bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin‐6, interleukin‐6 receptor gene variant, small‐vessel disease and incident dementia
Authors: Miwa K. , Okazaki S. , Sakaguchi M. , Mochizuki H. , Kitagawa K.
Published: January 2016

Background and purpose

Mixed neurogenerative and vascular dementia has emerged as the leading cause of dementia in the elderly. Inflammation is implicated in atherosclerosis, cerebral small‐vessel disease (SVD) as well as cognitive impairment. However, longitudinal data on the predictive value of circulating inflammatory markers including gene variants and magnetic resonance imaging (MRI) findings in incident dementia are scarce. It was investigated whether circulating interleukin‐6 (IL‐6), C‐reactive protein (CRP) and gene variants increase dementia risk.

Methods

In a cohort of Japanese participants with vascular risk factors in an observational study from 2001, the association between baseline IL‐6, CRP levels, gene variants [interleukin‐6 receptor (IL‐6R), rs2228145; IL‐6, rs2097677; CRP, rs3093059] and incident all‐cause dementia was evaluated. Baseline MRI was used to determine SVD (lacuna, white matter hyperintensities) and atrophy (medial‐temporal lobe atrophy, bicaudate ratio). Cox proportional hazards analyses were performed for predictors of dementia, adjusting for age, sex, apolipoprotein Eε4, education, cerebrovascular events, vascular risk factors and MRI findings.

Results

Of 803 subjects (mean 67.0 ± 8.5 years, males 59%), during a mean of 7.5 ± 3.2 years follow‐up, 60 incident dementia patients (Alzheimer's disease 31; vascular dementia 17; mixed‐type six; other six) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, MRI findings and IL‐6R variant (rs2228145), IL‐6 levels (relative risk 1.68, P = 0.048) or highest tertile (relative risk 2.38, P = 0.031) for all‐cause dementia remained significant. Although subjects with rs2228145 carrier had significantly higher IL‐6 levels, a significant association between rs2228145 and dementia was not observed. Conversely, CRP and remaining gene variants were not associated with dementia.

Conclusions

The deleterious effect of higher IL‐6 on dementia remains consistent irrespective of conventional risk factors, MRI findings and IL‐6R variant.
Influence of spatially dependent, modeled soil carbon emission factors on life‐cycle greenhouse gas emissions of corn and cellulosic ethanol
Authors: Qin Zhangcai , Dunn Jennifer B. , Kwon Hoyoung , Mueller Steffen , Wander Michelle M.
Published: January 2016

Converting land to biofuel feedstock production incurs changes in soil organic carbon (SOC) that can influence biofuel life‐cycle greenhouse gas (GHG) emissions. Estimates of these land use change (LUC) and life‐cycle GHG emissions affect biofuels' attractiveness and eligibility under a number of renewable fuel policies in the USA and abroad. Modeling was used to refine the spatial resolution and depth extent of domestic estimates of SOC change for land (cropland, cropland pasture, grassland, and forest) conversion scenarios to biofuel crops (corn, corn stover, switchgrass, Miscanthus, poplar, and willow) at the county level in the USA. Results show that in most regions, conversions from cropland and cropland pasture to biofuel crops led to neutral or small levels of SOC sequestration, while conversion of grassland and forest generally caused net SOC loss. SOC change results were incorporated into the Greenhouse Gases, Regulated Emissions, and Energy use in Transportation (GREET) model to assess their influence on life‐cycle GHG emissions of corn and cellulosic ethanol. Total LUC GHG emissions (g CO2eq MJ−1) were 2.1–9.3 for corn‐, −0.7 for corn stover‐, −3.4 to 12.9 for switchgrass‐, and −20.1 to −6.2 for Miscanthus ethanol; these varied with SOC modeling assumptions applied. Extending the soil depth from 30 to 100 cm affected spatially explicit SOC change and overall LUC GHG emissions; however, the influence on LUC GHG emission estimates was less significant in corn and corn stover than cellulosic feedstocks. Total life‐cycle GHG emissions (g CO2eq MJ−1, 100 cm) were estimated to be 59–66 for corn ethanol, 14 for stover ethanol, 18–26 for switchgrass ethanol, and −7 to −0.6 for Miscanthus ethanol. The LUC GHG emissions associated with poplar‐ and willow‐derived ethanol may be higher than that for switchgrass ethanol due to lower biomass yield.
T‐bet as a key regulator of mucosal immunity
Authors: Mohamed Rami , Lord Graham M.
Published: January 2016

Initially understood to be a key regulator of interferon‐γ‐producing helper T cells, our knowledge of T‐bet's functional roles has expanded to encompass a growing range of cellular lineages. In addition to regulating other interferon‐γ‐producing adaptive immune cells, it is now clear that T‐bet plays a fundamental role in the regulation of innate immune responses across mucosal surfaces. This homeostatic role is demonstrated by the spontaneous colitis that occurs when T‐bet is deleted from innate immune cells in RAG−/− mice. Using this model as a focal point, we review our understanding of T‐bet's regulation of adaptive and innate immune systems, focusing particularly on mucosal populations including innate lymphoid cells, dendritic cells and intraepithelial lymphocytes. With the increasingly diverse effects of T‐bet on different lineages, the classical binding‐centric paradigm of T‐bet's molecular functionality has increasingly struggled to account for the versatility of T‐bet's biological effects. Recent recognition of the synergistic interactions between T‐bet and other canonical transcription factors has led to a co‐operative paradigm that has provided greater explanatory power. Synthesizing insights from ChIP‐seq and comparative biology, we expand the co‐operative paradigm further and suggest a network approach as a powerful way to understand and model T‐bet's diverse functionality.
Transferring and implementing the general dynamic model of oceanic island biogeography at the scale of island fragments: the roles of geological age and topography in plant diversification in the Canaries
Authors: Otto Rüdiger , Whittaker Robert J. , von Gaisberg Markus , Stierstorfer Christian , Naranjo‐Cigala Agustín , Steinbauer Manuel J. , Borregaard Michael K. , Arévalo José Ramón , Garzón‐Machado Víctor , del Arco Marcelino , Fernández‐Palacios José María
Published: January 2016

Aim

The general dynamic model (GDM) of oceanic island biogeography integrates rates of immigration, speciation and extinction in relation to a humped trajectory of island area, species carrying capacity and topographic complexity through time, based on a simplified island ontogeny. In practice, many islands have more complex ontogenies, featuring surfaces of varying age. Here, we extend the GDM to apply at a local scale within islands, and test the predictions analytically within individual islands.

Location

El Hierro, La Palma and Tenerife (Canary Islands).

Methods

Following the GDM logic, we derive predictions for the distributions and richness of single island endemics (SIEs) across island landscapes of different age. We test these predictions by means of generalized linear models and binominal tests using gridded species occurrence data for vascular plant SIE species and a set of climatic, topographic and terrain age variables. We also examined phylogenetic divergence times for a subset of endemic lineages.

Results

Geological age, in interaction with slope, and topographic variables, best explained SIE richness at the landscape scale. About 70% of SIEs had ranges strongly biased to, or largely restricted to old terrain. Available phylogenetic divergence times of SIEs of radiated plant lineages suggested an origin on the older parts of the islands. Metrics of anthropogenic disturbance and habitat availability were unrelated to the observed SIE pattern.

Main conclusions

Our findings support the hypothesis that SIEs have evolved and accumulated on older and topographically complex terrain, while colonization processes predominate on the youngest parts. These results imply that evolutionary processes shape species distributions at the landscape scale within islands. This opens the perspective of extending the GDM framework to understand processes at a local scale within individual islands.
Accuracy and Usefulness of Select Methods for Assessing Complete Collection of 24‐Hour Urine: A Systematic Review
Authors: John Katherine A. , Cogswell Mary E. , Campbell Norm R. , Nowson Caryl A. , Legetic Branka , Hennis Anselm J. M. , Patel Sheena M.
Published: January 2016

Twenty‐four–hour urine collection is the recommended method for estimating sodium intake. To investigate the strengths and limitations of methods used to assess completion of 24‐hour urine collection, the authors systematically reviewed the literature on the accuracy and usefulness of methods vs para‐aminobenzoic acid (PABA) recovery (referent). The percentage of incomplete collections, based onPABA, was 6% to 47% (n=8 studies). The sensitivity and specificity for identifying incomplete collection using creatinine criteria (n=4 studies) was 6% to 63% and 57% to 99.7%, respectively. The most sensitive method for removing incomplete collections was a creatinine index <0.7. In pooled analysis (≥2 studies), mean urine creatinine excretion and volume were higher among participants with complete collection (P<.05); whereas, self‐reported collection time did not differ by completion status. Compared with participants with incomplete collection, mean 24‐hour sodium excretion was 19.6 mmol higher (n=1781 specimens, 5 studies) in patients with complete collection. Sodium excretion may be underestimated by inclusion of incomplete 24‐hour urine collections. None of the current approaches reliably assess completion of 24‐hour urine collection.
Effects of facial tooth movement on the periodontium in rats: a comparison between conventional and low force
Authors: Danz Jan C. , Bibby Bo M. , Katsaros Christos , Stavropoulos Andreas
Published: January 2016

Background

Bone dehiscences and gingival recession have been associated with orthodontic arch expansion. The aim of this study was to assess and compare periodontal modelling during application of two force levels.

Methods

The second and third upper molars were orthodontically moved buccally with conventional or low forces for 60 or 90 days in 32 rats. Ten non‐treated animals were used as controls. The influence of force level and time on dental, skeletal and periodontal parameters (i.e. height and thickness of gingiva and bone) was assessed on histomicrographs using a mixed linear model.

Results

Facial tooth position (725 μm, CI 379–1072 μm, distal root of the third molar) and maxillary skeletal width (295 μm, CI 168–421 μm) differed significantly between force groups. Despite bone apposition at the facial aspects of the moved roots, bone dehiscences were developing and bone thickness was decreasing during facial tooth movement. Development of gingival recession was scarce and in cases with extreme facial tooth movement. No remarkable differences between force levels were found for any of the periodontal parameters.

Conclusions

Facial tooth movement with conventional or low forces resulted in similar modelling of facial alveolar bone and gingiva.
Systemic administration of omeprazole interferes with bone healing and implant osseointegration: an in vivo study on rat tibiae
Authors: Al Subaie Ahmed , Emami Elham , Tamimi Iskandar , Laurenti Marco , Eimar Hazem , Abdallah Mohamed‐Nur , Tamimi Faleh
Published: January 2016

Background

Proton pump inhibitors, over‐the‐counter drugs taken by millions of patients, diminish bone accrual. Accordingly, we hypothesized that these drugs could impair bone healing and implant osseointegration. This study investigated the effect of post‐operative systemic administration of omeprazole on bone healing and implant osseointegration in rat tibiae.

Methods

In 24 Sprague–Dawley rats, a titanium implant was placed in the left tibia, and a bone defect was created in the right tibia. During the 2 weeks following surgery, 12 rats were treated with omeprazole (5 mg/kg, daily) and the other 12 with saline. Then, after euthanasia, the volume (mm3) of the cortical defect and the percentages of newly formed bone in the defect, were assessed using microcomputed tomography; peri‐implant bone volume/tissue volume and bone‐implant contact percentage were assessed by histomorphometry.

Results

Omeprazole‐treated rats presented larger cortical defects (2.75 ± 0.59 mm3, p = 0.003 versus 2.11 ± 0.36 mm3; p = 0.002) and a lower percentage of newly formed bone in the defects (28.62 ± 13.12; 45.89 ± 9.73; p = 0.003) than controls. Omeprazole‐treated rats presented lower peri‐implant bone volume/tissue volume (14.3 ± 7.3% versus 30.8 ± 11.0%; p < 0.001) and bone‐implant contact (23.3 ± 10.8% versus 41.8 ± 13.3%; p < 0.001) than controls.

Conclusion

Systemically administered omeprazole impairs bone healing and implant osseointegration.
A ‘reluctant’ critical review: ‘Manual for evidence‐based clinical practice (2015)’
Authors: Seshia Shashi S.
Published: January 2016

Background

The Users’ Guides to the Medical Literature Manual has been a major influence on the teaching and practice of health care globally.

Methods

The 3rd edition of the multi‐authored Manual was reviewed using the principles outlined in Evidence‐based Medicine (EBM) texts. One ‘clinical scenario’ was selected for critical appraisal, as were several chapters; objectivity was enhanced by citing references to support opinions.

Results (summary of the appraisal)

(1) Strengths: Clinical pearls, too numerous to list. Examples: (i) evidence is never enough to drive clinical decision making; (ii) do not rush to adopt new interventions; and (iii) question efficacy data based only on surrogate markers. (2) Weaknesses: The Manual shares shortcomings of textbooks discussed by Straus et al.: (i) references may not be current, important ones may be excluded and citations may be selective; (ii) often, opinion‐based; and (iii) delays between revisions. (3) Notable omissions: Little or no discussion of: (i) important segments of the population: those <18 years of age, >65 years of age and those with multimorbidity; (ii) surgical disciplines; (iii) Greenhalgh et al.'s essay on EBM; (iv) alternate views on the hierarchy of evidence; and (vi) critical thinking. (4) Additional issues: (i) Omission of important references on dabigatran (clinical scenario: chapter 13.1); (ii) authors’ advice (Chapter 13.3) to ‘bypass the discussion section of published research’; and (iii) the advocacy of pre‐appraised sources of evidence and network meta‐analysis without warnings about limitations, are critiqued.

Conclusion

The Manual has several clinical pearls but readers should also be aware of shortcomings.
The Relationship Between Nonsuicidal Self‐Injury and Family Functioning: Adolescent and Parent Perspectives
Authors: Kelada Lauren , Hasking Penelope , Melvin Glenn
Published: January 2016

We explored parent and adolescent reports of family functioning, how this differed if the parent was aware that their child self‐injured, and how parental awareness of self‐injury was related to self‐injury frequency, self‐injury severity, and help seeking. Participants were 117 parent–adolescent dyads, in 23 of which the adolescent self‐injured. Adolescents who self‐injured reported poorer family functioning than their parents, but parents who did not know about their child's self‐injury reported similar functioning to parents whose children did not self‐injure. Parents were more likely to know that their child self‐injured when the behavior was severe and frequent. Help‐seeking was more likely when parents knew about self‐injury. Family‐based interventions which emphasize perspective‐taking could be used to effectively treat self‐injury.
Broken Promises: Abstinence Pledging and Sexual and Reproductive Health
Authors: Paik Anthony , Sanchagrin Kenneth J. , Heimer Karen
Published: January 2016

Approximately 12% of girls and young women in the United States pledge abstinence. Yet most break their pledges, engaging in first intercourse before marriage. The extant literature reports few differences between pledge breakers and nonpledgers in sexually transmitted infections and nonmarital pregnancies. The present research maintains that previous studies may have obscured important differences in exposure risk and hypothesizes that female pledge breakers who have higher exposure risk are more likely to experience human papillomavirus (HPV) and nonmarital pregnancies. To test this hypothesis, this study uses the National Longitudinal Study of Adolescent to Adult Health, logistic regression, and event history modeling. The results show that, after accounting for differences in exposure risk, pledge breakers have higher risk of HPV and nonmarital pregnancy. As a set, the results are consistent with the argument that pledgers use condoms and contraceptives less consistently and highlight unintended consequences of abstinence promotion.
Prognostic Markers in Acute Babesia canis Infections
Authors: Eichenberger R.M. , Riond B. , Willi B. , Hofmann‐Lehmann R. , Deplazes P.
Published: January 2016

Background

Canine babesiosis, caused by Babesia canis, is a prevalent and clinically relevant disease in Europe. Severe acute babesiosis is characterized by a high mortality but prognosis is not always correlated with clinical signs nor with the level of parasitemia.

Objective

This study evaluated prognostic markers associated with poor outcomes in acute Babesia canis infections.

Animals and Methods

We compared the results of routine laboratory profiles, hand‐held lactate and glucose analyzer, and the acute phase response in 2 groups of naturally infected dogs (7 survivors and 8 nonsurvivors). Samples were collected at the time of first admission and before any treatment. Subsequently, the course of prognostic markers was followed in 3 dogs experimentally inoculated with B. canis.

Results

Nonsurvivors showed significantly higher concentrations of lactate, triglycerides and phosphate and lower hematocrit, leukocyte counts, total serum protein concentrations, and thrombocyte counts when compared to survivors. All nonsurvivors (8/8) had hyperlactatemia, whereas most survivors (6/7) had values within the reference range. All survivors had leucocyte counts within the reference range, unlike the nonsurvivors, which showed leukopenia. During the course of acute babesiosis, the variables serum lactate, triglyceride, and phosphate concentrations, and thrombocyte count only exceeded a prognostic threshold during acute crisis.

Conclusions and clinical importance

Poor outcome in acute B. canis infection is indicated by changes in the laboratory profile. Intensive care should be considered for dogs presenting with moderate anemia, severe thrombocytopenia, mild to moderate leukopenia, hyperlactatemia, moderately increased serum phosphate, and triglyceride concentrations, and moderately decreased total serum protein concentrations.
Hepatitis B virus: new therapeutic perspectives
Authors: Lin Chih‐Lin , Yang Hung‐Chih , Kao Jia‐Horng
Published: January 2016

Current antiviral therapies have dramatically improved the long‐term outcomes of patients with chronic hepatitis B virus (HBV) infection. Both interferon (IFN) and nucleos(t)ide analogue (NA) treatments have been shown to reduce the progression of liver disease in chronic hepatitis B (CHB) patients. However, persistent covalently closed circular DNA (cccDNA) can result in a viral relapse after discontinuation of antiviral treatment. On the basis of extensive research on the HBV lifecycle and virus–host interactions, several new agents focusing on viral and host targets are under development to cure HBV. New polymerase inhibitors, tenofovir alafenamide and besifovir provide effective and safer treatment for CHB patients. Agents targeting cccDNA, such as engineered site‐specific nucleases and RNA interference therapeutics could eliminate cccDNA or silence cccDNA transcription. Inhibitors of HBV nucleocapsid assembly suppress capsid formation and prevent synthesis of HBV DNA. The HBV entry inhibitor, Myrcludex‐B, has been shown to effectively inhibit amplification of cccDNA as well as the spread of intrahepatic infection. Agents targeting host factors that enhance innate and adaptive immune responses, including the lymphotoxin‐β receptor agonist, toll‐like receptor agonist, immune checkpoint inhibitors and adenovirus‐based therapeutic vaccine, could play a critical role in the elimination of HBV‐infected cells. With all of these promising approaches, we hope to reach the ultimate goal of a cure to HBV in the near future.
Hepatitis C virus: how to provide the best treatment with what I have
Authors: Nelson David R. , Peter Joy
Published: January 2016

The therapeutic landscape for the treatment of chronic hepatitis C virus infection has been rapidly evolving, and by 2016 there will be six approved, all‐oral regimens for use in patients in the USA and most of Western Europe. However, as many as patient populations will have limited access to new direct acting antiviral regimens, patients and physicians are often faced with the challenge of selecting the best regimen available, as opposed to the optimal treatment. In this paper, the challenges and opportunities in developing a high cure regimen for different patient populations will be discussed and highlighted through case‐based scenarios.
Is the benefit of treating patients with cirrhosis proven?
Authors: Bruno Savino , Boccaccio Vincenzo , Russo Maria Luisa , Maisonneuve Patrick
Published: January 2016

Hepatitis C virus (HCV)‐related cirrhosis is an extremely heterogeneous pathological condition with a wide spectrum of clinical manifestations, ranging from pre‐clinical to compensated and decompensated stages, each of which is characterized by a different clinical outcome. To measure the benefit of a sustained virological response (SVR) with interferon (IFN)‐based therapy, several studies have been performed in patients with compensated disease, while only a few have been performed in decompensated disease. Nevertheless, these studies have certain methodological weaknesses that may limit the accuracy of results. Access to new, more effective and safe direct acting antivirals (DAAs) has significantly changed these outcomes, with SVR rates that were not seen previously, making antiviral treatment available to patients with end‐stage liver disease. However, the clinical benefit of treating patients with late stage disease is still poorly understood and must be investigated. The existence of a point of no return beyond which a SVR is not beneficial has not yet been determined. All of these issues are discussed in this review.
Hepatitis E, the neglected one
Authors: Blasco‐Perrin Hélène , Abravanel Florence , Blasco‐Baque Vincent , Péron Jean Marie
Published: January 2016

Hepatitis E virus (HEV) infection is a worldwide disease. It is the first cause of acute viral hepatitis in the world with an estimated 20 million cases every year and 56 000 deaths. In developing countries, hepatitis E is a waterborne infection. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects with a significant mortality rate in pregnant women and patients with cirrhosis. In the developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. HEV can cause neurological disorders and in immunocompromised patients, chronic infections. The progression of acute hepatitis E is most often mild and resolves spontaneously. Diagnostic tools include anti‐HEV IgM antibodies in serum and/or viral RNA in the blood or stools by PCR. Ribavirin is used to treat chronic infection. A vaccine has been developed in China.
The adventure of delta
Authors: Rizzetto Mario
Published: January 2016

The hepatitis D virus (HDV) is unique in animal virology. It has a circular RNA genome that is the smallest of human viruses, requires the HBsAg capsid of the hepatitis B virus to assembly into infectious virions, parasitizes the transcriptional machinery of the host by hijacking cellular RNA polymerases to replicate its RNA genome and is replicated by a rolling circle mechanism unknown to mammalian cells. Hepatitis D is ubiquitous but prevalence varies throughout the world. It is the most severe form of chronic viral liver disorder; carriers of HBsAg superinfected by the HDV are the major victims and the reservoir of the infection. In the last 20 years vaccination against the hepatitis B virus (HBV) has decreased the circulation of HDV in industrialized countries; nevertheless hepatitis D is returning to Western Europe through immigration from HDV endemic areas. Hepatitis D is being rediscovered in the developing world. It has a significant medical impact on areas of Africa, Asia and South America where the partner HBV is not controlled; Pakistan and Mongolia appear to be worldwide the areas with the highest prevalence of the disease. A major obstacle in treatment is that the virus has no replicative function of its own to be targeted by antivirals. Peg‐Interferon remains the mainstay of treatment. New strategies are explored to prevent entry of the virion into hepatocytes by blocking the cellular HBsAg receptor or preventing the prenylation process of the large‐delta antigen necessary for the assembly of the HDV particle.
Iron and the liver
Authors: Pietrangelo Antonello
Published: January 2016

Humans have evolved to retain iron in the body and are exposed to a high risk of iron overload and iron‐related toxicity. Excess iron in the blood, in the absence of increased erythropoietic needs, can saturate the buffering capacity of serum transferrin and result in non‐transferrin‐bound highly reactive forms of iron that can cause damage, as well as promote fibrogenesis and carcinogenesis in the parenchymatous organs. A number of hereditary or acquired diseases are associated with systemic or local iron deposition or iron misdistribution in organs or cells. Two of these, the HFE‐ and non‐HFE hemochromatosis syndromes represent the paradigms of genetic iron overload. They share common clinical features and the same pathogenic basis, in particular, a lack of synthesis or activity of hepcidin, the iron hormone. Before hepcidin was discovered, the liver was simply regarded as the main site of iron storage and, as such, the main target of iron toxicity. Now, as the main source of hepcidin, it appears that the loss of the hepcidin‐producing liver mass or genetic and acquired factors that repress hepcidin synthesis in the liver may also lead to iron overload. Usually, there is low‐grade excess iron which, through oxidative stress, is sufficient to worsen the course of the underlying liver disease or other chronic diseases that are apparently unrelated to iron, such as chronic metabolic and cardiovascular diseases. In the future, modulation of hepcidin synthesis and activity or hepcidin hormone‐replacing strategies may become therapeutic options to cure iron‐related disorders.
HCV‐HIV co‐infected patients: no longer a ‘special’ population?
Authors: Sulkowski Mark S.
Published: January 2016

Prior to the advent of safe and highly effective hepatitis C virus (HCV) treatment, patients with human immunodeficiency virus (HIV)/HCV co‐infection were referred to as a ‘special’ population. This definition was based on more rapid HCV disease progression in the presence of HIV co‐infection, limited effectiveness of interferon‐based HCV treatment and potential drug interactions between medications used to treat HIV and those to treat HCV infection. Although the availability of interferon‐free, oral direct‐acting antivirals (DAAs) has dramatically increased the effectiveness of HCV treatment in patients with HIV co‐infection, this population still warrants special consideration. Specific issues for the treatment of patients with HIV/HCV co‐infection in the era of oral DAAs include a high HCV disease burden with ongoing HCV infection and re‐infection following successful treatment, frequent drug interactions that must be carefully evaluated and unanswered questions on the role of shorter HCV treatment durations.
Resource limitation underlying multiple masting models makes mast seeding sensitive to future climate change
Authors: Monks Adrian , Monks Joanne M. , Tanentzap Andrew J.
Published: January 2016

Mechanistic models can help resolve controversy over the responses of mast seeding plants to future environmental change.

We evaluate drivers of mast seeding by: developing and validating a new mechanistic resource‐based model of mast seeding using four 40‐yr Chionochloa (snow tussock) datasets; and comparing the performance of competing empirically‐based statistical models, that aim to approximate the mechanisms underlying mast seeding, in explaining simulated and observed data.

Our mechanistic model explained 90–99% of the variation in Chionochloa flowering, with higher rates of stored resource mobilisation and lower probability of climatic induction of flowering occurring at lower fertility sites. Inter‐annual variation in floral induction and the degree to which seeding is resource‐limited explained shifts in the relative performance of different empirical models fitted to data simulated from the mechanistic model. Empirical models explicitly capturing the interaction between the floral induction cue and internal resource state underlying the resource‐limited induction mechanism had > 8.7× the statistical support of alternatives when fitted to Chionochloa datasets.

We find support for resource‐limited floral induction with multiple empirical models consistent with this same mechanism. As both resource acquisition and flowering cues are climate sensitive, we expect climate change to impact upon patterns of mast seeding.
TNL‐mediated immunity in Arabidopsis requires complex regulation of the redundant ADR1 gene family
Authors: Dong Oliver Xiaoou , Tong Meixuezi , Bonardi Vera , El Kasmi Farid , Woloshen Virginia , Wünsch Lisa K. , Dangl Jeffery L. , Li Xin
Published: January 2016

Nucleotide‐binding leucine‐rich repeat proteins (NLRs) serve as intracellular immune receptors in animals and plants. Sensor NLRs perceive pathogen‐derived effector molecules and trigger robust host defense. Recent studies revealed the role of three coiled‐coil‐type NLRs (CNLs) of the ADR1 family – ADR1, ADR1‐L1 and ADR1‐L2 – as redundant helper NLRs, whose function is required for defense mediated by multiple sensor NLRs.

From a mutant snc1‐enhancing (MUSE) forward genetic screen in Arabidopsis targeted to identify negative regulators of snc1 that encodes a TIR‐type NLR (TNL), we isolated two alleles of muse15, both carrying mutations in ADR1‐L1. Interestingly, loss of ADR1‐L1 also enhances immunity‐related phenotypes in other autoimmune mutants including cpr1, bal and lsd1. This immunity‐enhancing effect is not mediated by increased SNC1 protein stability, nor is it fully dependent on the accumulation of the defense hormone salicylic acid (SA).

Transcriptional analysis revealed an upregulation of ADR1 and ADR1‐L2 in the adr1‐L1 background, which may overcompensate the loss of ADR1‐L1, resulting in enhanced immunity. Interestingly, autoimmunity of snc1 and chs2, which encode typical TNLs, is fully suppressed by the adr1 triple mutant, suggesting that the ADRs are required for TNL downstream signaling.

This study extends our knowledge on the interplay among ADRs and reveals their complexity in defense regulation.
Structurally distinct Arabidopsis thaliana NLR immune receptors recognize tandem WY domains of an oomycete effector
Authors: Goritschnig Sandra , Steinbrenner Adam D. , Grunwald Derrick J. , Staskawicz Brian J.
Published: January 2016

Nucleotide‐binding leucine‐rich repeat (NB‐LRR, or NLR) receptors mediate pathogen recognition. The Arabidopsis thaliana NLR RPP1 recognizes the tandem WY‐domain effector ATR1 from the oomycete Hyaloperonospora arabidopsidis through direct association with C‐terminal LRRs.

We isolated and characterized homologous NLR genes RPP1‐EstA and RPP1‐ZdrA from two Arabidopsis ecotypes, Estland (Est‐1) and Zdarec (Zdr‐1), responsible for recognizing a novel spectrum of ATR1 alleles.

RPP1‐EstA and ‐ZdrA encode nearly identical NLRs that are phylogenetically distinct from known immunity‐activating RPP1 homologs and possess greatly expanded LRR domains. Site‐directed mutagenesis and truncation analysis of ATR1 suggests that these homologs recognize a novel surface of the 2nd WY domain of ATR1, partially specified by a C‐terminal region of the LRR domain. Synteny comparison with RPP1 loci involved in hybrid incompatibility suggests that these functions evolved independently.

Closely related RPP1 homologs have diversified their recognition spectra through LRR expansion and sequence variation, allowing them to detect multiple surfaces of the same pathogen effector. Engineering NLR receptor specificity may require a similar combination of repeat expansion and tailored amino acid variation.
The effectiveness of nasal mask vs face mask ventilation in anesthetized, apneic pediatric subjects over 2 years of age: a randomized controlled trial
Authors: Itagaki Taiga , Gubin Tatyana A. , Sayal Puneet , Jiang Yandong , Kacmarek Robert M. , Anderson Thomas Anthony
Published: January 2016

Background

We hypothesized that anesthetized, apneic children could be ventilated equivalently or more efficiently by nasal mask ventilation (NMV) than face mask ventilation (FMV). The aim of this randomized controlled study was to test this hypothesis by comparing the expiratory tidal volume (Vte) between NMV and FMV.

Methods

After the induction of anesthesia, 41 subjects, 3–17 years of age without anticipated difficult mask ventilation, were randomly assigned to receive either NMV or FMV with neck extension. Both groups were ventilated with pressure control ventilation (PCV) at 20 cmH2O of peak inspiratory pressure (PIP) with positive end‐expiratory pressure (PEEP) levels of 0, 5, and 10 cmH2O. An additional mouth closing maneuver (MCM) was applied for the NMV group.

Results

The Vte was higher in the FMV group compared with the NMV group (median difference [95% CI]: 8.4 [5.5–11.6] ml·kg−1; P < 0.001) when MCM was not applied. NMV achieved less PEEP than FMV (median difference [95% CI]: 5.0 [4.3–5.3] cmH2O at 10 cmH2O; P < 0.001) though both groups achieved the set PIP level. In the NMV group, MCM markedly increased Vte (median increase [95% CI]: 5.9 [2.5–9.0] ml·kg−1; P < 0.005) and PEEP (median increase [95% CI]: 5.0 [0.6–8.6] cmH2O at 10 cmH2O; P < 0.005); however, PEEP was highly variable and lower than that of FMV (median difference [95% CI]: 2.5 [0.8–8.5] cmH2O at 10 cmH2O; P < 0.05).

Conclusions

In anesthetized, apneic children greater than 2 years of age ventilated with an anesthesia ventilator and neck extension, FMV established a greater Vte than NMV regardless of mouth status. NMV could not maintain the set PEEP level due to an air leak from the mouth. The MCM increased the Vte and PEEP.
A novel null HLA‐B allele, B*15:375N, due to a seven base pair deletion within exon 3
Authors: Planelles D. , Balas A. , Muñoz C. , Puig N. , Vicario J. L.
Published: January 2016

Characterization of a novel HLA‐B null allele, B*15:375N, with a seven base pair deletion in exon 3.
Ambush by Dre: A Case Study of the National Football League and the Challenges Arising from Conflicting Sponsorship Strategies
Authors: Naraine Michael L. , Séguin Benoît , MacIntosh Eric
Published: January 2016

In this case study, students are exposed to the issue of stakeholder management through the lens of the National Football League (NFL), using a contemporary example of ambush marketing and player endorsement deals as the primary context. The case depicts nonfictitious events that involve players and their disdain for league policies regarding donning brands and products that violate exclusivity agreements the league has with other companies. After identifying the origins of the circumstances, the case profiles the three principal stakeholder groups involved (i.e., the players, the ambushed sponsor, and the focal organization) through their respective leaders (i.e., DeMaurice Smith, executive director of the NFL players association, Bob Maresca, president of Bose Corporation, and Roger Goodell, Commissioner of the NFL). Using fictitious commentary, the case culminates with the three actors utilizing the services of a sports consultancy firm as they work together to determine the best course of action. Learning objectives include understanding collegiality in a professional setting, and mitigating conflicting sponsorship strategies.
Becoming Physically Literate for Life: Embracing the Functions, Forms, Feelings and Flows of Alternative and Mainstream Physical Activity
Authors: Lloyd Rebecca J.
Published: January 2016

Purpose:

To explore a conceptual shift from mechanism, the dominant ‘body-as-machine’ (Tinning, 2010) paradigm, to vitalism, the philosophical phenomenological tenets of physical literacy (Whitehead, 2010) upon which the curriculum of physical education in Canada is based, within the context of an alternative physical education program.

Method:

A motion-sensitive phenomenological approach (Lloyd & Smith, 2006b; 2015), conceptually framed by the Function2Flow (F2F) model, was conducted with a sample of N = 153 students from seven different schools in Ottawa (Canada) who booked the JungleSport climbing program of their own accord. Sources of information included phenomenological observations, small group interviews, and journal entries. Exemplars of two in depth student experiences are featured in this article.

Results & Discussion:

The phenomenological analysis of the climbing experiences, in addition to the F2F curriculum support tools that were developed, provide practical and philosophical pathways for understanding how we may broaden assessments of learning in physical education.
Leveling the Playing Field? Perspectives and Observations of Coed Intramural Flag Football Modifications
Authors: Wood Zacharias C. , Garn Alex C.
Published: January 2016

Although sport is regarded as a bastion of male hegemony, coed settings offer females the opportunity to compete alongside males. Coed environments, however, often include rule modifications that intend to facilitate female participation, which promote female inferiority assumptions. This study sought to critique modifications in the divisive world of coed flag football through the lens of benevolent sexism and the shifting standards model. Observational field notes and interview data gathered over a season revealed that the equity perceived to be legislated by rule modifications was overshadowed by negative outcomes, as modifications perpetuated stereotypes and reinforced an environment of male domination. We discuss the ubiquity of male superiority beliefs within coed flag football and implications of the unintended consequences of rule modifications.
Pseudomyxoma peritonei with intrathoracic extension: a rare disease with rarer presentation from low-grade mucinous adenocarcinoma of the appendix
Authors: Ghosh Raktim K , Somasundaram Mey , Ravakhah Keyvan , Hassan Chandra
Published: January 2016

Pseudomyxoma peritonei is an extremely rare disease, characterised by mucinous ascites and implants, diffusely involving the peritoneal surfaces. Recent pathological and genetic advances indicate that they mostly originate from an appendiceal adenoma or adenocarcinoma. The successful treatment of peritoneal carcinomatosis requires a comprehensive management plan including cytoreductive surgery, intraoperative intraperitoneal heated chemotherapy and postoperative systemic chemotherapy. It is extremely rare to have intrathoracic spread of the disease at initial presentation. Some of the possible hypotheses of neoplastic cells spreading into the pleural cavity include congenital or acquired pleura-peritoneal communications, invasion of lymphovascular space and, rarely, through direct invasion of the diaphragm.
Unusual cause of chest pain: empyema necessitans and tubercular osteomyelitis of the rib in an immunocompetent man
Authors: Dunphy Louise , Shetty Prashanth , Kavidasan Ajitkumar , Rice Alexandra
Published: January 2016

A 33-year-old man, born in India but resident in the UK for 5 years, presented to the emergency department with a 4-week history of a dry cough and right-sided pleuritic chest pain. He reported systemic features, including fever and unintentional weight loss. His medical history included vitamin D deficiency. He had travelled to India 10 months previously and denied any exposure to tuberculosis (TB). He was an ex-smoker with a 20 pack history. Respiratory examination confirmed decreased air entry of the right lower lobe and stony dullness on percussion. His C reactive protein was 178 mg/L. A chest radiograph identified a moderate-sized right-sided pleural effusion and destruction of the lateral aspect of the right fifth rib, strongly suggestive of underlying malignancy. Further investigation with a CT of the thorax identified a focal lytic lesion in the right fifth rib, at its lateral aspect, with expansion of the rib observed. Ultrasound-guided pleural aspiration confirmed an exudative pleural effusion. Gram stain revealed no organisms or polymorphs. Four days post admission, the patient was transferred to the regional thoracic surgery unit and underwent video-assisted thoracic surgery, bronchoscopy and drainage of his empyema. His Mantoux tuberculin skin test and his TB Elispot were negative, suggesting that TB infection was unlikely. Culture confirmed no growth after 48 h incubation. Histology of his pleural biopsy identified multiple non-confluent necrotising granulomatous inflammation with very occasional acid–alcohol-fast bacilli-like organisms, highly suspicious for mycobacterial infection. The isolate,Mycobacterium tuberculosis, was identified by Accuprobe and HAIN tests, respectively. MPT64 erythrocyte sedimentation rate (ESR) results from the fifth rib were positive forM. tuberculosis. This case report discusses the aetiology, clinical presentation and pathophysiology of both empyema necessitans and tubercular osteomyelitis of the rib.
Osteitis pubis after standard bipolar TURP surgery: insight into aetiology, diagnosis, management and prevention of this rarity
Authors: Davis Niall F , Torregiani William , Thornhill John
Published: January 2016

Transurethral resection of the prostate (TURP) surgery is standard treatment for symptomatic benign prostatic hyperplasia when medical therapy has failed. We describe a rare case of osteitis pubis secondary to a prostato-symphocoele sinus after standard bipolar TURP surgery. We also discuss diagnostic techniques and management strategies, and provide an insight into the aetiology of this rare phenomenon. Conservative management with intravenous antibiotics and an indwelling catheter was successful in our case. Treatment in more severe cases may include laparotomy with peritoneal or omental interposition or open retropubic radical prostatectomy to remove the entire sinus tract.
An unusual response with long term survival using erlotinib in NSCLC lung with brain metastases
Authors: Rastogi Madhup , Nanda Sambit Swarup , Prakash Chandra , Kulshreshtha Dinkar
Published: January 2016

We present a case of a middle-aged woman with adenocarcinoma of the lung and metastatic brain lesions. In view of her poor general condition and poor compliance to first-line chemotherapy, the patient was kept on tablet erlotinib after whole brain radiotherapy. This novel treatment resulted in a dramatic response with radiological regression in both the primary lung lesion and metastatic intracranial lesions translating in unexpected and ongoing 24-month survival.
Concurrent insulinoma and impaired glucose tolerance suspected as owing to obesity
Authors: Iizuka Katsumi , Fujisawa Taro , Takeda Jun
Published: January 2016

An obese 68-year-old woman was admitted for examination of fasting hypoglycaemia. A prolonged 18 h fast reduced her plasma glucose without suppressing insulin secretion, while plasma β-hydroxybutyrate levels were suppressed. Despite the prolonged fast, the glucose response to glucagon was increased by 25 mg/dL (1.39 mM) glucose, which is compatible with insulinoma. A 75 g oral glucose tolerance test (75 g OGTT) showed impaired glucose tolerance. An abdominal CT scan revealed a mass lesion in the uncinate process of the pancreas, a finding consistent with the results of angiography and selective artery calcium injection test. The patient then underwent a pancreaticoduodenectomy; the pancreatic mass was histologically diagnosed as benign insulinoma. After surgery, a prolonged 24 h fast caused no hypoglycaemia and the glucose tolerance capacity in 75 g OGTT improved. Eight months after surgery, the patient's body weight had reduced by 10 kg. This is therefore a case of concurrent insulinoma and impaired glucose tolerance.
Basic science behind the cardiovascular benefits of exercise
Authors: Wilson Mathew G , Ellison Georgina M , Cable N Tim
Published: January 2016

Cardiorespiratory fitness is a strong predictor of cardiovascular (CV) disease and all-cause mortality, with increases in cardiorespiratory fitness associated with corresponding decreases in CV disease risk. The effects of exercise upon the myocardium and vascular system are dependent upon the frequency, intensity and duration of the exercise itself. Following a prolonged period (≥6 months) of regular intensive exercise in previously untrained individuals, resting and submaximal exercising heart rates are typically 5–20 beats lower, with an increase in stroke volume of ∼20% and enhanced myocardial contractility. Structurally, all four heart chambers increase in volume with mild increases in wall thickness, resulting in greater cardiac mass due to increased myocardial cell size. With this in mind, the present paper aims to review the basic science behind the CV benefits of exercise. Attention will be paid to understanding (1) the relationship between exercise and cardiac remodelling; (2) the cardiac cellular and molecular adaptations in response to exercise, including the examination of molecular mechanisms of physiological cardiac growth and applying these mechanisms to identify new therapeutic targets to prevent or reverse pathological remodelling and heart failure; and (3) vascular adaptations in response to exercise. Finally, this review will briefly examine how to optimise the CV benefits of exercise by considering how much and how intense exercise should be.
Floral organogenesis in Urophysa rockii, a rediscovered endangered and rare species of Ranunculaceae
Authors: Zhao Liang , Gong Jing-zhi , Zhang Xiao-hui , Liu You-quan , Ma Xiao , Ren Yi
Published: January 2016

Urophysa is an Asian endemic genus in the Ranunculaceae, but data on floral organogenesis, which would be a useful complement to molecular data in clarifying the relationship with closely related taxa (Aquilegia and Semiaquilegia) in Ranunculaceae, are completely lacking. We used scanning electron microscopy and light microscopy to study the floral development of Urophysa rockii Ulbrich, a recently rediscovered species in this genus. The sepals are initiated spirally, whereas other organs are nonsimultaneously whorled; the floral phyllotaxis is whorled. Primordia of the sepals are lunular and truncate, but those of the petals and stamens are hemispherical and rounded. After sepal initiation, there is a delay in development, but the initiation of petals and stamens is continuous. The developmental sequence of the microspores in the stamens is centrifugal, although the stamens are initiated centripetally. The early developmental stages of the staminodes are similar to those of the stamens, although much smaller, so they may be phylogenetically homologous organs. The carpel primordia are lunular in shape and plicate. The mature ovule is anatropous and bitegmic. Urophysa shows similar floral development features as Aquilegia and Semiaquilegia, although with some differences, which supports the relationship inferred by DNA sequence data.