bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of conditioned media generated by polarized macrophages on the cellular behaviours of bone marrow mesenchymal stem cells
Authors: He Xiao‐Tao , Li Xuan , Yin Yuan , Wu Rui‐Xin , Xu Xin‐Yue , Chen Fa‐Ming
Published: November 2017

Macrophages (Mφs) are involved in a variety of physiological and pathological events including wound healing and tissue regeneration, in which they play both positive and negative roles depending on their polarization state. In this study, we investigated the cellular behaviours of bone marrow mesenchymal stem cells (BMMSCs) after incubation in different conditioned media (CMs) generated by unpolarized Mφs (M0) or polarized Mφs (M1 and M2). Mφ polarization was induced by stimulation with various cytokines, and CMs were obtained from in vitro Mφ cultures termed CM0, CM1 and CM2 based on each Mφ phenotype. We found that CM1 supported the proliferation and adipogenic differentiation of BMMSCs, whereas CM0 had a remarkable effect on cell osteogenic differentiation. To a certain degree, CM2 also facilitated BMMSC osteogenesis; in particular, cells incubated with CM2 exhibited an enhanced capacity to form robust stem cell sheets. Although incubation with CM1 also increased production of extracellular matrix components, such as fibronectin, COL‐1 and integrin β1during sheet induction, the sheets generated by CM2‐incubated cells were thicker than those generated by CM1‐incubated cells (P < 0.001). Our data suggest that each Mφ phenotype has a unique effect on BMMSCs. Fine‐tuning Mφ polarization following transplantation may serve as an effective method to modulate the therapeutic potential of BMMSCs.
Pulsed electric fields as an alternative to thermal processing for preservation of nutritive and physicochemical properties of beverages: A review
Authors: Gabrić Domagoj , Barba Francisco , Roohinejad Shahin , Gharibzahedi Seyed Mohammad Taghi , Radojčin Milivoj , Putnik Predrag , Bursać Kovačević Danijela
Published: November 2017

Fruit juices and other beverages constitute an important source of bioactive compounds, but thermal processing may reduce their contents thus decreasing natural nutritive value of foods. This has been recently led to the use of non‐thermal technologies, especially pulsed electric fields (PEF) as an interesting alternative to thermal pasteurization of beverages. Reported results show that PEF is a useful for pasteurization of fruit juices that can minimize changes in physicochemical and nutritional properties with retention of higher amounts of health‐related phytochemicals. This study presents an overview of the effect of PEF on the physicochemical (e.g., Brix, pH, viscosity, acidity, color, aroma, and flavor, etc.) and nutritional (e.g., fatty acids and free amino acids, bioactive compounds, antioxidant capacity, etc.) properties of beverages.

Practical applications

Pulsed electric fields is suitable technological option for pasteurization, able to preserve valued bioactive compounds in beverages. Over the last decade, PEF has attracted a significant interest from various food industries and found numerous applications. However, chemical profile of food matrices has great influence on PEF, hence success of the treatment has to be evaluated and reported for each particular food. Accordingly, this review made systematic overview of the effects of PEF processing on the physicochemistry and nutrition with focus on beverages manufactured from various raw materials. Provided data can be applied for steering future uses of the PEF in processing, as well as directions of the future research with this useful technology.
What the FLOQ? A quality improvement project to reduce unnecessary paediatric respiratory viral swabs in a peripheral metropolitan hospital
Authors: Aldridge Patrick , Horsley Emily , Rosettenstein Kerri , Wallis Thomas , Payne Barbara , Pallot Jeremy , Lakic Vladimir
Published: November 2017

Aim

To reduce the number of paediatric respiratory viral swabs (locally referred to as a FLOQ) performed across the authors clinical centre from a baseline of over 800 ($38 000) per year by 25% over 4 months from 6 February 2017 to 31 May 2017.

Methods

A quality improvement project ‘What the FLOQ?’ (WTF) was instigated from 6 February 2017 to complement the Emergency Department (ED) ‘Sensible Test Ordering Process’ project from 1 April 2017. Stakeholder engagement across ED and general paediatric staff was sought. Alterations in practice included education of staff, targeted feedback to groups frequently ordering a FLOQ and rationalising patients appropriate for testing. Monthly requests were tallied on a run chart for FLOQs ordered in ED and the paediatric ward. A monthly audit of FLOQs performed on ED‐discharged patients was conducted with feedback.

Results

Total FLOQ swabs decreased by 55% from 336 (February to May 2016) to 151 (February to May 2017). ED performed 66% less FLOQs from 237 (February to May 2016) to 82 (February to May 2017). There was no increase in the number of FLOQs performed on the paediatric ward February to May 2017. Monthly auditing of ED discharged patients under 2 years with a FLOQ went from 40 to 3%.

Conclusion

Rationalising patient groups appropriate for testing with targeted feedback and broad stakeholder engagement successfully reduced FLOQs performed by 55%. This has projected savings of over $21 000 by 12 months. WTF has reduced the number of invasive patient procedures performed, benefitting staff and patients. Sustaining this change will be achieved through ongoing staff education on rationalisation criteria and consultant only requests outside of these parameters.
Characterization of a Heterobasidion irregulare endo‐rhamnogalacturonase that mediate growth on pectin
Authors: Hu Yang , Kim Seombeong , Jeon Junhyun , Elfstrand Malin , Stenlid Jan , Lee Yong‐Hwan , Olson Åke
Published: November 2017

Heterobasidion irregulare is one of five Heterobasidion annosum sensu lato (s.l.) species, which are destructive pathogens in boreal and temperate forests of the northern hemisphere that causes root and butt rot in conifer. A gene encoding endo‐rhamnogalacturonase (HIRHG), which belongs to the glycoside hydrolase family 28 (GH28), was found in a quantitative trait loci (QTL) region for virulence in Heterobasidion. In this study, we showed that HIRHG is highly upregulated during necrotrophic infection of Norway spruce compared with growth in liquid culture and that the HIRHG encoded protein is produced during fungal growth on complex carbon sources. Phylogenetic analysis of endo‐rhamnogalacturonases revealed that rhamnogalacturonase genes have been lost in most of the biotrophic and hemibiotrophic plant pathogens investigated but were common in necrotrophic pathogens and saprophytic fungi. Heterologous expression of the HIRHG gene in the hemibiotrophic fungus Magnaporthe oryzae increased its capacity to grow on pectin; however, the transformed M. oryzae isolates showed significant less infection of rice leaves compared to the wild type.
Collapse of a unique insular bird–snake relationship
Authors: Sandfoss M. R. , Sheehy C. M. , Lillywhite H. B.
Published: November 2017

Seahorse Key (SHK) supports a population of Florida cottonmouth snakes, Agkistrodon conanti, which have a unique trophic association with colonially nesting waterbirds. Each spring >10 000 birds have nested on SHK and provided an influx of food in the form of fish carrion that snakes scavenge on the ground. Because of this allochthonous input of trophic resources, the cottonmouth population on SHK historically was dense, with snakes of large body size. Suddenly and unexpectedly, the entire waterbird colony abandoned its nests during April, 2015 and did not return. We examined data collected from 1999 to 2016 on the abundance and body size of SHK cottonmouths to quantify how the bird abandonment has affected the snake population. Our results show that abundance and body condition index (BCI) have decreased significantly, particularly on the west end of SHK where the bird rookery historically concentrated. Abundance of snakes (counts per survey) along a west beach transect was higher during the pre‐abandonment period (10.99 ± 8.11 SD) than during the post‐abandonment period (7.52 ± 4.64). Similarly, we observed a significant decrease in the BCI of snakes from the west end of SHK between the pre‐ (0.04 ± 0.10) and post‐abandonment periods (−0.12 ± 0.14). Loss of the bird rookery as a source of energy has negatively affected the SHK cottonmouth population. In contrast, numbers and body condition of cottonmouths appear to have increased on an adjacent island where ~3000 to 5000 waterbirds began nesting in 2015 and 2016.
Neoliberalism, Development, and the Costa Rican State
Authors: Morrissey Marietta
Published: November 2017

Costa Rica has been celebrated for its relatively high levels of economic development in a region marked by extreme poverty and income inequality. Recent scholarship has examined the competing and complementary interests of private capital and public institutions in pursuing an aggressive neoliberal growth strategy while preserving social programs created during the developmental period of the 1950s through the late 1970s. This article extends the inquiry by considering the position of the Costa Rican state in social and economic policy making and management. It considers Costa Rica from the perspective of developmental state theory, the construction of an “intermediary state” characterized by significant elements of autonomy but without the capacity to alter independently economic or social structures. The 2008–2011 recession, public indebtedness, and related demands of capital and labor have overwhelmed Costa Rican intermediate‐state capacity and undermined Costa Rica's covenant between economic growth and social protections.
The Chavist Revolution and the Justice System
Authors: Pérez‐Perdomo Rogelio , Santacruz Salazar Andrea
Published: November 2017

In past Venezuelan experiences with authoritarian regimes, the strongman handled the punishment of the opposition, and the courts dealt with nonpolitical cases. In today's “revolutionary” regime, courts are not only in charge of punishing dissidence but have also become the regime's main legitimation force. In December 2015, following a landslide victory by the opposition in parliamentary elections, the lame‐duck National Assembly appointed the Supreme Court justices in an irregular procedure that ignored the constitutional requirement for these positions. Consequently, the regime dominates the Supreme Court, which has deprived the National Assembly of its function, concentrating all powers in the President of the Republic. A controversial Supreme Court has become the only instrument supporting a regime that has lost the popular support completely, where citizens have taken to the streets to protest a government that has destroyed democracy and has subjected the country to deep political and economic crises.
The Effects of Policy Change on Brazil's Public Higher Education System
Authors: Gonçalves Brasil Felipe , de Mattos e Silva Ivan Henrique , Zambello Aline Vanessa
Published: November 2017

This descriptive article presents a case study of the effects of policy change on the public higher‐education system in Brazil, highlighting the significant differences in the system after President Lula's election in the mid‐2000s. The data collected show changes to higher‐education policy in the number of institutions, the number of spots offered, racial‐quota policies, access, and the offer of public services through the adoption of electronic‐government tools. The article also considers how these changes to the Brazilian system fit into studies carried out with two public‐policy analysis models, multiple streams, and punctuated equilibrium.
Coup‐Proofing and Beyond: The Regime‐Survival Strategies of Hugo Chávez
Authors: Martin Heather
Published: November 2017

After a long history of domestic political and economic instability, rampant corruption, and income inequality, former Venezuelan President Hugo Chávez entered the political arena in 1998, touting a campaign for change. After winning the presidency by a landslide in 1999, Chávez began to implement a series of policies that changed Venezuela forever. The elimination of presidential term limits was perhaps one of the most‐controversial moves that Chávez made during his presidency. Despite significant backlash from the Venezuelan population and protest by the opposition, Chávez remained in office for almost 14 years. This article explores the Chávez presidency from 1999–2013, concluding that his political longevity can be attributed to a series of regime‐survival strategies and coup‐proofing techniques implemented during his time in office.
Government Appropriation of Scientific Knowledge: How the Chile Solidario Poverty‐Alleviation Program Incorporated Social Capital
Authors: Osorio G. Cecilia , Puentes B. Germán
Published: November 2017

This article applies Kingdon's policy‐streams approach to analyze how the concept of social capital became part of the Chile Solidario program for poverty alleviation. Interviews with key actors in the program's policy‐making process provide data. The study shows that while social capital was a structural element of the program's framework, it is present only weakly during implementation, and the concept applied was closer to one of human capital. Policy makers incorporated social capital into the conceptual framework of the program to justify certain forms of intervention. Although they considered international organizations as key partners to promote certain policy approaches, they considered local academia as slow and misshapen to help them.
Circulating CXCL10 in cirrhotic portal hypertension might reflect systemic inflammation and predict ACLF and mortality
Authors: Lehmann Jennifer M. , Claus Karina , Jansen Christian , Pohlmann Alessandra , Schierwagen Robert , Meyer Carsten , Thomas Daniel , Manekeller Steffen , Claria Joan , Strassburg Christian P. , Trautwein Christian , Wasmuth Hermann E. , Berres Marie‐Luise , Trebicka Jonel
Published: November 2017

Background & Aims

CXCR% ligands play an important role in hepatic injury, inflammation and fibrosis. While CXCL9 and CXCL11 are associated with survival in patients receiving transjugular intrahepatic portosystemic shunt (TIPS), the role of CXCL10 in severe portal hypertension remains unknown.

Methods

A total of 89 cirrhotic patients were analysed. CXCL10 protein levels were measured in portal and hepatic blood at TIPS insertion and 2 weeks later in 24 patients. CXCL10 and IL8 levels were assessed in portal, hepatic, cubital vein and right atrium blood in a further 25 patients at TIPS insertion. Furthermore, real‐time PCR determined hepatic CXCL10‐mRNA in 40 cirrhotic patients.

Results

Hepatic CXCL10 showed no association with decompensation. By contrast, circulating CXCL10‐levels were higher in portal than in hepatic vein blood, suggesting an extrahepatic source of CXCL10 in cirrhosis. However, CXCL10 protein in blood samples from portal, hepatic, cubital veins and right atrium correlated excellently with each other and with IL‐8 levels. Higher CXCL10 circulating levels were associated with presence of ascites and higher Child scores. Higher CXCL10 circulating protein levels were associated with acute decompensation, acute‐on‐chronic liver failure (ACLF) and independently with mortality. Moreover, a decrease in CXCL10 protein levels after TIPS insertion was associated with better survival in each cohort and analysed together.

Discussion

Circulating CXCL10 possibly reflects systemic inflammation and it is correlated with acute decompensation, ACLF and complications in patients with severe portal hypertension receiving TIPS. CXCL10 predicts survival in these patients and a decrease in CXCL10 after TIPS may be considered a good prognostic factor.
Possible role of hyposensitivity of C‐fiber afferents at the proximal urethra in the development of urge urinary incontinence in patients with detrusor overactivity
Authors: Ichiyanagi Osamu , Nagaoka Akira , Naito Sei , Tsukigi Masaaki , Yagi Mayu , Kato Tomoyuki , Ishigooka Manabu , Tsuchiya Norihiko
Published: November 2017

Objective

The aim of the present study was to investigate associations between urethral sensation and urge urinary incontinence (UUI) in patients with and without detrusor overactivity (DO).

Methods

The medical records of 80 consecutive patients who underwent filling cystometry and urethral current perception threshold (CPT) tests were examined retrospectively. Following the exclusion of 4 patients not eligible for analysis, patients were classified into neurogenic DO, idiopathic DO, or DO‐negative groups based on neurological and cystometric findings (n = 30, 12, and 34, respectively). Eleven DO‐negative patients were defined as normal controls on cystometrograms (CMG) using the following exclusion criteria: bladder compliance <12.5 mL/cmH2O, volume >275 mL at first filling sensation, and comorbidities possibly affecting lower urinary tract function. Thus, 53 patients were finally included in the study. Proximal urethral CPT was evaluated with intraurethral square‐wave stimulation at 3 Hz to activate C‐fiber afferents.

Results

Median CPT was higher in neurogenic and idiopathic DO than in the normal CMG group (11.3 and 9.0 vs. 2.8 mA, respectively; P < .05), as well as in patients with UUI (n = 19) compared with non‐UUI patients (n = 34; 12.5 vs. 5.4 mA, respectively; P < .05). The proportion of UUI patients was significantly greater in the DO‐positive groups than in the normal CMG group (P < .05). CPTs were not associated with bladder capacity at the first filling sensation (r = 0.11).

Conclusion

Hyposensitive C‐fibers of the proximal urethra may contribute to the development of urodynamic DO as well as UUI in patients complaining of lower urinary tract symptoms.
Trend and business cycles with external markets: Non‐capacity generating semi‐autonomous expenditures and effective demand
Authors: Fiebiger Brett , Lavoie Marc
Published: November 2017

The Global Financial Crisis has underlined the importance of developments in the household sector to explaining macro patterns. Some recent papers have discussed the role of non‐capacity generating semi‐autonomous expenditures in growth theory. This literature ties together several aspects of heterodox thought: growth and distribution; the Sraffian supermultiplier; Duesenberry's relative income hypothesis; the endogenous money approach and Kalecki–Luxemburg external markets. The basic message is that non‐wage sources of effective demand, based on mortgage and consumer credit, can play a key role in inducing capacity investment and driving long‐run output growth. This article gives a broad overview of the role of financed‐induced semi‐autonomous expenditures in growth, cycles and crises, and thus criticizes some of the previous approaches that claim to mimic actual cycles while abstracting from these crucial determinants of economic activity.
Singular case of the driving instructor: Temporal and topographical disorientation
Authors: Futamura Akinori , Honma Motoyasu , Shiromaru Azusa , Kuroda Takeshi , Masaoka Yuri , Midorikawa Akira , Miller Michael W , Kawamura Mitsuru , Ono Kenjiro
Published: November 2017

Lesions of the medio‐parietal lobes are linked with topographical and temporal disorientation, and are of interest to understanding mental time. We examined a 39‐year‐old man who worked as a driving instructor before cerebral hemorrhage, and followed his case for 8 years including neuropsychological testing and brain imaging. The patient had mild anterograde episodic amnesia, but no semantic amnesia. He felt that time passed too quickly, and developed a compulsive routine to compensate, although he was able to count time at a normal speed. Furthermore, he was unable to accurately sketch the layout of his house and to make a cross‐reference type timetable for the future. Brain magnetic resonance imaging showed lesions of the left anterior–posterior cingulate gyrus, and N‐isopropyl‐[123I] p‐iodoamphetamine single‐photon emission computed tomography showed decreased blood flow mainly of the left medio‐parietal lobe.
Modeling the energy future
Authors: Case James
Published: November 2017

A bare‐bones dynamic model of an island economy is constructed for the purpose of discovering “socially optimal” fossil fuel depletion schedules. An entire family of candidates is identified, all members being significantly more gradual than the one currently in force. The active ingredient in the model is a real‐valued function of two real variables―the current extraction rate and the quantity extracted to date―which quantifies the need to expend energy in the course of delivering it to end users. The main conclusions are that fossil fuels are currently being extracted far too fast for the common good, while a wide variety of socially preferable schedules are overlooked.

Summary for Managers

Consider conservation! Several methods have proven successful in the past.

Before World War I, Standard Oil did it by monopolizing the industry.

During the 1930s, the Texas Railroad Commission invoked martial law.

OPEC has achieved intermittent success by forming a cartel.

The proposed carbon tax may be the fairest alternative.

Any method of slowing the extraction of fossil fuels will encounter resistance, as the public has long been addicted to cheap energy. Yet conservation will slow global warming, even as it economizes an increasingly scarce resource. Expect no painless alternative―there is none!
Gene effects of Cicer reticulatum on qualitative and quantitative traits in the cultivated chickpea
Authors: Adak Alper , Sari Duygu , Sari Hatice , Toker Cengiz
Published: November 2017

The gene effects of Cicer reticulatum on both double‐podding as qualitative traits and yield criteria as quantitative traits in interspecific hybridization with cultivated chickpea (Cicer arietinum) have not yet been elucidated, despite the easy acquisition of hybrid progeny between two species. This study sought to answer three questions concerning qualitative and quantitative traits in reciprocal crosses between C. arietinum and C. reticulatum. (i) Is there a similarity in the gene effects of flower colour, pigmentation and double‐podded traits in reciprocal interspecific crosses? (ii) What are the expressivity and penetrance of the double‐podded trait in interspecific crosses? (iii) Which heterosis predicts the occurrence and the extent of transgressive variation? The materials for this study were F1, F2 and F3 progeny derived from a reciprocal cross between C. arietinum and C. reticulatum. As qualitative traits, purple flower colour, pigmentation and single‐podded traits in C. reticulatum were governed by a dominant single gene. Purple flower colour and pigmentation were detected to be linked traits as all progeny had the same phenotypes. As quantitative traits, yield criteria in progeny which were double‐podded had higher values than the single‐podded counterparts. Expressivity and penetrance of the double‐podding trait were superior in progeny derived from C. reticulatum × C. arietinum. The results showed that fruitful heterosis was more useful than residual heterosis in F3 as residual heterosis was mostly negative and fruitful heterosis was suggested in self‐pollinated species such as chickpea that lacks inbreeding depression. Interspecific transgression was significant with respect to chickpea improvement because it represented a potential source of novel genetic variation.
Housing and Health
Authors: Angel Stefan , Bittschi Benjamin
Published: November 2017

Deprived housing is recognized as a source of poor health, but there is still little evidence of a causal relationship between housing and health. While existing literature identifies neighborhood effects and the individual dwelling as factors which affect health, it does not offer a joint examination of these factors. Moreover, endogeneity is a concern in analyses of both problems. Thus far, studies addressing endogeneity have done so through experimental design or instrumental variables. The first approach suffers from problems of external validity and the latter from the lack of reliable instruments. We therefore adopt an alternative strategy which considers both sources of endogeneity in order to identify the effects of housing on health by estimating fixed‐effect models. We reveal how housing problems affect health depending on living conditions and socioeconomic status. Our results therefore indicate that living in poor housing is an important short‐term socioeconomic determinant that directly affects health.
A controlled early group intervention study for unaccompanied minors: Can Expressive Arts alleviate symptoms of trauma and enhance life satisfaction?
Authors: Meyer DeMott Melinda A. , Jakobsen Marianne , Wentzel‐Larsen Tore , Heir Trond
Published: November 2017

This is the first controlled study of an expressive arts group intervention with unaccompanied minor asylum seeking children. The aim of the study was to examine whether such an intervention may alleviate symptoms of trauma and enhance life satisfaction and hope. One hundred forty five unaccompanied minor refugee boys with their stated age between 15 and 18 were allocated into a 10 session 5 weeks manualized expressive arts intervention (EXIT) or a life as usual (LAU) control group. The participants were assessed at onset and 4 times over a period of 25 months with a battery of instruments measuring post‐traumatic stress symptoms (PTSS), general psychological distress (HSCL‐25A), current life satisfaction (CLS) and expected life satisfaction (ELS). The instruments were presented in the participants’ native languages, using touch‐screen laptops and the computer program Multilingual Computer Assisted Interview (MultiCASI). There were significant time by group interactions in favor of the EXIT group for PTSS and CLS. At the end of the follow up the EXIT group had higher life satisfaction and hope for the future than the LAU group. A manualized EXIT group intervention can have a beneficial effect on helping minor refugee boys to cope with symptoms of trauma, strengthen their life satisfaction and develop hope for the future. Our findings support previous studies showing that the arts may help people in reconstructing meaning and connection with others by focusing on resources and creativity.
A systematic review and meta‐analysis of tertiary interventions in clinical burnout
Authors: Perski Olga , Grossi Giorgio , Perski Aleksander , Niemi Maria
Published: November 2017

Clinical burnout is one of the leading causes of work absenteeism in high‐ and middle‐income countries. There is hence a great need for the identification of effective intervention strategies to increase return‐to‐work (RTW) in this population. This review aimed to assess the effectiveness of tertiary interventions for individuals with clinically significant burnout on RTW and psychological symptoms of exhaustion, depression and anxiety. Four electronic databases (Ovid MEDLINE, PsychINFO, PubMed and CINAHL Plus) were searched in April 2016 for randomized and non‐randomized controlled trials of tertiary interventions in clinical burnout. Article screening and data extraction were conducted independently by two reviewers. Pooled odds ratios (ORs) and hazard ratios (HRs) were estimated with random‐effects meta‐analyses. Eight articles met the inclusion criteria. There was some evidence of publication bias. Included trials were of variable methodological quality. A significant effect of tertiary interventions compared with treatment as usual or wait‐list controls on time until RTW was found, HR = 4.5, 95% confidence interval (CI) = 2.15–9.45; however, considerable heterogeneity was detected. The effect of tertiary interventions on full RTW was not significant, OR = 1.33, 95% CI = 0.59–2.98. No significant effects on psychological symptoms of exhaustion, depression or anxiety were observed. In conclusion, tertiary interventions for individuals with clinically significant burnout may be effective in facilitating RTW. Successful interventions incorporated advice from labor experts and enabled patients to initiate a workplace dialogue with their employers.
Prevalence and correlates of tattooing in Norway: A large‐scale cross‐sectional study
Authors: Sagoe Dominic , Pallesen Ståle , Andreassen Cecilie Schou
Published: November 2017

To our knowledge, no previous large‐scale study has examined the prevalences and correlates of having only easily concealed tattoos, or readily visible tattoos. We conducted an exploratory online survey in Norway asking 15,654 (6,151 females) persons aged 16–91 (m = 33.65 ± 12.27) about various demographic, sports, substance use, mental health, personality, and tattooing questions. The estimated prevalence of tattooing was 20.8% (females: 23.8%, males: 17.9%), of which 13.3% had readily visible tattoos. Results of multivariate logistic regression analysis indicated that females, being older than 19 years, higher body mass index, lifetime anabolic‐androgenic steroid use (AAS), and higher scores on extraversion were associated with higher odds of having a tattoo. Factors associated with higher odds of having only easily concealed tattoos were being 40–49 (versus those ≤ 19) years old, being only high school or tertiary (versus being only primary school) educated, often or not (versus always) exercising in a gymnasium, and high scores on agreeableness. Females, and higher scores on extraversion and neuroticism were associated with higher odds of having at least one readily visible tattoo. Our findings delineate the significance of demographic variables, gymnasium exercise, AAS, and personality in the practice of tattooing.
Beyond disease susceptibility—Leveraging genome‐wide association studies for new insights into complex disease biology
Authors: Lee J. C.
Published: November 2017

Genetic studies in complex diseases have been highly successful, but have also been largely one‐dimensional: predominantly focusing on the genetic contribution to disease susceptibility. While this is undoubtedly important—indeed it is a pre‐requisite for understanding the mechanisms underlying disease development—there are many other important aspects of disease biology that have received comparatively little attention. In this review, I will discuss how existing genetic data can be leveraged to provide new insights into other aspects of disease biology, why such insights could change the way we think about complex disease, and how this could provide opportunities for better therapies and/or facilitate personalised medicine. To do this, I will use the example of Crohn's disease—a chronic form of inflammatory bowel disease that has been one of the main success stories in complex disease genetics. Indeed, thanks to genetic studies, we now have a much more detailed understanding of the processes involved in Crohn's disease development, but still know relatively little about what determines the subsequent disease course (prognosis) and why this differs so considerably between individuals. I will discuss how we came to realise that genetic variation plays an important role in determining disease prognosis and how this has changed the way we think about Crohn's disease genetics. This will illustrate how phenotypic data can be used to leverage new insights from genetic data and will provide a broadly applicable framework that could yield new insights into the biology of multiple diseases.
Genetic association of HLA‐DRB1 multiple polymorphisms with dermatomyositis in Chinese population
Authors: Lin JM , Zhang YB , Peng QL , Yang HB , Shi JL , Gu ML , Zhao WM , Wang GC
Published: November 2017

Genetic variation in HLA plays an important role in the pathogenesis of dermatomyositis (DM). The aim of this study was to investigate the association of HLA class II with DM in China. Two hundred and twenty‐four DM patients and 300 healthy controls were randomly enrolled at China‐Japan Friendship Hospital. High‐resolution typing of HLA‐DRB1 alleles was performed by sequencing based typing. The HLA‐DQA1 and HLA‐DQB1 alleles were determined by polymerase chain reaction sequence‐specific primers. The frequencies of HLA‐DRB1*09:01 (28.6% vs 11.3%, P < .0001, odds ratio, OR = 3.14, 95% confidence interval, CI = 2.47‐3.99) and HLA‐DRB1*12:01 (29.0% vs 11.0%, P < .0001, OR = 3.30, 95% CI = 2.59‐4.20) in DM patients were significantly higher than that in healthy controls. No significant difference was found in HLA‐DQA1 or DQB1 alleles between DM patients and healthy controls. Furthermore, DM patients with anti‐melanoma differentiation‐associated gene 5 antibody (anti‐MDA5) had a significantly higher frequency of HLA‐DRB1*12:01 compared to that for patients without anti‐MDA5 (P < .0001, OR = 4.77, 95% CI: 2.29‐9.93). Multivariate binary logistic regression analysis was performed to identify the risk factors for interstitial lung disease. The HLA‐DRB1*09:01 allele was a poor prognostic factor (P = .01, OR = 9.21, 95% CI: 1.47‐57.50) for DM patients with anti‐MDA5 autoantibody. In summary, our findings indicate that HLA‐DRB1*09:01 and HLA‐DRB1*12:01 alleles may contribute to susceptibility of adult DM in Han Chinese population. In addition, the DRB1*12:01 genotype is significantly associated with the presence of anti‐MDA5 antibody in DM patients.
Exhumation history and timing of supergene copper mineralisation in an arid climate: New thermochronological data from the Centinela District, Atacama, Chile
Authors: Sanchez Caroline , Brichau Stéphanie , Riquelme Rodrigo , Carretier Sébastien , Bissig Thomas , Lopez Cristopher , Mpodozis Constantino , Campos Eduardo , Regard Vincent , Hérail Gérard , Marquardt Carlos
Published: November 2017

Supergene copper mineralisation (SCM) processes occur during the unroofing of porphyry copper deposits. However, the geomorphological stage during which the main mineralisation occurs is still under debate. Here, we present 24 new thermochronological data from Cenozoic intrusives and compare them with the evolution of supergene mineralisation from the Centinela Mining District in the Atacama Desert. Our results indicate a two‐step cooling path: a rapid Late Eocene exhumation followed by a slow denudation. Previously published supergene mineralisation ages cluster after the main Upper Oligocene exhumation period. Ours is the first study that establishes the relationship between exhumation and supergene processes on the scale of a single mining district. It confirms that SCM took place during pediplanation, likely a required condition for efficient SCM under arid climatic conditions, in contrast to wet tropical environments where SCM occurs during rapid relief growth but has limited preservation potential.
A new species of Meristacarus from China, with supplementary description of Mixacarus (Phyllolohmannia) foliifer (Golosova, 1984) (Acari, Oribatida, Lohmanniidae)
Authors: Ren Guoru , Yang Maofa , Liang Wenqin , Xie Lixia
Published: November 2017

A new species of Lohmanniidae, Meristacarus pubescentius sp. nov., is described from soil and leaf litter of Hainan Province, South China. It can be distinguished from all other Meristacarus species by the following characters: anterior exobothridial setae thorn-like, shorter than the interlamellar setae by one-tenth, transverse bands S2–S4, S9, and S10 complete while S5–S8 are interrupted medially. The new species is most similar to M. douhereti Balogh & Balogh, 1983 in having setiform notogastral setae and the median setae shorter than the marginal setae, but differ from M. douhereti by the very short, thorn-like anterior exobothridial seta, heavily ciliated sensillus and notogastral seta e1 half as long as e2. A supplementary description of Mixacarus (Phyllolohmannia) foliifer (Golosova, 1984), a new record to the Chinese fauna, is given from the same locality. Keys to species of Meristacarus and Mixacarus (Phyllolohmannia) are presented.
Environmental Triazole Induces Cross-Resistance to Clinical Drugs and Affects Morphophysiology and Virulence of Cryptococcus gattii and C. neoformans
Authors: Bastos Rafael Wesley , Carneiro Hellem Cristina Silva , Oliveira Lorena Vívien Neves , Rocha Karen Maia , Freitas Gustavo José Cota , Costa Marliete Carvalho , Magalhães Thaís Furtado Ferreira , Carvalho Vanessa Silva Dutra , Rocha Cláudia Emanuela , Ferreira Gabriella Freitas , Paixão Tatiane Alves , Moyrand Frédérique , Janbon Guilhem , Santos Daniel Assis
Published: November 2017

Cryptococcus gattii
and
Cryptococcus neoformans
are environmental fungi that cause cryptococcosis, which is usually treated with amphotericin B and fluconazole. However, therapeutic failure is increasing because of the emergence of resistant strains. Because these species are constantly isolated from vegetal materials and the usage of agrochemicals is growing, we postulate that pesticides could be responsible for the altered susceptibility of these fungi to clinical drugs. Therefore, we evaluated the influence of the pesticide tebuconazole on the susceptibility to clinical drugs, morphophysiology, and virulence of
C. gattii
and
C. neoformans
strains. The results showed that tebuconazole exposure caused
in vitro
cross-resistance (CR) between the agrochemical and clinical azoles (fluconazole, itraconazole, and ravuconazole) but not with amphotericin B. In some strains, CR was observed even after the exposure ceased. Further, tebuconazole exposure changed the morphology, including formation of pseudohyphae in
C. neoformans
H99, and the surface charge of the cells. Although the virulence of both species previously exposed to tebuconazole was decreased in mice, the tebuconazole-exposed colonies recovered from the lungs were more resistant to azole drugs than the nonexposed cells. This
in vivo
CR was confirmed when fluconazole was not able to reduce the fungal burden in the lungs of mice. The tolerance to azoles could be due to increased expression of the
ERG11
gene in both species and of efflux pump genes (
AFR1
and
MDR1
) in
C. neoformans
. Our study data support the idea that agrochemical usage can significantly affect human pathogens present in the environment by affecting their resistance to clinical drugs.
Activity of Meropenem-Vaborbactam in Mouse Models of Infection Due to KPC-Producing Carbapenem-Resistant Enterobacteriaceae
Authors: Sabet Mojgan , Tarazi Ziad , Nolan Thomas , Parkinson Jonathan , Rubio-Aparicio Debora , Lomovskaya Olga , Dudley Michael N. , Griffith David C.
Published: November 2017

Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially
Klebsiella pneumoniae
carbapenemase (KPC)-producing, carbapenem-resistant
Enterobacteriaceae
. The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant
Enterobacteriaceae
, with meropenem MICs ranging from ≤0.06 to 8 mg/liter in the presence of 8 mg/liter vaborbactam. Mice were treated with meropenem alone or meropenem in combination with vaborbactam every 2 h for 24 h to provide exposures comparable to 2-g doses of each component in humans. Meropenem administered in combination with vaborbactam produced bacterial killing in all strains tested, while treatment with meropenem alone either produced less than 0.5 log CFU/tissue of bacterial killing or none at all. In the thigh model, 11 strains were treated with the combination of meropenem plus vaborbactam (300 plus 50 mg/kg of body weight). This combination produced from 0.8 to 2.89 logs of bacterial killing compared to untreated controls at the start of treatment. In the lung infection model, two strains were treated with the same dosage regimen of meropenem and vaborbactam. The combination produced more than 1.83 logs of bacterial killing against both strains tested compared to untreated controls at the start of treatment. Overall, these data suggest that meropenem-vaborbactam may have utility in the treatment of infections due to KPC-producing carbapenem-resistant
Enterobacteriaceae
.
Evaluation of Oritavancin Dosing Strategies against Vancomycin-Resistant Enterococcus faecium Isolates with or without Reduced Susceptibility to Daptomycin in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model
Authors: Belley Adam , Arhin Francis F. , Moeck Greg
Published: November 2017

The clinical development of nonsusceptibility to the lipopeptide antibiotic daptomycin remains a serious concern during therapy for infections caused by vancomycin-resistant
Enterococcus faecium
(VREfm). The long-acting lipoglycopeptide oritavancin exhibits potent
in vitro
activity against VREfm, although its safety and efficacy for treating clinical VREfm infections have not been established. In this study, novel dosing regimens of daptomycin and oritavancin were assessed against both VREfm and daptomycin-nonsusceptible VREfm isolates in an
in vitro
pharmacokinetic/pharmacodynamic model.
Comparative Assessment of Tedizolid Pharmacokinetics and Tissue Penetration between Diabetic Patients with Wound Infections and Healthy Volunteers via
In Vivo
Microdialysis
Authors: Stainton Sean M. , Monogue Marguerite L. , Baummer-Carr Arlinda , Shepard Ashley K. , Nugent James F. , Kuti Joseph L. , Nicolau David P.
Published: November 2017

Herein, we present pharmacokinetic and tissue penetration data for oral tedizolid in hospitalized patients with diabetic foot infections (DFI) compared with healthy volunteers. Participants received oral tedizolid phosphate 200 mg every 24 h for 3 doses to achieve steady state. A microdialysis catheter was inserted into the subcutaneous tissue near the margin of the wound for patients or into thigh tissue of volunteers. Following the third dose, 12 blood and 14 dialysate fluid samples were collected over 24 h to characterize tedizolid concentrations in plasma and interstitial extracellular fluid of soft tissue. Mean ± standard deviation (SD) tedizolid pharmacokinetic parameters in plasma for patients compared with volunteers, respectively, were as follows: maximum concentration (
C
max
), 1.5 ± 0.5 versus 2.7 ± 1.1 mg/liter (
P
= 0.005); time to
C
max
(
T
max
) (median [range]), 5.9 (1.2 to 8.0) versus 2.5 (2.0 to 3.0 h) (
P
= 0.003); half-life (t
1/2
), 9.1 ± 3.6 versus 8.9 ± 2.2 h (
P
= 0.932); and plasma area under the concentration-time curve for the dosing interval (AUC

p

), 18.5 ± 9.7 versus 28.7 ± 9.6 mg · h/liter (
P
= 0.004). The tissue area under the concentration-time curve (AUC

t

) for the dosing interval was 3.4 ± 1.5 versus 5.2 ± 1.6 mg · h/liter (
P
= 0.075). Tissue penetration median (range) was 1.1 (0.3 to 1.6) versus 0.8 (0.7 to 1.0) (
P
= 0.351). Despite lower plasma
C
max
and delayed
T
max
values for patients with DFI relative to healthy volunteers, the penetration into and exposure to tissue were similar. Based on available pharmacodynamic thresholds for tedizolid, the plasma and tissue exposures using the oral 200 mg once-daily regimen are suitable for further study in treatment of DFI.
Combating Multidrug-Resistant Pathogens with Host-Directed Nonantibiotic Therapeutics
Authors: Andersson Jourdan A. , Sha Jian , Kirtley Michelle L. , Reyes Emily , Fitts Eric C. , Dann Sara M. , Chopra Ashok K.
Published: November 2017

Earlier, we reported that three Food and Drug Administration-approved drugs, trifluoperazine (TFP; an antipsychotic), amoxapine (AXPN; an antidepressant), and doxapram (DXP; a breathing stimulant), identified from an
in vitro
murine macrophage cytotoxicity screen, provided mice with 40 to 60% protection against pneumonic plague when administered at the time of infection for 1 to 3 days. In the present study, the therapeutic potential of these drugs against pneumonic plague in mice was further evaluated when they were administered at up to 48 h postinfection. While the efficacy of TFP was somewhat diminished as treatment was delayed to 24 h, the protection of mice with AXPN and DXP increased as treatment was progressively delayed to 24 h. At 48 h postinfection, these drugs provided the animals with significant protection (up to 100%) against challenge with the agent of pneumonic or bubonic plague when they were administered in combination with levofloxacin. Likewise, when they were used in combination with vancomycin, all three drugs provided mice with 80 to 100% protection from fatal oral
Clostridium difficile
infection when they were administered at 24 h postinfection. Furthermore, AXPN provided 40 to 60% protection against respiratory infection with
Klebsiella pneumoniae
when it was administered at the time of infection or at 24 h postinfection. Using the same
in vitro
cytotoxicity assay, we identified an additional 76/780 nonantibiotic drugs effective against
K. pneumoniae
. For
Acinetobacter baumannii
, 121 nonantibiotic drugs were identified to inhibit bacterium-induced cytotoxicity in murine macrophages. Of these 121 drugs, 13 inhibited the macrophage cytotoxicity induced by two additional multiple-antibiotic-resistant strains. Six of these drugs decreased the intracellular survival of all three
A. baumannii
strains in macrophages. These results provided further evidence of the broad applicability and utilization of drug repurposing screening to identify new therapeutics to combat multidrug-resistant pathogens of public health concern.
Development of Subunit Vaccines That Provide High-Level Protection and Sterilizing Immunity against Acute Inhalational Melioidosis
Authors: Burtnick Mary N. , Shaffer Teresa L. , Ross Brittany N. , Muruato Laura A. , Sbrana Elena , DeShazer David , Torres Alfredo G. , Brett Paul J.
Published: November 2017

Burkholderia pseudomallei, the etiologic agent of melioidosis, causes severe disease in humans and animals. Diagnosis and treatment of melioidosis can be challenging, and no licensed vaccines currently exist. Several studies have shown that this pathogen expresses a variety of structurally conserved protective antigens that include cell surface polysaccharides and cell-associated and cell-secreted proteins. Based on those findings, such antigens have become important components of the subunit vaccine candidates that we are currently developing. In the present study, the 6-deoxyheptan capsular polysaccharide (CPS) fromB. pseudomalleiwas purified, chemically activated, and covalently linked to recombinant CRM197 diphtheria toxin mutant (CRM197) to produce CPS-CRM197. Additionally, tandem nickel-cobalt affinity chromatography was used to prepare highly purified recombinantB. pseudomalleiHcp1 and TssM proteins. Immunization of C57BL/6 mice with CPS-CRM197 produced high-titer IgG and opsonizing antibody responses against the CPS component of the glycoconjugate, while immunization with Hcp1 and TssM produced high-titer IgG and robust gamma interferon-secreting T cell responses against the proteins. Extending upon these studies, we found that when mice were vaccinated with a combination of CPS-CRM197 and Hcp1, 100% of the mice survived a lethal inhalational challenge withB. pseudomallei. Remarkably, 70% of the survivors had no culturable bacteria in their lungs, livers, or spleens, indicating that the vaccine formulation had generated sterilizing immune responses. Collectively, these studies help to better establish surrogates of antigen-induced immunity againstB. pseudomalleias well as provide valuable insights toward the development of a safe, affordable, and effective melioidosis vaccine.