bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroepidemiology and molecular characterization of hepatitis E virus infection in swine and occupationally exposed workers in Punjab, India
Authors: Bansal M. , Kaur S. , Deka D. , Singh R. , Gill J. P. S.
Published: April 2017

Hepatitis E virus (HEV) has two discrete epidemiological patterns: waterborne epidemics in developing countries only, caused by HEV genotype I, and sporadic zoonotic outbreaks in developing and developed countries caused by genotypes III and IV. This study was designed to investigate seroprevalence, molecular detection and the characterization of HEV by nested RT‐PCR in swine as well as the occupational risk to exposed human population in Punjab state of north‐western India. The occupational risk‐exposed group comprised of swine farmers (organized – mixed feed feeders and unorganized – swill feeders), slaughterhouse workers, sewage workers and veterinary internes. During the study period, blood and faecal samples were collected from 320 swine and 360 humans with both high and low occupational exposure risks. The overall seroprevalence of swine HEV was 65.00%, with a significantly higher seropositivity in growing pigs (2–8 months of age). The prevalence of HEV RNA in swine faecal samples by nRT‐PCR was 8.75% with a significantly higher detection in swill‐fed pigs. With humans in the high occupational exposure risk population, significantly higher anti‐HEV IgG seropositivity was observed (60.48%) as compared to control population (10.71%). Strong evidence of association between human anti‐HEV IgG seropositivity and certain occupational exposure risk groups was observed (p < 0.05). This indicates that unorganized swine farmers, slaughterhouse workers and sewage workers have higher odds of HEV infection in this study region. Percentage of nucleotide similarity between swine and human HEV isolates was less than that found in countries with zoonotic HEV outbreaks. Molecular characterization revealed the circulation of G IV and G I genotypes among swine and human population in Punjab state, respectively.
Some Sports Managers’ Views about Values Education through Sports
Authors: Balci Velittin , Erdeveciler Övünç
Published: April 2017

The indirect aim of this study is to ensure that sports and participation in sports are seen as new tools for values education. From this indirect goal, it was aimed to analyse the views of some Amateur Sports Club managers and supporters who were supposed to directly contribute to sports and the athletes about values education. The study was planned based on qualitative interview technique. In thematic framework of education values, questions were prepared in the form of semi-structured questionnaire appropriate for qualitative interview technique, and participants in the study were asked to answer these questions voluntarily. The working group formed a total of 41 people consisting of the presidents and vice-chairmen of some Amateur Sports Clubs operating in Ankara. In the findings of interviews made with the mentioned method; it has been observed that managers have prominent values such as ‘prestige’, ’tolerance’, ‘communication’, ‘love’, ‘sharing’, ‘diligence’, ‘health’, and ‘growing healthy people’. However, in the process of transferring these values to the people they work with, the managers who participated in the study came to the conclusion that their own awareness did not occur sufficiently.As a result, it can be said that there is no single meaning of personal awareness about values education, and some methods and paradigms have to be passed on concerning these universal values’ transfer to co-workers. Perhaps getting out of the ordinary for sports managers is like self-renew and likely to change the order of priorities.
Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS‐55) on adiposity and hepatic lipid composition in rat offspring
Authors: Toop Carla R. , Muhlhausler Beverly S. , O'Dea Kerin , Gentili Sheridan
Published: April 2017

Key points

Fructose‐containing sugars, including sucrose and high fructose corn syrup (HFCS), have been implicated in the epidemics of obesity and type 2 diabetes.

Few studies have evaluated the impact of perinatal exposure to these sugars on metabolic and physiological outcomes in the offspring.

Using a rat model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal and/or suckling periods were found to have altered adiposity and liver fat content and composition at weaning.

Plasma levels of free fatty acids remained elevated in young adulthood, but consumption of a control diet following weaning appeared to ameliorate most other effects of perinatal exposure to a maternal high‐sugar diet.

Guidelines for maternal nutrition should advise limiting consumption of fructose‐containing sugars, and it is particularly important that these recommendations include maternal nutrition during lactation.

Perinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10% (w/v) beverage containing sucrose or high fructose corn syrup‐55 (HFCS‐55) during the prenatal and/or suckling periods on offspring at 3 and 12 weeks, utilising a cross‐fostering approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose concentrations in offspring at 3 weeks, but did not alter glucose tolerance. Increased adiposity was observed in 3‐week‐old offspring exposed to sucrose or HFCS‐55 during suckling, with increased hepatic fat content in HFCS‐55‐exposed offspring. In terms of specific fatty acids, hepatic monounsaturated (omega‐7 and ‐9) fatty acid content was elevated at weaning, and was most pronounced in sucrose offspring exposed during both the prenatal and suckling periods, and HFCS‐55 offspring exposed during suckling only. By 12 weeks, the effects on adiposity and hepatic lipid composition were largely normalised. However, exposure to either sucrose or HFCS‐55 during the prenatal period only was associated with elevated plasma free fatty acids at weaning, and this effect persisted until 12 weeks. This study suggests that the type of sugar and the timing of exposure (prenatal or suckling periods) are both important for determining the impact on metabolic health outcomes in the offspring.
Characterization and Design of Functional Quasi-Random Nanostructured Materials Using Spectral Density Function
Authors: Yu Shuangcheng , Zhang Yichi , Wang Chen , Lee Won-kyu , Dong Biqin , Odom Teri W. , Sun Cheng , Chen Wei
Published: April 2017

Quasi-random nanostructures are playing an increasingly important role in developing advanced material systems with various functionalities. Current development of functional quasi-random nanostructured material systems (NMSs) mainly follows a sequential strategy without considering the fabrication conditions in nanostructure optimization, which limits the feasibility of the optimized design for large-scale, parallel nanomanufacturing using bottom-up processes. We propose a novel design methodology for designing isotropic quasi-random NMSs that employs spectral density function (SDF) to concurrently optimize the nanostructure and design the corresponding nanomanufacturing conditions of a bottom-up process. Alternative to the well-known correlation functions for characterizing the structural correlation of NMSs, the SDF provides a convenient and informative design representation that maps processing–structure relation to enable fast explorations of optimal fabricable nanostructures and to exploit the stochastic nature of manufacturing processes. In this paper, we first introduce the SDF as a nondeterministic design representation for quasi-random NMSs, as an alternative to the two-point correlation function. Efficient reconstruction methods for quasi-random NMSs are developed for handling different morphologies, such as the channel-type and particle-type, in simulation-based microstructural design. The SDF-based computational design methodology is illustrated by the optimization of quasi-random light-trapping nanostructures in thin-film solar cells for both channel-type and particle-type NMSs. Finally, the concurrent design strategy is employed to optimize the quasi-random light-trapping structure manufactured via scalable wrinkle nanolithography process.
Automatic Enumeration of Feasible Kinematic Diagrams for Split Hybrid Configurations With a Single Planetary Gear
Authors: Barhoumi Toumadher , Kum Dongsuk
Published: April 2017

Most of the prior studies on power-split hybrid electric vehicle's (PS-HEV) design focused on the powertrain configuration optimization. Yet, depicting the selected configuration is highly required for further design steps, ultimately manufacturing. This paper proposes an automatic approach to generate all the feasible kinematic diagrams for a given configuration with a single planetary gear (PG) set. While the powertrain configuration, which is the output of prior studies, illustrates the connection of the powertrain components to the PG, the kinematic diagram is a schematic diagram depicting the connections and arrangements of the components. First, positioning diagrams, specifying the position of the components with respect to each other and to the PG, are used to find all the possible arrangements. Then, given that the positioning diagrams have a one-to-one relationship with the kinematic diagrams, the feasible kinematic diagrams are identified using a set of feasibility rules applicable to the positioning diagrams. Finally, few guidelines are introduced to select good kinematic diagrams that best suit the overall vehicle design. Various configurations were investigated, and three of them including Prius and Voltec first-generation single PG configurations are discussed. The study reveals that the kinematic diagrams that have been patented are only a subset of all the feasible kinematic diagrams, and that even some good kinematic diagrams with better manufacturability are identified using this methodology. Thus, this methodology guarantees the search of the entire design space and the selection of kinematic diagrams that best suit the desired vehicle.
Claim of very early humans in Americas shocks researchers
Authors: Wade Lizzie
Published: April 2017

Skepticism greets report of smashed mastodon bones.
The vaccine wars
Authors: Wadman Meredith , You Jia
Published: April 2017

Debunking myths, owning real risks, and courting doubters.
Bridges, not walls?
Authors: Jarvis Michaela
Published: April 2017

AAAS Science Diplomacy event reveals complexity of U.S.-Mexico border issues
Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly
Authors: Mountoufaris George , Chen Weisheng V. , Hirabayashi Yusuke , O’Keeffe Sean , Chevee Maxime , Nwakeze Chiamaka L. , Polleux Franck , Maniatis Tom
Published: April 2017

Pattern formation in the brain

Neurons in the developing brain cooperate to build circuits. Mountoufaris
et al.
found that ∼50 variable protocadherin genes support a combinatorial identity code that allows millions of olfactory neuron axons to sort into ∼2000 glomeruli. Sharing olfactory receptors drives axons to one glomerulus, and protocadherin diversity allows the multiple axons to touch each other as they converge. On the other hand, Chen
et al.
found that a single C-type protocadherin underlies the tiled distribution of serotonergic neurons throughout the central nervous system. These neurons, which share protocadherin identity, enervate broad swaths evenly without touching neighboring neurons.

Science
, this issue p.
411
, p.
406
Rechargeable nickel–3D zinc batteries: An energy-dense, safer alternative to lithium-ion
Authors: Parker Joseph F. , Chervin Christopher N. , Pala Irina R. , Machler Meinrad , Burz Michael F. , Long Jeffrey W. , Rolison Debra R.
Published: April 2017

Zinc can compete with lithium

Although lithium-based batteries are ubiquitous, there are still challenges related to their longevity and safety, as well as concerns about material availability. Aqueous rechargeable batteries based on zinc might provide an alternative, but they have been plagued by the formation of dendrites during cycling. Parker
et al.
show that when zinc is formed into three-dimensional sponges, it can be used with nickel to form primary batteries that allow for deep discharge. Alternatively, the sponges can be used to produce secondary batteries that can be cycled thousands of times and can compete with lithium ion cells.

Science
, this issue p.
415
Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network
Authors: McConnell Michael J. , Moran John V. , Abyzov Alexej , Akbarian Schahram , Bae Taejeong , Cortes-Ciriano Isidro , Erwin Jennifer A. , Fasching Liana , Flasch Diane A. , Freed Donald , Ganz Javier , Jaffe Andrew E. , Kwan Kenneth Y. , Kwon Minseok , Lodato Michael A. , Mills Ryan E. , Paquola Apua C. M. , Rodin Rachel E. , Rosenbluh Chaggai , Sestan Nenad , Sherman Maxwell A. , Shin Joo Heon , Song Saera , Straub Richard E. , Thorpe Jeremy , Weinberger Daniel R. , Urban Alexander E. , Zhou Bo , Gage Fred H. , Lehner Thomas , Senthil Geetha , Walsh Christopher A. , Chess Andrew , Courchesne Eric , Gleeson Joseph G. , Kidd Jeffrey M. , Park Peter J. , Pevsner Jonathan , Vaccarino Flora M. ,   Brain Somatic Mosaicism Network, Barton Alison R. , Bekiranov Stefan , Bohrson Craig L. , Burbulis Ian E. , Chronister William , Coppola Gianfilippo , Daily Kenneth , D’Gama Alissa M. , Emery Sarah B. , Frisbie Trenton J. , Gao Tianliuyun , Gulyás-Kovács Attila , Haakenson Mark , Keil Jason M. , Kopera Huira C. , Lam Mandy M. , Lee Eunjung Alice , Marques-Bonet Tomas , Mathern Gary W. , Moldovan John B. , Oetjens Matthew T. , Omberg Larsson , Peters Mette A. , Pochareddy Sirisha , Pramparo Tiziano , Ratan Aakrosh , Sanavia Tiziana , Shi Lei , Skarica Mario , Wang Jia , Wang Meiyan , Wang Yifan , Wierman Margaret , Wolpert Matthew , Woodworth Mollie , Zhao Xuefang , Zhou Weichen
Published: April 2017

Single-cell diversity in the brain

The cells that make up an organism may all start from one genome, but somatic mutations mean that somewhere along the line of development, an organism's individual cellular genomes diverge. McConnell
et al.
review the implications and causes of single-cell genomic diversity for brain function. Somatic mutations caused by mobile genetic elements or errors in DNA repair may underlie certain neuropsychiatric disorders.

Science
, this issue p.
eaal1641
Pcdhαc2 is required for axonal tiling and assembly of serotonergic circuitries in mice
Authors: Chen Weisheng V. , Nwakeze Chiamaka L. , Denny Christine A. , O’Keeffe Sean , Rieger Michael A. , Mountoufaris George , Kirner Amy , Dougherty Joseph D. , Hen René , Wu Qiang , Maniatis Tom
Published: April 2017

Pattern formation in the brain

Neurons in the developing brain cooperate to build circuits. Mountoufaris
et al.
found that ∼50 variable protocadherin genes support a combinatorial identity code that allows millions of olfactory neuron axons to sort into ∼2000 glomeruli. Sharing olfactory receptors drives axons to one glomerulus, and protocadherin diversity allows the multiple axons to touch each other as they converge. On the other hand, Chen
et al.
found that a single C-type protocadherin underlies the tiled distribution of serotonergic neurons throughout the central nervous system. These neurons, which share protocadherin identity, enervate broad swaths evenly without touching neighboring neurons.

Science
, this issue p.
411
, p.
406
Toward site-specific and self-sufficient robotic fabrication on architectural scales
Authors: Keating Steven J. , Leland Julian C. , Cai Levi , Oxman Neri
Published: April 2017

An on-site mobile robotic platform autonomously constructed an open dome with complex curvature and variable wall thickness.
Pyrazinoic Acid Inhibits a Bifunctional Enzyme in Mycobacterium tuberculosis
Authors: Njire Moses , Wang Na , Wang Bangxing , Tan Yaoju , Cai Xingshan , Liu Yanwen , Mugweru Julius , Guo Jintao , Hameed H. M. Adnan , Tan Shouyong , Liu Jianxiong , Yew Wing Wai , Nuermberger Eric , Lamichhane Gyanu , Liu Jinsong , Zhang Tianyu
Published: April 2017

Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. While the mechanism of activation of this prodrug into pyrazinoic acid (POA) by
Mycobacterium tuberculosis
has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. Here, we report how a new PZA resistance determinant, the Asp67Asn substitution in Rv2783, confers
M. tuberculosis
resistance to PZA. Expression of the mutant allele but not the wild-type allele in
M. tuberculosis
recapitulates the PZA resistance observed in clinical isolates. In addition to catalyzing the metabolism of RNA and single-stranded DNA, Rv2783 also metabolized ppGpp, an important signal transducer involved in the stringent response in bacteria. All catalytic activities of the wild-type Rv2783 but not the mutant were significantly inhibited by POA. These results, which indicate that Rv2783 is a target of PZA, provide new insight into the molecular mechanism of the sterilizing activity of this drug and a basis for improving the molecular diagnosis of PZA resistance and developing evolved PZA derivatives to enhance its antituberculosis activity.
Impact of Health Care Exposure on Genotypic Antiseptic Tolerance in Staphylococcus aureus Infections in a Pediatric Population
Authors: McNeil J. Chase , Hultén Kristina G. , Mason Edward O. , Kaplan Sheldon L.
Published: April 2017

Staphylococcus aureus
possessing either the
smr
gene or the
qacA/B
genes is associated with decreased susceptibility to chlorhexidine gluconate (CHG) and other antiseptics. Previous studies of antiseptic-tolerant staphylococci have focused largely on high-risk populations, and the exact role of health care exposure in the acquisition of these organisms is unclear. We sought to describe the risk factors and features of infection caused by antiseptic-tolerant
S. aureus
in a general pediatric population. Isolates were selected from an ongoing
S. aureus
surveillance study. Every third sequential isolate in the year 2014 was selected for inclusion. All isolates underwent PCR for the genes
qacA/B
and
smr
. Medical records were reviewed. Five hundred six isolates were included in the study, with 377 (74.3%) being community acquired. One hundred (19.8%) isolates were
smr
positive and 79 (15.6%)
qacA/B
positive. In univariable analyses, the presence of either gene was associated with underlying medical conditions, nosocomial acquisition, recent hospitalization, central venous lines, and CHG exposure. In multivariable analyses, only differences between patients with chronic medical conditions (odds ratio [OR] = 1.72; 95% confidence interval [CI], 1.22 to 2.64) and nosocomial acquisition (OR = 2.48; 95% CI, 1.16 to 8.17) remained statistically significant. Among patients without risk factors, 27.9% had infection with an antiseptic-tolerant isolate.
smr
- or
qacA/B
-positive
S. aureus
isolates are common in children and are independently associated with nosocomial acquisition and underlying medical conditions. These findings imply a role for the health care environment in acquisition of these organisms. However, genotypic antiseptic tolerance was seen in >25% of healthy children with an
S. aureus
infection, indicating that these organism are prevalent in the community as well.
Correlation between
gyrA
and CmeR Box Polymorphism and Fluoroquinolone Resistance in Campylobacter jejuni Isolates in China
Authors: Zhang Tengfei , Cheng Yiluo , Luo Qingping , Lu Qin , Dong Jun , Zhang Rongrong , Wen Guoyuan , Wang Honglin , Luo Ling , Wang Hongcai , Liu Guoping , Shao Huabin
Published: April 2017

Sequence analysis of 79 ciprofloxacin-resistant
Campylobacter jejuni
isolates collected in China showed resistance-related sequence variations in
gyrA
and CmeR-Box. All the isolates contain an identical Thr-86-Ile substitution in GyrA. Several novel CmeR-Box variations, including point substitutions, deletion, and insertion, were identified. The point insertion or deletion led to dramatically reduced binding of CmeR to the
cmeABC
promoter, which significantly increases the expression of
cmeABC
and contributes to the high fluoroquinolone resistance.
Treatment with Entinostat Heals Experimental Cholera by Affecting Physical and Chemical Barrier Functions of Intestinal Epithelia
Authors: Sarker Protim , Banik Atanu , Stromberg Roger , Gudmundsson Gudmundur H. , Raqib Rubhana , Agerberth Birgitta
Published: April 2017

We have shown previously that oral treatment with sodium butyrate or phenylbutyrate in an experimental model of shigellosis improves clinical outcomes and induces the expression of the antimicrobial peptide CAP-18 in the large intestinal epithelia. In a subsequent study, we found that entinostat, an aroylated phenylenediamine compound, has similar therapeutic potential against shigellosis. In this study, we aimed to evaluate entinostat as a potential candidate for host-directed therapy against cholera in an experimental model.
Vibrio cholerae
-infected rabbits were treated with two different dose regimens of entinostat: either 0.5 mg twice daily for 2 days or 1 mg once daily for 2 days. The effects of treatment on clinical outcomes and
V. cholerae
shedding (CFU count in stool) were observed. Immunohistochemical analysis was carried out to assess CAP-18 expression in ileal and jejunal mucosae. The serum zonulin level was measured by an enzyme-linked immunosorbent assay (ELISA) to evaluate gut permeability. Infection of rabbits with
V. cholerae
downregulated CAP-18 expression in the ileal epithelium; the expression was replenished by oral treatment with entinostat at either dose regimen. The level of zonulin, a marker of gut permeability, in serum was upregulated after infection, and this upregulation was counteracted after treatment with entinostat. Entinostat treatment also led to recovery from cholera and a decline in the
V. cholerae
count in stool. In conclusion, the improved clinical outcome of cholera for rabbits treated with entinostat is associated with the induction of CAP-18 and the reduction of gut epithelial permeability.
Regulation of a Glycerol-Induced Quinoprotein Alcohol Dehydrogenase by σ
54
and a LuxR-Type Regulator in Azospirillum brasilense Sp7
Authors: Singh Vijay Shankar , Dubey Ashutosh Prakash , Gupta Ankush , Singh Sudhir , Singh Bhupendra Narain , Tripathi Anil Kumar
Published: April 2017

Azospirillum brasilense
Sp7 uses glycerol as a carbon source for growth and nitrogen fixation. When grown in medium containing glycerol as a source of carbon, it upregulates the expression of a protein which was identified as quinoprotein alcohol dehydrogenase (ExaA). Inactivation of
exaA
adversely affects the growth of
A. brasilense
on glycerol. A determination of the transcription start site of
exaA
revealed an RpoN-dependent −12/−24 promoter consensus. The expression of an
exaA
::
lacZ
fusion was induced maximally by glycerol and was dependent on σ
54
. Bioinformatic analysis of the sequence flanking the −12/−24 promoter revealed a 17-bp sequence motif with a dyad symmetry of 6 nucleotides upstream of the promoter, the disruption of which caused a drastic reduction in promoter activity. The electrophoretic mobility of a DNA fragment containing the 17-bp sequence motif was retarded by purified EraR, a LuxR-type transcription regulator that is transcribed divergently from
exaA
. EraR also showed a positive interaction with RpoN in two-hybrid and pulldown assays.

IMPORTANCE
Quinoprotein alcohol dehydrogenase (ExaA) plays an important role in the catabolism of alcohols in bacteria. Although
exaA
expression is thought to be regulated by a two-component system consisting of EraS and EraR, the mechanism of regulation was not known. This study shows the details of the regulation of expression of the
exaA
gene in
A. brasilense
. We have shown here that
exaA
of
A. brasilense
is maximally induced by glycerol and harbors a σ
54
-dependent promoter. The response regulator EraR binds to an inverted repeat located upstream of the
exaA
promoter. This study shows that a LuxR-type response regulator (EraR) binds upstream of the
exaA
gene and physically interacts with σ
54
. The unique feature of this regulation is that EraR is a LuxR-type transcription regulator that lacks the GAFTGA motif, a characteristic feature of the enhancer binding proteins that are known to interact with σ
54
in other bacteria.
Regulation, Function, and Detection of Protein Acetylation in Bacteria
Authors: Carabetta Valerie J. , Cristea Ileana M.
Published: April 2017

N
ε
-Lysine acetylation is now recognized as an abundant posttranslational modification (PTM) that influences many essential biological pathways. Advancements in mass spectrometry-based proteomics have led to the discovery that bacteria contain hundreds of acetylated proteins, contrary to the prior notion of acetylation events being rare in bacteria. Although the mechanisms that regulate protein acetylation are still not fully defined, it is understood that this modification is finely tuned via both enzymatic and nonenzymatic mechanisms. The opposing actions of Gcn5-related
N
-acetyltransferases (GNATs) and deacetylases, including sirtuins, provide the enzymatic control of lysine acetylation. A nonenzymatic mechanism of acetylation has also been demonstrated and proven to be prominent in bacteria, as well as in mitochondria. The functional consequences of the vast majority of the identified acetylation sites remain unknown. From studies in mammalian systems, acetylation of critical lysine residues was shown to impact protein function by altering its structure, subcellular localization, and interactions. It is becoming apparent that the same diversity of functions can be found in bacteria. Here, we review current knowledge of the mechanisms and the functional consequences of acetylation in bacteria. Additionally, we discuss the methods available for detecting acetylation sites, including quantitative mass spectrometry-based methods, which promise to promote this field of research. We conclude with possible future directions and broader implications of the study of protein acetylation in bacteria.
Use of GeneXpert Remnants for Drug Resistance Profiling and Molecular Epidemiology of Tuberculosis in Libreville, Gabon
Authors: Alame-Emane Amel Kévin , Pierre-Audigier Catherine , Aboumegone-Biyogo Oriane Cordelia , Nzoghe-Mveang Amandine , Cadet-Daniel Véronique , Sola Christophe , Djoba-Siawaya Joël Fleury , Gicquel Brigitte , Takiff Howard E.
Published: April 2017

Multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of
Mycobacterium tuberculosis
pose major problems for global health. The GeneXpert MTB/RIF (Xpert) assay rapidly detects resistance to rifampin (RIF
r
), but for detection of the additional resistance that defines MDR-TB (MDR tuberculosis) and XDR-TB, and for molecular epidemiology, specimen cultures and a biosafe infrastructure are generally required. We sought to determine whether the remnants of sputa prepared for the Xpert assay could be used directly to find mutations associated with drug resistance and to study molecular epidemiology, thus providing precise characterization of MDR-TB cases in countries lacking biosafety level 3 (BSL3) facilities for
M. tuberculosis
cultures. After sputa were processed and run on the Xpert instrument, the leftovers of the samples prepared for the Xpert assay were used for PCR amplification and sequencing or for a line probe assay to detect mutations associated with resistance to additional drugs, as well as for molecular epidemiology with spoligotyping and selective mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing. Of 130 sputum samples from Gabon tested with the Xpert assay, 124 yielded interpretable results; 21 (17%) of these were determined to be RIF
r
. Amplification and sequencing or a line probe assay of the Xpert remnants confirmed 18/21 samples as MDR, corresponding to 12/116 (9.5%) new and 6/8 (75%) previously treated TB patients. Spoligotyping and MIRU typing with hypervariable loci identified an MDR Beijing strain present in five samples. We conclude that the remnants of samples processed for the Xpert assay can be used in PCRs to find mutations associated with the resistance to the additional drugs that defines MDR and XDR-TB and to study molecular epidemiology without the need for culturing or a biosafe infrastructure.
Mouse Saliva Inhibits Transit of Influenza Virus to the Lower Respiratory Tract by Efficiently Blocking Influenza Virus Neuraminidase Activity
Authors: Gilbertson Brad , Ng Wy Ching , Crawford Simon , McKimm-Breschkin Jenny L. , Brown Lorena E.
Published: April 2017

We previously identified a novel inhibitor of influenza virus in mouse saliva that halts the progression of susceptible viruses from the upper to the lower respiratory tract of micein vivoand neutralizes viral infectivity in MDCK cells. Here, we investigated the viral target of the salivary inhibitor by using reverse genetics to create hybrid viruses with some surface proteins derived from an inhibitor-sensitive strain and others from an inhibitor-resistant strain. These viruses demonstrated that the origin of the viral neuraminidase (NA), but not the hemagglutinin or matrix protein, was the determinant of susceptibility to the inhibitor. Comparison of the NA sequences of a panel of H3N2 viruses with differing sensitivities to the salivary inhibitor revealed that surface residues 368 to 370 (N2 numbering) outside the active site played a key role in resistance. Resistant viruses contained an EDS motif at this location, and mutation to either EES or KDS, found in highly susceptible strains, significantly increasedin vitrosusceptibility to the inhibitor and reduced the ability of the virus to progress to the lungs when the viral inoculum was initially confined to the upper respiratory tract. In the presence of saliva, viral strains with a susceptible NA could not be efficiently released from the surfaces of infected MDCK cells and had reduced enzymatic activity based on their ability to cleave substratein vitro. This work indicates that the mouse has evolved an innate inhibitor similar in function, though not in mechanism, to what humans have created synthetically as an antiviral drug for influenza virus.

IMPORTANCEDespite widespread use of experimental pulmonary infection of the laboratory mouse to study influenza virus infection and pathogenesis, to our knowledge, mice do not naturally succumb to influenza. Here, we show that mice produce their own natural form of neuraminidase inhibitor in saliva that stops the virus from reaching the lungs, providing a possible mechanism through which the species may not experience severe influenza virus infection in the wild. We show that the murine salivary inhibitor targets the outer surface of the influenza virus neuraminidase, possibly occluding entry to the enzymatic site rather than binding within the active site like commercially available neuraminidase inhibitors. This knowledge sheds light on how the natural inhibitors of particular species combat infection.
Comparative Genomics of Chrysochromulina Ericina Virus and Other Microalga-Infecting Large DNA Viruses Highlights Their Intricate Evolutionary Relationship with the Established Mimiviridae Family
Authors: Gallot-Lavallée Lucie , Blanc Guillaume , Claverie Jean-Michel
Published: April 2017

Chrysochromulina ericina virus CeV-01B (CeV) was isolated from Norwegian coastal waters in 1998. Its icosahedral particle is 160 nm in diameter and encloses a 474-kb double-stranded DNA (dsDNA) genome. This virus, although infecting a microalga (the haptophyceaeHaptolina ericina, formerlyChrysochromulina ericina), is phylogenetically related to members of theMimiviridaefamily, initially established with the acanthamoeba-infecting mimivirus and megavirus as prototypes. This family was later split into two genera (MimivirusandCafeteriavirus) following the characterization of a virus infecting the heterotrophic stramenopileCafeteria roenbergensis(CroV). CeV, as well as two of its close relatives, which infect the unicellular photosynthetic eukaryotesPhaeocystis globosa(Phaeocystis globosa virus [PgV]) andAureococcus anophagefferens(Aureococcus anophagefferens virus [AaV]), are currently unclassified by the International Committee on Viral Taxonomy (ICTV). The detailed comparative analysis of the CeV genome presented here confirms the phylogenetic affinity of this emerging group of microalga-infecting viruses with theMimiviridaebut argues in favor of their classification inside a distinct clade within the family. Although CeV, PgV, and AaV share more common features among them than with the largerMimiviridae, they also exhibit a large complement of unique genes, attesting to their complex evolutionary history. We identified several gene fusion events and cases of convergent evolution involving independent lateral gene acquisitions. Finally, CeV possesses an unusual number of inteins, some of which are closely related despite being inserted in nonhomologous genes. This appears to contradict the paradigm of allele-specific inteins and suggests that theMimiviridaeare especially efficient in spreading inteins while enlarging their repertoire of homing genes.

IMPORTANCEAlthough it infects the microalgaChrysochromulina ericina, CeV is more closely related to acanthamoeba-infecting viruses of theMimiviridaefamily than to any member of thePhycodnaviridae, the ICTV-approved family historically including all alga-infecting large dsDNA viruses. CeV, as well as its relatives that infect the microalgaePhaeocystic globosa(PgV) andAureococcus anophagefferens(AaV), remains officially unclassified and a source of confusion in the literature. Our comparative analysis of the CeV genome in the context of this emerging group of alga-infecting viruses suggests that they belong to a distinct clade within the establishedMimiviridaefamily. The presence of a large number of unique genes as well as specific gene fusion events, evolutionary convergences, and inteins integrated at unusual locations document the complex evolutionary history of the CeV lineage.
Cellular Cholesterol Facilitates the Postentry Replication Cycle of Herpes Simplex Virus 1
Authors: Wudiri George A. , Nicola Anthony V.
Published: April 2017

Cholesterol is an essential component of cell membranes and is required for herpes simplex virus 1 (HSV-1) entry (1–3). Treatment of HSV-1-infected Vero cells with methyl beta-cyclodextrin from 2 to 9 h postentry reduced plaque numbers. Transport of incoming viral capsids to the nuclear periphery was unaffected by the cholesterol reduction, suggesting that cell cholesterol is important for the HSV-1 replicative cycle at a stage(s) beyond entry, after the arrival of capsids at the nucleus. The synthesis and release of infectious HSV-1 and cell-to-cell spread of infection were all impaired in cholesterol-reduced cells. Propagation of HSV-1 on DHCR24
−/−
fibroblasts, which lack the desmosterol-to-cholesterol conversion enzyme, resulted in the generation of infectious extracellular virions (HSV
des
) that lack cholesterol and likely contain desmosterol. The specific infectivities (PFU per viral genome) of HSV
chol
and HSV
des
were similar, suggesting cholesterol and desmosterol in the HSV envelope support similar levels of infectivity. However, infected DHCR24
−/−
fibroblasts released ∼1 log less infectious HSV
des
and ∼1.5 log fewer particles than release of cholesterol-containing particles (HSV
chol
) from parental fibroblasts, suggesting that the hydrocarbon tail of cholesterol facilitates viral synthesis. Together, the results suggest multiple roles for cholesterol in the HSV-1 replicative cycle.

IMPORTANCE
HSV-1 infections are associated with a wide range of clinical manifestations that are of public health importance. Cholesterol is a key player in the complex interaction between viral and cellular factors that allows HSV-1 to enter host cells and establish infection. Previous reports have demonstrated a role for cellular cholesterol in the entry of HSV-1 into target cells. Here, we employed both chemical treatment and cells that were genetically defined to synthesize only desmosterol to demonstrate that cholesterol is important at stages following the initial entry and transport of viral capsids to the nucleus. Viral protein expression, encapsidation of the viral genome, and the release of mature virions were impacted by the reduction of cellular cholesterol. Cholesterol was also critical for cell-to-cell spread of infection. These findings provide new insights into the cholesterol dependence of HSV-1 replication.
Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen: Replicating and Shielding Viral DNA during Viral Persistence
Authors: Weidner-Glunde Magdalena , Mariggiò Giuseppe , Schulz Thomas F.
Published: April 2017

Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong latency. The viral latency-associated nuclear antigen (LANA) promotes viral persistence by tethering the viral genome to cellular chromosomes and by participating in latent DNA replication. Recently, the structure of the LANA C-terminal DNA binding domain was solved and new cytoplasmic variants of LANA were discovered. We discuss how these findings contribute to our current view of LANA structure and assembly and of its role during viral persistence.
A pseudotumour of the thigh: tensor fasciae latae muscle hypertrophy due to an underlying abductor tendon tear
Authors: Meijer Ruben Petrus Johannes , Jasper Jorrit , Snoeker Barbara , Jansen Joris
Published: April 2017

We present a patient with an asymptomatic unilateral swelling of the anterolateral thigh. MRI showed hypertrophy of the tensor fasciae latae muscle due to an underlying gluteus minimus tendon tear.

Abductor tendon tears can present with swelling of the thigh due to secondary tensor fasciae latae muscle hypertrophy.
Epidemiology of injuries in judo: a cross-sectional survey of severe injuries based on time loss and reduction in sporting level
Authors: Akoto Ralph , Lambert Christophe , Balke Maurice , Bouillon Bertil , Frosch Karl-Heinz , Höher Jürgen
Published: April 2017

Background

Sport injury severity can be detected by duration of time loss and reduction of sporting performance.

Aim

To detect injury type-specific time loss duration and sporting performance reduction in judo.

Methods

An online survey of active and former judo athletes was conducted (exclusion criterion: incomplete questionnaire). Only injuries causing more than 3 weeks’ time loss were recorded. Athletes classified themselves into performance classes. Injury type-specific frequencies were recorded according to gender, age and performance level. Injury severity was assessed by time loss duration and performance reduction.

Results

The study included 4659 athletes (65% male, 38% competitive sports). The most commonly injured body regions were the upper extremity (41%) and the lower extremity (39%). Anterior cruciate ligament (ACL) ruptures were the most severe injury type (time loss: 4% of cases 3–6 weeks, 6% 6–12 weeks, 26% 3–6 months, 32% 6–9 months, 18% 9–12 months, 14%>12 months; performance reduction: 32% same level, 39% slightly reduced, 24% strongly reduced, 5% stopped judo). The second most severe type of injury was a vertebral disc prolapse (time loss: 26% 3–6 weeks, 31% 6–12 weeks, 20% 3–6 months, 7% 6–9 months, 3% 9–12 months 13%>12 months; reduction of sporting performance: 39% same level, 34% slightly reduced, 20% strongly reduced, 8% stopped judo).

Conclusion

Across genders and performance levels, ACL ruptures and vertebral disc prolapses were the most severe injuries with respect to time loss and sporting performance reduction.
The Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5): Background and rationale
Authors: Davis Gavin A , Purcell Laura , Schneider Kathryn J , Yeates Keith Owen , Gioia Gerard A , Anderson Vicki , Ellenbogen Richard G , Echemendia Ruben J , Makdissi Michael , Sills Allen , Iverson Grant L , Dvořák Jiří , McCrory Paul , Meeuwisse Willem , Patricios Jon , Giza Christopher C , Kutcher Jeffrey S
Published: April 2017

This article presents the Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5). The Sport Concussion Assessment Tool was introduced in 2004, following the 2nd International Conference on Concussion in Sport in Prague, Czech Republic. Following the 4th International Consensus Conference, held in Zurich, Switzerland, in 2012, the SCAT 3rd edition (Child SCAT3) was developed for children aged between 5 and12 years. Research to date was reviewed and synthesised for the 5th International Consensus Conference on Concussion in Sport in Berlin, Germany, leading to the current revision of the test, the Child SCAT5. This article describes the development of the Child SCAT5.
Measuring, manipulating and exploiting behaviours of adult mosquitoes to optimise malaria vector control impact
Authors: Killeen Gerry F , Marshall John M , Kiware Samson S , South Andy B , Tusting Lucy S , Chaki Prosper P , Govella Nicodem J
Published: April 2017

Residual malaria transmission can persist despite high coverage with effective long-lasting insecticidal nets (LLINs) and/or indoor residual spraying (IRS), because many vector mosquitoes evade them by feeding on animals, feeding outdoors, resting outdoors or rapidly exiting from houses after entering them. However, many of these behaviours that render vectors resilient to control with IRS and LLINs also make them vulnerable to some emerging new alternative interventions. Furthermore, vector control measures targeting preferred behaviours of mosquitoes often force them to express previously rare alternative behaviours, which can then be targeted with these complementary new interventions. For example, deployment of LLINs against vectors that historically fed predominantly indoors on humans typically results in persisting transmission by residual populations that survive by feeding outdoors on humans and animals, where they may then be targeted with vapour-phase insecticides and veterinary insecticides, respectively. So while the ability of mosquitoes to express alternative behaviours limits the impact of LLINs and IRS, it also creates measurable and unprecedented opportunities for deploying complementary additional approaches that would otherwise be ineffective. Now that more diverse vector control methods are finally becoming available, well-established entomological field techniques for surveying adult mosquito behaviours should be fully exploited by national malaria control programmes, to rationally and adaptively map out new opportunities for their effective deployment.
Improving opioid safety practices in primary care: protocol for the development and evaluation of a multifaceted, theory-informed pilot intervention for healthcare providers
Authors: Leece Pamela , Buchman Daniel Z , Hamilton Michael , Timmings Caitlyn , Shantharam Yalnee , Moore Julia , Furlan Andrea D
Published: April 2017

Introduction

In North America, drug overdose deaths are reaching unprecedented levels, largely driven by increasing prescription opioid-related deaths. Despite the development of several opioid guidelines, prescribing behaviours still contribute to poor patient outcomes and societal harm. Factors at the provider and system level may hinder or facilitate the application of evidence-based guidelines; interventions designed to address such factors are needed.

Methods and analysis

Using implementation science and behaviour change theory, we have planned the development and evaluation of a comprehensive Opioid Self-Assessment Package, designed to increase adherence to the Canadian Opioid Guideline among family physicians. The intervention uses practical educational and self-assessment tools to provide prescribers with feedback on their current knowledge and practices, and resources to improve their practice. The evaluation approach uses a pretest and post-test design and includes both quantitative and qualitative methods at baseline and 6 months. We will recruit a purposive sample of approximately 10 family physicians in Ontario from diverse practice settings, who currently treat patients with long-term opioid therapy for chronic pain. Quantitative data will be analysed using basic descriptive statistics, and qualitative data will be analysed using the Framework Method.

Ethics and dissemination

The University Health Network Research Ethics Board approved this study. Dissemination plan includes publications, conference presentations and brief stakeholder reports. This evidence-informed, theory-driven intervention has implications for national application of opioid quality improvement tools in primary care settings. We are engaging experts and end users in advisory and stakeholder roles throughout our project to increase its national relevance, application and sustainability. The performance measures could be used as the basis for health system quality improvement indicators to monitor opioid prescribing. Additionally, the methods and approach used in this study could be adapted for other opioid guidelines, or applied to other areas of preventive healthcare and clinical guideline implementation processes.
Effectiveness of befriending interventions: a systematic review and meta-analysis
Authors: Siette Joyce , Cassidy Megan , Priebe Stefan
Published: April 2017

Objective

Befriending is an emotional supportive relationship in which one-to-one companionship is provided on a regular basis by a volunteer. It is commonly and increasingly offered by the voluntary sector for individuals with distressing physical and mental conditions. However, the effectiveness of this intervention on health outcomes is largely unknown. We aim to conduct a systematic review of the benefits of befriending.

Design

Systematic review.

Methods

A systematic search of electronic databases was conducted to identify randomised controlled trials and quasi-experimental trials of befriending for a range of physical and mental health indications including depression, anxiety, mental illness, cancer, physical illness and dementia. Main outcomes included patient-relevant and disease-specific outcomes, such as depression, loneliness, quality of life, self-esteem, social support and well-being.

Results

A total of 14 trials (2411 participants) were included; 7 were judged at low risk of bias. Most trials showed improvement in symptoms associated with befriending but these associations did not reach statistical significance in all trials. Befriending was significantly associated with better patient-reported outcomes across primary measures (standardised mean difference 0.18 (95% CI, −0.002 to 0.36, I2=26%, seven trials)). However, there was no significant benefit on single outcomes, including depression, quality of life, loneliness ratings, self-esteem measures, social support structures and well-being.

Conclusions

There was moderate quality evidence to support the use of befriending for the treatment of individuals with different physical and mental health conditions. This evidence refers to an overall improvement benefit in patient-reported primary outcomes, although with a rather small effect size. The current evidence base does not allow for firm conclusions on more specific outcomes. Future trials should hypothesise a model for the precise effects of befriending and use specified inclusion and outcome criteria.