121 older adults who resided in urban, suburban, or rural neighborhoods. Perceptions of street connectivity, crime and traffic safety, and overall satisfaction were associated with specific types of walking behaviors, and the strength of the relationships differed by neighborhood type. Sociodemographic variables such as age and sex were associated with certain types and amounts of older adults’ walking behaviors both across and within each neighborhood type. The results of this study support the importance of perceived street connectivity regardless of neighborhood type and perceived crime safety in rural neighborhoods to impact the walking behavior among older adults.
Feasibility Study: Colombian Caribbean Folk Dances to Increase Physical Fitness and Health-Related Quality of Life in Older Women
Authors: Pacheco Ernesto , Hoyos Diana P. , Watts Willinton J. , Lema Lucía , Arango Carlos M.
Published: September 2015

The objectives of the study were to describe the feasibility of an intervention in older women based on folk dances of the Colombian Caribbean region, and to analyze the effects of the intervention on physical fitness and health-related quality of life (HRQoL). A pilot study was conducted in a sample of 27 participants, 15 in the intervention group (IG) and 12 in the comparison group (CG). Caribbean Colombian dance rhythms were introduced as an intervention that lasted 12 weeks. Recruitment and retention was not optimal. Treatment fidelity components indicated that intervention was administered as intended. IG participants showed positive and statistically significant changes in some components of physical fitness. No significant changes were observed in HRQoL indicators for either group. In conclusion, the intervention was feasible, but recruitment and retention was challenging. Folk dances of the Colombian Caribbean region provoked significant results in physical fitness but not in HRQoL.
Self-Selected Walking Speed Is Predictive of Daily Ambulatory Activity in Older Adults
Authors: Middleton Addie , Fulk George D. , Beets Michael W. , Herter Troy M. , Fritz Stacy L.
Published: September 2015

Daily ambulatory activity is associated with health and functional status in older adults; however, assessment requires multiple days of activity monitoring. The objective of this study was to determine the relative capabilities of self-selected walking speed (SSWS), maximal walking speed (MWS), and walking speed reserve (WSR) to provide insight into daily ambulatory activity (steps per day) in community-dwelling older adults. Sixty-seven older adults completed testing and activity monitoring (age 80.39 [6.73] years). SSWS (R2 = .51), MWS (R2 = .35), and WSR calculated as a ratio (R2 = .06) were significant predictors of daily ambulatory activity in unadjusted linear regression. Cutpoints for participants achieving < 8,000 steps/day were identified for SSWS (≤ 0.97 m/s, 44.2% sensitivity, 95.7% specificity, 10.28 +LR, 0.58 −LR) and MWS (≤ 1.39 m/s, 60.5% sensitivity, 78.3% specificity, 2.79 +LR, 0.50 −LR). SSWS may be a feasible proxy for assessing and monitoring daily ambulatory activity in older adults.
Genetic evidence for a Smoothened-Gα
i
signaling axis in mammals
Authors: Ogden Stacey K.
Published: September 2015

Smoothened functions as a G protein–coupled receptor to promote proliferation of mouse mammary epithelial cells.
In Vitro
Activities of Novel Antimicrobial Combinations against Extensively Drug-Resistant Acinetobacter baumannii
Authors: Córdoba J. , Coronado-Álvarez N. M. , Parra D. , Parra-Ruiz J.
Published: September 2015

Extensively drug-resistant (XDR)
Acinetobacter
spp. have emerged as a cause of nosocomial infections, especially under conditions of intensive care. Unfortunately, resistance to colistin is increasing and there is a need for new therapeutic options. We aimed to study the effect of some novel combinations against XDR
Acinetobacter baumannii
in an
in vitro
pharmacokinetics-pharmacodynamics (PK/PD) model. Three nonrelated clinical strains of XDR
A. baumannii
were investigated. Antibiotic-simulated regimens were colistin at 3 MU every 8 h (q8h) (first dose, 6 MU), daptomycin at 10 mg/kg of body weight q24h, imipenem at 1 g q8h, and ertapenem at 1 g q24h. Combination regimens included colistin plus daptomycin, colistin plus imipenem, and imipenem plus ertapenem. Samples were obtained at 0, 1, 2, 4, 8, and 24 h. Among the single-agent regimens, only the colistin regimen resulted in significant reductions in log
10
CFU per milliliter compared to the control for all the strains tested. Although colistin achieved bactericidal activity at 4 h, it was not able to reach the limit of detection (1 log
10
CFU/ml). One strain had significant regrowth at 24 h without the emergence of resistance. Daptomycin-colistin combinations led to a significant reduction in levels of log
10
CFU per milliliter that were better than those achieved with colistin as a single-agent regimen, reaching the limit of detection at 24 h against all the strains. The combination of imipenem plus ertapenem outperformed the colistin regimen, although the results did not reach the limit of detection, with significant regrowth at 24 h. Similarly, colistin-plus-imipenem combinations reduced the levels of log
10
CFU per milliliter at 8 h, with significant regrowth at 24 h but with development of resistance to colistin. We have shown some potentially useful alternatives for the treatment of extensively drug-resistant
A. baumannii
. Among them, the daptomycin-colistin combination was the most effective and should be investigated in future studies.
Thymidine-Dependent Staphylococcus aureus Small-Colony Variants Are Induced by Trimethoprim-Sulfamethoxazole (SXT) and Have Increased Fitness during SXT Challenge
Authors: Kriegeskorte Andre , Lorè Nicola Ivan , Bragonzi Alessandra , Riva Camilla , Kelkenberg Marco , Becker Karsten , Proctor Richard A. , Peters Georg , Kahl Barbara C.
Published: September 2015

Trimethoprim-sulfamethoxazole (SXT) is a possible alternative for the treatment of community- and hospital-acquired methicillin-resistant
Staphylococcus aureus
(MRSA) due to the susceptibility of most MRSA strains to the drug. However, after long-term treatment with SXT, thymidine-dependent (TD) SXT-resistant small-colony variants (SCVs) emerge. In TD-SCVs, mutations of thymidylate synthase ([TS]
thyA
) occur. Until now, it has never been systematically investigated that SXT is triggering the induction and/or selection of TD-SCVs. In our study, we performed induction, reversion, and competition experiments
in vitro
and
in vivo
using a chronic mouse pneumonia model to determine the impact of SXT on the emergence of TD-SCVs. SCVs were characterized by light and transmission electron microscopy (TEM) and auxotrophism testing. Short-term exposure of
S. aureus
to SXT induced the TD-SCV phenotype in
S. aureus
SH1000, while selection of TD-SCVs with
thyA
mutations occurred after long-term exposure. In reversion experiments with clinical and laboratory TD-SCVs, all revertants carried compensating mutations at the initially identified mutation site. Competition experiments
in vitro
and
in vivo
revealed a survival and growth advantage of the Δ
thyA
mutant under low-thymidine availability and SXT exposure although this advantage was less profound
in vivo
. Our results show that SXT induces the TD-SCV phenotype after short-term exposure, while long-term exposure selects for
thyA
mutations, which provide an advantage for TD-SCVs under specified conditions. Thus, our results further an understanding of the dynamic processes occurring during SXT exposure with induction and selection of
S. aureus
TD-SCVs.
Uncoupling Environmental pH and Intrabacterial Acidification from Pyrazinamide Susceptibility in Mycobacterium tuberculosis
Authors: Peterson Nicholas D. , Rosen Brandon C. , Dillon Nicholas A. , Baughn Anthony D.
Published: September 2015

Pyrazinamide (PZA) is a first-line antitubercular drug for which the mode of action remains unresolved.
Mycobacterium tuberculosis
lacks measurable susceptibility to PZA under standard laboratory growth conditions. However, susceptibility to this drug can be induced by cultivation of the bacilli in an acidified growth medium. Previous reports suggested that the active form of PZA, pyrazinoic acid (POA), operates as a proton ionophore that confers cytoplasmic acidification when
M. tuberculosis
is exposed to an acidic environment. In this study, we demonstrate that overexpression of the PZA-activating enzyme PncA can confer PZA susceptibility to
M. tuberculosis
under neutral and even alkaline growth conditions. Furthermore, we find that wild-type
M. tuberculosis
displays increased susceptibility to POA relative to PZA in neutral and alkaline media. Utilizing a strain of
M. tuberculosis
that expresses a pH-sensitive green fluorescent protein (GFP), we find that unlike the bona fide ionophores monensin and carbonyl cyanide 3-chlorophenylhydrazone, PZA and POA do not induce rapid uncoupling or cytoplasmic acidification under conditions that promote susceptibility. Thus, based on these observations, we conclude that the antitubercular action of POA is independent of environmental pH and intrabacterial acidification.
Acinetobacter baumannii Extracellular OXA-58 Is Primarily and Selectively Released via Outer Membrane Vesicles after Sec-Dependent Periplasmic Translocation
Authors: Liao Yu-Ting , Kuo Shu-Chen , Chiang Ming-Hsien , Lee Yi-Tzu , Sung Wang-Chou , Chen You-Hsuan , Chen Te-Li , Fung Chang-Phone
Published: September 2015

Carbapenem-resistant
Acinetobacter baumannii
(CRAb) shelter cohabiting carbapenem-susceptible bacteria from carbapenem killing via extracellular release of carbapenem-hydrolyzing class D β-lactamases, including OXA-58. However, the mechanism of the extracellular release of OXA-58 has not been elucidated.
In silico
analysis predicted OXA-58 to be translocated to the periplasm via the Sec system. Using cell fractionation and Western blotting, OXA-58 with the signal peptide and C terminus deleted was not detected in the periplasmic and extracellular fractions. Overexpression of enhanced green fluorescent protein fused to the OXA-58 signal peptide led to its periplasmic translocation but not extracellular release, suggesting that OXA-58 is selectively released. The majority of the extracellular OXA-58 was associated with outer membrane vesicles (OMVs). The OMV-associated OXA-58 was detected only in a strain overexpressing OXA-58. The presence of OXA-58 in OMVs was confirmed by a carbapenem inactivation bioassay, proteomic analysis, and transmission electron microscopy. Imipenem treatment increased OMV formation and caused cell lysis, resulting in an increase in the OMV-associated and OMV-independent release of extracellular OXA-58. OMV-independent OXA-58 hydrolyzed nitrocefin more rapidly than OMV-associated OXA-58 but was more susceptible to proteinase K degradation. Rose bengal, an SecA inhibitor, inhibited the periplasmic translocation and OMV-associated release of OXA-58 and abolished the sheltering effect of CRAb. This study demonstrated that the majority of the extracellular OXA-58 is selectively released via OMVs after Sec-dependent periplasmic translocation. Addition of imipenem increased both OMV-associated and OMV-independent OXA-58, which may have different biological roles. SecA inhibitor could abolish the carbapenem-sheltering effect of CRAb.
VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection
Authors: Gebremariam Teclegiorgis , Wiederhold Nathan P. , Fothergill Annette W. , Garvey Edward P. , Hoekstra William J. , Schotzinger Robert J. , Patterson Thomas F. , Filler Scott G. , Ibrahim Ashraf S.
Published: September 2015

We studied the efficacy of the investigational drug VT-1161 against mucormycosis. VT-1161 had more potent
in vitro
activity against
Rhizopus arrhizus
var.
arrhizus
than against
R. arrhizus
var.
delemar
. VT-1161 treatment demonstrated dose-dependent plasma drug levels with prolonged survival time and lowered tissue fungal burden in immunosuppressed mice infected with
R. arrhizus
var.
arrhizus
and was as effective as high-dose liposomal amphotericin B treatment. These results support further development of VT-1161 against mucormycosis.
Maternal Vaccination with a Fimbrial Tip Adhesin and Passive Protection of Neonatal Mice against Lethal Human Enterotoxigenic Escherichia coli Challenge
Authors: Luiz Wilson B. , Rodrigues Juliana F. , Crabb Joseph H. , Savarino Stephen J. , Ferreira Luis C. S.
Published: September 2015

Globally, enterotoxigenicEscherichia coli(ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 × 107bacteria resulted in 50% lethal doses (LD50) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20× LD50challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose-dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation.
Pulmonary Immunostimulation with MALP-2 in Influenza Virus-Infected Mice Increases Survival after Pneumococcal Superinfection
Authors: Reppe Katrin , Radünzel Peter , Dietert Kristina , Tschernig Thomas , Wolff Thorsten , Hammerschmidt Sven , Gruber Achim D. , Suttorp Norbert , Witzenrath Martin
Published: September 2015

Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection, withStreptococcus pneumoniaebeing the most prevalent causal pathogen and hence often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged withS. pneumoniaeon day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly neutrophils, into the alveolar space of IAV-infected mice, without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection.
Interleukin-10 Modulates Antigen Presentation by Dendritic Cells through Regulation of NLRP3 Inflammasome Assembly during Chlamydia Infection
Authors: Omosun Yusuf , McKeithen Danielle , Ryans Khamia , Kibakaya Caroline , Blas-Machado Uriel , Li Duo , Singh Rajesh , Inoue Koichi , Xiong Zhi-Gang , Eko Francis , Black Carolyn , Igietseme Joseph , He Qing
Published: September 2015

Interleukin-10 (IL-10) has been implicated in susceptibility to genital chlamydial infection and the development of tubal pathologies. IL-10 limitation also resulted in the rapid elicitation of immune responses againstChlamydia, and decreased levels of IL-10 correlated with protective anti-Chlamydiaimmunity. To investigate the molecular basis for these effects, we compared the reproductive pathologies and fertility rates inChlamydia-infected wild-type (WT) and IL-10-knockout (IL-10−/−) mice; we also analyzed the expression of the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily, IL-1β production, NLRP3 inflammasome assembly and activation, and the immunostimulatory capacity and apoptotic predilection ofChlamydia-exposed dendritic cells (DCs) from WT and IL-10−/−mice. Our results revealed that, in addition to the rapid clearance of infection, genitally infected IL-10−/−mice were protected from tubal pathologies and infertility, whereas WT (IL-10+/+) mice were not.Chlamydia-pulsed IL-10−/−DCs expressed larger numbers of TLR4/IL-1R molecules and had enhanced IL-1β production. In addition, NLRP3 inflammasome assembly was suppressed in IL-10−/−DCs through the inhibition of the P2X purinoceptor 7 (P2X7) receptor (P2X7R), an ATP-gated ion channel, and a decrease in intracellular Ca2+levels, which inhibited DC apoptosis. Thus, the potent immunostimulatory capacity of IL-10-deficient DCs is due, at least in part, to the suppression of the intracellular inflammasome assembly, which prevents DC apoptosis, allowing efficient antigen presentation. The results indicate that IL-10 deficiency enables efficient antigen presentation by DCs for rapid and enhanced immune activation againstChlamydia, which results in rapid microbial clearance, which prevents tubal pathologies during infection. Our finding has important implications for the induction of protective immunity againstChlamydiaand other infectious and noninfectious diseases by vaccines.
Children's palliative care in low- and middle-income countries
Authors: Downing Julia , Powell Richard A , Marston Joan , Huwa Cornelius , Chandra Lynna , Garchakova Anna , Harding Richard
Published: September 2015

One-third of the global population is aged under 20 years. For children with life-limiting conditions, palliative care services are required. However, despite 80% of global need occurring in low- and middle-income countries (LMICs), the majority of children's palliative care (CPC) is provided in high-income countries. This paper reviews the status of CPC services in LMICs—highlighting examples of best practice among service models in Malawi, Indonesia and Belarus—before reviewing the status of the extant research in this field. It concludes that while much has been achieved in palliative care for adults, less attention has been devoted to the education, clinical practice, funding and research needed to ensure children and young people receive the palliative care they need.
Ascariasis of the pancreatic duct
Authors: Klimovskij Michail , Dulskas Audrius , Kraulyte Zita , Mikalauskas Saulius
Published: September 2015

Ascariasis is a common helminthic disease worldwide, although Lithuania and other European countries are not considered endemic areas. The presence of theAscarisworm in the biliary tree causes choledocholithiasis-like symptoms. We report a case of pancreatic duct ascariasis causing such symptoms. A 73-year-old Lithuanian woman underwent endoscopic retrograde cholangiopancreatography (ERCP) suspecting choledocholithiasis. Contrast injection into the common bile duct demonstrated a slightly dilated biliary tree without any filling defects, and the tail of anAscarisworm protruding from the opening of the papilla Vater. The worm was captured by a snare but escaped deep into the duct. After a small wirsungotomy the worm was retrieved from the pancreatic duct. The patient received a 150 mg dose of levamisole orally repeated 7 days later and was discharged after complete resolution of symptoms. This first reported sporadic case of pancreatic duct ascariasis in Lithuania was successfully treated with ERCP and Levamisole.
‘It doesn't do the care for you': a qualitative study of health care professionals' perceptions of the benefits and harms of integrated care pathways for end of life care
Authors: Sleeman Katherine E , Koffman Jonathan , Bristowe Katherine , Rumble Caroline , Burman Rachel , Leonard Sara , Noble Jo , Dampier Odette , Bernal William , Morgan Myfanwy , Hopkins Philip , Prentice Wendy , Higginson Irene J
Published: September 2015

Objectives

To understand healthcare professionals’ perceptions of the benefits and potential harms of integrated care pathways for end-of-life care, to inform the development of future interventions that aim to improve care of the dying.

Design

Qualitative interview study with maximum variation sampling and thematic analysis.

Participants

25 healthcare professionals, including doctors, nurses and allied health professionals, interviewed in 2009.

Setting

A 950-bed South London teaching hospital.

Results

4 main themes emerged, each including 2 subthemes. Participants were divided between (1) those who described mainly the benefits of integrated care pathways, and (2) those who talked about potential harms. Benefits focused on processes of care, for example, clearer, consistent and comprehensive actions. The recipients of these benefits were staff members themselves, particularly juniors. For others, this perceived clarity was interpreted as of potential harm to patients, where over-reliance on paperwork lead to prescriptive, less thoughtful care, and an absolution from decision-making. Independent of their effects on patient care, integrated care pathways for dying had (3) a symbolic value: they legitimised death as a potential outcome and were used as a signal that the focus of care had changed. However, (4) a weak infrastructure, including scanty education and training in end-of-life care and a poor evidence base, that appeared to undermine the foundations on which the Liverpool Care Pathway was built.

Conclusions

The potential harms of integrated care pathways for the dying identified in this study were reminiscent of criticisms subsequently published by the Neuberger review. These data highlight: (1) the importance of collecting, reporting and using qualitative data when developing and evaluating complex interventions; (2) that comprehensive education and training in palliative care is critical for the success of any new intervention; (3) the need for future interventions to be grounded in patient-centred outcomes, not just processes of care.
Clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (acronym CLARITY): a multicentre phase IIb randomised active-controlled clinical trial
Authors: Sivaprasad Sobha , Prevost A Toby , Bainbridge James , Edwards Rhiannon Tudor , Hopkins David , Kelly Joanna , Luthert Phil , Murphy Caroline , Ramu Jayashree , Sarafraz-Shekary Negin , Vasconcelos Joana , White-Alao Beverley , Hykin Philip
Published: September 2015

Introduction

Proliferative diabetic retinopathy (PDR) is the main cause of severe visual loss in people with diabetes mellitus. The standard treatment for this condition is panretinal photocoagulation (PRP). This laser treatment is inherently destructive, with predictable adverse effects on visual function, and a safer alternative is required. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors can induce short-term regression of retinal neovascularisation. The aim of this randomised controlled trial is to determine the efficacy, safety and cost-effectiveness of intravitreal aflibercept, an inhibitor of VEGF-A, VEGF-B and placental growth factor (PLGF), in PDR, and to investigate the impact on local oxygenation.

Methods and analysis

This is a phase IIb randomised controlled single-masked multicentre clinical trial to determine the impact of repeated intravitreal aflibercept injections in the treatment and prevention of PDR. 220 participants with treatment-naïve or treated but active retinal neovascularisation in at least one eye will be randomly allocated 1:1 to intravitreal aflibercept injections or PRP for a period of 52 weeks. The primary outcome is the change in best-corrected visual acuity in the study eye at 52 weeks. Secondary outcomes include changes from baseline in other visual functions, anatomical changes and cost-effectiveness. Ocular and non-ocular adverse events will also be reported over 52 weeks.

Ethics and dissemination

The study has been approved by the National Research Ethics Service (NRES) committee with respect to scientific content and compliance with applicable research and human subjects’ regulations. Findings will be reported through scientific publications and research conferences. The results of this study will provide clinical evidence for the feasibility, efficacy safety and cost-effectiveness of intravitreal aflibercept for PDR.

Trial registration number

ISRCTN 32207582.
SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): revised publication guidelines from a detailed consensus process
Authors: Ogrinc Greg , Davies Louise , Goodman Daisy , Batalden Paul , Davidoff Frank , Stevens David
Published: September 2015

Since the publication of Standards for QUality Improvement Reporting Excellence (SQUIRE 1.0) guidelines in 2008, the science of the field has advanced considerably. In this manuscript, we describe the development of SQUIRE 2.0 and its key components. We undertook the revision between 2012 and 2015 using (1) semistructured interviews and focus groups to evaluate SQUIRE 1.0 plus feedback from an international steering group, (2) two face-to-face consensus meetings to develop interim drafts and (3) pilot testing with authors and a public comment period. SQUIRE 2.0 emphasises the reporting of three key components of systematic efforts to improve the quality, value and safety of healthcare: the use of formal and informal theory in planning, implementing and evaluating improvement work; the context in which the work is done and the study of the intervention(s). SQUIRE 2.0 is intended for reporting the range of methods used to improve healthcare, recognising that they can be complex and multidimensional. It provides common ground to share these discoveries in the scholarly literature (http://www.squire-statement.org).
Preparing patients with cancer who work and treatment responsiveness
Authors: Kamau Caroline
Published: September 2015

Background

Many patients with life-limiting illnesses continue to work because of financial reasons and because work provides good psychosocial support. A lack of appropriate advice/support through patient education could, however, make having a job detrimental to well-being (eg, symptom worsening).

Aim

This study investigated the frequency with which patients received information that empowers their understanding of their condition, treatment, side effects of treatment and the likely impact on occupational functioning.

Design

A cross-sectional study.

Setting/participants

An analysis of survey data from 3457 patients with cancer in employment.

Results

Logistic regression showed that patients who received information about the impact of cancer on work life or education are 1.72 times more likely to have a positive treatment outcome. Patients who receive written information about the type of cancer are 1.99 times more likely to have a positive treatment outcome. Also, patients who receive written information before a cancer-related operation are 1.90 times more likely to have a positive treatment outcome. Information about the side effects of cancer treatment produces worse odds of a positive treatment outcome (0.65–1). A stepwise logistic regression analysing the effects irrespective of current employment status in 6710 patients showed that preparing them produces nearly twice better odds of cancer treatment responsiveness.

Conclusions

Palliative care teams should consider ways of actively advising patients who work. Whereas the results showed evidence of good practice in cancer care, there is a need to ensure that all working patients with potentially life-limiting illnesses receive similar support.
Republished: Delayed relapse in pseudotumor cerebri due to new stenosis after transverse sinus stenting
Authors: Winters Hugh Stephen , Parker Geoff , Halmagyi Gabor Michael , Mehta Ankur , Atkins Thomas
Published: September 2015

A patient presented with recurrent severe pseudotumor cerebri (PTC). Transverse sinus stenting is a very effective treatment option, however stenosis and intracranial hypertension can recur. In our patient, stenting initially resulted in resolution of papilloedema. However, after 5 years, a new stenosis developed which required further stenting. This case highlights the fact that, in patients with PTC who undergo transverse sinus stenting, a small proportion require repeat treatment due to formation of a new stenosis, usually adjacent to the existing stent. Patients with severe disease, such as ours, may be at higher risk of recurrence. Regardless of the severity, all patients who undergo stenting should have regular ocular follow-up.
Cardiovascular and selected comorbidities in early arthritis and early spondyloarthritis, a comparative study: results from the ESPOIR and DESIR cohorts
Authors: Gherghe Ana Maria , Dougados Maxime , Combe Bernard , Landewé Robert , Mihai Carina , Berenbaum Francis , Mariette Xavier , Wolterbeek Ron , van der Heijde Désirée
Published: September 2015

Objectives

To investigate the prevalence of comorbidities in early rheumatoid arthritis (ERA) and early axial spondyloarthritis (ESpA) versus the general population.

Methods

Baseline data of 689 patients with ERA from the Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort (age 48.2±12.1 years, symptoms duration 14.2±14.5 weeks) and 645 patients with ESpA from Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR; age 32.8±8.4 years, axial symptoms duration 79.0±45.7 weeks) were analysed. Metabolic and cardiovascular diseases (CVD), infections and neoplasia were determined in each cohort. The prevalence (95% CI) of several comorbidities was compared with that in the French general population. For patients without CVD, the 10-year risk of developing CVD was calculated using the Framingham and SCORE equations. The heart age was calculated using the 2008 Framingham points system.

Results

42% of patients with ERA and 20.3% of patients with ESpA had at least 1 comorbidity; the most common were arterial hypertension (AHT) and dyslipidaemia. AHT prevalence (95% CI) in ERA (18.2% (15.5% to 21.3%)), but not in ESpA (5.08% (3.57% to 7.14%)), was significantly increased (p<0.05) compared with the general population (7.58%). Prevalence of tuberculosis history was higher in ERA (4.7% (3.3% to 6.6%)), and ESpA (0.99% (0.4% to 2.3%)) than in the general population (0.02%; both p<0.05). No differences were observed in malignancies, coronary heart disease or diabetes. In ERA, among patients without a history of CVD, an intermediate to high CVD risk was found. The heart age exceeded the real age by 4.1±9.6 years in ERA and by 2.1±7.0 years in ESpA (p<0.001).

Conclusions

We found an increased prevalence of AHT and tuberculosis history in ERA and ESpA, and an increased CVD risk. These results should prompt rheumatologists to check these comorbidities early in the disease.