bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of liver transplantation on endocrine function: a systematic review
Authors: Gariani Karim , Toso Christian , Philippe Jacques , Orci Lorenzo A.
Published: May 2016

Patients with chronic liver disease (CLD) often experience secondary endocrine dysfunction. Therefore, because the liver plays a major role in endocrine function, liver transplantation (LT) may also be beneficial for the restoration of hormonal regulation. This systematic review collects and interprets the available literature on the effect ofLTon endocrine and sexual function in adult patients. A systematic review was conducted by searching Pubmed (including Medline) andEMBASEfor studies published from database inception until November 2015. We collected all relevant studies that discussed changes in hormonal and sexual function afterLT. Studies were included if they assessed the effect ofLTon sexual function or one of the following components of the hormone/endocrine axis: the hypothalamus–pituitary–gonadal axis, growth hormone (GH), insulin‐like growth factor‐1 (IGF‐1) or thyroid function. The results are reported according to the Meta‐analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Twenty‐one studies with a total of 1274 patients were included. The results collected from the included studies suggested thatLTimproves the hormonal perturbation associated withCLDby restoring physiological levels of circulatingGH,IGF‐1, testosterone, estradiol, prolactin, follicle‐stimulating hormone (FSH) and luteinizing hormone (LH). Thyroid function was not affected byLT, and sexual function was partially improved afterLT. This systematic review suggests thatLTis associated with an improvement in endocrine and sexual function in patients withCLD. This information should encourage clinicians who treatCLDpatients to identify endocrine disturbances in this population, inform their patients of the effects ofLTand assess post‐transplantation improvements.
Genetic and morphological evidence of a geographically widespread hybrid zone between two crocodile species,Crocodylus acutusandCrocodylus moreletii
Authors: Pacheco‐Sierra Gualberto , Gompert Zachariah , Domínguez‐Laso Jerónimo , Vázquez‐Domínguez Ella
Published: May 2016

Hybrid zones represent natural laboratories to study gene flow, divergence and the nature of species boundaries between closely related taxa. We evaluated the level and extent of hybridization betweenCrocodylus moreletiiandCrocodylus acutususing genetic and morphological data on 300 crocodiles from 65 localities. To our knowledge, this is the first genetic study that includes the entire historic range and sympatric zone of the two species. Contrary to expectations, Bayesian admixture proportions and maximum‐likelihood estimates of hybrid indexes revealed that most sampled crocodiles were admixed and that the hybrid zone is geographically extensive, extending well beyond their historical region of sympatry. We identified a few geographically isolated, nonadmixed populations of both parental species. Hybrids do not appear to be F1s or recent backcrosses, but rather are more likely later‐generation hybrids, suggesting that hybridization has been going on for several to many generations and is mostly the result of natural processes.Crocodylus moreletiiis not the sister species ofC. acutus, suggesting that the hybrid zone formed from secondary contact rather than primary divergence. Nonadmixed individuals from the two species were distinguishable based on morphological characters, whereas hybrids had a complex mosaic of morphological characters that hinders identification in the wild. Very few nonadmixedC. acutusandC. moreletiipopulations exist in the wild. Consequently, the last nonadmixedC. moreletiipopulations have become critically endangered. Indeed, not only the parental species but also the naturally occurring hybrids should be considered for their potential conservation value.
Kudiezi Injection® Alleviates Blood–Brain Barrier Disruption After Ischemia‐Reperfusion in Rats
Authors: Chen Fu‐Qin , Li Quan , Pan Chun‐Shui , Liu Yu‐Ying , Yan Li , Sun Kai , Mao Xiao‐Wei , Mu Hong‐Na , Wang Ming‐Xia , Wang Chuan‐She , Fan Jing‐Yu , Cui Yuan‐Chen , Zhang Yun‐Pei , Yang Jia‐Yi , Bai Wen , Han Jing‐Yan
Published: May 2016

Objective

This study was designed to examine the effect of KDZ, on the BBB disruption in rat underwent MCAO and reperfusion.

Methods

Male Sprague–Dawley rats (260–280 g) were subjected to 60 minutes MCAO followed by reperfusion. KDZ (4 mL/kg) was administrated before ischemia. The Evans blue extravasation, albumin leakage, brain water content, TJ proteins, caveolin‐1, p‐caveolin‐1, Src, and p‐Src were evaluated. Neurological scores, cerebral infarction, and CBF were assessed. The binding affinity of KDZ to Src was examined.

Results

I/R evoked a range of insults including Evans blue extravasation, albumin leakage, brain water content increase, CBF decrease, cerebral infarction, and neurological deficits, all of which were attenuated by KDZ. Meanwhile, KDZ inhibited TJ proteins down‐expression, expression of caveolin‐1, phosphorylation of caveolin‐1 and Src after I/R. In addition, SPR revealed binding of KDZ to Src with high affinity.

Conclusions

KDZ protects BBB from disruption and improves cerebral outcomes following I/R via preventing the degradation of TJ proteins, caveolin‐1 expression, and inhibiting p‐caveolin‐1 and p‐Src, which were most likely attributable to the ability of its main ingredients to bind to Src and inhibit its phosphorylation.
The effect of dietary interventions and nutritional supplementation on bone mineral density in otherwise healthy adults with osteopenia: A systematic review
Authors: Porter J. , Adderley M. , Bonham M. , Costa R. J. S. , Dart J. , McCaffrey T. , Ryan L. , Davidson Z. E.
Published: May 2016

There are many health and economic consequences for patients with osteopenia, the precursor to osteoporosis. A range of treatments may provide positive outcomes for otherwise healthy adults, including dietary and exercise approaches, either alone or in combination. The primary aim of this systematic review was to evaluate the effect of dietary approaches (including diet alone, diet with dietary supplements, both with or without physical activity intervention) on bone mineral density (BMD) to treat adults aged ≥18 years who were classified as having osteopenia. Six databases (Ovid MEDLINE including Ovid Medline in process, Cochrane Library, EMBASE, CINAHL Plus, Web of Science and Scopus) were searched systematically to identify randomised controlled trials of dietary approaches to treat osteopenic adults published from 1994 to November 2014. Study eligibility was determined, and included studies were assessed for risk of bias. Outcome data, particularly the primary outcomes of BMD T‐ and Z‐scores or other measures of bone density, were combined narratively. The searches yielded 3511 papers, with three studies fulfilling the inclusion criteria. These studies included 254 participants, all free‐living post‐menopausal females with confirmed osteopenia. Vitamin D interventions were tested in all included studies, with none showing significant differences between intervention and placebo groups on BMD. This review has identified a lack of evidence to guide clinical practice in this area. Opportunities exist for future research to determine the effect of non‐pharmacological approaches to osteopenia treatment in healthy populations, especially research that considers younger‐aged and male populations, physical activity, habitual dietary intake and key bone health nutrients.
Hot topics in nutrition research in Ireland
Authors: Nugent A. P.
Published: May 2016

This article provides a flavour of some of the nutrition‐related research underway in Ireland at present. Specific areas range from biomarker discovery and personalised nutrition to assessments of food, nutrient and food chemical intake using data collected as part of national food surveys. Other areas include the influence of genetics, diet and lifestyle on diet and health outcomes, targeted programmes to assist lifestyle change in ‘at risk’ groups, such as those at risk of cardiovascular disease. Irish researchers are also collaborating with the food industry to identify and characterise functional foods and bioactives, which can be commercialised. Much of this research feeds into European Union‐wide ventures ranging from Joint Programme Initiatives to the activities of the European Food Safety Authority.
Diet and gout – what is the role of purines?
Authors: Lockyer S. , Stanner S.
Published: May 2016

Anecdotally, consumption of ‘rich’ foods and drinks, such as cheese and port, has been associated with the development of gout, a painful condition linked to high serum uric acid which normally affects joints in the extremities, such as toes. Risk factors for gout include obesity, genetics and use of certain medications, and men appear to be more at risk. In addition, sufferers report that certain foods trigger gout flares, although there is a paucity of evidence from randomised controlled trials investigating the effect of specific foods on circulating uric acid. Observational studies have consistently identified a positive relationship between gout and some, but not all, foods higher in compounds known as purines, which have been demonstrated to increase serum uric acid in their purified form under controlled conditions. This evidence indicates that foods which should be avoided or consumed infrequently by gout sufferers are offal, seafood and alcohol, especially beer, whereas dairy foods seem to be protective. Current dietary guidelines for the prevention and management of gout share common features and largely reflect international healthy eating guidelines, but differences exist in terms of reference to particular foods or nutrients such as fructose, vitamin C and cherries. More randomised controlled trials are needed to fully ascertain the effects of dietary components on gout risk and to generate more consistent guidelines.
The Eatwell Guide refreshed
Authors: Buttriss J. L.
Published: May 2016

This article provides a brief history about UK food‐based dietary guidelines as a prelude to discussion about new the Eatwell Guide and changes to 5 A DAY messaging launched in March 2016. Included is a summary of the main changes made and the methodology used to steer the development of the new Eatwell Guide (linear programming). Brief reference is also made to the principal differences between the new UK guide and food‐based guidelines used in other parts of the world.
Relationship between dyslipidemia and vascular repair after cervical artery dissection
Authors: Yamada Shuichi , Ohnishi Hideyuki , Kuga Yoshihiro , Kodama Yuji , Hayashi Masato , Takahashi Kenkichi , Takamura Yoshiaki , Nakase Hiroyuki , Nakagawa Ichiro
Published: May 2016

Background

In some cases of cervical artery dissection, vascular repair subsequently occurs at the stenotic or occluded sites. The factors responsible for this type of vascular repair remain unknown, but some reports from in vitro and animal models suggest that it is related to lipid metabolism.

Aim

In the present study, we investigated the relationship between vascular repair and dyslipidemia in cervical artery dissection.

Methods

Patients with internal carotid artery and vertebral artery dissection who were admitted between April 2012 and March 2015 were included. Vascular repair was evaluated using magnetic resonance angiography. All patients were treated conservatively using antihypertensive and antiplatelet drugs, and also with statins in the presence of dyslipidemia. In this study, we investigated the relationship between vascular repair and dyslipidemia in cervical artery dissection.

Results

Vascular repair was observed in 34 out of 55 patients (61.8%, repair group). Total cholesterol (203 mg/dL in repair group vs 225 mg/dL in non‐repair group), low‐density lipoprotein cholesterol (119 mg/dL vs 140 mg/dL), low‐density lipoprotein cholesterol/high‐density lipoprotein cholesterol ratio (2.09 vs 2.74) and triglycerides (117 mg/dL vs 154 mg/dL) were significantly negatively correlated with vascular repair. However, statin use was not significantly related to this type of repair.

Conclusions

We showed a relationship between vascular repair after cervical artery dissection and dyslipidemia. As cervical artery dissection often occurs at a relatively young age, vascular repair and the management of dyslipidemia are important issues to consider for the prevention of arteriosclerotic cerebrovascular diseases in later life.
Living well in light of science
Authors: McMahon Darrin M.
Published: May 2016

This article discusses some findings of the modern science of happiness in the context of historical understandings of happiness. Comparing teachings of the ancient wisdom traditions to those of modern positive psychology and social science, I argue that there is surprising correspondence between the two. The happy life, both ancients and modern agree, involves training and the development and mastery of particular character traits.
Rainforest carbon financing in New Zealand: A case study of REDD+ on Māori land
Authors: Weaver Sean Andrew
Published: May 2016

This study examines a case study of the Rarakau Rainforest Conservation Project on Māori‐owned land in western Southland – New Zealand's first and only REDD+ project. It explores the potential for REDD+ projects on Māori land throughout the country. Key findings show that REDD+ is technically feasible in New Zealand, but commercially dependent on (currently low) demand in the domestic retail carbon offset and ‘corporate social responsibility’ market. Market research suggests that there is sufficient demand to cater to the needs of a small number of REDD+ projects, but insufficient demand to roll out a nation‐wide scheme.
Magnetoencephalographic recording of auditory mismatch negativity in response to duration and frequency deviants in a single session in patients with schizophrenia
Authors: Suga Motomu , Nishimura Yukika , Kawakubo Yuki , Yumoto Masato , Kasai Kiyoto
Published: May 2016

Aim

Auditory mismatch negativity (MMN) and its magnetoencephalographic (MEG) counterpart (MMNm) are an established biological index in schizophrenia research. MMN in response to duration and frequency deviants may have differential relevance to the pathophysiology and clinical stages of schizophrenia. MEG has advantage in that it almost purely detects MMNm arising from the auditory cortex. However, few previous MEG studies on schizophrenia have simultaneously assessed MMNm in response to duration and frequency deviants or examined the effect of chronicity on the group difference.

Methods

Forty‐two patients with chronic schizophrenia and 74 matched control subjects participated in the study. Using a whole‐head MEG, MMNm in response to duration and frequency deviants of tones was recorded while participants passively listened to an auditory sequence.

Results

Compared to healthy subjects, patients with schizophrenia exhibited significantly reduced powers of MMNm in response to duration deviant in both hemispheres, whereas MMNm in response to frequency deviant did not differ between the two groups. These results did not change according to the chronicity of the illness.

Conclusion

These results, obtained by using a sequence‐enabling simultaneous assessment of both types of MMNm, suggest that MEG recording of MMN in response to duration deviant may be a more sensitive biological marker of schizophrenia than MMN in response to frequency deviant. Our findings represent an important first step towards establishment of MMN as a biomarker for schizophrenia in real‐world clinical psychiatry settings.
Cross‐Milieu Terrorist Collaboration: Using Game Theory to Assess the Risk of a Novel Threat
Authors: Ackerman Gary A. , Zhuang Jun , Weerasuriya Sitara
Published: May 2016

This article uses a game‐theoretic approach to analyze the risk of cross‐milieu terrorist collaboration—the possibility that, despite marked ideological differences, extremist groups from very different milieus might align to a degree where operational collaboration against Western societies becomes possible. Based upon theoretical insights drawn from a variety of literatures, a bargaining model is constructed that reflects the various benefits and costs for terrorists’ collaboration across ideological milieus. Analyzed in both sequential and simultaneous decision‐making contexts and through numerical simulations, the model confirms several theoretical arguments. The most important of these is that although likely to be quite rare, successful collaboration across terrorist milieus is indeed feasible in certain circumstances. The model also highlights several structural elements that might play a larger role than previously recognized in the collaboration decision, including that the prospect of nonmaterial gains (amplification of terror and reputational boost) plays at least as important a role in the decision to collaborate as potential increased capabilities does. Numerical simulation further suggests that prospects for successful collaboration over most scenarios (including operational) increase when a large, effective Islamist terrorist organization initiates collaboration with a smaller right‐wing group, as compared with the other scenarios considered. Although the small number of historical cases precludes robust statistical validation, the simulation results are supported by existing empirical evidence of collaboration between Islamists and right‐ or left‐wing extremists. The game‐theoretic approach, therefore, provides guidance regarding the circumstances under which such an unholy alliance of violent actors is likely to succeed.
Perception of Climate Risk among Rural Farmers in Vietnam: Consistency within Households and with the Empirical Record
Authors: Cullen Alison C. , Anderson C. Leigh
Published: May 2016

Rural farmers in Vietnamese communes perceive climate risk and potential impacts on livelihood within a complex context that may influence individual and household decisions. In a primary survey of 1,145 residents of the Thach Ha district of Ha Tinh province, we gathered data regarding perception about stability in climate, potential risks to livelihood, demographic characteristics, orientation toward risk, and interest in expanding economic activity. Temporal analysis of meteorological and economic indicator data forms an empirical basis for comparison with human perception. We ask the basic question: Are rural farmers’ perceptions of climate consistent with the historical record and reproducible within households? We find that respondents do perceive climate anomalies, with some anchoring on recent extreme events as revealed by climate observational data, and further that spouses disproportionately share perceptions relative to randomly simulated pairings. To put climate‐related risk perception in a larger context, we examine patterns across a range of risks to livelihood faced by farmers (livestock disease, pests, markets, health), using dimension reduction techniques. We find that our respondents distinguish among potential causes of low economic productivity, with substantial emphasis on climate‐related impacts. They do not express uniform concern across risks, but rather average patterns reveal common modes and distinguish climate concern. Still, among those expressing concern about climate‐related risks to livelihood we do not find an association with expressed intention to pursue changes in economic activity as a risk management response.
Radiographers' perceptions of their professional rights in diagnostic radiography: a qualitative interview study
Authors: Matilainen Kati , Ahonen Sanna‐Mari , Kankkunen Päivi , Kangasniemi Mari
Published: May 2016

Background

Considering the ethics of each profession is important as inter‐professional collaboration increases. Professional ethics creates a basis for radiographers' work, as it includes values and principles, together with rights and duties that guide and support professionals. However, little is known about radiographers' rights when it comes to professional ethics.

The Aim

The aim of this study was to describe radiographers' perceptions and experiences of their professional rights. The ultimate aim was to increase the understanding of professional ethics in this context and support radiographers' ethical pondering in diagnostic radiography.

Methodology

A qualitative method was used. Semistructured group interviews with 15 radiographers were conducted in spring 2013 at two publicly provided diagnostic imaging departments in Finland. Data were analysed by inductive content analysis. All the participants were women, and they had worked as radiographers for an average of 18 years.

Findings

Based on our analysis, radiographers' professional rights consisted of rights related to their expertise in radiography and the rights related to working conditions that ensured their wellbeing. Expertise‐based rights included rights to plan, conduct and assess radiological care with patient advocacy. Radiographers have the right to contribute to a culture of safe radiation in their organisation and to use their professional knowledge to achieve their main target, which is the safe imaging of patients. Radiographers also have right to work in conditions that support their well‐being, including the legal rights stated in their employment contract, as well as their rights concerning resources at work.

Conclusions

Radiographers' professional rights are an elementary and multidimensional part of their clinical practice. In future, more theoretical and empirical research is needed to deepen the understanding of their rights in the clinical practice and support radiographers on issues related to this aspect of their work.
A discussion of differences in preparation, performance and postreflections in participant observations within two grounded theory approaches
Authors: Berthelsen Connie Bøttcher , Lindhardt Tove , Frederiksen Kirsten
Published: May 2016

This paper presents a discussion of the differences in using participant observation as a data collection method by comparing the classic grounded theory methodology of Barney Glaser with the constructivist grounded theory methodology by Kathy Charmaz. Participant observations allow nursing researchers to experience activities and interactions directly in situ. However, using participant observations as a data collection method can be done in many ways, depending on the chosen grounded theory methodology, and may produce different results. This discussion shows that how the differences between using participant observations in classic and constructivist grounded theory can be considerable and that grounded theory researchers should adhere to the method descriptions of performing participant observations according to the selected grounded theory methodology to enhance the quality of research.
Ghetto–Society–Problem: A Discourse Analysis of Nationalist Othering
Authors: Bakkær Simonsen Kristina
Published: May 2016

This article examines the role of the ghetto in Danish political discourse. While ghetto studies have previously been conducted within the field of urban sociology, the article departs from this tradition in offering a discourse analytical perspective on the former Danish government's strategy against ghettoization (The Ghetto Plan). Integrating perspectives from the literature on nationalism with Laclau and Mouffe's discourse analytical framework, the analysis argues that the ghetto marks an antagonistic anti‐identity to Danish society. This discursive construction of the ghetto against society has the effect of confirming Danish identity, while at the same time precluding possibilities of the ghetto's integration in society. Highlighting these implications, the study feeds into societal debates on integration, and suggests a framework for studying nationalist othering in a discourse analytical perspective.
Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane
Authors: Chichger Havovi , Cleasby Mark E. , Srai Surjit K. , Unwin Robert J. , Debnam Edward S. , Marks Joanne
Published: May 2016

New Findings

What is the central question of this study?

Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown.

What is the main finding and its importance?

In vivo models of metabolic disruption (Goto–Kakizaki type II diabetic rat and junk‐food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT‐ and GLUT‐mediated glucose uptake. A fasted model of metabolic disruption (high‐fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors.

SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet‐induced insulin resistance. The study used Goto–Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk‐food or high‐fat diets. Levels of protein kinase C‐βI (PKC‐βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT‐ and SGLT‐mediated d‐[3H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT‐ and SGLT‐mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC‐βI and SGLT1 protein. Junk‐food and high‐fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC‐βI. However, the junk‐food diet also increased SGLT1 and SGLT2 levels at the proximal tubule BBM. Glucose reabsorption across the proximal tubule BBM, via GLUT2, SGLT1 and SGLT2, is not solely dependent on glycaemic status, but is also influenced by diet‐induced changes in glucose metabolism. We conclude that different metabolic disturbances result in complex adaptations in renal glucose transporter protein levels and function.
Intervisceral artery origins in patients with abdominal aortic aneurysmal disease; evidence for systemic vascular remodelling
Authors: Bailey Damian M. , Evans Tom G. , Thomas Kate Gower , White Richard D. , Twine Chistopher P. , Lewis Michael H. , Williams Ian M.
Published: May 2016

New Findings

What is the central question of this study?

To what extent focal abdominal aortic aneurysmal (AAA) disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between distances of the intervisceral artery origins and AAA location/size in patients with disease compared with healthy patients.

What is the main finding and its importance?

Intervisceral artery distances were shown to be consistently greater in AAA patients, highlighting the systemic nature of AAA disease that extends proximally to the abdominal aorta and its branches. The anatomical description of the natural variation in visceral artery origins has implications for the design of stent grafts and planning complex open aortic surgery.

The initial histopathology of abdominal aortic aneurysmal (AAA) disease is atherosclerotic, later diverting towards a distinctive dilating rather than occlusive aortic phenotype. To what extent focal AAA disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between the intervisceral artery origins and AAA location/size in patients with AAA disease (AAA+) relative to those without (AAA−). Preoperative contrast‐enhanced computerized tomograms were reviewed in 90 consecutive AAA+ patients scheduled for open repair who underwent an infrarenal (n = 45), suprarenal (n = 26) or supracoeliac clamp (n = 19). These were compared with 39 age‐matched AAA− control patients. Craniocaudal measurements were recorded from the distal origin of the coeliac artery to the superior mesenteric artery and from the origin of the superior mesenteric artery to both renal artery origins. Serial blood samples were obtained for estimation of the glomerular filtration rate before and after surgery. Intervisceral artery origins were shown to be consistently greater in AAA+ patients (P < 0.05 versus AAA−), although unrelated to AAA diameter (P > 0.05). Postoperative renal function became progressively more impaired the more proximal the clamp placement (estimated glomerular filtration rate for supracoeliac < suprarenal < infrarenal clamps, P < 0.05). These findings highlight the systemic nature of AAA disease that extends proximally to the abdominal aorta and its branches. The anatomical description of the natural variation in visceral artery origins has implications for the design of stent grafts and planning complex open aortic surgery.
Nonlinear cochlear mechanics
Authors: Zweig George
Published: May 2016

An earlier paper characterizing the linear mechanical response of the organ of Corti [J. Acoust. Soc. Am. 138, 1102–1121 (2015)] is extended to the nonlinear domain. Assuming the existence of nonlinear oscillators nonlocally coupled through the pressure they help create, the oscillator equations are derived and examined when the stimuli are modulated tones and clicks. The nonlinearities are constrained by the requirements of oscillator stability and the invariance of zero crossings in the click response to changes in click amplitude. The nonlinear oscillator equations for tones are solved in terms of the fluid pressure that drives them, and its time derivative, presumably a proxy for forces created by outer hair cells. The pressure equation is reduced to quadrature, the integrand depending on the oscillators' responses. The resulting nonlocally coupled nonlinear equations for the pressure, and oscillator amplitudes and phases, are solved numerically in terms of the fluid pressure at the stapes. Methods for determining the nonlinear damping directly from measurements are described. Once the oscillators have been characterized from their tone and click responses, the mechanical response of the cochlea to natural sounds may be computed numerically. Signal processing inspired by cochlear mechanics opens up a new area of nonlocal nonlinear time-frequency analysis.
Can the elongated hindwing tails of fluttering moths serve as false sonar targets to divert bat attacks?
Authors: Lee Wu-Jung , Moss Cynthia F.
Published: May 2016

It has long been postulated that the elongated hindwing tails of many saturniid moths have evolved to create false sonar targets to divert the attack of echolocation-guided bat predators. However, rigorous echo-acoustic evidence to support this hypothesis has been lacking. In this study, fluttering luna moths (Actias luna), a species with elongated hindwing tails, were ensonified with frequency modulated chirp signals from all angles of orientation and across the wingbeat cycle. High-speed stereo videography was combined with pulse compression sonar processing to characterize the echo information available to foraging bats. Contrary to previous suggestions, the results show that the tail echoes are weak and do not dominate the sonar returns, compared to the large, planar wings and the moth body. However, the distinctive twisted morphology of the tails create persistent echoes across all angles of orientation, which may induce erroneous sonar target localization and disrupt accurate tracking by echolocating bats. These findings thus suggest a refinement of the false target hypothesis to emphasize sonar localization errors induced by the twisted tails, and highlight the importance of physics-based approaches to study the sensory information involved in the evolutionary arms race between moths and their bat predators.
The transcription factor FOXF1 promotes prostate cancer by stimulating the mitogen-activated protein kinase ERK5
Authors: Fulford Logan , Milewski David , Ustiyan Vladimir , Ravishankar Navin , Cai Yuqi , Le Tien , Masineni Sreeharsha , Kasper Susan , Aronow Bruce , Kalinichenko Vladimir V. , Kalin Tanya V.
Published: May 2016

Prostate cancers positive for FOXF1 depend on the kinase ERK5.
Science Signaling
Podcast for 10 May 2016: PKCα in Alzheimer’s disease
Authors: Newton Alexandra C. , Tanzi Rudolph E. , VanHook Annalisa M.
Published: May 2016

Activating mutations in PKCα are associated with and may contribute to the pathology of Alzheimer’s disease.
Paper of note in
Science Translational Medicine
Authors: Ferrarelli Leslie K.
Published: May 2016

This week’s article describes why combinatorial treatments are necessary for some progressive inflammatory diseases.
Papers of note in
Science
Authors: VanHook Annalisa M.
Published: May 2016

This week’s articles highlight protein engineering, epigenetics, nuclear biology, and cellular responses that contribute to neurological disorders.
Microglia combat addiction
Authors: Ferrarelli Leslie K.
Published: May 2016

Drugs that activate microglia suppress excitatory glutamatergic synapses to reduce cocaine-craving behaviors in mice.
Potential Use of Fosfomycin-Tromethamine for Treatment of Recurrent Campylobacter Species Enteritis
Authors: Aguilar-Company Juan , Los-Arcos Ibai , Pigrau Carles , Rodríguez-Pardo Dolors , Larrosa María Nieves , Rodríguez-Garrido Virginia , Sihuay-Diburga Denisse , Almirante Benito
Published: May 2016

We report 2 cases of recurrent
Campylobacter coli
enteritis caused by macrolide- and fluoroquinolone-resistant strains in 2 patients with hypogammaglobulinemia, successfully treated with a prolonged course of fosfomycin-tromethamine with no side effects. Fosfomycin-tromethamine may be a feasible alternative therapy for recurrent enteritis caused by
Campylobacter
species resistant to first-line drugs.
Comparison of the Exposure Time Dependence of the Activities of Synthetic Ozonide Antimalarials and Dihydroartemisinin against K13 Wild-Type and Mutant Plasmodium falciparum Strains
Authors: Yang Tuo , Xie Stanley C. , Cao Pengxing , Giannangelo Carlo , McCaw James , Creek Darren J. , Charman Susan A. , Klonis Nectarios , Tilley Leann
Published: May 2016

Fully synthetic endoperoxide antimalarials, namely, OZ277 (RBx11160; also known as arterolane) and OZ439 (artefenomel), have been approved for marketing or are currently in clinical development. We undertook an analysis of the kinetics of the
in vitro
responses of
Plasmodium falciparum
to the new ozonide antimalarials. For these studies we used a K13 mutant (artemisinin resistant) isolate from a region in Cambodia and a genetically matched (artemisinin sensitive) K13 revertant. We used a pulsed-exposure assay format to interrogate the time dependence of the response. Because the ozonides have physicochemical properties different from those of the artemisinins, assay optimization was required to ensure that the drugs were completely removed following the pulsed exposure. Like that of artemisinins, ozonide activity requires active hemoglobin degradation. Short pulses of the ozonides were less effective than short pulses of dihydroartemisinin; however, when early-ring-stage parasites were exposed to drugs for periods relevant to their
in vivo
exposure, the ozonide antimalarials were markedly more effective.
Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages
Authors: Durão Paulo , Gülereşi Daniela , Proença João , Gordo Isabel
Published: May 2016

The evolution of multiple-antibiotic-resistant bacteria is an increasing global problem. Even though mutations causing resistance usually incur a fitness cost in the absence of antibiotics, the magnitude of such costs varies across environments and genomic backgrounds. We studied how the combination of mutations that confer resistance to rifampin (Rif
r
) and streptomycin (Str
r
) affects the fitness of
Escherichia coli
when it interacts with cells from the immune system, i.e., macrophages (Mϕs). We found that 13 Rif
r
Str
r
doubly resistant genotypes, of the 16 tested, show a survival advantage inside Mϕs, indicating that double resistance can be highly beneficial in this environment. Our results suggest that there are multiple paths to acquire multiple-drug resistance in this context, i.e., if a clone carrying Rif
r
allele H526 or S531 acquires a second mutation conferring Str
r
, the resulting double mutant has a high probability of showing increased survival inside Mϕs. On the other hand, we found two cases of sign epistasis between mutations, leading to a significant decrease in bacterial survival. Remarkably, infection of Mϕs with one of these combinations, K88R+H526Y, resulted in an altered pattern of gene expression in the infected Mϕs. This indicates that the fitness effects of resistance may depend on the pattern of gene expression of infected host cells. Notwithstanding the benefits of resistance found inside Mϕs, the Rif
r
Str
r
mutants have massive fitness costs when the bacteria divide outside Mϕs, indicating that the maintenance of double resistance may depend on the time spent within and outside phagocytic cells.
Recombinant Human Peptidoglycan Recognition Proteins Reveal Antichlamydial Activity
Authors: Bobrovsky Pavel , Manuvera Valentin , Polina Nadezhda , Podgorny Oleg , Prusakov Kirill , Govorun Vadim , Lazarev Vassili
Published: May 2016

Peptidoglycan recognition proteins (PGLYRPs) are innate immune components that recognize the peptidoglycan and lipopolysaccharides of bacteria and exhibit antibacterial activity. Recently, the obligate intracellular parasite
Chlamydia trachomatis
was shown to have peptidoglycan. However, the antichlamydial activity of PGLYRPs has not yet been demonstrated. The aim of our study was to test whether PGLYRPs exhibit antibacterial activity against
C. trachomatis
. Thus, we cloned the regions containing the human
Pglyrp1
,
Pglyrp2
,
Pglyrp3
, and
Pglyrp4
genes for subsequent expression in human cell lines. We obtained stable HeLa cell lines that secrete recombinant human PGLYRPs into culture medium. We also generated purified recombinant PGLYRP1, -2, and -4 and confirmed their activities against Gram-positive (
Bacillus subtilis
) and Gram-negative (
Escherichia coli
) bacteria. Furthermore, we examined the activities of recombinant PGLYRPs against
C. trachomatis
and determined their MICs. We also observed a decrease in the infectious ability of chlamydial elementary bodies in the next generation after a single exposure to PGLYRPs. Finally, we demonstrated that PGLYRPs attach to
C. trachomatis
elementary bodies and activate the expression of the chlamydial two-component stress response system. Thus, PGLYRPs inhibit the development of chlamydial infection.
De Novo
Guanine Biosynthesis but Not the Riboswitch-Regulated Purine Salvage Pathway Is Required for Staphylococcus aureus Infection
In Vivo
Authors: Kofoed Eric M. , Yan Donghong , Katakam Anand K. , Reichelt Mike , Lin Baiwei , Kim Janice , Park Summer , Date Shailesh V. , Monk Ian R. , Xu Min , Austin Cary D. , Maurer Till , Tan Man-Wah
Published: May 2016

De novo
guanine biosynthesis is an evolutionarily conserved pathway that creates sufficient nucleotides to support DNA replication, transcription, and translation. Bacteria can also salvage nutrients from the environment to supplement the
de novo
pathway, but the relative importance of either pathway during
Staphylococcus aureus
infection is not known. In
S. aureus
, genes important for both
de novo
and salvage pathways are regulated by a guanine riboswitch. Bacterial riboswitches have attracted attention as a novel class of antibacterial drug targets because they have high affinity for small molecules, are absent in humans, and regulate the expression of multiple genes, including those essential for cell viability. Genetic and biophysical methods confirm the existence of a bona fide guanine riboswitch upstream of an operon encoding xanthine phosphoribosyltransferase (
xpt
), xanthine permease (
pbuX
), inosine-5′-monophosphate dehydrogenase (
guaB
), and GMP synthetase (
guaA
) that represses the expression of these genes in response to guanine. We found that
S. aureus
guaB
and
guaA
are also transcribed independently of riboswitch control by alternative promoter elements. Deletion of
xpt-pbuX-guaB-guaA
genes resulted in guanine auxotrophy, failure to grow in human serum, profound abnormalities in cell morphology, and avirulence in mouse infection models, whereas deletion of the purine salvage genes
xpt-pbuX
had none of these effects. Disruption of
guaB
or
guaA
recapitulates the
xpt-pbuX-guaB-guaA
deletion
in vivo
. In total, the data demonstrate that targeting the guanine riboswitch alone is insufficient to treat
S. aureus
infections but that inhibition of
guaA
or
guaB
could have therapeutic utility.

IMPORTANCE
De novo
guanine biosynthesis and purine salvage genes were reported to be regulated by a guanine riboswitch in
Staphylococcus aureus
. We demonstrate here that this is not true, because alternative promoter elements that uncouple the
de novo
pathway from riboswitch regulation were identified. We found that in animal models of infection, the purine salvage pathway is insufficient for
S. aureus
survival in the absence of
de novo
guanine biosynthesis. These data suggest targeting the
de novo
guanine biosynthesis pathway may have therapeutic utility in the treatment of
S. aureus
infections.
Radiodermatitis after spinal arteriovenous fistula embolisation
Authors: Marinello Elena , Causin Francesco , Brumana Marta Benedetta , Alaibac Mauro
Published: May 2016

We report acute radiation dermatitis on a patient's back and left arm, which developed 4 weeks after endovascular embolisation of a spinal arteriovenous malformation. Vesciculation and erosions were followed by a gradual re-epithelisation of the skin resulting in rectangular hyperpigmented patches that resolved almost completely within 1 month. Fluoroscopic radiodermatitis has been reported with more frequency over the past decades because of the rise in duration and number of procedures performed under fluoroscopic guidance. Articles concerning this issue are mostly limited to case reports after coronary interventions, renal artery catheterisations, transjugular intrahepatic portosystemic shunt procedures and embolisations of intracranial arteriovenous malformation. To the best of our knowledge, only two cases of radiation dermatitis after spinal arteriovenous malformation embolisation have been reported to date.
Nasal and conjunctival screening prior to refractive surgery: an observational and cross-sectional study
Authors: Kitazawa Koji , Sotozono Chie , Sakamoto Masako , Sasaki Miho , Hieda Osamu , Yamasaki Toshihide , Kinoshita Shigeru
Published: May 2016

Objectives

To investigate bacterial flora of clinically healthy conjunctiva and nasal cavity among patients prior to refractive surgery, as well as the characteristics of patients with methicillin-resistantStaphylococcus aureus(MRSA) colonisation.

Design

Observational and cross-sectional study.

Setting

A single-centre study in Japan.

Participants

120 consecutive patients pre-refractive surgery.

Primary and secondary outcome measures methods

Samples were obtained from the right conjunctival sac and the nasal cavity of 120 consecutive patients prior to refractive surgery and were then measured for the levels of the minimum inhibitory concentration (MIC) of antibiotics. Patients were interviewed regarding their occupation, family living situation and any personal history of atopic dermatitis, asthma, smoking or contact lens wear.

Results

Propionibacterium acnes(P. acnes) (32.5%) andStaphylococcus epidermidis(4.2%) were detected from the conjunctival sac.S. epidermidiswas the most commonly isolated (68.3%) in the nasal cavity. Of the 30 patients (25.0%) with colonisation byS. aureus, 2 patients, both of whom were healthcare workers with atopic dermatitis, were found to be positive for MRSA in the nasal cavity. A history of contact lens wear, asthma or smoking, as well as patient gender and age, was not associated with MRSA colonisation.

Conclusions

There were only 2 patients who were colonised with MRSA, both of whom were healthcare workers with atopic dermatitis.P. acneswas predominantly found in the conjunctival sac. Further study is needed to investigate the involvement between nasal and conjunctival flora, and risk factors for infectious complications.
Validity of whole slide images for scoring HER2 chromogenic in situ hybridisation in breast cancer
Authors: Al-Janabi Shaimaa , Horstman Anja , van Slooten Henk-Jan , Kuijpers Chantal , Lai-A-Fat Clifton , van Diest Paul J , Jiwa Mehdi
Published: May 2016

Aim

Whole slide images (WSIs) have stimulated a paradigm shift from conventional to digital pathology in several applications within pathology. Due to the fact that WSIs have not yet been approved for primary diagnostics, validating their use for different diagnostic purposes is still mandatory. The aim of this study was to test the validity of WSI in assessing human epidermal growth factor receptor 2 (HER2) status in breast cancer specimens using chromogenic in situ hybridisation (CISH).

Materials and methods

Ninety-six HER2 CISH slides were scored by two observers on a light microscope (400× viewing magnification) and on WSI (40× scanning magnification, one focus plane) with a minimum of 6 weeks washout period. The concordance between digital and microscopic HER2 scores was assessed.

Results

Digitally, 93/96 cases could be assessed (96.8%). Microscopic and digital evaluation of HER2 amplification status were concordant in 68/93 cases ((73.1%, 95% CI: 0.639 −0.823), κ 0.588). CISH underscoring was most noticeable in the amplified and equivocal categories while the highest level concordance was seen in cases with a normal copy number. Additionally there was a noticeable tendency to underestimate the average HER2 scores on WSI: lower in 59 and higher in 11 cases. There was no major difference in time spent for microscopic scoring (86.9 s) and digital scoring (81.7 s).

Conclusions

There was a reasonable concordance between microscopic scoring and WSI-based scoring of HER2 copy number of CISH slides. Nevertheless, WSIs scanned on a single focal plane are insufficient to assess HER2 gene amplification status by scoring CISH due to the noticeable tendency towards digitally underestimating the number of HER2 spots. Scanning at multiple focus planes may offer better resolution for improved digital CISH spot counting.