bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of intracytoplasmic sperm injection (ICSI) in normospermic men may result in lower clinical pregnancy and live birth rates
Authors: Sustar Kylie , Rozen Genia , Agresta Franca , Polyakov Alex
Published: June 2019

Background

While intracytoplasmic sperm injection (ICSI) was developed for overcoming male infertility, it is increasingly being used for non‐male factor indications, without consensus regarding the safety and efficacy of this approach.

Aims

To determine whether ICSI offers any benefit compared to standard in vitro fertilisation (IVF), in the setting of normal semen parameters.

Materials and Methods

Retrospective analysis of reproductive outcomes in 3363 stimulated cycles (IVF = 1661; ICSI = 1702), in patients treated between 2009–2015, was performed. Selected couples had no male factor infertility. Couples with abnormal semen parameters (based on WHO 2010 guidelines), presence of anti‐sperm antibodies and low oocyte yield of ≤4 oocytes, were excluded. The outcomes analysed included: (1) fertilisation rate (FR); (2) clinical pregnancy rate (CPR); and (3) live birth rate (LBR), by method of fertilisation used (IVF vs ICSI) and controlling for significant confounders.

Results

FR, CPR and LBR were significantly higher in the IVF group compared with ICSI (67.1% vs 62.3%, 23.06% vs 16.8%, 17.22% vs 13.2%, respectively). Pregnancy rate with ICSI was approximately 30% lower than with IVF, even when controlling for significant factors such as day of embryo transfer and number of embryos transferred. This translates to one less pregnancy in every 15 cycles where ICSI was used without clear indication.

Conclusions

Our data suggest that ICSI may be detrimental to clinical outcomes and contributes to the wider understanding of use of ICSI in normospermic men.
Regulation of immunity and allergy by helminth parasites
Authors: Maizels Rick M.
Published: June 2019

There is increasing interest in helminth parasite modulation of the immune system, both from the fundamental perspective of the “arms race” between host and parasite, and equally importantly, to understand if parasites offer new pathways to abate and control untoward immune responses in humans. This article reviews the epidemiological and experimental evidence for parasite down‐regulation of host immunity and immunopathology, in allergy and other immune disorders, and recent progress towards defining the mechanisms and molecular mediators which parasites exploit in order to modulate their host. Among these are novel products that interfere with epithelial cell alarmins, dendritic cell activation, macrophage function and T‐cell responsiveness through the promotion of an immunoregulatory environment. These modulatory effects assist parasites to establish and survive, while dampening immune reactivity to allergens, autoantigens and microbiome determinants.
In vitro evaluation of an adaptive Starling‐like controller for dual rotary ventricular assist devices
Authors: Stephens Andrew , Gregory Shaun , Tansley Geoff , Busch Andrew , Salamonsen Robert
Published: June 2019

Rotary ventricular assist devices (VADs) operated clinically under constant speed control (CSC) cannot respond adequately to changes in patient cardiac demand, resulting in sub‐optimal VAD flow regulation. Starling‐like control (SLC) of VADs mimics the healthy ventricular flow regulation and automatically adjusts VAD speed to meet varying patient cardiac demand. The use of a fixed control line (CL – the relationship between ventricular preload and VAD flow) limits the flow regulating capability of the controller, especially in the case of exercise. Adaptive SLC (ASLC) overcomes this limitation by allowing the controller to adapt the CL to meet a diverse range of circulatory conditions. This study evaluated ASLC, SLC and CSC in a biventricular supported mock circulation loop under the simulated conditions of exercise, sleep, fluid loading and systemic hypertension. Each controller was evaluated on its ability to remain within predefined limits of VAD flow, preload, and afterload. The ASLC produced superior cardiac output (CO) during exercise (10.1 L/min) compared to SLC (7.3 L/min) and CSC (6.3 L/min). The ASLC produced favourable haemodynamics during sleep, fluid loading and systemic hypertension and could remain within a predefined haemodynamic range in three out of four simulations, suggesting improved haemodynamic performance over SLC and CSC.
Complex neural representation of odour information in the olfactory bulb
Authors: Li Anan , Rao Xiaoping , Zhou Yang , Restrepo Diego
Published: June 2019

The most important task of the olfactory system is to generate a precise representation of odour information under different brain and behavioural states. As the first processing stage in the olfactory system and a crucial hub, the olfactory bulb plays a key role in the neural representation of odours, encoding odour identity, intensity and timing. Although the neural circuits and coding strategies used by the olfactory bulb for odour representation were initially identified in anaesthetized animals, a large number of recent studies focused on neural representation of odorants in the olfactory bulb in awake behaving animals. In this review, we discuss these recent findings, covering (a) the neural circuits for odour representation both within the olfactory bulb and the functional connections between the olfactory bulb and the higher order processing centres; (b) how related factors such as sniffing affect and shape the representation; (c) how the representation changes under different states; and (d) recent progress on the processing of temporal aspects of odour presentation in awake, behaving rodents. We highlight discussion of the current views and emerging proposals on the neural representation of odorants in the olfactory bulb.
Claudin‐15 forms a water channel through the tight junction with distinct function compared to claudin‐2
Authors: Rosenthal Rita , Günzel Dorothee , Piontek Jörg , Krug Susanne M. , Ayala‐Torres Carlos , Hempel Caroline , Theune Dian , Fromm Michael
Published: June 2019

Aim

Claudin‐15 is mainly expressed in the small intestine and indirectly involved in glucose absorption. Similar to claudin‐2 and ‐10b, claudin‐15 is known to form a paracellular channel for small cations. Claudin‐2, but not claudin‐10b, also forms water channels. Here we experimentally tested whether claudin‐15 also mediates water transport and if yes, whether water transport is Na+‐coupled, as seen for claudin‐2.

Methods

MDCK C7 cells were stably transfected with claudin‐15. Ion and water permeability were investigated in confluent monolayers of control and claudin‐15‐expressing cells. Water flux was induced by an osmotic or ionic gradient.

Results

Expression of claudin‐15 in MDCK cells strongly increased cation permeability. The permeability ratios for monovalent cations indicated a passage of partially hydrated ions through the claudin‐15 pore. Accordingly, its pore diameter was determined to be larger than that of claudin‐2 and claudin‐10b. Mannitol‐induced water flux was elevated in claudin‐15‐expressing cells compared to control cells. In contrast to the Na+‐coupled water flux of claudin‐2 channels, claudin‐15‐mediated water flux was inhibited by Na+ flux. Consequently, water flux was increased in Na+‐free solution. Likewise, Na+ flux was decreased after induction of water flux through claudin‐15.

Conclusion

Claudin‐15, similar to claudin‐2, forms a paracellular cation and water channel. In functional contrast to claudin‐2, water and Na+ fluxes through claudin‐15 inhibit each other. Claudin‐15 allows Na+ to retain part of its hydration shell within the pore. This then reduces the simultaneous passage of additional water through the pore.
DNA methylation is associated with inhaled corticosteroid response in persistent childhood asthmatics
Authors: Wang Alberta L. , Gruzieva Olena , Qiu Weiliang , Kebede Merid Simon , Celedón Juan C. , Raby Benjamin A. , Söderhäll Cilla , DeMeo Dawn L. , Weiss Scott T. , Melén Erik , Tantisira Kelan G.
Published: June 2019

Background

Response to inhaled corticosteroids is highly variable, and the association between DNA methylation and treatment response is not known.

Objective

To examine the association between peripheral blood DNA methylation and inhaled corticosteroid response in children with persistent asthma.

Methods

Epigenome‐wide DNA methylation was analysed in individuals on inhaled corticosteroids in three independent and ethnically diverse cohorts—Childhood Asthma Management Program (CAMP); Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE); and Genetic Epidemiology of Asthma in Costa Rica Study (GACRS). Treatment response was evaluated using two definitions, the absence of emergency department visits and/or hospitalizations and the absence oral corticosteroid use while on inhaled corticosteroid therapy. CpG sites meeting nominal significance (P < 0.05) for each outcome were combined in a three‐cohort meta‐analysis with adjustment for multiple testing. DNA methylation was correlated with gene expression using Pearson and partial correlations.

Results

In 154 subjects from CAMP, 72 from BAMSE, and 168 from GACRS, relative hypomethylation of cg00066816 (171 bases upstream ofIL12B) was associated with the absence of emergency department visits and/or hospitalizations (Q = 0.03) in all cohorts and lowerIL12Bexpression (ρ = 0.34,P = 0.01) in BAMSE. Relative hypermethylation of cg04256470 (688 bases upstream ofCORT) was associated with the absence of oral corticosteroid use (Q = 0.04) in all cohorts and higherCORTexpression (ρ = 0.20,P = 0.045) in CAMP.

Conclusion and Clinical Relevance

Differential DNA methylation ofIL12BandCORTare associated with inhaled corticosteroid treatment response in persistent childhood asthmatics. Pharmaco‐methylation can identify novel markers of treatment sensitivity in asthma.
Motivated monitoring by institutional investors and firm investment efficiency
Authors: Ward Charles , Yin Chao , Zeng Yeqin
Published: June 2019

We find that motivated monitoring by institutional investors mitigates firm investment inefficiency, estimated by Richardson's (2006) approach. This relation is robust when using the annual reconstitution of the Russell indexes as exogenous shocks to institutional ownership during the period 1995–2015 and after classifying institutional ownership by institution type. We also show that closer monitoring mitigates the problem of both over‐investing free cash flows and under‐investment due to managers’ career concerns. Finally, we document that the effectiveness of the monitoring by institutional investors appears to increase monotonically with respect to the firm's relative importance in their portfolios.
The development of search filters for adverse effects of medical devices in medline and embase
Authors: Golder Su , Farrah Kelly , Mierzwinski‐Urban Monika , Wright Kath , Loke Yoon Kong
Published: June 2019

Background

Objectively derived search filters for adverse drug effects and complications in surgery have been developed but not for medical device adverse effects.

Objective

To develop and validate search filters to retrieve evidence on medical device adverse effects from ovid medline and embase.

Methods

We identified systematic reviews from Epistemonikos and the Health Technology Assessment (hta) database. Included studies within these reviews that reported on medical device adverse effects were randomly divided into three test sets and one validation set of records. Using word frequency analysis from one test set, we constructed a sensitivity maximising search strategy. This strategy was refined using two other test sets, then validated.

Results

From 186 systematic reviews which met our inclusion criteria, 1984 unique included studies were available from medline and 1986 from embase. Generic adverse effects searches in medline and embase achieved 84% and 83% sensitivity. Recall was improved to over 90%, however, when specific adverse effects terms were added.

Conclusion

We have derived and validated novel search filters that retrieve over 80% of records with medical device adverse effects data in medline and embase. The addition of specific adverse effects terms is required to achieve higher levels of sensitivity.
Metal‐responsive RNA polymerase extracytoplasmic function (ECF) sigma factors
Authors: Moraleda‐Muñoz Aurelio , Marcos‐Torres Francisco Javier , Pérez Juana , Muñoz‐Dorado José
Published: June 2019

In order to survive, bacteria must adapt to multiple fluctuations in their environment, including coping with changes in metal concentrations. Many metals are essential for viability, since they act as cofactors of indispensable enzymes. But on the other hand, they are potentially toxic because they generate reactive oxygen species or displace other metals from proteins, turning them inactive. This dual effect of metals forces cells to maintain homeostasis using a variety of systems to import and export them. These systems are usually inducible, and their expression is regulated by metal sensors and signal‐transduction mechanisms, one of which is mediated by extracytoplasmic function (ECF) sigma factors. In this review, we have focused on the metal‐responsive ECF sigma factors, several of which are activated by iron depletion (FecI, FpvI and PvdS), while others are activated by excess of metals such as nickel and cobalt (CnrH), copper (CarQ and CorE) or cadmium and zinc (CorE2). We focus particularly on their physiological roles, mechanisms of action and signal transduction pathways.
Dog sperm DNA: Raw semen evaluation with Toluidine blue stain
Authors: Monachesi Norma E. , Neild Deborah , Carretero Maria
Published: June 2019

The toluidine blue (TB) stain has been used in different species to evaluate the degree of chromatin condensation. The objectives of this study were as follows: simplify the TB stain to evaluate sperm in canine raw semen, verify the staining patterns for this species using this simplified technique and establish a protocol for using dithiothreitol (DTT) as a positive control for TB staining in dogs. Twenty‐one ejaculates were collected from 7 adult male dogs; semen was extended, fixed with ethanol 96° and stained with TB using 2 staining times: 15 and 30 min. In addition, 3 incubation times with 1% DTT were assayed (2, 5 and 30 min). Three staining patterns were established: light blue colouring (TB negative, normal chromatin condensation), light violet (TB intermediate, some degree of chromatin decondensation) and dark blue‐violet (TB positive, high degree of chromatin decondensation). No significant differences (p > 0.05) were observed between the staining times (15 and 30 min) for any of the TB patterns. All DTT incubation times (2, 5 and 30 min) showed 100% sperm positive to TB. To conclude, it was possible to simplify the TB stain and determine the different patterns in canine spermatozoa. Also, DTT can be used both as a positive control for the stain and to evaluate individual susceptibility to decondensation in vitro.
Do or do not. There is no try in restoration ecology
Authors: Lortie Christopher J. , St John Julie , Spangler Will
Published: June 2019

Change is a fundamental component of contemporary restoration ecology. The environment, the research, and the ideas in this discipline are rapidly evolving and changing. The California Society for Ecological Restoration annual meeting was an inclusive, diverse meeting that significantly advanced new thinking in the field and provided an exemplar of the value of scientific discourse at meetings. The restoration work in this region also amplified and identified trends in the scientific community at large. A total of three future‐oriented strategic issues emerged from the discourse at this meeting. (1) Restoration ecologists need to consider alternative definitions of local for interventions within a region. (2) Restoration is never complete and must always incorporate people. (3) Indirect outcomes and the process of restoration have merit despite challenges of immediate identification of benefits. The science presented served as a platform for these advanced strategic issue examinations, and the grandest of challenges for restoration ecology necessarily includes people in every equation and embraces values and perceptions over longer time frames.
Handheld flow meter improves COPD detectability regardless of using a conventional questionnaire: A split‐sample validation study
Authors: Fujita Misuzu , Nagashima Kengo , Takahashi Sho , Suzuki Kiminori , Fujisawa Takehiko , Hata Akira
Published: June 2019

Background and objective

Improved detectability of chronic obstructive pulmonary disease (COPD) using a handheld flow meter (HFM) with symptom‐based questionnaires has not been sufficiently evaluated. This study aimed to identify the benefit of using an HFM in COPD screening.

Methods

A total of 2008 participants, who were ≥ 40 years of age, from Isumi City, Japan, were recruited. We developed two novel point systems for detecting COPD, one incorporated score of HFM alone (sHFM) and the other incorporated the score of International Primary Care Airway Group questionnaire (IPAG) and HFM (sIPAG + HFM). Validation using random sample allocation (split‐sample validation) was carried out to assess the predictive performance of these models.

Results

Participants were assigned to a data set for model creation (n = 1007) or a data set for model assessment (n = 1001) to perform split‐sample validation. Decision curve analysis showed that the net benefits of sHFM and sIPAG + HFM were higher than that of the IPAG score (sIPAG) and specificity of the former two were also significantly higher than that of sIPAG. However, the curves of sHFM and sIPAG + HFM were crossing and practically the same with no significant difference in sensitivity and specificity.

Conclusion

This study confirms that HFM is significantly advantageous in detecting COPD despite the use of a conventional questionnaire.
Effect of fertilizers and irrigation on multi‐configuration electromagnetic induction measurements
Authors: Kaufmann Manuela S. , von Hebel Christian , Weihermüller Lutz , Baumecker Michael , Döring Thomas , Schweitzer Kathlin , Hobley Eleanor , Bauke Sara L. , Amelung Wulf , Vereecken Harry , van der Kruk Jan
Published: June 2019

Electromagnetic induction (EMI) data are often used to investigate spatial and temporal patterns of soil texture, soil water content and soil salinity. We hypothesized that the EMI methodology might thus also offer potential to detect agricultural legacy effects originating from fertilizer application and irrigation of different fields. Therefore, we performed EMI measurements on two long‐term field experiments (LTFE) at Thyrow near Berlin (Germany) that differed in agricultural management with regard to long‐term irrigation in combination with mineral (NPK and lime) and organic amendments (straw and farmyard manure). Two different rigid‐boom multi‐coil EMI instruments were used to measure simultaneously the apparent electrical conductivity (ECa) over nine different depth ranges to study the entire soil profile from topsoil to deep subsoil. Additionally, soil samples were taken from the different treatments to ground‐truth the measurements and disentangle the nutrient application or irrigation effects from natural soil heterogeneity. The soil samples indicated a rather homogenous soil and the correlation between soil parameters or states were not significant. However, the treatments showed significant differences in measured ECa values. In general, ECa values were largest on regularly irrigated as well as on mineral and organic fertilized plots, with regular irrigation exhibiting the largest impact on EMI records even though the last application was months before the EMI measurement. Overall, this study reveals that EMI data can support the classical in situ assessment of agricultural management effects within LTFE, while offering new potentials in detecting and understanding legacy effects of agricultural management on spatial soil properties at farm level.
Evaluation of the effect of urine dip vs urine drip on multi‐test strip results
Authors: Boag Alisdair M. , Breheny Craig , Handel Ian , Gow Adam G.
Published: June 2019

Standard operating procedures, including World Health Organization guidelines for packed cell volume, are established for in‐clinic laboratory tests. No independent, evidence‐based guidelines exist for dipstick urinalysis; however, manufacturer's instructions state to dip the stick into urine. In veterinary medicine, small volume urine samples could preclude dipping; therefore, a single drip per pad from a pipette or syringe is often performed. This study aimed to examine the differences between these two urine application methods prior to analysis, with the hypothesis that the method type would not effect on test results of dipstick analysis. To standardize the strip analysis method, a Siemens Clinitek Status + analyzer was used with Multistix10SG dipsticks. Three investigators tested urines from 53 dogs with a range of diseases by both methods. Results were assessed for the degree of agreement between the methods and within method variability. Overall, the agreement between methods was high. Within each method, the drip method variability was higher than that of the dip method (P = 0.012). Disagreements between methods were present, with pH and blood having the lowest agreement levels. Glucose was more likely to be positive on the drip compared with the dip methodology. This study demonstrates potential clinically relevant differences between the two methods and a higher level of variability with the drip methodology. Therefore, while the drip method could be used for practical reasons (eg, low sample volumes), this study supports the manufacturer's recommended method of dipping the dip stick into urine rather than dripping urine onto each pad with a pipette or syringe.
The Sparthan Three-Dimensional Printed Exo-Glove: A Preliminary Evaluation of Performance Via Case Study
Authors: Georgiou Tomás A. , Asnaghi Davide , Liang Alva , Agogino Alice M.
Published: June 2019

This paper describes the development and testing of a low-cost three-dimensional (3D) printed wearable hand exoskeleton to assist people with limited finger mobility and grip strength. The function of the presented orthosis is to support and enable light intensity activities of daily living and improve the ability to grasp and hold objects. The Sparthan Exoskeleton prototype utilizes a cable-driven design applied to individual digits with motors. The initial prototype is presented in this paper along with a preliminary evaluation of durability and performance efficacy.
Anisotropic Material Characterization of Human Cervix Tissue Based on Indentation and Inverse Finite Element Analysis
Authors: Shi Lei , Yao Wang , Gan Yu , Zhao Lily Y. , Eugene McKee W. , Vink Joy , Wapner Ronald J. , Hendon Christine P. , Myers Kristin
Published: June 2019

The cervix is essential to a healthy pregnancy as it must bear the increasing load caused by the growing fetus. Preterm birth is suspected to be caused by the premature softening and mechanical failure of the cervix. The objective of this paper is to measure the anisotropic mechanical properties of human cervical tissue using indentation and video extensometry. The human cervix is a layered structure, where its thick stromal core contains preferentially aligned collagen fibers embedded in a soft ground substance. The fiber composite nature of the tissue provides resistance to the complex three-dimensional loading environment of pregnancy. In this work, we detail an indentation mechanical test to obtain the force and deformation response during loading which closely matches in vivo conditions. We postulate a constitutive material model to describe the equilibrium material behavior to ramp-hold indentation, and we use an inverse finite element method based on genetic algorithm (GA) optimization to determine best-fit material parameters. We report the material properties of human cervical slices taken at different anatomical locations from women of different obstetric backgrounds. In this cohort of patients, the anterior internal os (the area where the cervix meets the uterus) of the cervix is stiffer than the anterior external os (the area closest to the vagina). The anatomic anterior and posterior quadrants of cervical tissue are more anisotropic than the left and right quadrants. There is no significant difference in material properties between samples of different parities (number of pregnancies reaching viable gestation age).
Additive Manufacturing of Horizontal and 3D Functionally Graded 316L/Cu10Sn Components via Multiple Material Selective Laser Melting
Authors: Wei Chao , Sun Zhe , Chen Qian , Liu Zhu , Li Lin
Published: June 2019

Production of functionally graded materials (FGMs, i.e., a gradual transition from one material to another) and components is challenging using conventional manufacturing techniques. Additive manufacturing (AM) provides a new opportunity for producing FGMs. However, current metal AM technologies including powder-bed fusion are limited to producing single material components or vertical FGM parts, i.e., a different material composition in different layers but not within the same layer, and in situ changing materials is challenging. In this paper, we demonstrate the fabrication of horizontal and 3D 316L/Cu10Sn components with FGM within the same layer and in different layers, via a proprietary multiple selective powder delivery array device incorporated into a selective laser melting system that allowed the deposition of up to six different materials point by point. The manufactured component macrostructure, microstructure, microhardness, and phases were examined. Smooth transition from one material to the other was realized. Also, an interesting phenomenon was found that the maximum hardness was at 50% 316L and 50% Cu10Sn. The work would open up a new opportunity for the manufacturing of true 3D functionally graded components using additive manufacturing and for the rapid development of new metal alloy systems.
Reconstruction of an early viola da gamba informed by physical modeling
Authors: Chatziioannou Vasileios
Published: June 2019

The reconstruction of an early viola da gamba is considered, using virtual prototyping by means of the finite element method. Based on iconographic sources, previous research has postulated an instrument design lacking a soundpost and a bass bar. This led to the hypothesis of a top plate with variable thickness. In order to investigate the acoustic efficiency of such a design, a finite element model of the instrument is formulated. The structural accuracy of the model is qualitatively verified by comparing calculated modal shapes with those of a reconstructed instrument, visualized with the aid of Chladni patterns and electronic speckle pattern interferometry. Furthermore, simulating the interaction between the vibrating surfaces of the instrument and the surrounding air shows that the posited asymmetric design can radiate sound more efficiently than a design involving a symmetric top plate. However, the asymmetry introduced by the gradually thickening top plate is weaker than that usually enforced by the presence of a soundpost and a bass bar. Therefore, low frequency structural modes of the instrument are less easily excited by a force acting parallel to the top plate.
Associations Between Social and Physical Environments and Older Adults’ Walking for Transportation and Recreation
Authors: Leung Ka Man , Chung Pak-Kwong
Published: June 2019

This study examined the associations between physical environment, social environment, and walking for transportation and recreation among older adults in Hong Kong. Cross-sectional data from 450 older adults (79 years or younger [71.9%], female [79.7%]) from 18 districts in Hong Kong were used. The participants’ perceptions of their physical and social environments were collected, and their walking behaviors were self-reported. The results revealed that positive physical environment facilitators and social environments were associated with increased total walking. Only positive physical environment facilitators were associated with increased walking for transportation, and physical and social environments had no notable effect on walking for recreation. These findings suggest that policy makers and walking intervention designers should develop strategies to enhance physical and social environments to promote total walking and walking for transportation.
“We Are All Broncos”: Hockey, Tragedy, and the Formation of Canadian Identity
Authors: Kennedy Liam , Silva Derek , Coelho Madelaine , Cipolli William
Published: June 2019

There exists a broad body of scholarly work that focuses on how communities, and individuals therein, mobilize, respond, and harvest collective action in response to tragedy. Despite this interest, there remains a dearth of empirical investigation into the complex intersections of tragedy, sport, and community. Utilizing qualitative approaches to discourse analysis and quantitative measures of sentiment, semantic, and content analysis of news media articles (n = 151) and public tweets (n = 126,393), this paper explores the ways in which public responses to the 2018 Humboldt Broncos bus crash present a relatively narrow representation of both Canadian and local Prairie identity. We conclude with a discussion of some of the implications of collective action in response to specific forms of tragedy.
In vivo liquid biopsy using Cytophone platform for photoacoustic detection of circulating tumor cells in patients with melanoma
Authors: Galanzha Ekaterina I. , Menyaev Yulian A. , Yadem Aayire C. , Sarimollaoglu Mustafa , Juratli Mazen A. , Nedosekin Dmitry A. , Foster Stephen R. , Jamshidi-Parsian Azemat , Siegel Eric R. , Makhoul Issam , Hutchins Laura F. , Suen James Y. , Zharov Vladimir P.
Published: June 2019

Noninvasive label-free photoacoustic detection of circulating tumor cells was demonstrated directly in the bloodstream of patients with melanoma.
A workout plan to prevent metastasis
Authors: Kerr Bethany A.
Published: June 2019

Stimulating osteocytes with mechanical forces representative of exercise reduces breast cancer extravasation in a microfluidic model.
Repeated Detection of Carbapenemase-Producing Escherichia coli in Gulls Inhabiting Alaska
Authors: Ahlstrom Christina A. , Ramey Andrew M. , Woksepp Hanna , Bonnedahl Jonas
Published: June 2019

Here, we report the first detection of carbapenemase-producing
Escherichia coli
in Alaska and in wildlife in the United States. Wild bird (gull) feces sampled at three locations in Southcentral Alaska yielded isolates that harbored plasmid-encoded
bla
KPC-2
or chromosomally encoded
bla
OXA-48
and genes associated with antimicrobial resistance to up to eight antibiotic classes.
Wildlife Is Overlooked in the Epidemiology of Medically Important Antibiotic-Resistant Bacteria
Authors: Dolejska Monika , Literak Ivan
Published: June 2019

Wild animals foraging in the human-influenced environment are colonized by bacteria with clinically important antibiotic resistance. The occurrence of such bacteria in wildlife is influenced by various biological, ecological, and geographical factors which have not yet been fully understood.
Cooperative Roles of Nitric Oxide-Metabolizing Enzymes To Counteract Nitrosative Stress in Enterohemorrhagic Escherichia coli
Authors: Shimizu Takeshi , Matsumoto Akio , Noda Masatoshi
Published: June 2019

Enterohemorrhagic
Escherichia coli
(EHEC) has at least three enzymes, NorV, Hmp, and Hcp, that act independently to lower the toxicity of nitric oxide (NO), a potent antimicrobial molecule. This study aimed to reveal the cooperative roles of these defensive enzymes in EHEC against nitrosative stress.
Multiplex Real-Time PCR-short
TUB
Assay for Detection of the Mycobacterium tuberculosis Complex in Smear-Negative Clinical Samples with Low Mycobacterial Loads
Authors: Alcaide Fernando , Trastoy Rocío , Moure Raquel , González-Bardanca Mónica , Ambroa Antón , López María , Bleriot Inés , Blasco Lucia , Fernandez-García Laura , Tato Marta , Bou German , Tomás María
Published: June 2019

Tuberculosis (TB) remains a major health problem worldwide. Control of TB requires rapid, accurate diagnosis of active disease. However, extrapulmonary TB is very difficult to diagnose because the clinical specimens have very low bacterial loads. Several molecular methods involving direct detection of the
Mycobacterium tuberculosis
complex (MTBC) have emerged in recent years.
Porcine Reproductive and Respiratory Syndrome Virus Activates Lipophagy To Facilitate Viral Replication through Downregulation of NDRG1 Expression
Authors: Wang Jiang , Liu Jiao-Yang , Shao Ke-Yu , Han Ying-Qian , Li Guo-Li , Ming Sheng-Li , Su Bing-Qian , Du Yong-Kun , Liu Zhong-Hu , Zhang Gai-Ping , Yang Guo-Yu , Chu Bei-Bei
Published: June 2019

Porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped single-positive-stranded RNA virus, causes acute respiratory distress in piglets and reproductive failure in sows. It has led to tremendous economic losses in the swine industry worldwide since it was first documented in the late 1980s. Vaccination is currently the major strategy used to control the disease. However, conventional vaccines and other strategies do not provide satisfactory or sustainable prevention. Therefore, safe and effective strategies to control PRRSV are urgently required. The significance of our research is that we demonstrate a previously unreported relationship between PRRSV, NDRG1, and lipophagy in the context of viral infection. Furthermore, our data point to a new role for NDRG1 in autophagy and lipid metabolism. Thus, NDRG1 and lipophagy will have significant implications for understanding PRRSV pathogenesis for developing new therapeutics.
Poverty dynamics and health in late childhood in the UK: evidence from the Millennium Cohort Study
Authors: Lai Eric T C , Wickham Sophie , Law Catherine , Whitehead Margaret , Barr Benjamin , Taylor-Robinson David
Published: June 2019

Objective

To assess the prevalence of different trajectories of exposure to child poverty and their association with three indicators of adolescent physical and mental health in UK children.

Methods

We analysed data on 10 652 children from a large, prospective, nationally representative sample in the UK Millennium Cohort Study. The outcomes were mental health, measured by the Strengths and Difficulties Questionnaire (SDQ), physical health, measured by obesity and any longstanding illness, at age 14. The exposure was relative poverty (<60% of median of equivalised household income), measured at 9 months, 3, 5, 7, 11 and 14 years. Poverty trajectories were characterised using latent class analysis. ORs and 95% CIs were estimated using multivariable logistic regression, adjusted for maternal education and ethnicity.

Results

Four poverty trajectories were identified: never in poverty (62.4%), poverty in early childhood (13.4%), poverty in late childhood (5.0%) and persistent poverty (19.4%). Compared with children who never experienced poverty, those in persistent poverty were at increased risk of mental health problems (SDQ score≥17 (adjusted OR (aOR): 3.17; 95% CI: 2.40 to 4.19)), obesity (aOR: 1.57; 95% CI: 1.20 to 2.04) and longstanding illness (aOR: 1.98; 95% CI: 1.55 to 2.52). Poverty in early childhood was related to higher risk of obesity than that in late childhood, while the opposite is observed for mental health problems and longstanding illness.

Conclusions

Persistent poverty affects one in five children in the UK. Any exposure to poverty was associated with worse physical and mental health outcomes. Policies that reduce child poverty and its consequences are likely to improve health in adolescence.
NeuroSAFE robot-assisted laparoscopic prostatectomy versus standard robot-assisted laparoscopic prostatectomy for men with localised prostate cancer (NeuroSAFE PROOF): protocol for a randomised controlled feasibility study
Authors: Dinneen Eoin , Haider Aiman , Allen Clare , Freeman Alex , Briggs Tim , Nathan Senthil , Brew-Graves Chris , Grierson Jack , Williams Norman R , Persad Raj , Oakley Neil , Adshead Jim M , Huland Hartwig , Haese Alexander , Shaw Greg
Published: June 2019

Introduction

Robot-assisted laparoscopic prostatectomy (RALP) offers potential cure for localised prostate cancer but is associated with considerable toxicity. Potency and urinary continence are improved when the neurovascular bundles (NVBs) are spared during a nerve spare (NS) RALP. There is reluctance, however, to perform NS RALP when there are concerns that the cancer extends beyond the capsule of the prostate into the NVB, as NS RALP in this instance increases the risk of a positive surgical margin (PSM). The NeuroSAFE technique involves intraoperative fresh-frozen section analysis of the posterolateral aspect of the prostate margin to assess whether cancer extends beyond the capsule. There is evidence from large observational studies that functional outcomes can be improved and PSM rates reduced when the NeuroSAFE technique is used during RALP. To date, however, there has been no randomised controlled trial (RCT) to substantiate this finding. The NeuroSAFE PROOF feasibility study is designed to assess whether it is feasible to randomise men to NeuroSAFE RALP versus a control arm of ‘standard of practice’ RALP.

Methods

NeuroSAFE PROOF feasibility study will be a multicentre, single-blinded RCT with patients randomised 1:1 to either NeuroSAFE RALP (intervention) or standard RALP (control). Treatment allocation will occur after trial entry and consent. The primary outcome will be assessed as the successful accrual of 50 men at three sites over 15 months. Secondary outcomes will be used to aid subsequent power calculations for the definitive full-scale RCT and will include rates of NS; PSM; biochemical recurrence; adjuvant treatments; and patient-reported functional outcomes on potency, continence and quality of life.

Ethics and dissemination

NeuroSAFE PROOF has ethical approval (Regional Ethics Committee reference 17/LO/1978). NeuroSAFE PROOF is supported by National Institute for Healthcare Research Research for Patient Benefit funding (NIHR reference PB-PG-1216-20013). Findings will be made available through peer-reviewed publications.

Trial registration number

NCT03317990.
Cohort profile : Bandim Health Project’s (BHP) rural Health and Demographic Surveillance System (HDSS)—a nationally representative HDSS in Guinea-Bissau
Authors: Thysen Sanne Marie , Fernandes Manuel , Benn Christine Stabell , Aaby Peter , Fisker Ane Bærent
Published: June 2019

Purpose

Bandim Health Project (BHP) monitors health and survival of women and children in a nationally representative rural Health and Demographic Surveillance System (HDSS) in Guinea-Bissau. The HDSS was set up in 1989–1990 to collect data on health interventions and child mortality.

Participants

The HDSS covers 182 randomly selected clusters across the whole country. The cohort is open, and women and children enter the cohort, when they move into the selected clusters, and leave the cohort, when they move out or die, or when children reach 5 years of age. Data are collected through biannual or more frequent household visits. At all village visits, information on pregnancies, vital status, vaccination status, arm circumference, use of bed nets and other basic information is collected for women and children. Today, more than 25 000 women and 23 000 children below the age of 5 years are under surveillance.

Findings to date

Research from the BHP has given rise to the hypothesis that vaccines, in addition to their targeted effects, have important non-specific effects altering the susceptibility to other infections. Initially, it was observed that mortality among children vaccinated with the live BCG or measles vaccines was much lower than the mortality among unvaccinated children, a difference, which could not be explained by prevention of tuberculosis and measles infections. In contrast, mortality tended to be higher for children who had received the non-live Diphtheria-Tetanus-Pertussis vaccine compared with children who had not received this vaccine. Since the effect differed for the different vaccines, no bias explained the contrasting findings.

Future plans

New health interventions are introduced with little assessment of real-life effects. Through the HDSS, we can describe both the implementation of interventions (eg, the vaccination programme) and their effects. Furthermore, the intensive follow-up allows the implementation of randomised trials testing potential better vaccination programmes.
Risk factors for repetitive doctor’s consultations due to cough: a cross-sectional study in a Finnish employed population
Authors: Koskela Heikki O , Lätti Anne M , Pekkanen Juha
Published: June 2019

Objectives

Cough is the most common symptom prompting people to consult a doctor, thus representing a huge cost to the healthcare. This burden could be reduced by decreasing the number of repetitive consultations by the same individuals. Therefore, it would be valuable to recognise the factors that associate with repetitive doctor’s consultations due to cough.

Design

A cross-sectional, email survey.

Setting

Public service employees in two Finnish towns.

Participants

The questionnaire was sent to 13 980 subjects; 3695 (26.4 %) participated.

Interventions

The questionnaire sought detailed information about participant characteristics, all disorders diagnosed by a doctor, various symptoms and doctor’s consultations. Those with current cough were inquired about cough characteristics and filled in the Leicester Cough Questionnaire (LCQ).

Primary outcome

Repetitive (≥3) doctor’s consultations due to cough during the previous 12 months.

Results

There were 205 participants (5.5% of the participants) with repetitive consultations. They accounted for 848 out of the 1681 doctor’s consultations (50.4%) due to cough. Among all participants, repetitive consultations were mainly related to the presence of asthma (adjusted OR (aOR) 2.90 (2.01 to 4.19)) and chronic rhinosinusitis (aOR 2.40 (1.74 to 3.32)). Among the 975 participants with current cough, repetitive consultations were mainly related to a low LCQ total score (aOR 3.84 (2.76 to 5.34) per tertile). Comorbidity, depressive symptoms and smoking were also associated with repetitive consultations.

Conclusions

A modest proportion of subjects with repetitive consultations is responsible for every second doctor’s consultation due to cough. The typical features of these subjects could be identified. These findings can help to focus on certain subpopulations in order to plan interventions to reduce the healthcare burden attributable to cough.
Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay
Authors: Vors Cécile , Joumard-Cubizolles Laurie , Lecomte Manon , Combe Emmanuel , Ouchchane Lemlih , Drai Jocelyne , Raynal Ketsia , Joffre Florent , Meiller Laure , Le Barz Mélanie , Gaborit Patrice , Caille Aurélie , Sothier Monique , Domingues-Faria Carla , Blot Adeline , Wauquier Aurélie , Blond Emilie , Sauvinet Valérie , Gésan-Guiziou Geneviève , Bodin Jean-Pierre , Moulin Philippe , Cheillan David , Vidal Hubert , Morio Béatrice , Cotte Eddy , Morel-Laporte Françoise , Laville Martine , Bernalier-Donadille Annick , Lambert-Porcheron Stéphanie , Malpuech-Brugère Corinne , Michalski Marie-Caroline
Published: June 2019

Objective

To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health.

Design

A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients.

Results

Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut.

Conclusion

The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota.

Trial registration number

NCT02099032andNCT02146339; Results.
Turning subtypes into disease axes to improve prediction of COPD progression
Authors: Chen Junxiang , Cho Michael , Silverman Edwin K , Hokanson John E , Kinney Greg L , Crapo James D , Rennard Stephen , Dy Jennifer , Castaldi Peter
Published: June 2019

Chronic obstructive pulmonary disease (COPD) is an umbrella definition encompassing multiple disease processes. COPD heterogeneity has been described as distinct subgroups of individuals (subtypes) or as continuous measures of COPD variability (disease axes). There is little consensus on whether subtypes or disease axes are preferred, and the relative value of disease axes and subtypes for predicting COPD progression is unknown. Using a propensity score approach to learn disease axes from pairs of subtypes, we demonstrate that these disease axes predict prospective forced expiratory volume in 1 s decline and emphysema progression more accurately than the subtype pairs from which they were derived.
Longer symptom onset to aspiration time predicts success of needle aspiration in primary spontaneous pneumothorax
Authors: Vuillard Constance , Dib Fadia , Achamlal Jallal , Gaudry Stéphane , Roux Damien , Chemouny Myriam , Javaud Nicolas , Dreyfuss Didier , Ricard Jean-Damien , Messika Jonathan
Published: June 2019

Background

Needle aspiration (NA) is recommended as first-line treatment of primary spontaneous pneumothorax (PSP). We aimed to assess NA success and the effect of a longer symptom onset to NA time.

Methods

A discovery phase was retrospectively conducted in the intensive care unit of Louis Mourier Hospital (January 2000 to December 2011) followed by a prospective validation cohort (January 2012 to August 2015). The primary outcome was immediate NA success defined by the absence of need for chest tube insertion within 24 hours of the procedure.

Results

In the discovery phase, 130 patients were admitted for PSP and 98 had NA as first-line treatment (75%). The immediate success rate of NA was 34.7% and was higher when it was performed ≥48 hours after symptom onset (57.7% vs 25%; p=0.004). In the prospective cohort, 87 patients were admitted for PSP; 71 (82%) had NA as first-step treatment. The immediate success rate was 40.8%. NA was more successful when it was performed after 48 hours of symptoms’ onset (34.5% vs 7.1%; p=0.005). A delay between the first symptom and NA procedure ≥48 hours was associated with a higher success of NA (OR=13.54; 95% CI 1.37 to 133). A smaller pneumothorax estimated by Light’s index was associated with NA success (OR=0.95; 95% CI 0.92 to 0.98). To what extent some of these pneumothoraces would have had a spontaneous resolution remains unknown.

Conclusion

When managing PSP with NA, a longer symptom onset to NA time was associated with NA success.

Trial registration number

NCT02528734.