bluuebunny/crossref_metadata_2025 huggingface dataset:
Epiphytic bromeliads in a changing world: the effect of elevated CO2 and varying water supply on growth and nutrient relations
Authors: Wagner K. , Zotz G.
Published: February 2018

Global climate change is likely to impact all plant life. Vascular epiphytes represent a life form that may be affected more than any other by possible changes in precipitation leading to water shortage, but negative effects of drought may be mitigated through increasing levels of atmospheric CO2.

We studied the response of three epiphytic Aechmea species to different CO2 and watering levels in a full‐factorial climate chamber study over 100 days. All species use crassulacean acid metabolism (CAM). Response variables were relative growth rate (RGR), nocturnal acidification and foliar nutrient levels (N, P, K, Mg).

Both elevated CO2 and increased water supply stimulated RGR, but the interaction of the two factors was not significant. Nocturnal acidification was not affected by these factors, indicating that the increase in growth in these CAM species was due to higher assimilation in the light. Mass‐based foliar nutrient contents were consistently lower under elevated CO2, but most differences disappeared when expressed on an area basis.

Compared to previous studies with epiphytes, in which doubling of CO2 increased RGR, on average, by only 14%, these Aechmea species showed a relatively strong growth stimulation of up to +61%. Consistent with earlier findings with other bromeliads, elevated CO2 did not mitigate the effect of water shortage.
Polls and Elections: Institutional Dynamics and Nominating Processes: The Latest Twists on a Familiar Story or the Emergence of a Brave New World?
Authors: Sawyer Elizabeth M. , Shafer Byron E.
Published: February 2018

The presidential nominating contests of 2016 were extremely fertile ground for hypothesizing by media analysts about alternative outcomes. Lacking much theoretical grounding, most of these were almost destined to be embarrassed by actual events—and 2016 proved extremely good at that. Yet the practical collapse of these journalistic hypotheticals does raise insistent theoretical questions, most of which are variants of one central puzzle: Were the nominating dynamics of 2016 ever very different from those of previous years? If so, how? If not, why not? There is in fact an established theoretical approach in political science with which to frame some answers. This article sets out to embed those answers within that established wisdom.
Assessing ocular activity during performance of motor skills using electrooculography
Authors: Gallicchio Germano , Cooke Andrew , Ring Christopher
Published: February 2018

Eye‐tracking research has revealed that, compared to novices, experts make longer ocular fixations on the target of an action when performing motor skills; that is, they have a longer quiet eye. Remarkably, the reason why a longer quiet eye aids movement has yet to be established. There is a need for interdisciplinary research and new measures to accelerate progress on the mechanistic understanding of the phenomenon. With the aim to provide researchers with new tools, we assessed the utility of electrooculography (EOG) to examine ocular activity while 10 experts and 10 novices putted golf balls. We measured quiet eye durations, distinguishing its pre‐ and postmovement initiation components, and developed a novel time‐varying index of ocular activity, eye quietness, computed as the variability of the EOG in short time intervals: lower values correspond with greater quietness. Finally, we measured movement durations using a combination of infrared and sound sensors. Experts had longer postmovement initiation quiet eye compared to novices; however, total and premovement quiet eye durations did not differ between groups. Eye quietness was inversely correlated with quiet eye duration, and was greatest immediately after movement initiation. Importantly, movement duration correlated positively with postmovement initiation quiet eye and negatively with eye quietness shortly after movement initiation. This study demonstrates the utility of assessing ocular activity during performance of motor skills using EOG. Additionally, these findings provide evidence that expert–novice differences in ocular activity may reflect differences in the kinematics (e.g., movement duration) of how experts and novices execute motor skills.
Cardiorespiratory fitness not sedentary time or physical activity is associated with cardiometabolic risk in active older adults
Authors: Pollock R. D. , Duggal N. A. , Lazarus N. R. , Lord J. M. , Harridge S. D. R.
Published: February 2018

Sedentary time (ST) and moderate‐to‐vigorous physical activity (MVPA) are associated with cardiometabolic health. Cardiorespiratory fitness (CRF) is also implicated but often overlooked in health recommendations. This study assessed the relationships between ST, MVPA, CRF, and cardiometabolic health in highly active older individuals. 125 healthy amateur cyclists aged 55 to 79 years had their ST and MVPA levels assessed by actigraphy over a 7‐day period. CRF was assessed using a maximal effort cycle ergometry test to determine VO2max with results normalized to both body mass and fat‐free mass measured by DXA. Markers of cardiometabolic risk (blood glucose, triglycerides, cholesterol, HDL, LDL, Insulin, HOMA IR, blood pressure, and body fat) were assessed and used to determine cumulative cardiometabolic risk. Multiple linear regression was used to assess ST, MVPA, and CRF associations with cardiometabolic health with the relationship between activity levels and CRF determined. CRF was associated with training volume (P = .003), but not ST or MVPA. A high CRF was associated with lower cumulative cardiometabolic risk, body fat percentage, triglyceride, and HDL levels (P < .05 in all cases). MVPA was negatively associated with body fat percentage, while ST was not associated with any marker of cardiometabolic risk when adjusting for activity levels. An association between CRF and cardiometabolic risk even in a group of older individuals with high fitness levels highlights the importance that CRF may have in maintaining health.
Noninvasive quantitative analysis of ceramide in skin of healthy Chinese population
Authors: Cheng S.‐S. , Chang Y.‐L. , Fei W.‐M. , Zhai W.‐F. , Cheng H. , Yang S. , Zhang X.‐J.
Published: February 2018

Objective

The objective of this study was to make noninvasive quantitative analysis of ceramide (CER) in skin of healthy Chinese population by high performance liquid chromatography tandem mass spectrometry.

Methods

Seven healthy subjects were selected and the stratified skin samples were available using cyanoacrylate adhesion method. High performance liquid chromatography tandem mass spectrometry, use ceramide Subclass Standard C42H85NO3 Quantification of the 12 corresponding ceramide subclass in the epidermis on the 7 skin samples, which cannot get all the standard of ceramides subclass since the stratum corneum ceramide is complex and diverse. Data were collected and analyzed using full‐flow lipid analysis software (LipidSearch).

Results

All the seven skin samples contained 12 subclasses of ceramide and the samples were quantitated with ceramide C42H85NO3 standard. The average contents were 33.63, 27.59, 108.57, 220.75, 149.20, 43.06, and 22.78 μg/mL, respectively.

Conclusion

Ceramide is an important lipid in the epidermis and is closely related to the skin barrier function. There are 12 subtypes of ceramide detected in the skin of Chinese healthy people, and there is a difference in the concentration between individuals. The difference may be associated with the skin barrier condition, and may also be related to the unavoidable error in the process of sampling, treatment, and detection.
Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients
Authors: Dubberke E.R. , Reske K.A. , Olsen M.A. , Bommarito K. , Cleveland A.A. , Silveira F.P. , Schuster M.G. , Kauffman C.A. , Avery R.K. , Pappas P.G. , Chiller T.M.
Published: February 2018

Background

Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described.

Methods

We performed a prospective, multicenter study of CDI within 365 days post‐allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post‐transplant and while hospitalized and contacted monthly up to 18 months post‐transplantation.

Results

Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post‐index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post‐index date (HR = 4.7, P = .09).

Conclusions

The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post‐transplant period.
Risk factors for Clostridium difficile infection in intestinal transplant recipients during the first year post‐transplant
Authors: Guzman L. , Qiu F. , Kalil A.C. , Mercer D.F. , Langnas A. , Florescu D.F.
Published: February 2018

Background

Clostridium difficile is the most common cause of healthcare‐associated infectious diarrhea. Risk factors for C. difficile infections (CDI) in intestinal transplant recipients (ITR) are not well‐defined. The aim of our study was to assess specific risk factors for CDI in ITR.

Methods

This is a 1:3 case–control study that included 29 ITR who developed CDI (cases) and 87 ITR without CDI (controls) observed during the first year post‐transplantation. Wilcoxon rank sum and Fisher's exact tests were used to compare variables. Univariate and multivariable conditional logistic regressions analysis were performed to identify risk factors for CDI.

Results

The multivariable conditional logistic regression analysis showed that proton pump inhibitors (PPI) administration (odds ratio [OR] = 0.06; 95% confidence interval [CI]: 0.007‐0.52; P = .01) was the only factor associated with lower rates of CDI. Outcomes for cases vs controls: rejection episodes 24.14% vs 20.69% (P = .7), graft loss 0% vs 2.3% (P = .99), and survival rate 1 year post‐transplantation 79.3% (59.6‐90.1%) vs 87.2% (78.1‐92.7%) (P = .38).

Conclusions

Proton pump inhibitor administration might be protective for CDI in ITR. Risks factors for CDI might be different in ITR compared to other populations; anatomical differences and medications administered in the post‐transplantation period may affect intestinal microbiota.
Interleukin‐8 mediates neutrophil‐endothelial interactions in pig‐to‐human xenogeneic models
Authors: French Beth M. , Sendil Selin , Sepuru Krishna Mohan , Ranek Jolene , Burdorf Lars , Harris Donald , Redding Emily , Cheng Xiangfei , Laird Christopher T. , Zhao Yuming , Cerel Benjamin , Rajarathnam Krishna , Pierson Richard N. , Azimzadeh Agnes M.
Published: February 2018

Background

Human neutrophils are sequestered by pig lung xenografts within minutes during ex vivo perfusion. This phenomenon is not prevented by pig genetic modifications that remove xeno‐antigens or added human regulatory molecules intended to down‐regulate activation of complement and coagulation pathways. This study investigated whether recipient and donor interleukin‐8 (IL‐8), a chemokine known to attract and activate neutrophils during inflammation, is elaborated in the context of xenogeneic injury, and whether human or pig IL‐8 promote the adhesion of human neutrophils in in vitro xenograft models.

Methods

Plasma levels of pig, human or non‐human primate (NHP) IL‐8 from ex vivo pig lung perfusion experiments (n = 10) and in vivo pig‐to‐baboon lung transplantation in baboons (n = 22) were analysed by ELISA or Luminex. Human neutrophils stimulated with human or pig IL‐8 were analysed for CD11b expression, CD18 activation, oxidative burst and adhesion to resting or TNF‐activated endothelial cells (EC) evaluated under static and flow (Bioflux) conditions. For some experiments, human neutrophils were incubated with Reparixin (IL‐8/CXCL8 receptor blocker) and then analysed as in the in vitro experiments mentioned above.

Results

Plasma levels of pig IL‐8 (~6113 pg/mL) increased more than human (~1235 pg/mL) between one and four hours after initiation of ex vivo lung perfusion. However, pig IL‐8 levels remained consistently low (<60 pg/mL) and NHP IL‐8 plasma levels increased by ~2000 pg/mL after four hours in a pig‐to‐baboon lung xenotransplantation. In vitro, human neutrophils’ CD11b expression, CD18 activation and oxidative burst all increased in a dose‐dependent manner following exposure to either pig or human IL‐8, which also were associated with increased adhesion to EC in both static and flow conditions. Reparixin inhibited human neutrophil activation by both pig and human IL‐8 in a dose‐dependent fashion. At 0.1 mg/mL, Reparixin inhibited the adhesion of IL‐8‐activated human neutrophils to pAECs by 84 ± 2.5%.

Conclusions

Pig IL‐8 increased in an ex vivo model of pig‐to‐human lung xenotransplantation but is not detected in vivo, whereas human or NHP IL‐8 is elevated to a similar degree in both models. Both pig and human IL‐8 activate human neutrophils and increase their adhesion to pig aortic ECs, a process significantly inhibited by the addition of Reparixin to human neutrophils. This work implicates IL‐8, whether of pig or human origin, as a possible factor mediating in lung xenograft inflammation and injury and supports the evaluation of therapeutic targeting of this pathway in the context of xenotransplantation.
UBC‐Nepal expedition: The use of oral antioxidants does not alter cerebrovascular function at sea level or high altitude
Authors: Hansen Alexander B. , Hoiland Ryan L. , Lewis Nia C. S. , Tymko Michael M. , Tremblay Joshua C. , Stembridge Michael , Nowak‐Flück Daniela , Carter Howard H. , Bailey Damian M. , Ainslie Philip N.
Published: February 2018

New Findings

What is the central question of the study?

Does the use of antioxidants alter cerebrovascular function and blood flow at sea level (344 m) and/or high altitude (5050 m)?

What is the main finding and its importance?

This is the first study to investigate whether antioxidant administration alters cerebrovascular regulation and blood flow in response to hypercapnia, acute hypoxia and chronic hypoxia in healthy humans. We demonstrate that an acute dose of antioxidants does not alter cerebrovascular function and blood flow at sea level (344 m) or after 12 days at high altitude (5050 m).

Hypoxia is associated with an increase in systemic and cerebral formation of free radicals and associated reactants that may be linked to impaired cerebral vascular function and neurological sequelae. To what extent oral antioxidant prophylaxis impacts cerebrovascular function in humans throughout the course of acclimatization to the hypoxia of terrestrial high altitude has not been examined. Thus, the purpose of the present study was to examine the influence of orally ingested antioxidants at clinically relevant doses (vitamins C and E and α‐lipoic acid) on cerebrovascular regulation at sea level (344 m; n = 12; female n = 2 participants) and at high altitude (5050 m; n = 9; female n = 2) in a randomized, placebo‐controlled and double‐blinded crossover design. Hypercapnic and hypoxic cerebrovascular reactivity tests of the internal carotid artery (ICA) were conducted at sea level, and global and regional cerebral blood flow (CBF; i.e. ICA and vertebral artery) were assessed 10–12 days after arrival at 5050 m. At sea level, acute administration of antioxidants did not alter cerebral hypoxic cerebrovascular reactivity (pre versus post: 1.5 ± 0.7 versus 1.2 ± 0.8%∆CBF/−%∆; P = 0.96) or cerebral hypercapnic cerebrovascular reactivity (pre versus post: 5.7 ± 2.0 versus 5.8 ± 1.9%∆CBF/∆mmHg; P = 0.33). Furthermore, global CBF (P = 0.43) and cerebral vascular conductance (ICA P = 0.08; vertebral artery P = 0.32) were unaltered at 5050 m after antioxidant administration. In conclusion, these data show that an oral antioxidant cocktail known to attenuate systemic oxidative stress failed to alter cerebrovascular function at sea level and CBF during acclimatization to high altitude.
Injury, repair, inflammation and metaplasia in the stomach
Authors: Meyer Anne R. , Goldenring James R.
Published: February 2018

The development of intestinal‐type gastric cancer is preceded by the emergence of metaplastic cell lineages in the gastric mucosa. In particular, intestinal metaplasia and spasmolytic polypeptide‐expressing metaplasia (SPEM) have been associated with the pathological progression to intestinal‐type gastric cancer. The development of SPEM represents a physiological response to damage that recruits reparative cells to sites of mucosal injury. Metaplastic cell lineages are characterized by mucus secretion, adding a protective barrier to the epithelium. Increasing evidence indicates that the influence of alarmins and cytokines is required to initiate the process of metaplasia development. In particular, IL‐33 derived from epithelial cells stimulates IL‐13 production by specialized innate immune cells to induce chief cell transdifferentiation into SPEM following the loss of parietal cells from the corpus of the stomach. While SPEM represents a physiological healing response to acute injury, persistent injury and chronic inflammation can perpetuate a recurring pattern of reprogramming and metaplasia that is a risk factor for gastric cancer development. The transdifferentiation of zymogen secreting cells into mucous cell metaplasia may represent both a general repair mechanism in response to mucosal injury in many epithelia as well as a common pre‐neoplastic pathway associated with chronic injury and inflammation.

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Phase 1 Study To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Oral Doses of DS-2969b, a Novel GyrB Inhibitor, in Healthy Subjects
Authors: Vandell Alexander G. , Inoue Satoshi , Dennie Justin , Nagasawa Yasuo , Gajee Roohi , Pav Joe , Zhang George , Zamora Cynthia , Masuda Nobuhisa , Senaldi Giorgio
Published: February 2018

DS-2969b is a novel GyrB inhibitor in development for the treatment of
Clostridium difficile
infection (CDI). The aim of this study was to assess the safety, tolerability, pharmacokinetics, and effects on the normal gastrointestinal microbiota of multiple daily oral ascending doses of DS-2969b in healthy subjects. The study enrolled three sequential ascending-dose cohorts (60 mg, 200 mg, and 400 mg). In each cohort, subjects received an oral dose of DS-2969b or placebo (six subjects received DS-2969b, and two received placebo) each morning for 14 days. DS-2969b was safe and well tolerated at all dose levels examined. All adverse events related to DS-2969b were mild and predominantly related to the gastrointestinal tract. DS-2969a (free form of DS-2969b) plasma concentrations increased with increasing doses; however, both the maximum concentration of drug in serum (
C
max
) and the area under the concentration-time curve (AUC) increased less than dose proportionally. In all cohorts, sufficient fecal levels of DS-2969a were achieved within 24 h following the administration of the first dose and maintained for at least 17 days. Following treatment with DS-2969b, clear reductions in the populations of
Clostridium coccoides
and
Bifidobacterium
groups were observed. However, populations of three other bacterial groups examined (
Bacteroides fragilis
,
Clostridium leptum
, and
Prevotella
) were not affected. Data from this study support and encourage the further development of DS-2969b as a novel treatment for CDI.
Sofosbuvir and Ribavirin Liver Pharmacokinetics in Patients Infected with Hepatitis C Virus
Authors: Babusis Darius , Curry Michael P. , Kirby Brian , Park Yeojin , Murakami Eisuke , Wang Ting , Mathias Anita , Afdhal Nezam , McHutchison John G. , Ray Adrian S.
Published: February 2018

Sofosbuvir and ribavirin exert their anti-hepatitis C virus (anti-HCV) activity following metabolic activation in the liver. However, intrahepatic concentrations of the pharmacologically active nucleotide metabolites in humans are poorly characterized due to the inaccessibility of tissue and technical challenges with measuring nucleotide levels. A clinical study assessing the efficacy of sofosbuvir and ribavirin administered prior to liver transplantation to prevent HCV recurrence provided a unique opportunity to quantify nucleotide concentrations in human liver. We analyzed nucleotides using high-performance liquid chromatography coupled to tandem mass spectrometry in liver tissue from 30 HCV-infected patients with hepatocellular carcinoma who were administered sofosbuvir (400 mg/day) and ribavirin (1,000 to 1,200 mg/day) for 3 to 52 weeks prior to liver transplantation. Median total hepatic metabolite concentrations (the sum of nucleoside and mono-, di-, and triphosphates) were 77.1 μM for sofosbuvir and 361 μM for ribavirin in patients on therapy at the time of transplantation. Ribavirin and sofosbuvir efficiently loaded the liver, with total hepatic metabolite concentrations exceeding maximal levels in plasma by approximately 30-fold. Ribavirin metabolite levels suggest that its monophosphate is in great excess of its inhibition constant for IMP dehydrogenase and that its triphosphate is approaching the binding constant for incorporation by the HCV NS5B RNA-dependent RNA polymerase. In accordance with the potent antiviral activity of sofosbuvir, these results demonstrate that the liver triphosphate levels achieved following sofosbuvir administration greatly exceed the inhibition constant for HCV NS5B. In conclusion, this study expands the quantitative understanding of the pharmacology of sofosbuvir and ribavirin by establishing efficient hepatic delivery in the clinic. (This study has been registered at ClinicalTrials.gov under identifier NCT01559844.)
Deposition of Bacteria and Bacterial Spores by Bathroom Hot-Air Hand Dryers
Authors: Huesca-Espitia Luz del Carmen , Aslanzadeh Jaber , Feinn Richard , Joseph Gabrielle , Murray Thomas S. , Setlow Peter
Published: February 2018

Hot-air hand dryers in multiple men's and women's bathrooms in three basic science research areas in an academic health center were screened for their deposition on plates of (i) total bacteria, some of which were identified, and (ii) a kanamycin-resistant
Bacillus subtilis
strain, PS533, spores of which are produced in large amounts in one basic science research laboratory. Plates exposed to hand dryer air for 30 s averaged 18 to 60 colonies/plate; but interior hand dryer nozzle surfaces had minimal bacterial levels, plates exposed to bathroom air for 2 min with hand dryers off averaged ≤1 colony, and plates exposed to bathroom air moved by a small fan for 20 min had averages of 15 and 12 colonies/plate in two buildings tested. Retrofitting hand dryers with HEPA filters reduced bacterial deposition by hand dryers ∼4-fold, and potential human pathogens were recovered from plates exposed to hand dryer air whether or not a HEPA filter was present and from bathroom air moved by a small fan. Spore-forming colonies, identified as
B. subtilis
PS533, averaged ∼2.5 to 5% of bacteria deposited by hand dryers throughout the basic research areas examined regardless of distance from the spore-forming laboratory, and these were almost certainly deposited as spores. Comparable results were obtained when bathroom air was sampled for spores. These results indicate that many kinds of bacteria, including potential pathogens and spores, can be deposited on hands exposed to bathroom hand dryers and that spores could be dispersed throughout buildings and deposited on hands by hand dryers.

IMPORTANCE
While there is evidence that bathroom hand dryers can disperse bacteria from hands or deposit bacteria on surfaces, including recently washed hands, there is less information on (i) the organisms dispersed by hand dryers, (ii) whether hand dryers provide a reservoir of bacteria or simply blow large amounts of bacterially contaminated air, and (iii) whether bacterial spores are deposited on surfaces by hand dryers. Consequently, this study has implications for the control of opportunistic bacterial pathogens and spores in public environments including health care settings. Within a large building, potentially pathogenic bacteria, including bacterial spores, may travel between rooms, and subsequent bacterial/spore deposition by hand dryers is a possible mechanism for spread of infectious bacteria, including spores of potential pathogens if present.
Single-Cell Analysis of the Impact of Host Cell Heterogeneity on Infection with Foot-and-Mouth Disease Virus
Authors: Xin Xiu , Wang Hailong , Han Lingling , Wang Mingzhen , Fang Hui , Hao Yao , Li Jiadai , Zhang Hu , Zheng Congyi , Shen Chao
Published: February 2018

Viral infection and replication are affected by host cell heterogeneity, but the mechanisms underlying the effects remain unclear. Using single-cell analysis, we investigated the effects of host cell heterogeneity, including cell size, inclusion, and cell cycle, on foot-and-mouth disease virus (FMDV) infection (acute and persistent infections) and replication. We detected various viral genome replication levels in FMDV-infected cells. Large cells and cells with a high number of inclusions generated more viral RNA copies and viral protein and a higher proportion of infectious cells than other cells. Additionally, we found that the viral titer was 10- to 100-fold higher in cells in G
2
/M than those in other cell cycle phases and identified a strong correlation between cell size, inclusion, and cell cycle heterogeneity, which all affected the infection and replication of FMDV. Furthermore, we demonstrated that host cell heterogeneity influenced the adsorption of FMDV due to differences in the levels of FMDV integrin receptors expression. Collectively, these results further our understanding of the evolution of a virus in a single host cell.

IMPORTANCE
It is important to understand how host cell heterogeneity affects viral infection and replication. Using single-cell analysis, we found that viral genome replication levels exhibited dramatic variability in foot-and-mouth disease virus (FMDV)-infected cells. We also found a strong correlation between heterogeneity in cell size, inclusion number, and cell cycle status and that all of these characteristics affect the infection and replication of FMDV. Moreover, we found that host cell heterogeneity influenced the viral adsorption as differences in the levels of FMDV integrin receptors' expression. This study provided new ideas for the studies of correlation between FMDV infection mechanisms and host cells.
Dynamics of Evolution of Poliovirus Neutralizing Antigenic Sites and Other Capsid Functional Domains during a Large and Prolonged Outbreak
Authors: Shaw Jing , Jorba Jaume , Zhao Kun , Iber Jane , Chen Qi , Adu Festus , Adeniji Adekunle , Bukbuk David , Baba Marycelin , Henderson Elizabeth , Dybdahl-Sissoko Naomi , McDonald Sharla , Weldon William C. , Gumede Nicksy , Oberste M. Steven , Kew Olen M. , Burns Cara C.
Published: February 2018

We followed the dynamics of capsid amino acid replacement among 403 Nigerian outbreak isolates of type 2 circulating vaccine-derived poliovirus (cVDPV2) from 2005 through 2011. Four different functional domains were analyzed: (i) neutralizing antigenic (NAg) sites, (ii) residues binding the poliovirus receptor (PVR), (iii) VP1 residues 1 to 32, and (iv) the capsid structural core. Amino acid replacements mapped to 37 of 43 positions across all 4 NAg sites; the most variable and polymorphic residues were in NAg sites 2 and 3b. The most divergent of the 120 NAg variants had no more than 5 replacements in all NAg sites and were still neutralized at titers similar to those of Sabin 2. PVR-binding residues were less variable (25 different variants; 0 to 2 replacements per isolate; 30/44 invariant positions), with the most variable residues also forming parts of NAg sites 2 and 3a. Residues 1 to 32 of VP1 were highly variable (133 different variants; 0 to 6 replacements per isolate; 5/32 invariant positions), with residues 1 to 18 predicted to form a well-conserved amphipathic helix. Replacement events were dated by mapping them onto the branches of time-scaled phylogenies. Rates of amino acid replacement varied widely across positions and followed no simple substitution model. Replacements in the structural core were the most conservative and were fixed at an overall rate ∼20-fold lower than the rates for the NAg sites and VP1 1 to 32 and ∼5-fold lower than the rate for the PVR-binding sites. Only VP1 143-Ile, a non-NAg site surface residue and known attenuation site, appeared to be under strong negative selection.

IMPORTANCE
The high rate of poliovirus evolution is offset by strong selection against amino acid replacement at most positions of the capsid. Consequently, poliovirus vaccines developed from strains isolated decades ago have been used worldwide to bring wild polioviruses almost to extinction. The apparent antigenic stability of poliovirus obscures a dynamic of continuous change within the neutralizing antigenic (NAg) sites. During 7 years of a large outbreak in Nigeria, the circulating type 2 vaccine-derived polioviruses generated 120 different NAg site variants via multiple independent pathways. Nonetheless, overall antigenic evolution was constrained, as no isolate had fixed more than 5 amino acid differences from the Sabin 2 NAg sites, and the most divergent isolates were efficiently neutralized by human immune sera. Evolution elsewhere in the capsid was also constrained. Amino acids binding the poliovirus receptor were strongly conserved, and extensive variation in the VP1 amino terminus still conserved a predicted amphipathic helix.
Association between social health insurance and choice of hospitals among internal migrants in China: a national cross-sectional study
Authors: Wang Haiqin , Zhang Donglan , Hou Zhiying , Yan Fei , Hou Zhiyuan
Published: February 2018

Objectives

There is a tendency to pursue higher-level hospitalisation services in China, especially for internal migrants. This study aims to investigate the choices of hospitalisation services among internal migrants, and evaluate the association between social health insurance and hospitalisation choices.

Methods

Data were from a 2014 nationally representative cross-sectional sample of internal migrants aged 15–59 years in China. Descriptive analyses were used to perform the distribution of healthcare facility levels for hospitalisation services, and multinomial logistic regression was applied to examine the association between social health insurance and hospitalisation choices.

Results

Of the 6121 inpatient care users, only 11.50% chose the primary healthcare facilities for hospitalisation services, 44.91% chose the secondary hospitals and 43.59% preferred the tertiary hospitals. The choices presented large regional variations across the country. Compared with the uninsured, social health insurance had no statistically significant effect on patient choices of healthcare facility levels among internal migrants in China, whereas socioeconomic status was positively associated with the choices.

Conclusions

Social health insurance had little influence on the hospital choice among the internal migrants. Thus, social health insurance should be consolidated and portable to enhance the proper incentive of health insurance on healthcare seeking behaviours.
Interventions to increase access to or uptake of physical health screening in people with severe mental illness: a realist review
Authors: Lamontagne-Godwin Frédérique , Burgess Caroline , Clement Sarah , Gasston-Hales Melanie , Greene Carolynn , Manyande Anne , Taylor Deborah , Walters Paul , Barley Elizabeth
Published: February 2018

Objectives

To identify and evaluate interventions aimed at increasing uptake of, or access to, physical health screening by adults with severe mental illness; to examine why interventions might work.

Design

Realist review.

Setting

Primary, secondary and tertiary care.

Results

A systematic search identified 1448 studies, of which 22 met the inclusion criteria. Studies were from Australia (n=3), Canada (n=1), Hong Kong (n=1), UK (n=11) and USA (n=6). The studies focused on breast cancer screening, infection preventive services and metabolic syndrome (MS) screening by targeting MS-related risk factors. The interventions could be divided into those focusing on (1) health service delivery changes (12 studies), using quality improvement, randomised controlled trial, cluster randomised feasibility trial, retrospective audit, cross-sectional study and satisfaction survey designs and (2) tests of tools designed to facilitate screening (10 studies) using consecutive case series, quality improvement, retrospective evaluation and pre–post audit study designs. All studies reported improved uptake of screening, or that patients had received screening they would not have had without the intervention. No estimation of overall effect size was possible due to heterogeneity in study design and quality. The following factors may contribute to intervention success: staff and stakeholder involvement in screening, staff flexibility when taking physical measurements (eg, using adapted equipment), strong links with primary care and having a pharmacist on the ward.

Conclusions

A range of interventions may be effective, but better quality research is needed to determine any effect size. Researchers should consider how interventions may work when designing and testing them in order to target better the specific needs of this population in the most appropriate setting. Behaviour-change interventions to reduce identified barriers of patient and health professional resistance to screening this population are required. Resource constraints, clarity over professional roles and better coordination with primary care need to be addressed.
JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study
Authors: Milara Javier , Ballester Beatriz , Morell Anselm , Ortiz José L , Escrivá Juan , Fernández Estrella , Perez-Vizcaino Francisco , Cogolludo Angel , Pastor Enrique , Artigues Enrique , Morcillo Esteban , Cortijo Julio
Published: February 2018

Background

Pulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation (V)/perfusion (Q) mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown.

Objective

The study of JAK2 as potential target to treat PH in IPF.

Methods and results

JAK2 expression was increased in pulmonary arteries (PAs) from IPF (n=10; 1.93-fold; P=0.0011) and IPF+PH (n=9; 2.65-fold; P<0.0001) compared with PA from control subjects (n=10). PA remodelling was evaluated in human pulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells (HPASMCs) from patients with IPF in vitro treated with the JAK2 inhibitor JSI-124 or siRNA-JAK2 and stimulated with transforming growth factor beta. Both JSI-124 and siRNA-JAK2 inhibited the HPAEC to mesenchymal transition and the HPASMCs to myofibroblast transition and proliferation. JAK2 inhibition induced small PA relaxation in precision-cut lung slice experiments. PA relaxation was dependent of the large conductance calcium-activated potassium channel (BKCa). JAK2 inhibition activated BKCa channels and reduced intracellular Ca2+. JSI-124 1 mg/kg/day, reduced bleomycin-induced lung fibrosis, PA remodelling, right ventricular hypertrophy, PA hypertension and V/Q mismatching in rats. The animal studies followed the ARRIVE guidelines.

Conclusions

JAK2 participates in PA remodelling and tension and may be an attractive target to treat IPF associated to PH.
Using body measurements to estimate body weight in gilts
Authors: Al Ard Khanji Mohammad Sheik , Llorente César , Falceto María Victoria , Bonastre Cristina , Mitjana Olga , Tejedor María Teresa
Published: February 2018

The absence of a scale on pig farms has led to indirect body weight (BW) estimation using regression models based on body measurements. The objectives of the present study were to (1) develop prediction equations for weight estimation in gilts using body measurements (FF: flank-to-flank distance; L: length; HG: heart girth; BF2: ultrasound backfat measurement; LD: loin depth; and BCS: body condition score) and (2) validate the use of an existing prediction equation for BW in gilts (HG2 × L × 69.3 = HGLW), only used for finishing pigs. Data set A (derivation, Large White × Landrace) included 42 gilts at first insemination, 45 gilts at the end of first gestation, and 58 gilts at weaning. Data set B (validation, Large White × Landrace) comprised of 14 gilts at first insemination, 15 gilts at the end of first gestation, and 19 gilts at weaning. Models were developed for each physiological state but a better BW prediction was obtained from an overall model, including an adjustment for physiological state (S1 and S2): −168.89 +1.06L +1.28HG +58.02S1 +33.03S2 +10.92BCS −1.10BF2 (adjusted R2 = 0.90). This model was validated under conditions found in the present study. Estimations using HGLW showed greater residual means than regression models.
Accuracy of predicting chemical body composition of gilts and sows
Authors: Miller E.G. , Huber L. , Levesque C.L. , de Lange C.F.M.
Published: February 2018

Physical and chemical body composition of gilts and parity 3 sows were used to determine current prediction equation accuracy and propose alternative prediction equations that incorporate additional variables. Longissimus dorsi muscle depth and parity can be combined with body weight and backfat to improve gilt and sow body composition prediction.
Conventional solid fermentation alters mycotoxin contents and microbial diversity analyzed by high-throughput sequencing of a Fusarium mycotoxin-contaminated diet
Authors: Yang L.J. , Yang Z.B. , Yang W.R. , Li H.R. , Zhang C.Y. , Jiang S.Z. , Li X.M.
Published: February 2018

Fusarium mycotoxins, commonly present in corn and its derived products for animals, has caused significant economic impact on swine reproduction in the People’s Republic of China. The objective of the present study, therefore, was to evaluate changes in mycotoxin contents and microbial diversity by conventional solid fermentation of a contaminated diet. Three diets were evaluated, as follows: control group, basal diet; test group 1 (25 Toxin), basal diet in which corn and corn gluten meal were replaced with 25% mycotoxin-contaminated corn and corn gluten meal, respectively; test group 2 (50 Toxin), basal diet in which corn and corn gluten meal were replaced with 50% mycotoxin-contaminated corn and corn gluten meal, respectively. Compound strains were used for solid-state fermentation of the compound feed. Under the present experimental conditions, conventional solid fermentation altered microbial diversity, as demonstrated by high-throughput sequencing of a Fusarium mycotoxin-contaminated diet, and the content of zearalenone (ZEA) was reduced significantly. However, deleterious effects were also observed with regard to the contents of deoxynivalenol (DON) and fumonisin B1 (FUMB1). These results may have implications for animals consuming Fusarium mycotoxin-contaminated food or feed by conventional solid fermentation.
Estimating gas volume from headspace pressure in a batch culture system
Authors: Romero-Pérez Atmir , Beauchemin Karen A.
Published: February 2018

Two in vitro batch culture experiments were conducted to obtain a total of 1811 paired data for headspace gas pressure (GP; PSI) and volume (GV; mL). Data were used to generate and evaluate an equation to estimate GV from GP under our laboratory conditions (GV = 4.7047 GP + 0.0512 GP2).
Effect of grain type and dried distillers grains plus solubles oil concentration on site of digestion in cattle fed finishing diets
Authors: Rodenhuis Mary A. , Keomanivong Faithe E. , Bauer Marc L. , Swanson Kendall C.
Published: February 2018

The objective of this experiment was to determine the effects of grain type (rolled corn vs. rolled barley) and oil concentration of dried corn distillers grains plus solubles (DDGS; moderate = 7.9% vs. low = 4.5% ether extract) on site of digestion. Seven ruminally and duodenally cannulated Holstein steers (716 ± 8.9 kg) were used in a 4 × 7 Youden square with experimental periods of 24 d. True ruminal organic matter (OM) and crude protein (CP) digestibility (% of intake) as well as intestinal (% of entering duodenum) and total tract starch digestibility was greater (P ≤ 0.03) in steers fed diets containing barley than in steers fed diets containing corn. Ruminal disappearance and ruminal, intestinal, and total tract OM, CP, and starch digestibility were not influenced (P ≥ 0.11) by feeding diets containing DDGS with differing oil concentration. Total tract lipid digestibility (%) was greater (P < 0.001) in steers fed diets containing moderate-oil DDGS than low-oil DDGS. These data indicate that including a low-oil DDGS, as compared with a moderate-oil DDGS, in finishing diets containing rolled corn or rolled barley does not influence intake or site of digestion of nonlipid components.
Mesenteric arteries from stroke-prone spontaneously hypertensive rats exhibit an increase in nitric-oxide-dependent vasorelaxation
Authors: Wynne Brandi M. , Labazi Hicham , Lima Victor V. , Carneiro Fernando S. , Webb R. Clinton , Tostes Rita C. , Giachini Fernanda R.
Published: February 2018

The endothelium is crucial for the maintenance of vascular tone by releasing several vasoactive substances, including nitric oxide (NO). Systemic mean arterial pressure is primarily regulated by the resistance vasculature, which has been shown to exhibit increased vascular reactivity, and decreased vasorelaxation during hypertension. Here, we aimed to determine the mechanism for mesenteric artery vasorelaxation of the stroke-prone spontaneously hypertensive rat (SHRSP). We hypothesized that endothelial NO synthase (eNOS) is upregulated in SHRSP vessels, increasing NO production to compensate for the endothelial dysfunction. Concentration–response curves to acetylcholine (ACh) were performed in second-order mesenteric arteries; we observed decreased relaxation responses to ACh (maximum effect elicited by the agonist) as compared with Wistar-Kyoto (WKY) controls. Vessels from SHRSP incubated with Nω-nitro-l-arginine methyl ester and (or) indomethacin exhibited decreased ACh-mediated relaxation, suggesting a primary role for NO-dependent relaxation. Vessels from SHRSP exhibited a significantly decreased relaxation response with inducible NO synthase (iNOS) inhibition, as compared with WKY vessels. Western blot analysis showed increased total phosphorylated NF-κB, and phosphorylated and total eNOS in SHRSP vessels. Overall, these data suggest a compensatory role for NO by increased eNOS activation. Moreover, we believe that iNOS, although increasing NO bioavailability to compensate for decreased relaxation, leads to a cycle of further endothelial dysfunction in SHRSP mesenteric arteries.
Precambrian olistoliths masquerading as sills from Death Valley, California
Authors: Vandyk T. M. , Le Heron D. P. , Chew D. M. , Amato J. M. , Thirlwall M. , Dehler C. M. , Hennig J. , Castonguay S. R. , Knott T. , Tofaif S. , Ali D. O. , Manning C. J. , Busfield M. E. , Doepke D. , Grassineau N.
Published: February 2018

Olistolith production and magmatism are processes commonly associated with extensional tectonic settings, such as rift basins. We present a cautionary exemplar from one such Precambrian basin, in which we reinterpret metabasite bodies, previously documented as sills, to be olistoliths. We nevertheless demonstrate that, on the basis of field observation alone, the previous but erroneous sill interpretation is parsimonious. Indeed, it is only by using isotopic age and compositional analysis that the true identities of these metabasite olistoliths are revealed. We present new data from metabasites and metasedimentary strata of the Kingston Peak Formation (Cryogenian) and Crystal Spring Formation (Mesoproterozoic) of Death Valley, USA. These include field observations, U–Pb apatite ages, U–Pb zircon ages (detrital and igneous) and whole-rock geochemistry. These data also provide a new maximum age for the base of the Pahrump Group and suggest that the Crystal Spring Diabase was more tholeiitic than previously thought. Similar sill/olistolith misinterpretations may have occurred elsewhere, potentially producing erroneous age and tectonic-setting interpretations of surrounding strata. This is particularly relevant in Precambrian rocks, where fossil age constraints are rare. This is illustrated herein using a potential example from the Neoproterozoic literature of the Lufilian belt, Africa. We caution others against Precambrian olistoliths masquerading as sills.

Supplementary material:
Details of a meta-igneous boulder from P12 of the Silurian Hills, LA-ICP-MS and whole-rock geochemistry methods and standards, and U–Pb apatite and zircon isotopic data, including standards and selected cathodoluminescence images, are available at
https://doi.org/10.6084/m9.figshare.c.3990639
A new structural and kinematic framework for the Alborán Domain (Betic–Rif arc, western Mediterranean orogenic system)
Authors: Williams Jason R. , Platt John P.
Published: February 2018

The processes that drastically thinned and rapidly exhumed the Alborán Domain in southern Spain are poorly understood. Geological maps, cross-sections and a synthesis of previous work in the Alpujárride Complex provide a new structural framework for the Alborán Domain, with major revision of the previously defined lithotectonic units. Alborán continental lithosphere was buried and thickened in the Paleogene (D
1
) and subsequently thinned during late-orogenic extension in the early Miocene. Regional patterns of stretching lineations and late recumbent folds record important spatiotemporal changes in the kinematics of extension. East-directed shear (D
2
) is preserved in deep orogenic levels and thinned the crustal sequence during rapid exhumation and high-temperature metamorphism. North-directed shear (D
3
/D
4
) is preserved in upper orogenic levels and reworked earlier structures during the later stages of exhumation and cooling. This large-scale switch in the direction of finite stretching resulted from the interaction between components of orogen-parallel (D
2
) and orogen-perpendicular (D
3
/D
4
) extension, and associated vertical and lateral gradients in strain. We provide a novel kinematic model for gravity-driven extensional collapse of the Alborán Domain, compatible with both westward motion of the Alborán Domain relative to the Iberian margin and subsequent northward extensional flow and emplacement of Alborán lithosphere onto the Iberian margin.

Supplementary material:
A list of sample names, coordinates and descriptions, plus a Google Earth .kmz file of sample locations is available at
https://doi.org/10.6084/m9.figshare.5508643
. A geological sketch map of the Sierra de las Estancias, indicating the trend of stretching lineations in the Alpujárride Complex and location of major geological boundaries is available at
https://doi.org/10.6084/m9.figshare.5513398
.