bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogen reduction combined with rapid diagnostic tests to reduce the risk of transfusion‐transmitted infections in Uganda
Authors: Butler Elissa K. , McCullough Jeffrey
Published: February 2018

BACKGROUND

Blood safety and transfusion‐transmitted infections (TTIs) are a major concern in low‐resource areas. Laboratory screening of donors, a key contributor to blood safety, is usually done by enzyme‐linked immunosorbent assay (ELISA) methods, which use expensive reagents and necessitate complex instruments and sophisticated laboratory staff. Rapid diagnostic tests (RDTs) are less expensive and easier to perform but have less sensitivity. Pathogen reduction technology (PRT) reduces transfusion transmission of malaria and may be effective in decreasing other TTIs. We explored the potential to improve blood safety by combining PRT and RDTs in comparison with current ELISA testing.

STUDY DESIGN AND METHODS

We identified the sensitivity of RDTs available in Uganda and the sensitivity of currently used ELISA. Data from a riboflavin‐and‐UV–based photochemical treatment PRT were used. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and malaria were studied. Probability models were developed for estimation of the number of infectious units of blood for each of these four infections using either current ELISA or the combination of RDT and PRT.

RESULTS

Compared to currently used ELISA, the combination of RDTs and PRT could reduce the rate of infectious units by 100, 20, 98, and 83% for HIV, HBV, HCV, and malaria, respectively, and would prevent use of 758 units of infectious blood per 10,000 units transfused.

CONCLUSION

The combination of RDTs and PRT may improve blood safety in low‐resource areas.
Changes in plasma unit distributions to hospitals over a 10‐year period
Authors: Seheult Jansen N. , Shaz Beth , Bravo Marjorie , Croxon Harry , Devine Dana , Doncaster Cheryl , Field Stephen , Flanagan Peter , Germain Marc , Grégoire Yves , Kamel Hany , Karafin Matthew , Kelting Nancy , Lewis Marc , O'Brien Cath , Murphy Michael F. , Rossmann Susan , Sayers Merlyn , Shinar Eilat , Takanashi Minoko , Titlestad Kjell , Yazer Mark H. ,   the Biomedical Excellence for Safer Transfusions (BEST) Collaborative
Published: February 2018

BACKGROUND

There are many influences on a hospital's demand for plasma. Pharmaceuticals are now being administered for many indications instead of plasma, although trauma resuscitation now emphasizes increased and early intervention with plasma. This multinational study evaluated changes in blood center plasma unit distributions over a 10‐year period.

STUDY DESIGN AND METHODS

Data on the total number and the ABO groups of plasma unit distributions were obtained from nine American blood collectors (ABCs) and nine national or provincial blood services (NPBS) from 2007 through 2016. Plasma distributions to trauma hospitals by five ABCs and four NPBS were also analyzed.

RESULTS

The overall number of plasma unit distributions from ABCs decreased by 23.1% from 2007 to 2016, but the relative proportion of distributed AB plasma units increased during the same period. The NPBS (excluding the Japanese Red Cross [JRC]) also had a 35.4% decrease in the overall number of plasma unit distributions with an increase in the relative proportion of AB plasma distributions between 2007 and 2016. The JRC, however, reported an increase in the overall number of plasma distributions by 13.5% in 2016 compared to 2007. The proportion of low‐titer A plasma distributions increased to 1.6% of total plasma distributions by ABCs in 2016. There was a trend of distributing increasing proportions of group AB plasma units to trauma hospitals over the 10‐year period.

CONCLUSION

Although the number of plasma unit distributions has decreased at many blood collectors over time, the proportion of AB units has increased at both ABCs and NPBS.
Iron deficiency and preoperative anaemia in patients scheduled for elective hip‐ and knee arthroplasty – an observational study
Authors: Jans Ø. , Nielsen C. S. , Khan N. , Gromov K. , Troelsen A. , Husted H.
Published: February 2018

Background and objectives

Preoperative anaemia is prevalent in elderly patients scheduled for major orthopaedic surgery and is associated with increased transfusion risk and postoperative morbidity. New guidelines recommend preoperative correction of anaemia and iron deficiency in all patients with a Hb < 13 g/dl. However, iron deficiency and other causes of preoperative anaemia in hip‐ (THA) and knee (TKA) arthroplasty are only sparsely studied.

Materials and Methods

Preoperative Hb and iron status were prospectively collected from 882 unselected elective fast‐track THA/TKA patients and analysed according to both WHO anaemia criteria (Hb < 12 g/dl females, <13 g/dl males) and Hb < 13 g/dl for both genders. Iron deficiency (ID) and other possible anaemia causes were classified by ferritin, transferrin saturation, P‐cobalamin, P‐folate, C‐reactive protein and creatinine.

Results

Ninety‐five (10·8%) and 243 (27·6%) of the study population were WHO anaemic or had a Hb < 13 g/dl, respectively. Transfusion was more common in anaemic vs. non‐anaemic patients 43 vs. 13%; (P < 0·001), and in patients with Hb < 13 g/dl vs. Hb > 13 g/dl 28 vs. 11% (P < 0·001). 154 (17·5%) of all patients had ID, and ID was the most common cause of anaemia with a prevalence of 41% in WHO anaemic patients and 33% in patients with Hb < 13 g/dl. A further 19 (20%) and 46 (19%) patients, respectively, had evidence of iron sequestration.

Conclusion

Anaemia is prevalent prior to THA and TKA with iron deficiency as the most common and reversible cause.
Frequency of an accessory popliteal efferent lymphatic pathway in dogs
Authors: Mayer Monique N. , Sweet Katherine A. , Patsikas Michael N. , Sukut Sally L. , Waldner Cheryl L.
Published: February 2018

Staging and therapeutic planning for dogs with malignant disease in the popliteal lymph node are based on the expected patterns of lymphatic drainage from the lymph node. The medial iliac lymph nodes are known to receive efferent lymph from the popliteal lymph node; however, an accessory popliteal efferent pathway with direct connection to the sacral lymph nodes has also been less frequently reported. The primary objective of this prospective, anatomic study was to describe the frequency of various patterns of lymphatic drainage of the popliteal lymph node. With informed client consent, 50 adult dogs with no known disease of the lymphatic system underwent computed tomographic lymphography after ultrasound‐guided, percutaneous injection of 350 mg/ml iohexol into a popliteal lymph node. In all 50 dogs, the popliteal lymph node drained directly to the ipsilateral medial iliac lymph node through multiple lymphatic vessels that coursed along the medial thigh. In 26% (13/50) of dogs, efferent vessels also drained from the popliteal lymph node directly to the internal iliac and/or sacral lymph nodes, coursing laterally through the gluteal region and passing over the dorsal aspect of the pelvis. Lymphatic connections between the right and left medial iliac and right and left internal iliac lymph nodes were found. Based on our findings, the internal iliac and sacral lymph nodes should be considered when staging or planning therapy for dogs with malignant disease in the popliteal lymph node.
Dynamic Flexoelectric Actuation and Vibration Control of Beams
Authors: Fan Mu , Deng Bolei , Tzou Hornsen
Published: February 2018

A flexoelectric cantilever beam actuated by the converse flexoelectric effect is evaluated and its analytical and experimental data are compared in this study. A line-electrode on the top beam surface and a bottom surface electrode are used to generate an electric field gradient in the beam, so that internal stresses can be induced and applied to distributed actuations. The dynamic control effectiveness of the beam is investigated with a mathematical model and is validated by laboratory experiments. Analyses show that the actuation stress induced by the converse flexoelectric effect is in the longitudinal direction and results in a bending control moment to the flexoelectric beam since the stress in the thickness is inhomogeneous. It is found that thinner line-electrode radius and thinner flexoelectric beam lead to larger control effects on the beam. The position of the line-electrode on the top surface of the beam also influences the control effect. When the line-electrode is close to the fixed end, it induces a larger tip displacement than that is close to the free end. Analytical results agree well with laboratory experimental data. This study of flexoelectric actuation and control provides a fundamental understanding of flexoelectric actuation mechanisms.
Extended Smooth Orthogonal Decomposition for Modal Analysis
Authors: Hu Zhi-Xiang , Huang Xiao , Wang Yixian , Wang Feiyu
Published: February 2018

The smooth orthogonal decomposition (SOD) is an output-only modal analysis method, which has simple structure and gives good results for undamped or lightly damped vibration systems. In the present study, the SOD method is extended to incorporate various measurements that contain the displacement, the velocity, the acceleration, and even the jerk (derivation of the acceleration). Several generalized eigenvalue problems (EVPs) are put forward considering different measurement combinations, and it is proved that all these EVPs can reduce to the eigenvalue problems of the undamped vibration system. These different methods are called extended smooth orthogonal decomposition (ESOD) methods in this paper. For the damped vibration system, the frequencies obtained by different ESOD methods are different from each other. Thus, a cost function is defined and a search algorithm is proposed to find the optimal frequency and damping ratio that can explain these differences. Although the search algorithm is derived for the single-degree-of-freedom (SDOF) vibration systems, it is effective for the multi-degrees-of-freedom (MDOF) vibration system after assuming that the smooth orthogonal coordinates (SOCs) computed by the ESOD methods are approximate to the modal coordinate responses. In order to verify the ESOD methods and the search algorithm, simulations are carried out and the results indicate that all ESOD methods reach correct results for undamped vibration systems and the search algorithm can give accurate frequency and damping ratio for damped systems. In addition, the effects of measurement noises are considered and the results show that the proposed method has anti-noise property to some extent.
Time reversal focusing of high amplitude sound in a reverberation chamber
Authors: Willardson Matthew L. , Anderson Brian E. , Young Sarah M. , Denison Michael H. , Patchett Brian D.
Published: February 2018

Time reversal (TR) is a signal processing technique that can be used for intentional sound focusing. While it has been studied in room acoustics, the application of TR to produce a high amplitude focus of sound in a room has not yet been explored. The purpose of this study is to create a virtual source of spherical waves with TR that are of sufficient intensity to study nonlinear acoustic propagation. A parameterization study of deconvolution, one-bit, clipping, and decay compensation TR methods is performed to optimize high amplitude focusing and temporal signal focus quality. Of all TR methods studied, clipping is shown to produce the highest amplitude focal signal. An experiment utilizing eight horn loudspeakers in a reverberation chamber is done with the clipping TR method. A peak focal amplitude of 9.05 kPa (173.1 dB peak re 20 μPa) is achieved. Results from this experiment indicate that this high amplitude focusing is a nonlinear process.
Low RMRratio as a Surrogate Marker for Energy Deficiency, the Choice of Predictive Equation Vital for Correctly Identifying Male and Female Ballet Dancers at Risk
Authors: Staal Sarah , Sjödin Anders , Fahrenholtz Ida , Bonnesen Karen , Melin Anna Katarina
Published: February 2018

Ballet dancers are reported to have an increased risk for energy deficiency with or without disordered eating behavior. A low ratio between measured (m) and predicted (p) resting metabolic rate (RMRratio < 0.90) is a recognized surrogate marker for energy deficiency. We aimed to evaluate the prevalence of suppressed RMR using different methods to calculate pRMR and to explore associations with additional markers of energy deficiency. Female (n = 20) and male (n = 20) professional ballet dancers, 19–35 years of age, were enrolled. mRMR was assessed by respiratory calorimetry (ventilated open hood). pRMR was determined using the Cunningham and Harris–Benedict equations, and different tissue compartments derived from whole-body dual-energy X-ray absorptiometry assessment. The protocol further included assessment of body composition and bone mineral density, blood pressure, disordered eating (Eating Disorder Inventory-3), and for females, the Low Energy Availability in Females Questionnaire. The prevalence of suppressed RMR was generally high but also clearly dependent on the method used to calculate pRMR, ranging from 25% to 80% in males and 35% to 100% in females. Five percent had low bone mineral density, whereas 10% had disordered eating and 25% had hypotension. Forty percent of females had elevated Low Energy Availability in Females Questionnaire score and 50% were underweight. Suppressed RMR was associated with elevated Low Energy Availability in Females Questionnaire score in females and with higher training volume in males. In conclusion, professional ballet dancers are at risk for energy deficiency. The number of identified dancers at risk varies greatly depending on the method used to predict RMR when using RMRratio as a marker for energy deficiency.
Incidence of Shoulder Injury in Elite Wheelchair Athletes Differ Between Sports: A Critically Appraised Topic
Authors: Fairbairn Jessica R. , Huxel Bliven Kellie C.
Published: February 2018

Clinical Scenario: Until recently, injury epidemiology data on elite Paralympic athletes were limited. Current data suggest high rates of shoulder injury in wheelchair athletes. Differences in shoulder injury rates between sports have not been reported in this population. Clinical Question: Is the incidence of shoulder injury in elite wheelchair athletes different between sports? Summary of Key Findings: Shoulder injury rates are high in elite wheelchair athletes, particularly in sports such as field events and fencing that require a stable base (eg, trunk, core control) from which to perform. Wheelchair racing requires repetitive motions that contribute to shoulder injuries, but rates are lower than field sports and fencing. Wheelchair curling and sledge hockey have low shoulder injury risk. Clinical Bottom Line: Shoulder injury rates vary based on sport in elite wheelchair athletes. In addition to incorporating shoulder complex specific rehabilitation for overuse shoulder injuries, clinicians should focus on core and trunk stabilization in elite wheelchair athletes competing in sports, such as field events and fencing. Strength of Recommendation: Grade C evidence exists that reports shoulder injury rates among elite wheelchair athletes differ based on sport participation.
Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity
Authors: Otta Dayane Andriotti , de Araújo Fernanda Fortes , de Rezende Vitor Bortolo , Souza-Fagundes Elaine Maria , Elói-Santos Silvana Maria , Costa-Silva Matheus Fernandes , Santos Raiany Araújo , Costa Heloísa Alves , Siqueira-Neto Jair Lage , Martins-Filho Olindo Assis , Teixeira-Carvalho Andréa
Published: February 2018

In seeking substitutions for the current Chagas disease treatment, which has several relevant side effects, new therapeutic candidates have been extensively investigated. In this context, a balanced interaction between mediators of the host immune response seems to be a key element for therapeutic success, as a proinflammatory microenvironment modulated by interleukin-10 (IL-10) is shown to be relevant to potentiate anti-
Trypanosoma cruzi
drug activity. This study aimed to identify the potential immunomodulatory activities of the anti-
T. cruzi
K777, pyronaridine (PYR), and furazolidone (FUR) compounds in peripheral blood mononuclear cells (PBMC) from noninfected (NI) subjects and chronic Chagas disease (CD) patients. Our results showed low cytotoxicity to PBMC populations, with 50% cytotoxic concentrations (CC
50
) of 71.0 μM (K777), 9.0 μM (PYR), and greater than 20 μM (FUR). In addition, K777 showed no impact on the exposure index (EI) of phytohemagglutinin-stimulated leukocytes (PHA), while PYR and FUR treatments induced increased EI of monocytes and T lymphocytes at late stages of apoptosis in NI subjects. Moreover, K777 induced a more prominent proinflammatory response (tumor necrosis factor alpha-positive [TNF-α
+
] CD8
+
/CD4
+
, gamma interferon-positive [IFN-γ
+
] CD4
+
/CD8
+
modulated by interleukin-10-positive [IL-10
+
] CD4
+
T/CD8
+
T) than did PYR (TNF-α
+
CD8
+
, IL-10
+
CD8
+
) and FUR (TNF-α
+
CD8
+
, IL-10
+
CD8
+
). Signature analysis of intracytoplasmic cytokines corroborated the proinflammatory/modulated (K777) and proinflammatory (PYR and FUR) profiles previously found. In conclusion, the lead compound K777 may induce beneficial changes in the immunological profile of patients presenting the chronic phase of Chagas disease and may contribute to a more effective therapy against the disease.
Time to Multidrug-Resistant Tuberculosis Treatment Initiation in Association with Treatment Outcomes in Shanghai, China
Authors: Chen Yong , Yuan Zhengan , Shen Xin , Wu Jie , Wu Zheyuan , Xu Biao
Published: February 2018

In high tuberculosis (TB)-burden countries such as China, the diagnosis of multidrug-resistant tuberculosis (MDR-TB) using conventional drug susceptibility testing (DST) takes months, making treatment delay inevitable. Poor outcomes of MDR-TB might be associated with delayed, even inappropriate, treatment. The purposes of this study were to investigate the time to MDR-TB treatment initiation and to assess the association between early treatment and treatment outcomes. Between April 2011 and December 2014, this population-based retrospective cohort study collected the demographic and clinical characteristics and the drug susceptibility profiles of all registered MDR-TB patients in Shanghai, China. The dates of TB and MDR-TB diagnoses, DST performance, and treatment initiation were extracted to calculate the times to treatment. In total, 284 of 346 MDR-TB patients were eligible for analysis, and 68.3% (194/284) had favored outcomes. The median time to treatment initiation from TB diagnosis was 172 days among those with favored outcomes and 190 days among those with poor outcomes. Treatments initiated within 60 days after performing DST (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.22 to 5.36) and empirical treatments (OR, 2.09; 95% CI, 1.01 to 4.32) were positively associated with favored outcomes. Substantial delays to MDR-TB treatment were observed when conventional DST was used. Early treatment predicted favored outcomes. Rapid diagnostic methods should be scaled up and improvements should be made in patient management and information linkage to reduce treatment delay.
Penetration of Cefotaxime into Cerebrospinal Fluid in Neonates and Young Infants
Authors: Chen Xing-Kai , Shi Hai-Yan , Leroux Stephanie , Xu Hai-Yan , Zhou Yue , Zheng Yi , Huang Xin , Li Yan , Jacqz-Aigrain Evelyne , Zhao Wei
Published: February 2018

Cefotaxime is the first-line treatment for meningitis in neonates and young infants. However, limited data on cefotaxime cerebrospinal fluid (CSF) concentrations in neonates and young infants were available. The aim of the present study was to evaluate the penetration of cefotaxime into CSF in neonates and young infants. Blood and CSF samples were collected from neonates and young infants treated with cefotaxime using an opportunistic pharmacokinetic sampling strategy, and concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The analysis was performed using NONMEM and R software. Thirty neonates and young infants (postmenstrual age range, 25.4 to 47.4 weeks) were included. A total of 67 plasma samples and 30 CSF samples were available for analysis. Cefotaxime plasma and CSF concentrations ranged from 2.30 to 175.42 mg/liter and from 0.39 to 25.38 mg/liter, respectively. The median ratio of the CSF concentration to the plasma concentration was 0.28 (range, 0.06 to 0.76). Monte Carlo simulation demonstrated that 88.4% and 63.9% of hypothetical neonates treated with 50 mg/kg of body weight three times a day (TID) would reach the pharmacodynamic target (the percentage of the dosing interval that the free antimicrobial drug concentration remains above the MIC, 70%) using the standard EUCAST MIC susceptibility breakpoints of 2 mg/liter and 4 mg/liter, respectively. The penetration of cefotaxime into the CSF of neonates and young infants was evaluated using an opportunistic sampling approach. A dosage regimen of 50 mg/kg TID could cover the most causative pathogens with MICs of <2 mg/liter. Individual dosage adaptation was required for more resistant bacterial strains, such as
Staphylococcus aureus
.
Polyporales Brown Rot Species Fomitopsis pinicola: Enzyme Activity Profiles, Oxalic Acid Production, and Fe
3+
-Reducing Metabolite Secretion
Authors: Shah Firoz , Mali Tuulia , Lundell Taina K.
Published: February 2018

Basidiomycota fungi in the order Polyporales are specified to decomposition of dead wood and woody debris and thereby are crucial players in the degradation of organic matter and cycling of carbon in the forest ecosystems. Polyporales wood-decaying species comprise both white rot and brown rot fungi, based on their mode of wood decay. While the white rot fungi are able to attack and decompose all the lignocellulose biopolymers, the brown rot species mainly cause the destruction of wood polysaccharides, with minor modification of the lignin units. The biochemical mechanism of brown rot decay of wood is still unclear and has been proposed to include a combination of nonenzymatic oxidation reactions and carbohydrate-active enzymes. Therefore, a linking approach is needed to dissect the fungal brown rot processes. We studied the brown rot Polyporales species
Fomitopsis pinicola
by following mycelial growth and enzyme activity patterns and generating metabolites together with Fenton-promoting Fe
3+
-reducing activity for 3 months in submerged cultures supplemented with spruce wood. Enzyme activities to degrade hemicellulose, cellulose, proteins, and chitin were produced by three Finnish isolates of
F. pinicola
. Substantial secretion of oxalic acid and a decrease in pH were notable. Aromatic compounds and metabolites were observed to accumulate in the fungal cultures, with some metabolites having Fe
3+
-reducing activity. Thus,
F. pinicola
demonstrates a pattern of strong mycelial growth leading to the active production of carbohydrate- and protein-active enzymes, together with the promotion of Fenton biochemistry. Our findings point to fungal species-level “fine-tuning” and variations in the biochemical reactions leading to the brown rot type of wood decay.

IMPORTANCE
Fomitopsis pinicola
is a common fungal species in boreal and temperate forests in the Northern Hemisphere encountered as a wood-colonizing saprotroph and tree pathogen, causing a severe brown rot type of wood degradation. However, its lignocellulose-decomposing mechanisms have remained undiscovered. Our approach was to explore both the enzymatic activities and nonenzymatic Fenton reaction-promoting activities (Fe
3+
reduction and metabolite production) by cultivating three isolates of
F. pinicola
in wood-supplemented cultures. Our findings on the simultaneous production of versatile enzyme activities, including those of endoglucanase, xylanase, β-glucosidase, chitinase, and acid peptidase, together with generation of low pH, accumulation of oxalic acid, and Fe
3+
-reducing metabolites, increase the variations of fungal brown rot decay mechanisms. Furthermore, these findings will aid us in revealing the wood decay proteomic, transcriptomic, and metabolic activities of this ecologically important forest fungal species.
Stress Response Protein BolA Influences Fitness and Promotes Salmonella enterica Serovar Typhimurium Virulence
Authors: Mil-Homens Dalila , Barahona Susana , Moreira Ricardo N. , Silva Inês J. , Pinto Sandra N. , Fialho Arsénio M. , Arraiano Cecília M.
Published: February 2018

The intracellular pathogen
Salmonella enterica
serovar Typhimurium has emerged as a major cause of foodborne illness, representing a severe clinical and economic concern worldwide. The capacity of this pathogen to efficiently infect and survive inside the host depends on its ability to synchronize a complex network of virulence mechanisms. Therefore, the identification of new virulence determinants has become of paramount importance in the search of new targets for drug development. BolA-like proteins are widely conserved in all kingdoms of life. In
Escherichia coli
, this transcription factor has a critical regulatory role in several mechanisms that are tightly related to bacterial virulence. Therefore, in the present work we used the well-established infection model
Galleria mellonella
to evaluate the role of BolA protein in
S
. Typhimurium virulence. We have shown that BolA is an important player in
S
. Typhimurium pathogenesis. Specifically, the absence of BolA leads to a defective virulence capacity that is most likely related to the remarkable effect of this protein on
S
. Typhimurium evasion of the cellular response. Furthermore, it was demonstrated that BolA has a critical role in bacterial survival under harsh conditions since BolA conferred protection against acidic and oxidative stress. Hence, we provide evidence that BolA is a determining factor in the ability of
Salmonella
to survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence.

IMPORTANCE
BolA has been described as an important protein for survival in the late stages of bacterial growth and under harsh environmental conditions. High levels of BolA in stationary phase and under stresses have been connected with a plethora of phenotypes, strongly suggesting its important role as a master regulator. Here, we show that BolA is a determining factor in the ability of
Salmonella
to survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence. This work constitutes a relevant step toward an understanding of the role of BolA protein and may have an important impact on future studies in other organisms. Therefore, this study is of utmost importance for understanding the genetic and molecular bases involved in the regulation of
Salmonella
virulence and may contribute to future industrial and public health care applications.
An N-Terminal Retention Module Anchors the Giant Adhesin LapA of Pseudomonas fluorescens at the Cell Surface: a Novel Subfamily of Type I Secretion Systems
Authors: Smith T. Jarrod , Font Maria E. , Kelly Carolyn M. , Sondermann Holger , O'Toole George A.
Published: February 2018

LapA of
Pseudomonas fluorescens
Pf0-1 belongs to a diverse family of cell surface-associated bacterial adhesins that are secreted via the type I secretion system (T1SS). We previously reported that the periplasmic protease LapG cleaves the N terminus of LapA at a canonical dialanine motif to release the adhesin from the cell surface under conditions unfavorable to biofilm formation, thus decreasing biofilm formation. Here, we characterize LapA as the first type I secreted substrate that does not follow the “one-step” rule of T1SS. Rather, a novel N-terminal element, called the retention module (RM), localizes LapA at the cell surface as a secretion intermediate. Our genetic, biochemical, and molecular modeling analyses support a model wherein LapA is tethered to the cell surface through its T1SS outer membrane TolC-like pore, LapE, until LapG cleaves LapA in the periplasm. We further demonstrate that this unusual retention strategy is likely conserved among LapA-like proteins, and it reveals a new subclass of T1SS ABC transporters involved in transporting this group of surface-associated LapA-like adhesins. These studies demonstrate a novel cell surface retention strategy used throughout the
Proteobacteria
and highlight a previously unappreciated flexibility of function for T1SS.

IMPORTANCE
Bacteria have evolved multiple secretion strategies to interact with their environment. For many bacteria, the secretion of cell surface-associated adhesins is key for initiating contact with a preferred substratum to facilitate biofilm formation. Our work demonstrates that
P. fluorescens
uses a previously unrecognized secretion strategy to retain the giant adhesin LapA at its cell surface. Further, we identify likely LapA-like adhesins in various pathogenic and commensal proteobacteria and provide phylogenetic evidence that these adhesins are secreted by a new subclass of T1SS ABC transporters.
Validation of the Pockit Dengue Virus Reagent Set for Rapid Detection of Dengue Virus in Human Serum on a Field-Deployable PCR System
Authors: Tsai Jih-Jin , Liu Li-Teh , Lin Ping-Chang , Tsai Ching-Yi , Chou Pin-Hsing , Tsai Yun-Long , Chang Hsiao-Fen Grace , Lee Pei-Yu Alison
Published: February 2018

Dengue virus (DENV) infection, a mosquito-borne disease, is a major public health problem in tropical countries. Point-of-care DENV detection with good sensitivity and specificity enables timely early diagnosis of DENV infection, facilitating effective disease management and control, particularly in regions of low resources. The Pockit dengue virus reagent set (GeneReach Biotech), a reverse transcription insulated isothermal PCR (RT-iiPCR), is available to detect all four serotypes of DENV on the field-deployable Pockit system, which is ready for on-site applications. In this study, analytical and clinical performances of the assay were evaluated. The index assay did not react with 14 non-DENV human viruses, indicating good specificity. Compared to the U.S. CDC DENV-1–4 real-time quantitative RT-PCR (qRT-PCR) assay, testing with serial dilutions of virus-spiked human sera demonstrated that the index assay had detection endpoints that were separately comparable with the 4 serotypes. Excellent reproducibility was observed among repeat tests done by six operators at three sites. In clinical performance, 195 clinical sera collected around Kaohsiung city in 2012 and 21 DENV-4-spiked sera were tested with the RT-iiPCR and qRT-PCR assays in parallel. The 121 (11 DENV-1, 78 DENV-2, 11 DENV-3, and 21 DENV-4) qRT-PCR-positive and 95 qRT-PCR-negative samples were all positive and negative by the RT-iiPCR reagent results, respectively, demonstrating high (100%) interrater agreement (95% confidence interval [CI95%], ∼98.81% to 100%; κ = 1). With analytical and clinical performance equivalent to those of the reference qRT-PCR assay, the index PCR assay on the field-deployable system can serve as a highly sensitive and specific on-site tool for DENV detection.
The Slow March toward Rapid Phenotypic Antimicrobial Susceptibility Testing: Are We There Yet?
Authors: Doern Christopher D.
Published: February 2018

Antimicrobial susceptibility testing (AST) provides critical information for the management of patients with infections. The gold standard methods for assessing organism susceptibility are still based on growth and require incubation over relatively long periods of time. Until now, little progress has been made in developing rapid, growth-based, phenotypic AST systems. This commentary puts the recently FDA-cleared Accelerate PhenoTest (P. Pancholi et al., J Clin Microbiol 56:e01329-17, 2018,
https://doi.org/10.1128/JCM.01329-17
) in context by providing a historical perspective on attempts to accelerate phenotypic susceptibility results. In addition, some promising new innovations that promise to shorten the turnaround time for phenotypic AST will be briefly reviewed.
The Ontogeny of a Neutrophil: Mechanisms of Granulopoiesis and Homeostasis
Authors: Lawrence Shelley M. , Corriden Ross , Nizet Victor
Published: February 2018

Comprising the majority of leukocytes in humans, neutrophils are the first immune cells to respond to inflammatory or infectious etiologies and are crucial participants in the proper functioning of both innate and adaptive immune responses. From their initial appearance in the liver, thymus, and spleen at around the eighth week of human gestation to their generation in large numbers in the bone marrow at the end of term gestation, the differentiation of the pluripotent hematopoietic stem cell into a mature, segmented neutrophil is a highly controlled process where the transcriptional regulators C/EBP-α and C/EBP-ε play a vital role. Recent advances in neutrophil biology have clarified the life cycle of these cells and revealed striking differences between neonatal and adult neutrophils based on fetal maturation and environmental factors. Here we detail neutrophil ontogeny, granulopoiesis, and neutrophil homeostasis and highlight important differences between neonatal and adult neutrophil populations.
Children and young people’s versus parents’ responses in an English national inpatient survey
Authors: Hargreaves Dougal S , Sizmur Steve , Pitchforth Jacqueline , Tallett Amy , Toomey Sara L , Hopwood Bridget , Schuster Mark A , Viner Russell M
Published: February 2018

Objective

Despite growing interest in children and young people’s (CYP) perspectives on healthcare, they continue to be excluded from many patient experience surveys. This study investigated the feasibility of, and additional information gained by, measuring CYP experiences of a recent hospital admission.

Design

Cross-sectional analysis of national survey data.

Setting

Inpatients aged 8–15 years in eligible National Health Service hospitals, July–September 2014.

Participants

6204 parents/carers completed the parent section of the survey. The CYP section of the survey was completed by CYP themselves (n=3592), parents (n=849) or jointly (n=1763).

Main outcome measures

Pain relief, involvement, quality of staff communication, perceived safety, ward environment, overall experience.

Analyses

Single-measures intraclass correlations (ICCs) were used to assess the concordance between CYP and parent responses about the same inpatient episode. Multilevel logistic regression models, adjusted for individual characteristics, were used to compare the odds of positive responses when the CYP section of the survey was completed by parents, by CYP themselves or jointly.

Results

The CYP section of the survey was completed independently by 57.8% of CYP. Agreement between CYP and parent responses was reasonably good for pain relief (ICC=0.61 (95% CI 0.58 to 0.63)) and overall experience (ICC=0.70 (95% CI 0.68 to 0.72)), but much lower for questions comparing professionals’ communication with CYP and with their parents (ICC range=0.28 (95% CI 0.24 to 0.32) to 0.51 (95% CI 0.47 to 0.54)). In the regression models, CYP were significantly less likely than parents to report feeling safe (adjusted OR (AOR)=0.54 (95% CI 0.38 to 0.76)), involvement in decisions (AOR=0.66 (95% CI 0.46 to 0.94)) or adequate privacy (AOR=0.68 (95% CI 0.52 to 0.89)).

Conclusions

Including CYP (8–15 years) in patient experience surveys is feasible and enhances what is known from parents’ responses.
Antibiotics for uncomplicated skin abscesses: systematic review and network meta-analysis
Authors: Wang Wen , Chen Wenwen , Liu Yanmei , Siemieniuk Reed Alexander C , Li Ling , Martínez Juan Pablo Díaz , Guyatt Gordon H , Sun Xin
Published: February 2018

Objective

To assess the impact of adjunctive antibiotic therapy on uncomplicated skin abscesses.

Design

Systematic review and network meta-analysis.

Data sources

Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov.

Study selection

A BMJ Rapid Recommendation panel provided input on design, important outcomes and the interpretation of the results. Eligible randomised controlled trials (RCTs) included a comparison of antibiotics against no antibiotics or a comparison of different antibiotics in patients with uncomplicated skin abscesses, and reported outcomes prespecified by the linked guideline panel.

Review methods

Reviewers independently screened abstracts and full texts for eligibility, assessed risk of bias and extracted data. We performed random-effects meta-analyses that compared antibiotics with no antibiotics, along with a limited number of prespecified subgroup hypotheses. We also performed network meta-analysis with a Bayesian framework to compare effects of different antibiotics. Quality of evidence was assessed with The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results

Fourteen RCTs including 4198 patients proved eligible. Compared with no antibiotics, antibiotics probably lower the risk of treatment failure (OR 0.58, 95% CI 0.37 to 0.90; low quality), recurrence within 1 month (OR 0.48, 95% CI 0.30 to 0.77; moderate quality), hospitalisation (OR 0.55, 95% CI 0.32 to 0.94; moderate quality) and late recurrence (OR 0.64, 95% CI 0.48 to 0.85; moderate quality). However, relative to no use, antibiotics probably increase the risk of gastrointestinal side effects (trimethoprim and sulfamethoxazole (TMP-SMX): OR 1.28, 95% CI 1.04 to 1.58; moderate quality; clindamycin: OR 2.29, 95% CI 1.35 to 3.88; high quality) and diarrhoea (clindamycin: OR 2.71, 95% CI 1.50 to 4.89; high quality). Cephalosporins did not reduce the risk of treatment failure compared with placebo (moderate quality).

Conclusions

In patients with uncomplicated skin abscesses, moderate-to-high quality evidence suggests TMP-SMX or clindamycin confer a modest benefit for several important outcomes, but this is offset by a similar risk of adverse effects. Clindamycin has a substantially higher risk of diarrhoea than TMP-SMX. Cephalosporins are probably not effective.
Physical activity and trajectories in cognitive function: English Longitudinal Study of Ageing
Authors: Hamer Mark , Muniz Terrera Graciela , Demakakos Panayotes
Published: February 2018

Background

There are limited data on physical activity in relation to trajectories in cognitive function. The aim was to examine the association of physical activity with trajectories in cognitive function, measured from repeated assessments over 10 years.

Methods

We conducted a 10-year follow-up of 10 652 (aged 65±10.1 years) men and women from the English Longitudinal Study of Ageing, a cohort of community dwelling older adults. Self-reported physical activity was assessed at baseline and neuropsychological tests of memory and executive function were administered at regular 2-year intervals. Data from six repeated measurements of memory over 10 years and five repeated measurements of executive function over 8 years were used.

Results

The multivariable models revealed relatively small baseline differences in cognitive function by physical activity status in both men and women. Over the 10-year follow-up, physically inactive women experienced a greater decline in their memory (−0.20 recalled words, 95% CI −0.29 to −0.11, per study wave) and in executive function ability (−0.33 named animals; −0.54 to −0.13, per study wave) in comparison with the vigorously active reference group. In men, there were no differences in memory (−0.08 recalled words, 95% CI −0.18 to 0.01, per study wave), but small differences in executive function (−0.23 named animals; −0.46 to −0.01, per study wave) between inactive and vigorously active.

Conclusion

Physical activity was associated with preservation of memory and executive function over 10 years follow-up. The results were, however, more pronounced in women.
Contribution of spinal 5-HT5A receptors to the antinociceptive effects of systemically administered cannabinoid agonist WIN 55,212-2 and morphine
Authors: Aksu Ahmet Goktan , Gunduz Ozgur , Ulugol Ahmet
Published: February 2018

The antinociceptive effects of cannabinoids and opioids have been known for centuries. Serotonin and its receptors are also known to play important roles in nociception. However, the contribution of spinal 5-HT5A receptors in antinociceptive effects of cannabinoids and opioids has not been studied. We conducted this study to clarify spinal mechanisms of the actions of the antinociceptive effects of cannabinoids and opioids. Hot plate and tail flick tests were used to assess the antinociceptive activity in Balb/c mice. WIN 55,212-2, a nonselective CB1 and CB2 agonist, and morphine exerted significant antinociceptive effects at 1, 3, and 10 mg/kg doses administered intraperitoneally in both hot plate and tail flick tests. The selective 5-HT5A receptor antagonist SB-699551 (10 nmol/mouse) was administered intrathecally 10 min before the agonists. SB-699551 significantly reduced the antinociceptive effect of both WIN 55,212-2 and morphine. In the rotarod test, WIN 55,212-2 disrupted the motor coordination at a dose of 10 mg/kg, while morphine did not affect this function at any dose. Our findings show that spinal 5-HT5A receptors are involved in the antinociceptive effects of WIN 55,212-2 and morphine.
Coagonist of glucagon-like peptide-1 and glucagon receptors ameliorates nonalcoholic fatty liver disease
Authors: Patel Vishal , Joharapurkar Amit , Kshirsagar Samadhan , Patel Maulik , Sutariya Brijesh , Patel Hiren , Pandey Dheerendra , Patel Dipam , Ranvir Ramchandra , Kadam Shekhar , Bahekar Rajesh , Jain Mukul
Published: February 2018

Nonalcoholic fatty liver disease (NAFLD) is often associated with obesity and type 2 diabetes. Coagonists of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) are under clinical investigation for the treatment of obesity and type 2 diabetes. In this study, we have demonstrated the effect of a balanced coagonist in the treatment of NAFLD using mouse models. GLP-1R agonist exendin-4, glucagon, and coagonist (Aib2 C24 chimera2) were administered to C57BL6/J mice, in which NAFLD was induced by carbon tetrachloride (CCl4) treatment after high-fat diet (HFD) feeding, and choline-deficient, L-amino-acid-defined HFD (CDAHFD) feeding. Repeated dose administration of coagonist significantly attenuated liver inflammation and steatosis induced by acute and long-term treatment with CCl4 in HFD-fed mice. Coagonist markedly attenuated the CDAHFD-induced expression of TIMP-1, MMP-9, TNF-α, MCP-1, COL1A1, and α-SMA. It also inhibited progression of hepatic steatosis and fibrosis in mice. Exendin-4 was better than glucagon, but coagonist was most effective in reduction of hepatic inflammation as well as steatosis. Coagonist of GLP-1R and GCGR improved NAFLD in C57BL6/J mice. This effect is mediated by reduction in lipotoxicity and inflammation in liver.
A Median Nerve Anterior Transposition Procedure for Multi-Recurrent Hemodialysis-Related Carpal Tunnel Syndrome
Authors: Okutsu Ichiro , Hamanaka Ikki , Yoshida Aya
Published: February 2018

Background: Some long-term hemodialysis patients suffer from multi-recurrent carpal tunnel syndrome because amyloid originating from β2-microglobulin continues to be deposited mainly in the flexor tendons, tendon sheaths and flexor retinaculum during maintenance hemodialysis. These amyloid deposits inside carpal canal (tunnel) tissues increase carpal canal pressure and this leads to compression of the median nerve. When multi-recurrent carpal tunnel syndrome occurs, previous operative scarring of soft tissue may prohibit further enlargement of the carpal canal even if any carpal canal decompression procedure is used. For this reason, we developed a median nerve anterior transposition procedure, as a new approach in the treatment of multi-recurrent hemodialysis-related carpal tunnel syndrome.

Methods: Median nerve anterior transposition procedures were performed on seven hands in six patients with multi-recurrent carpal tunnel syndrome. The mean age of the patients was 68.3 years and the mean hemodialysis duration was 35.3 years. Mean follow-up period was 9.9 months. The median nerve is transposed from inside to outside of the carpal canal under local and infiltration anesthesia without a pneumatic tourniquet on an outpatient basis. This procedure is based on the same principles applied in ulnar nerve anterior transposition procedures for cubital tunnel syndrome.

Results: Main preoperative patient complaints were intolerable tingling and/or pain in the diseased hands throughout the day. Following the surgeries, preoperative clinical symptoms began to subside and eventually improved in all hands. Postoperative abductor pollicis brevis muscle power using manual muscle testing improved except in one hand. Abnormal preoperative distal motor and sensory latency were improved except in two hands following the surgeries.

Conclusions: The median nerve anterior transposition procedure is a beneficial treatment for patients suffering from hemodialysis-related multi-recurrent carpal tunnel syndrome.
Architectural Principles for Cloud Software
Authors: Pahl Claus , Jamshidi Pooyan , Zimmermann Olaf
Published: February 2018

A cloud is a distributed Internet-based software system providing resources as tiered services. Through service-orientation and virtualization for resource provisioning, cloud applications can be deployed and managed dynamically. We discuss the building blocks of an architectural style for cloud-based software systems. We capture style-defining architectural principles and patterns for control-theoretic, model-based architectures for cloud software. While service orientation is agreed on in the form of service-oriented architecture and microservices, challenges resulting from multi-tiered, distributed and heterogeneous cloud architectures cause uncertainty that has not been sufficiently addressed. We define principles and patterns needed for effective development and operation of adaptive cloud-native systems.
Fuzzy Clustering of Crowdsourced Test Reports for Apps
Authors: Jiang He , Chen Xin , He Tieke , Chen Zhenyu , Li Xiaochen
Published: February 2018

DevOps is a new approach to drive a seamless Application (App) cycle from development to delivery. As a critical part to promote the successful implementation of DevOps, testing can significantly improve team productivity and reliably deliver user experience. However, it is difficult to use traditional testing to cover diverse mobile phones, network environments, operating systems, and so on. Hence, many large companies crowdsource their App testing tasks to workers from open platforms. In crowdsourced testing, test reports submitted by workers may be highly redundant, and their quality may vary sharply. Meanwhile, multi-bug test reports may be submitted, and their root causes are hard to diagnose. Hence, it is a time-consuming and tedious task for developers to manually inspect these test reports. To help developers address the above challenges, we issue the new problem of Fuzzy Clustering Test Reports (FULTER). Aiming to resolve FULTER, a series of barriers need to be overcome. In this study, we propose a new framework named Test Report Fuzzy Clustering Framework (TERFUR) by aggregating redundant and multi-bug test reports into clusters to reduce the number of inspected test reports. First, we construct a filter to remove invalid test reports to break through the
invalid barrier
. Then, a preprocessor is built to enhance the descriptions of short test reports to break through the
uneven barrier
. Last, a two-phase merging algorithm is proposed to partition redundant and multi-bug test reports into clusters that can break through the
multi-bug barrier
. Experimental results over 1,728 test reports from five industrial Apps show that TERFUR can cluster test reports by up to 78.15% in terms of
AverageP
, 78.41% in terms of
AverageR
, and 75.82% in terms of
AverageF1
and outperform comparative methods by up to 31.69%, 33.06%, and 24.55%, respectively. In addition, the effectiveness of TERFUR is validated in prioritizing test reports for manual inspection.