bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective evaluation of prognostic indicators in dogs with head trauma: 72 cases (January–March 2011)
Authors: Sharma Diya , Holowaychuk Marie K.
Published: June 2015

Objective

To investigate the prognostic value of clinical and laboratory variables and scoring systems in dogs with head trauma.

Design

Retrospective study (January–March, 2011).

Setting

University teaching hospital.

Animals

Seventy‐two client‐owned dogs with a history of head trauma occurring ≤5 days prior to hospital admission. Dogs were excluded if they had an unconfirmed history of trauma, preexisting neurologic disease, or insufficient data available in the medical record.

Interventions

None.

Measurements and Main Results

Data from hospital admission were collected, including vital signs; blood pressure; pulse oximetry; venous blood gases and electrolyte concentrations; plasma lactate and blood glucose concentrations; PCV; total plasma protein concentration; activated clotting time; WBC count; and serum albumin, creatinine, total bilirubin, and BUN concentrations. Modified Glasgow Coma Scale (MGCS), mentation, and animal trauma triage (ATT) scores were also calculated. Treatment with mannitol, hypertonic saline (HS), corticosteroids, benzodiazepines, or phenobarbital, and requirement for endotracheal intubation were also recorded. Outcome was classified as survival or nonsurvival to hospital discharge. Decreased pulse oximetry, pH, bicarbonate concentration, or base excess, and increased potassium concentration, lactate concentration, BUN concentration, ATT score, or mentation score were risk factors for nonsurvival. Decreased MGCS score was the strongest predictor of nonsurvival; a score ≤ 11 was 84% sensitive and 73% specific for predicting nonsurvival. Dogs were more likely to die before discharge if they required HS or endotracheal intubation.

Conclusions

Dogs that did not survive following head trauma were more likely to have poor perfusion, severe concurrent injuries reflected by increased ATT scores, severe traumatic brain injury as evidenced by decreased MGCS or increased mentation scores, or requirement for HS administration or endotracheal intubation.
Effects of dipyrone, meloxicam, or the combination on hemostasis in conscious dogs
Authors: Zanuzzo Felipe S. , Teixeira‐Neto Francisco J. , Thomazini Camila M. , Takahira Regina K. , Conner Bobbi , Diniz Miriely S.
Published: June 2015

Objective

To compare the effects of dipyrone, meloxicam, and of the combination of these drugs on hemostasis in dogs.

Design

Prospective, blinded, randomized crossover study.

Setting

Research laboratory at a veterinary teaching hospital.

Animals

Six adult dogs.

Interventions

Animals received 4 intravenous treatments with 15‐day washout intervals: control (physiological saline, 0.1 mL/kg), meloxicam (0.2 mg/kg), dipyrone (25 mg/kg), and dipyrone‐meloxicam (25 and 0.2 mg/kg, respectively). A jugular catheter was placed for drug injection and for collecting samples for whole blood platelet aggregation (WBPA) and thromboelastometry assays at baseline, 1, 2, 3, 5, and 8 hours after treatment administration. The percent change from baseline of lag time and of the area under the curve (AUC) of impedance changes in response to collagen‐induced platelet activation were recorded during WBPA. Thromboelastometry‐derived parameters included clotting time, clot formation time, alpha‐angle, and maximum clot firmness. The buccal mucosal bleeding time was evaluated by a blinded observer at baseline, 1, 3, and 5 hours after treatment injection.

Measurements and Main Results

No significant changes in WBPA and thromboelastometry were recorded in the control treatment. Dipyrone significantly (P< 0.05) increased the lag time for 2 hours and decreased the AUC for 3 hours after injection. Meloxicam did not alter WBPA. Dipyrone‐meloxicam significantly increased lag time for 2 hours and decreased the AUC for 5 hours after treatment injection. Experimental treatments did not differ from the control treatment for thromboelastometry and buccal mucosal bleeding time.

Conclusions

While meloxicam does not alter hemostasis by the methods evaluated, dipyrone inhibits platelet aggregation for up to 3 hours. Meloxicam‐dipyrone combination causes more prolonged inhibition of platelet function than dipyrone alone. Decreased platelet aggregation induced by dipyrone and dipyrone‐meloxicam does not appear to impact the viscoelastic properties of the blood clot nor increase the risk of bleeding in dogs without preexisting hemostatic disorders.
Prospective evaluation of the incidence of wound infection in rattlesnake envenomation in dogs
Authors: Carr Amy , Schultz Jennifer
Published: June 2015

Objective

To evaluate the incidence of wound infection following crotalidae envenomation in dogs and determine if the use of prophylactic antibiotics is warranted.

Design

Prospective observational study.

Setting

A 24‐hour private practice specialty and emergency center in Murrieta, California.

Animals

One hundred and two dogs with acute rattlesnake envenomation.

Interventions

One hundred and forty‐three consecutive cases of suspected acute rattlesnake envenomation were evaluated between March of 2012 and May of 2013. One hundred and two cases received no antimicrobials as part of management. Eight cases were placed on prophylactic antimicrobials by the primary care veterinarian prior to referral and were excluded. Two cases were excluded because they were initiated on antimicrobials during hospitalization for reasons unrelated to snakebite. Three cases involved cats and were excluded. Three patients died acutely near the time of presentation and were excluded. Twenty‐one cases of suspected envenomation were excluded for lack of strong evidence of snakebite. Four cases were lost to follow‐up and were excluded. Follow‐up was conducted within 2 weeks either by phone or by direct inspection of the wound.

Results

Of the 102 patients included in the study only 1 infection developed. This patient developed an abscess subsequent to suspected compartment syndrome.

Conclusion

The incidence of wound infection in rattlesnake envenomation is low, and the use of prophylactic antimicrobials is not recommended. The use of antimicrobials should be reserved for wounds with necrosis or abscess and the choice of antimicrobial should be based on a culture and sensitivity of the wound.
Wound healing and all‐cause mortality in 958 wound patients treated in home care
Authors: Zarchi Kian , Martinussen Torben , Jemec Gregor B.E.
Published: June 2015

Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound‐healing experts is indicated. We, therefore, conducted an observational cohort study to investigate wound healing and all‐cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home‐care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound healing, death, or the end of follow‐up on December 2012. In total, 958 consecutive patients received wound care by home‐care nurses, corresponding to a 1‐year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died. During the first 3 weeks of therapy, healing was most likely to occur in surgical wounds (surgical vs. other wounds: adjusted hazard ratio [AHR] 2.21, 95% confidence interval 1.50–3.23), while from 3 weeks to 3 months of therapy, cancer wounds, and pressure ulcers were least likely to heal (cancer vs. other wounds: AHR 0.12, 0.03–0.50; pressure vs. other wounds: AHR 0.44, 0.27–0.74). Cancer wounds and pressure ulcers were further associated with a three times increased probability of mortality compared with other wounds (cancer vs. other wounds: AHR 3.19, 1.35–7.50; pressure vs. other wounds: AHR 2.91, 1.56–5.42). In summary, the wound type was found to be a significant predictor of healing and mortality with cancer wounds and pressure ulcers being associated with poor prognosis.
Hypoxia, AMPK activation and uterine artery vasoreactivity
Authors: Skeffington K. L. , Higgins J. S. , Mahmoud A. D. , Evans A. M. , Sferruzzi‐Perri A. N. , Fowden A. L. , Yung H. W. , Burton G. J. , Giussani D. A. , Moore L. G.
Published: June 2015

Key points

Uterine artery vasodilatation is a key mechanism for increasing utero‐placental blood flow and fetal nutrient supply.

Since the pioneering work of Joseph Barcroft, the natural laboratory of high altitude has been used to study the mechanisms regulating uterine artery blood supply and fetal growth.

Genes near the metabolic sensor adenosine monophosphate‐activated protein kinase (AMPK) have been implicated in genetic protection from high altitude‐associated fetal growth restriction.

We show that AMPK is present in utero‐placental tissues and has vasodilator effects in murine uterine arteries, and that exposure to chronic hypoxia sufficient to decrease fetal growth increases the vasodilator actions of AMPK in opposing phenylephrine‐induced vasoconstriction.

These results point to AMPK as being a key link between maternal vascular responses to pregnancy and fetal growth. Manipulation of AMPK may be a novel mechanism for developing new therapies in pregnancies complicated by chronic hypoxia.

Genes near adenosine monophosphate‐activated protein kinase‐α1 (PRKAA1) have been implicated in the greater uterine artery (UtA) blood flow and relative protection from fetal growth restriction seen in altitude‐adapted Andean populations. Adenosine monophosphate‐activated protein kinase (AMPK) activation vasodilates multiple vessels but whether AMPK is present in UtA or placental tissue and influences UtA vasoreactivity during normal or hypoxic pregnancy remains unknown. We studied isolated UtA and placenta from near‐term C57BL/6J mice housed in normoxia (n = 8) or hypoxia (10% oxygen, n = 7–9) from day 14 to day 19, and placentas from non‐labouring sea level (n = 3) or 3100 m (n = 3) women. Hypoxia increased AMPK immunostaining in near‐term murine UtA and placental tissue. RT‐PCR products for AMPK‐α1 and ‐α2 isoforms and liver kinase B1 (LKB1; the upstream kinase activating AMPK) were present in murine and human placenta, and hypoxia increased LKB1 and AMPK‐α1 and ‐α2 expression in the high‐ compared with low‐altitude human placentas. Pharmacological AMPK activation by A769662 caused phenylephrine pre‐constricted UtA from normoxic or hypoxic pregnant mice to dilate and this dilatation was partially reversed by the NOS inhibitor l‐NAME. Hypoxic pregnancy sufficient to restrict fetal growth markedly augmented the UtA vasodilator effect of AMPK activation in opposition to PE constriction as the result of both NO‐dependent and NO‐independent mechanisms. We conclude that AMPK is activated during hypoxic pregnancy and that AMPK activation vasodilates the UtA, especially in hypoxic pregnancy. AMPK activation may be playing an adaptive role by limiting cellular energy depletion and helping to maintain utero‐placental blood flow in hypoxic pregnancy.
Nonequilibrium Thermal Response of Porous Media in Unsteady Heat Conduction With Sinusoidally Changing Boundary Temperature
Authors: Xu Huijin , Gong Liang , Zhao Changying , Yin Ying
Published: June 2015

The thermal response of porous foam filled with a solid material was theoretically investigated under unsteady heat conduction with a sinusoidally changing boundary temperature. The local thermal nonequilibrium (LTNE) effect between the porous foam and the infill was obvious, and the two-equation model is employed for the unsteady heat conduction in porous-solid system. The temperature difference, which was defined as the time average of the absolute value of the difference between the temperatures of the porous solid and the infill, was proposed for quantitatively describing the LTNE effect in porous media. The LTNE phenomenon for unsteady heat conduction in porous media is influenced by the fluctuation period of the thermal boundary, foam morphology, and the thermal diffusivities of the porous solid and the infill. The LTNE effect of unsteady porous-media heat conduction was evident in the region near the thermal disturbance boundary. The maximum temperature difference was found on the curve of temperature difference versus fluctuation period, which means that the thermal response characteristics of porous composites resonate with periodically changing thermal disturbance. The fluctuation period corresponding to the maximum temperature difference has positive correlations with thermal diffusion resistance for unsteady porous-media heat conduction.
Effect of Entry Temperature on Forced Convection Heat Transfer With Viscous Dissipation in Thermally Developing Region of Concentric Annuli
Authors: Kumar M. M. J. , Satyamurty V. V.
Published: June 2015

Steady laminar forced convection heat transfer in the thermal entrance region of concentric annuli has been studied considering viscous dissipation characterized by the Brinkman number. The inner and outer pipes have been kept at constant and equal temperature. Two cases of entry temperatures have been considered, case 1: an entry temperature that varies with the radial coordinate, obtained by an adiabatically prepared fluid, i.e., attained by the fluid due to viscous dissipation in an adiabatic concentric annular duct and case 2: the conventional uniform entry temperature. The numerical results presented include the nondimensional temperature profiles, Nusselt numbers, and heat transferred from (or to) the inner and outer pipes. It has been shown from the numerical solutions that it is necessary to employ the dissipative entry temperature in place of conventional uniform entry temperature for higher Brinkman numbers. The results for circular pipes follow when the radius ratio takes the limiting value of zero.
Modeling of photocurrent and lag signals in amorphous selenium x-ray detectors
Authors: Siddiquee Sinchita , Kabir M. Z.
Published: June 2015

A mathematical model for transient photocurrent and lag signal in x-ray imaging detectors has been developed by considering charge carrier trapping and detrapping in the energy distributed defect states under exponentially distributed carrier generation across the photoconductor. The model for the transient and steady-state carrier distributions and hence the photocurrent has been developed by solving the carrier continuity equation for both holes and electrons. The residual (commonly known as lag signal) current is modeled by solving the trapping rate equations considering the thermal release and trap filling effects. The model is applied to amorphous selenium (a-Se) detectors for both chest radiography and mammography. The authors analyze the dependence of the residual current on various factors, such as x-ray exposure, applied electric field, and temperature. The electron trapping and detrapping mostly determines the residual current in a-Se detectors. The lag signal is more prominent in chest radiographic detector than in mammographic detectors. The model calculations are compared with the published experimental data and show a very good agreement.
Atomic gold–enabled three-dimensional lithography for silicon mesostructures
Authors: Luo Zhiqiang , Jiang Yuanwen , Myers Benjamin D. , Isheim Dieter , Wu Jinsong , Zimmerman John F. , Wang Zongan , Li Qianqian , Wang Yucai , Chen Xinqi , Dravid Vinayak P. , Seidman David N. , Tian Bozhi
Published: June 2015

Complex shapes from chemical lithography

Lithographic printing of semi-conductors builds up complex patterns one layer at a time. The process involves multiple steps to mask, print, and etch each layer. Luo
et al.
tweaked the same process used to grow silicon nanowires to pattern them into complex three-dimensional (3D) shapes. Gold acted as a catalyst to grow and elongate silicon nanowires from the vapor phase. Varying the pressure of the growth process altered the rate of gold diffusion along the surface of the wire. Upon etching the wires, the non-uniform coating of gold acted as a lithographic mask. The authors were thus able to make complex-shaped silicon spicules with a series of ridges and notches by strictly chemical means.

Science
, this issue p.
1451
Genomic determinants of coral heat tolerance across latitudes
Authors: Dixon Groves B. , Davies Sarah W. , Aglyamova Galina V. , Meyer Eli , Bay Line K. , Matz Mikhail V.
Published: June 2015

Some like it hot

Coral reefs are threatened by increasing temperatures. Acute temperature increases stress and damage corals. However, more gradual temperature changes can result in adaptation and subsequent tolerance for higher temperatures. Dixonet al.show that the heat tolerance that currently exists across coral populations from different latitudes can be inherited. Thus, natural variation in temperature tolerance may facilitate rapid adaptation among corals as our climate warms.

Science, this issue p.1460
The cancer test
Authors: Kaiser Jocelyn
Published: June 2015

A nonprofit's effort to replicate 50 top cancer papers is shaking up labs.
Alan Stern's worldly ventures
Authors: Hand Eric
Published: June 2015

Golden Spike and Uwingu are two of Stern's side efforts.
Factor-dependent processivity in human eIF4A DEAD-box helicase
Authors: García-García Cuauhtémoc , Frieda Kirsten L. , Feoktistova Kateryna , Fraser Christopher S. , Block Steven M.
Published: June 2015

Unwinding RNA for protein synthesis

During the first steps of protein synthesis, the small subunit of the ribosome scans the 5′ end of the mRNA, looking for the protein start codon. This process involves one of the translation initiation factors, eIF4A, which helps to remove any RNA structures that might impede the ribosome's search. García-García
et al.
used single-molecule optical trap assays to show that eIF4A, in combination with two other translation initiation factors, is able to continuously and directionally unwind a double-stranded RNA hairpin. The factors unwound RNA in steps roughly equal to a turn of the RNA double helix.

Science
, this issue p.
1486
BMP gradients: A paradigm for morphogen-mediated developmental patterning
Authors: Bier Ethan , De Robertis Edward M.
Published: June 2015

BMP mophogens direct growth and fate

As shown in classic fate-mapping studies, tissues and organs arise from specific regions of the embryo. Work over the past few decades has identified molecular players directing this choreographed development. Bone morphogenetic proteins (BMPs) and their antagonists establish domains in developing embryos. Bier and De Robertis review historical events for key discoveries in this area. They go on to lay out the current understanding of how diffusible morphogens form gradients to subdivide germ layers into distinct territories and organize body axes, regulate growth, and maintain stem cell niches.

Science
, this issue
10.1126/science.aaa5838
A 12 Å carotenoid translocation in a photoswitch associated with cyanobacterial photoprotection
Authors: Leverenz Ryan L. , Sutter Markus , Wilson Adjélé , Gupta Sayan , Thurotte Adrien , Bourcier de Carbon Céline , Petzold Christopher J. , Ralston Corie , Perreau François , Kirilovsky Diana , Kerfeld Cheryl A.
Published: June 2015

Protection from too much light

Photosynthetic organisms protect themselves from too much light using pigment photoswitches that absorb excess energy. Leverenz
et al.
analyzed the structure of an active, energy-dissipating form of the orange carotenoid protein (OCP) from a cyanobacterium. When activated by excess light, OCP moves its hydrophobic carotenoid pigment 12 Å within the protein to accommodate nonphotochemical quenching by the broader photosynthetic antenna complex.

Science
, this issue p.
1463
Comment on “Number-space mapping in the newborn chick resembles humans’ mental number line”
Authors: Mangalam Madhur , Karve Shraddha Madhav
Published: June 2015

Rugani
et al
. (Reports, 30 January 3015, p. 534) tested 3-day-old domestic chicks using an innovative experimental setup and demonstrate the presence of the mental number line. We raise concerns regarding this conclusion by highlighting the possible loopholes in the experimental design and the data analysis procedures. We further suggest auxiliary experiments that can substantiate the authors’ claim.
Comment on “Number-space mapping in the newborn chick resembles humans’ mental number line”
Authors: Harshaw Christopher
Published: June 2015

Rugani
et al
. (Reports, 30 January 2015, p. 534) presented evidence that domestic chicks employ a “mental number line.” I argue that the hypothesis testing used to support this claim unjustifiably assumes that domestic chicks are unbiased when choosing between identical stimuli presented to their left and right.
Ecological communities by design
Authors: Fredrickson James K.
Published: June 2015

Synthetic ecology requires knowledge of how microbial communities function
Identification of the algal dimethyl sulfide–releasing enzyme: A missing link in the marine sulfur cycle
Authors: Alcolombri Uria , Ben-Dor Shifra , Feldmesser Ester , Levin Yishai , Tawfik Dan S. , Vardi Assaf
Published: June 2015

Sourcing the smell of the seaside

Marine phytoplankton plays a critical role in the global sulfur cycle. Algae, for instance, are the main source of the aromatic compound dimethylsulfide (DMS) released from the oceans into the atmosphere. Alcolombri
et al.
identified the lyase enzyme responsible for DMS production in the bloom-forming marine phytoplankton
Emiliania huxleyi
(see the Perspective by Johnston). The presence of this gene in other globally distributed phytoplankton and corals suggests that it may serve as a reliable indicator of DMS production across diverse phyla. Because DMS gets oxidized to sulfur aerosols, which act as cloud condensation nuclei, this enzyme is a key global biogeochemical catalyst.

Science
, this issue p.
1466
; see also p.
1430
Overcoming Kerr-induced capacity limit in optical fiber transmission
Authors: Temprana E. , Myslivets E. , Kuo B.P.-P. , Liu L. , Ataie V. , Alic N. , Radic S.
Published: June 2015

Getting around the capacity crunch

The growing appetite for an ever-faster Internet and enhanced long-haul communication requires the pumping of more light down optic fibers. However, light-induced nonlinearities limit how much light can be pumped into the fiber without compromising the signal. This limitation has led to the prospect of a “capacity crunch.” Temprana
et al.
eliminated the effects of nonlinearity by using digital back-propagation methods with mutually coherent laser pulses from a single frequency comb.

Science
, this issue p.
1445
Topology, spin, and light
Authors: Stone Michael
Published: June 2015

Evanescent solutions to Maxwell's equations correspond to surface modes with strong spin-momentum locking.

[Also see Report by

Bliokh
et al.

]
Who can cleave DMSP?
Authors: Johnston Andrew W. B.
Published: June 2015

A DMSP lyase from an abundant marine eukaryote differs fundamentally from known bacterial enzymes.

[Also see Report by

Alcolombri
et al.

]
A HUSH for transgene expression
Authors: Brummelkamp Thijn R. , Steensel Bas van
Published: June 2015

A protein complex represses genes that insert into heterochromatin.

[Also see Report by

Tchasovnikarova
et al.

]
Bearing down on hydrogen
Authors: Ackland Graeme J.
Published: June 2015

Shockwaves are used to turn deuterium into a liquid metal.

[Also see Report by

Knudson
et al.

]
Solving reproducibility
Authors: Buck Stuart
Published: June 2015

The reproducibility problem in science is a familiar issue, not only within the scientific community, but with the general public as well. Recent developments in social psychology (such as fraudulent research by D. Stapel) and cell biology (the Amgen Inc. and Bayer AG reports on how rarely they could reproduce published results) have become widely known. Nearly every field is affected, from clinical trials and neuroimaging, to economics and computer science. Obvious solutions include more research on statistical and behavioral fixes for irreproducibility, activism for policy changes, and demanding more pre-registration and data sharing from grantees. Two Perspectives in this issue (pp. 1420 and 1422) describe how journals and academic institutions can foster a culture of reproducibility. Transparency is central to improving reproducibility, but it is expensive and time-consuming. What can be done to alleviate those obstacles?
International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE
Authors: Laurie Karen L. , Engelhardt Othmar G. , Wood John , Heath Alan , Katz Jacqueline M. , Peiris Malik , Hoschler Katja , Hungnes Olav , Zhang Wenqing , Van Kerkhove Maria D.
Published: June 2015

The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future.
Protective Immunity and Reduced Renal Colonization Induced by Vaccines Containing Recombinant Leptospira interrogans Outer Membrane Proteins and Flagellin Adjuvant
Authors: Monaris D. , Sbrogio-Almeida M. E. , Dib C. C. , Canhamero T. A. , Souza G. O. , Vasconcellos S. A. , Ferreira L. C. S. , Abreu P. A. E.
Published: June 2015

Leptospirosis is a global zoonotic disease caused by different
Leptospira
species, such as
Leptospira interrogans
, that colonize the renal tubules of wild and domestic animals. Thus far, attempts to develop effective leptospirosis vaccines, both for humans and animals, have failed to induce immune responses capable of conferring protection and simultaneously preventing renal colonization. In this study, we evaluated the protective immunity induced by subunit vaccines containing seven different recombinant
Leptospira interrogans
outer membrane proteins, including the carboxy-terminal portion of the immunoglobulinlike protein A (LigA
C
) and six novel antigens, combined with aluminum hydroxide (alum) or
Salmonella
flagellin (FliC) as adjuvants. Hamsters vaccinated with the different formulations elicited high antigen-specific antibody titers. Immunization with LigA
C
, either with alum or flagellin, conferred protective immunity but did not prevent renal colonization. Similarly, animals immunized with LigA
C
or LigA
C
coadministered with six leptospiral proteins with alum adjuvant conferred protection but did not reduce renal colonization. In contrast, immunizing animals with the pool of seven antigens in combination with flagellin conferred protection and significantly reduced renal colonization by the pathogen. The present study emphasizes the relevance of antigen composition and added adjuvant in the efficacy of antileptospirosis subunit vaccines and shows the complex relationship between immune responses and renal colonization by the pathogen.
Novel Molecular Assay for Simultaneous Identification of Neglected Lungworms and Heartworms Affecting Cats
Authors: Di Cesare Angela , Veronesi Fabrizia , Frangipane di Regalbono Antonio , Iorio Raffaella , Traversa Donato
Published: June 2015

Feline lungworms and heartworms are stimulating the interest of the scientific community due to their clinical impact and apparent geographical expansion. Diagnosis of the infections caused by these nematodes is indeed challenging. This report describes a novel multiplex PCR able to identify simultaneously three species of lungworms (
Aelurostrongylus abstrusus
and
Troglostrongylus brevior
) and heartworms (
Angiostrongylus chabaudi
) affecting felids. Epidemiological and clinical perspectives are discussed.
Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pig-Tailed Macaques by Using a Systems Biology Approach
Authors: Vishwanathan S. A. , Burgener A. , Bosinger S. E. , Tharp G. K. , Guenthner P. C. , Patel N. B. , Birse K. , Hanson D. L. , Westmacott G. R. , Henning T. R. , Radzio J. , Garcia-Lerma J. G. , Ball T. B. , McNicholl J. M. , Kersh E. N.
Published: June 2015

Our earlier studies with pig-tailed macaques demonstrated various simian-human immunodeficiency virus (SHIV) susceptibilities during the menstrual cycle, likely caused by cyclic variations in immune responses in the female genital tract. There is concern that high-dose, long-lasting, injectable progestin-based contraception could mimic the high-progesterone luteal phase and predispose women to human immunodeficiency type 1 (HIV-1) acquisition and transmission. In this study, we adopted a systems biology approach employing proteomics (tandem mass spectrometry), transcriptomics (RNA microarray hybridization), and other specific protein assays (enzyme-linked immunosorbent assays and multiplex chemokine and cytokine measurements) to characterize the effects of hormonal changes on the expression of innate factors and secreted proteins in the macaque vagina. Several antiviral factors and pathways (including acute-phase response signaling and complement system) were overexpressed in the follicular phase. Conversely, during the luteal phase there were factors overexpressed (including moesins, syndecans, and integrins, among others) that could play direct or indirect roles in enhancing HIV-1 infection. Thus, our study showed that specific pathways and proteins or genes might work in tandem to regulate innate immunity, thus fostering further investigation and future design of approaches to help counter HIV-1 acquisition in the female genital tract.

IMPORTANCEHIV infection in women is poorly understood. High levels of the hormone progesterone may make women more vulnerable to infection. This could be the case during the menstrual cycle, when using hormone-based birth control, or during pregnancy. The biological basis for increased HIV vulnerability is not known. We used an animal model with high risk for infection during periods of high progesterone. Genital secretions and tissues during the menstrual cycle were studied. Our goal was to identify biological factors upregulated at high progesterone levels, and we indeed show an upregulation of genes and proteins which enhance the ability of HIV to infect when progesterone is high. In contrast, during low-progesterone periods, we found more HIV inhibitory factors. This study contributes to our understanding of mechanisms that may regulate HIV infection in females under hormonal influences. Such knowledge is needed for the development of novel prevention strategies.
Alfalfa Leaf Curl Virus: an Aphid-Transmitted Geminivirus
Authors: Roumagnac Philippe , Granier Martine , Bernardo Pauline , Deshoux Maëlle , Ferdinand Romain , Galzi Serge , Fernandez Emmanuel , Julian Charlotte , Abt Isabelle , Filloux Denis , Mesléard François , Varsani Arvind , Blanc Stéphane , Martin Darren P. , Peterschmitt Michel
Published: June 2015

The family
Geminiviridae
comprises seven genera differentiated by genome organization, sequence similarity, and insect vector. Capulavirus, an eighth genus, has been proposed to accommodate two newly discovered highly divergent geminiviruses that presently have no known vector. Alfalfa leaf curl virus, identified here as a third capulavirus, is shown to be transmitted by
Aphis craccivora.
This is the first report of an aphid-transmitted geminivirus.
A Dual Role for the Nonreceptor Tyrosine Kinase Pyk2 during the Intracellular Trafficking of Human Papillomavirus 16
Authors: Gottschalk Elinor Y. , Meneses Patricio I.
Published: June 2015

The infectious process of human papillomaviruses (HPVs) has been studied considerably, and many cellular components required for viral entry and trafficking continue to be revealed. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during HPV16 pseudovirion infection of human keratinocytes. We found that Pyk2 is necessary for infection and appears to be involved in the intracellular trafficking of the virus. Small interfering RNA-mediated reduction of Pyk2 resulted in a significant decrease in infection but did not prevent viral entry at the plasma membrane. Pyk2 depletion resulted in altered endolysosomal trafficking of HPV16 and accelerated unfolding of the viral capsid. Furthermore, we observed retention of the HPV16 pseudogenome in the
trans
-Golgi network (TGN) in Pyk2-depleted cells, suggesting that the kinase could be required for the viral DNA to exit the TGN. While Pyk2 has previously been shown to function during the entry of enveloped viruses at the plasma membrane, the kinase has not yet been implicated in the intracellular trafficking of a nonenveloped virus such as HPV. Additionally, these data enrich the current literature on Pyk2's function in human keratinocytes.

IMPORTANCE
In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during human papillomavirus (HPV) infection of human skin cells. Infections with high-risk types of HPV such as HPV16 are the leading cause of cervical cancer and a major cause of genital and oropharyngeal cancer. As a nonenveloped virus, HPV enters cells by interacting with cellular receptors and established cellular trafficking routes to ensure that the viral DNA reaches the nucleus for productive infection. This study identified Pyk2 as a cellular component required for the intracellular trafficking of HPV16 during infection. Understanding the infectious pathways of HPVs is critical for developing additional preventive therapies. Furthermore, this study advances our knowledge of intracellular trafficking processes in keratinocytes.
Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction
Authors: Panikkar Archana , Smith Corey , Hislop Andrew , Tellam Nick , Dasari Vijayendra , Hogquist Kristin A. , Wykes Michelle , Moss Denis J. , Rickinson Alan , Balfour Henry H. , Khanna Rajiv
Published: June 2015

Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells.
Traumatic episodes and mental health effects in young men and women in Rwanda, 17 years after the genocide
Authors: Rugema Lawrence , Mogren Ingrid , Ntaganira Joseph , Krantz Gunilla
Published: June 2015

Objectives

To investigate mental health effects associated with exposure to trauma in Rwanda during the 1994 genocide period, and over the lifetime, in Rwandan men and women aged 20–35 years.

Setting

This was a cross-sectional population-based study conducted in the southern province of Rwanda. Data was collected during December 2011 to January 2012.

Participants

A total population of 917 individuals were included, 440 (48%) men and 477 (52%) women aged 20–35 years. Number of households for inclusion in each village was selected proportional to the total number of households in each selected village. The response rate was 99.8%. Face-to-face interviewing was done by experienced and trained clinical psychologists, following a structured questionnaire.

Results

Women were slightly less exposed during the genocide period (women 35.4% and men 37.5%; p=0.537), but more women than men were exposed to traumatic episodes over their lifetime (women 83.6%, n=399; men 73.4%, n=323; p<0.001). Current major depressive episodes (MDE) were twice as prevalent in women as in men. Traumatic episodes experienced in the genocide period severely affected men's current mental health status with relative risk (RR) 3.02 (95% CI 1.59 to 5.37) for MDE past and with RR 2.15 (95% CI 1.21 to 3.64) for suicidality. Women's mental health was also affected by trauma experienced in the genocide period but to an even higher extent, by similar trauma experienced in the lifetime with RR 1.91 (95% CI 1.03 to 3.22) for suicidality and RR 1.90 (95% CI 1.34 to 2.42) for generalised anxiety disorder, taking spousal physical/sexual violence into consideration.

Conclusions

Depression, post-traumatic stress disorder, anxiety and suicidal attempts are prevalent in Rwanda, with rates twice as high in women compared with men. For women, exposure to physical and sexual abuse was independently associated with all these disorders. Early detection of gender-based violence through homes and community interventions is important.
Enduring health effects of asbestos use in Belgian industries: a record-linked cohort study of cause-specific mortality (2001–2009)
Authors: Van den Borre Laura , Deboosere Patrick
Published: June 2015

Objective

To investigate cause-specific mortality among asbestos workers and potentially exposed workers in Belgium and evaluate potential excess in mortality due to established and suspected asbestos-related diseases.

Design

This cohort study is based on an individual record linkage between the 1991 Belgian census and cause-specific mortality information for Flanders and Brussels (2001–2009).

Setting

Belgium (Flanders and Brussels region).

Participants

The study population consists of 1 397 699 male workers (18–65 years) with 72 074 deaths between 1 October 2001 and 31 December 2009. Using a classification of high-risk industries, mortality patterns between 2056 asbestos workers, 385 046 potentially exposed workers and the working population have been compared.

Outcome measures

Standardised mortality ratios (SMRs) and 95% CIs are calculated for manual and non-manual workers.

Results

Our findings show clear excess in asbestos-related mortality in the asbestos industry with SMRs for mesothelioma of 4071 (CI 2327 to 6611) among manual workers and of 4489 (CI 1458 to 10 476) among non-manual workers. Excess risks in asbestos-related mortality are also found in the chemical industry, the construction industry, the electrical generation and distribution industry, the basic metals manufacturing industry, the metal products manufacturing industry, the railroad industry, and the shipping industry. Oral cancer mortality is significantly higher for asbestos workers (SMR 383; CI 124 to 894), railroad workers (SMR 192; CI 112 to 308), shipping workers (SMR 172; CI 102 to 271) and construction workers (SMR 125; CI 100 to 153), indicating a possible association with occupational asbestos exposure. Workers in all four industries have elevated mortality rates for cancer of the mouth. Only construction workers experience significantly higher pharyngeal cancer mortality (SMR 151; CI 104 to 212).

Conclusions

The study identifies vulnerable groups of Belgian asbestos workers, demonstrating the current-day health repercussions of historical asbestos use. Results support the hypothesis of a possible association between the development of oral cancer and occupational asbestos exposure.
Exposure to traffic and lung function in adults: a general population cohort study
Authors: Carlsen Hanne Krage , Modig Lars , Levinsson Anna , Kim Jeong-Lim , Toren Kjell , Nyberg Fredrik , Olin Anna-Carin
Published: June 2015

Objectives

To investigate the association between living near dense traffic and lung function in a cohort of adults from a single urban region.

Design

Cross-sectional results from a cohort study.

Setting

The adult-onset asthma and exhaled nitric oxide (ADONIX) cohort, sampled during 2001–2008 in Gothenburg, Sweden. Exposure was expressed as the distance from participants’ residential address to the nearest road with dense traffic (>10 000 vehicles per day) or very dense traffic (>30 000 vehicles per day). The exposure categories were: low (>500 m; reference), medium (75–500 m) or high (<75 m).

Participants

The source population was a population-based cohort of adults (n=6153). The study population included 5441 participants of European descent with good quality spirometry and information about all outcomes and covariates.

Outcome measures

Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured at a clinical examination. The association with exposure was examined using linear regression adjusting for age, gender, body mass index, smoking status and education in all participants and stratified by sex, smoking status and respiratory health status.

Results

We identified a significant dose–response trend between exposure category and FEV1(p=0.03) and borderline significant trend for FVC (p=0.06) after adjusting for covariates. High exposure was associated with lower FEV1(−1.0%, 95% CI −2.5% to 0.5%) and lower FVC (−0.9%, 95% CI −2.2% to 0.4%). The effect appeared to be stronger in women. In highly exposed individuals with current asthma or chronic obstructive pulmonary disease, FVC was lower (−4.5%, 95% CI −8.8% to −0.1%).

Conclusions

High traffic exposure at the residential address was associated with lower than predicted FEV1and FVC lung function compared with living further away in a large general population cohort. There were particular effects on women and individuals with obstructive disease.
Socioeconomic status and self-reported health among middle-aged Japanese men: results from a nationwide longitudinal study
Authors: Wada Koji , Higuchi Yoshiyuki , Smith Derek R
Published: June 2015

Objective

To examine potential associations between socioeconomic factors and self-rated health among a national sample of Japanese men aged 50–59 years between 2005 and 2010, including the 2008 global financial crisis.

Design

Prospective cohort study.

Setting

Randomly selected 2515 census areas from a total of 1.8 million census areas in Japan.

Participants

This study utilised data from a national, longitudinal survey conducted by the Ministry of Health, Labour and Welfare. Starting in 2005, 16 738 Japanese men aged 50–59 years were recruited and sent a questionnaire each year. We analysed data for the 6-year period (2005–2010) from participants who had worked for over 20 years in the same industry (n=9727).

Main outcome measures

We focused on worsening self-rated health status by occupation, education and employment contract.

Results

Working in the manufacturing industry was associated with worsening self-rated health scores when compared to those working in management (HR=1.19; 95% CI 1.04 to 1.37). A relationship between education level and worsening self-rated health was also identified as follows: junior high school (HR=1.49; 95% CI 1.31 to 1.69), high school (HR=1.29; 95% CI 1.17 to 1.42), and vocational college (HR=1.25; 95% CI 1.07 to 1.46), when compared with those holding university-level qualifications. Precarious employment (HR=1.17; 95% CI 1.00 to 1.37) was also associated with worsening self-rated health status in the current study.

Conclusions

This study suggests that working in manufacturing for more than 20 years and having lower education levels may have a significant impact on the self-rated health of middle-aged Japanese men. This may reflect a progressive decline in Japanese working conditions following the global financial crisis and/or the impact of lower socioeconomic status.
Relationship between low response to clopidogrel and periprocedural ischemic events with coil embolization for intracranial aneurysms
Authors: Asai Takumi , Miyachi Shigeru , Izumi Takashi , Matsubara Noriaki , Haraguchi Kenichi , Yamanouchi Takashi , Ota Keisuke , Shintai Kazunori , Tajima Hayato , Wakabayashi Toshihiko
Published: June 2015

Objectives

Low response to antiplatelet drugs is one of the risk factors for ischemic events. We examined the influence of low response to clopidogrel on symptomatic ischemic events and new ischemic MRI lesions with endovascular intracranial aneurysmal coil embolization.

Materials and methods

Between August 2010 and July 2013, 189 procedures in 181 consecutive patients who underwent endovascular coiling and received clopidogrel before treatment were investigated retrospectively. Platelet aggregation activity was examined by VerifyNow analysis. Low response to clopidogrel was defined as P2Y12 reaction units ≥230 in this study. Symptomatic ischemic complications within 30 days and postoperative new ischemic lesions on MRI–diffusion weighted imaging were evaluated.

Results

66 of 189 (34.9%) cases were low responders to clopidogrel. Ischemic complications occurred in 2 of 66 (3.0%) low responders compared with 6 of 123 (4.9%) responders (p=0.72). A new high intensity spot larger than 5 mm was significantly more frequent in low responders (26 of 66; 39.4%) than in responders (26 of 121; 21.2%; p=0.01). On multivariate analysis, independent risk factors for larger new ischemic lesions were low response to clopidogrel, smokers, posterior location, and aneurysms with a larger neck.

Conclusions

Low response to clopidogrel had little effect on clinical outcome although it increased asymptomatic large ischemic lesions in this cohort.
Effective vaccination against rabies in puppies in rabies endemic regions
Authors: Morters M. K. , McNabb S. , Horton D. L. , Fooks A. R. , Schoeman J. P. , Whay H. R. , Wood J. L. N. , Cleaveland S.
Published: June 2015

In rabies endemic regions, a proportionally higher incidence of rabies is often reported in dogs younger than 12 months of age, which includes puppies less than 3 months of age; this presents a serious risk to public health. The higher incidence of rabies in young dogs may be the effect of low vaccination coverage in this age class, partly as a result of the perception that immature immune systems and maternal antibodies inhibit seroconversion to rabies vaccine in puppies less than three months of age. Therefore, to test this perception, the authors report the virus neutralising antibody titres from 27 dogs that were vaccinated with high quality, inactivated rabies vaccine aged three months of age and under as part of larger serological studies undertaken in Gauteng Province, South Africa, and the Serengeti District, Tanzania. All of these dogs seroconverted to a single dose of vaccine with no adverse reactions reported and with postvaccinal peak titres ranging from 2.0 IU/ml to 90.5 IU/ml. In light of these results, and the risk of human beings contracting rabies from close contact with puppies, the authors recommend that all dogs in rabies endemic regions, including those less than three months of age, are vaccinated with high quality, inactivated vaccine.