Alexithymia and problematic alcohol use: A critical update

Publication date: February 2018
Source:Addictive Behaviors, Volume 77
Author(s): K.E. Cruise, R. Becerra
There has been a substantial growth in empirical research aimed at examining the co-occurrence of alexithymia and problematic alcohol use and alcohol use disorder (AUD) since Thorberg, Young, Sullivan, and Lyvers (2009) original review article. The objective of the present paper is therefore to provide a critical update review of research on alexithymia and problematic alcohol use published since 2009. A systematic search was conducted through PsychINFO, Medline, and ProQuest databases to obtain relevant literature published between 2009 and 2016. Studies that involved measures of alexithymia and problematic alcohol use among clinical and non-clinical samples were included. Prevalence rates of alexithymia among Alcohol Dependent (AD) samples were identified between 30 and 49%, and were therefore much lower than originally reported. The findings of this update review highlight an indirect relationship between alexithymia and alcohol problem severity that is mediated by a number of psychological drinking constructs (e.g., alcohol expectancy, drinking motives, craving and alcohol related intrusive thoughts) and psychological risk factors for the development of alcohol related problems (e.g., mood and emotion dysregulation, attachment, trauma, and cognitive function). In addition, this review provides reasonable evidence to support alexithymia as an independent risk factor for alcohol related problems among clinical samples only. In conclusion, alexithymia is a multifaceted construct that has a complex relationship with various risk factors and psychological drinking constructs. The growing body of research highlights the demand for understanding the interrelationships between alexithymia, psychosocial risk factors, and problematic alcohol use in order to tailor and target therapeutic interventions.



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Defining the phenotype of young adults with family histories of alcohol and other substance use disorders: Studies from the family health patterns project

Publication date: February 2018
Source:Addictive Behaviors, Volume 77
Author(s): Ashley Acheson, Andrea S. Vincent, Andrew J. Cohoon, William R. Lovallo
Individuals with a family history of alcohol and other drug use disorders (FH+) are at increased risk for developing substance use disorders themselves relative to those with no such histories (FH−). Here we sought to identify key characteristics associated with FH+ status and alcohol and other drug use disorder status in a large cohort of FH+ and FH− young adults.We conducted principal component analyses on demographic, temperament, and cognitive measures differentiating 506 FH+ and 528 FH− young adults. Three principal components were identified, and these component scores were then used to predict the odds of being FH+ and the odds of having an alcohol or other drug use disorder. Component 1 consisted of measures indexing internalizing traits, with higher component scores indicating greater depressive, anxious, and emotional instability tendencies. Component 2 consisted of measures of externalizing traits as well as exposure to early life adversity (ELA), with higher scores indicating less impulse control, more antisocial behavior, and greater ELA exposure. Component 3 consisted of estimated intelligence, delay discounting, and demographic characteristics, with higher scores indicating lower estimated intelligence, greater discounting of delayed rewards, less education, and lower childhood socioeconomic status. For each 1-point increase in the Component 1, 2, and 3 scores, the odds of being classified FH+ increased by 2%, 8%, and 4%, respectively. Similar findings were observed when individuals with alcohol or other drug use disorders were removed from the analyses. Finally, greater Component 2 scores were also associated with increased odds of having an alcohol or other drug use disorder. Collectively, these findings provide a more comprehensive understanding of the FH+ phenotype in young adults and help form a basis for further studies on biological mechanisms underlying risk for substance use disorders. The present findings also provide further support for a prominent role of ELA in promoting risk for problem alcohol and other drug use.



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The impact of the legalization of recreational marijuana on college students

Publication date: February 2018
Source:Addictive Behaviors, Volume 77
Author(s): Jacob Jones, K. Nicole Jones, Jenny Peil
In January of 2014 the Regulate Marijuana like Alcohol Act or, Amendment 64, went into effect in Colorado. Even though it was the first state to enact recreational legalization, attitudes towards marijuana use have been changing for decades. Prompted by medical marijuana legalization, studies have found mixed results in regards to the impact that legalization has on frequency of use and abuse. With college students having the highest rates of use in the United States (U.S.), whether legal or not, it was important to explore the impact that legalization has on this population. In the current study, rates of marijuana and alcohol use in college students before and after recreational legalization were explored. Data was collected in four waves from October 2013 to March 2015, to be able to determine the trends in marijuana and alcohol use, and relationship between the substances. In addition, grade point average was measured as a possible consequence of marijuana use. We found the frequency of marijuana use in Colorado college students is much higher than the national average t(94445)=24.424, p<0.001, especially the percentage of daily or almost daily users, t(2191)=10.373, p<0.001. There were significant differences between the marijuana non-users and the once a week or more often but not daily marijuana users in grade point average, F(6, 227)=2.935, p<0.001. In addition, it seems that the relationship between alcohol and marijuana use in general is decreasing since the passing of Amendment 64, but not among the binge drinkers.



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The crop-residue of fiber hemp cv. Futura 75: from a waste product to a source of botanical insecticides

Abstract

In the attempt to exploit the potential of the monoecious fiber hemp cv. Futura 75 in new fields besides textile, cosmetics and food industry, its crop-residue given by leaves and inflorescences was subjected to hydrodistillation to obtain the essential oils. These are niche products representing an ideal candidate for the development of natural insecticides for the control and management of mosquito vectors, houseflies and moth pests. After GC-MS analysis highlighting a safe and legal chemical profile (THC in the range 0.004–0.012% dw), the leaf and inflorescence essential oils were investigated for the insecticidal potential against three insect targets: the larvae of Culex quinquefasciatus and Spodoptera littoralis and the adults of Musca domestica. The essential oil from inflorescences, showing (E)-caryophyllene (21.4%), myrcene (11.3%), cannabidiol (CBD, 11.1%), α-pinene (7.8%), terpinolene (7.6%), and α-humulene (7.1%) as the main components, was more effective than leaf oil against these insects, with LD₅₀ values of 65.8 μg/larva on S. littoralis, 122.1 μg/adult on M. domestica, and LC₅₀ of 124.5 μl/l on C. quinquefasciatus larvae. The hemp essential oil moderately inhibited the acetylcholinesterase (AChE), which is a target enzyme in pesticide science. Overall, these results shed light on the future application of fiber hemp crop-residue for the development of effective, eco-friendly and sustainable insecticides.

http://ift.tt/2zk5H3e

Sustainable bioreduction of toxic levels of chromate in a denitrifying granular sludge reactor

Abstract

Biological removal of chromate [Cr(VI)] in the presence or absence of nitrate by granular sludge biofilms was investigated in batch experiments and in a sequencing batch reactor (SBR). Denitrifying granular sludge cultivated from activated sludge was able to directly reduce Cr(VI) in the presence of an electron donor. Bioreduction was dependent on the initial Cr(VI) and the granular sludge concentrations. Bioreduction of Cr(VI) was followed by Cr(III) precipitation or entrapment in the granular sludge which was corroborated with decrease in total soluble Cr and increase in inorganic content of biomass. Batch experiments revealed that Cr(VI) addition has no major influence on high-strength nitrate (3000 mg L⁻¹) denitrification, but nitrite denitrification was slowed-down. However, SBR experiment demonstrated successful denitrification as well as Cr(VI) removal due to enrichment of Cr(VI)-tolerant denitrifying bacteria. In fact, stable SBR performance in terms of complete and sustained removal of 0.05, 0.1, 0.2, 0.3, 0.5 and 0.75 mM Cr(VI) and denitrification of 3000 mg L⁻¹ was observed during 2 months of operation. Active biomass and electron donor-dependent Cr(VI) removal, detection of Cr(III) in the biomass and recovery of ~ 92% of the Cr from the granular sludge biofilms confirms bioreduction followed by precipitation or entrapment of Cr(III) as the principal chromate removal mechanism. Metagenomic bacterial community analysis showed enrichment of Halomonas sp. in denitrifying granular sludge performing either denitrification or simultaneous reduction of nitrate and chromate.

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The impact of developmental coordination disorder on educational achievement in secondary school

Publication date: January 2018
Source:Research in Developmental Disabilities, Volume 72
Author(s): Ian Harrowell, Linda Hollén, Raghu Lingam, Alan Emond
BackgroundDevelopmental coordination disorder (DCD) is a common developmental disorder but its long term impact on health and education are poorly understood.AimTo assess the impact of DCD diagnosed at 7 years, and co-occurring developmental difficulties, on educational achievement at 16 years.MethodsA prospective cohort study using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). National General Certificate of Secondary Education (GCSE) exam results and Special Educational Needs provision were compared for adolescents with DCD (n=284) and controls (n=5425).ResultsAdolescents with DCD achieved a median of 2 GCSEs whilst controls achieved a median of 7 GCSEs. Compared to controls, adolescents with DCD were much less likely to achieve 5 or more GCSEs in secondary school (OR 0.27, 95% CI 0.21–0.34), even after adjustment for gender, socio-economic status and IQ (OR 0.6, 95% CI 0.44–0.81). Those with DCD were more likely to have persistent difficulties with reading, social communication and hyperactivity/inattention, which all affected educational achievement. Nearly 40% of adolescents with DCD were not in receipt of additional formal support during school.ConclusionsDCD has a significant impact on educational achievement and therefore life chances. Co-occurring problems with reading skills, social communication difficulties and hyperactivity/inattention are common and contribute to educational difficulties. Greater understanding of DCD among educational and medical professionals and policy makers is crucial to improve the support provided for these individuals.



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Implementation and evaluation of health passport communication tools in emergency departments

Publication date: January 2018
Source:Research in Developmental Disabilities, Volume 72
Author(s): Marina Heifetz, Yona Lunsky
BackgroundPeople with IDD (intellectual or developmental disabilities) and their families consistently report dissatisfaction with their emergency department experience. Clear care plans and communication tools may not only improve the quality of patient care, but also can prevent unnecessary visits and reduce the likelihood of return visits.AimsTo evaluate communication tools to be used by people with IDD in psychiatric and general emergency departments in three different regions of Ontario.Methods and proceduresHealth passport communication tools were locally tailored and implemented in each of the three regions. A total of 28 questionnaires and 18 interviews with stakeholders (e.g., hospital staff, community agency representatives, families) were completed across the regions to obtain feedback on the implementation of health passports with people with IDD.Outcomes and resultsParticipants felt that the health passport tools provided helpful information, improved communication between patients with IDD and hospital staff, and were user friendly. Continued efforts are needed to work with communities on maintenance of this tool, ensuring all hospital staff are utilizing the information.Conclusions and implicationsThese findings emphasize the merits of health passport tools being implemented in the health system to support communication between patients with IDD and health care practitioners and the importance of tailoring tools to local settings.



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Mental rotation ability and everyday-life spatial activities in individuals with Down syndrome

Publication date: January 2018
Source:Research in Developmental Disabilities, Volume 72
Author(s): Chiara Meneghetti, Enrico Toffalini, Barbara Carretti, Silvia Lanfranchi
Although certain visuospatial abilities, such as mental rotation, are crucially important in everyday activities, they have been little explored in individuals with Down syndrome (DS). This study investigates: i) mental rotation ability in individuals with DS; and ii) its relation to cognitive abilities and to everyday spatial activities. Forty-eight individuals with DS and 48 typically-developing (TD) children, matched on measures of vocabulary and fluid intelligence, were compared on their performance in a rotation task that involved detecting which of two figures would fit into a hole if rotated (five angles of rotation were considered: 0°, 45°, 90°, 135°, 180°). Participants were also assessed on their visuospatial and verbal cognitive abilities, and on their parents and/or educators reports regarding their everyday spatial activities. Results showed that: (i) individuals with DS were less accurate in mental rotation than TD children, with larger differences between the groups for smaller angles of rotation; individuals with DS could not mentally rotate through 180°, while TD children could; (ii) mental rotation ability was related to fluid intelligence and to spatial activities (though other cognitive abilities are also involved in the latter) to a similar degree in the DS group and the matched TD children. These results are discussed with regard to the atypical development domain and spatial cognition models.



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The effects of multi-component weight management interventions on weight loss in adults with intellectual disabilities and obesity: A systematic review and meta-analysis of randomised controlled trials

Publication date: January 2018
Source:Research in Developmental Disabilities, Volume 72
Author(s): Leanne Harris, Craig Melville, Heather Murray, Catherine Hankey
BackgroundAdults with intellectual disabilities have been shown to experience higher rates of obesity in comparison to the general population.AimTo examine the effectiveness of randomised controlled trials of multi-component weight management interventions for adults with intellectual disabilities and overweight/obesity.Methods and proceduresA systematic search of six electronic databases was conducted from database inception to January 2016. Risk of bias was assessed by the Cochrane Collaboration tool. Behavioural change techniques were defined by coding against the Coventry Aberdeen LOndon REfined (CALO-RE) taxonomy. Meta-analyses were conducted as Weighted Mean Difference (WMD) between intervention and control/comparator intervention.Outcomes and resultsSix randomised controlled trials were included. The interventions did not adhere to clinical recommendations [the inclusion of an energy deficit diet (EDD), physical activity, and behaviour change techniques]. Meta-analysis revealed that current multi-component weight management interventions are not more effective than no treatment (WMD: −0.38kg; 95% CI −1.34kg to 0.58kg; p=0.44).Conclusion and implicationsThere is a paucity of randomised controlled trials of multi-component weight management interventions for adults with intellectual disabilities and overweight/obesity. Current interventions, based on a health education approach are ineffective. Future long-term interventions that include an EDD and adhere to clinical recommendations on the management of obesity are warranted.



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Are WISC IQ scores in children with mathematical learning disabilities underestimated? The influence of a specialized intervention on test performance

Publication date: January 2018
Source:Research in Developmental Disabilities, Volume 72
Author(s): Katharina Lambert, Birgit Spinath
BackgroundIntelligence measures play a pivotal role in the diagnosis of mathematical learning disabilities (MLD). Probably as a result of math-related material in IQ tests, children with MLD often display reduced IQ scores. However, it remains unclear whether the effects of math remediation extend to IQ scores.AimsThe present study investigated the impact of a special remediation program compared to a control group receiving private tutoring (PT) on the WISC IQ scores of children with MLD.MethodsWe included N=45 MLD children (7–12 years) in a study with a pre- and post-test control group design. Children received remediation for two years on average.ResultsThe analyses revealed significantly greater improvements in the experimental group on the Full-Scale IQ, and the Verbal Comprehension, Perceptual Reasoning, and Working Memory indices, but not Processing Speed, compared to the PT group. Children in the experimental group showed an average WISC IQ gain of more than ten points.ConclusionResults indicate that the WISC IQ scores of MLD children might be underestimated and that an effective math intervention can improve WISC IQ test performance. Taking limitations into account, we discuss the use of IQ measures more generally for defining MLD in research and practice.



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Modeling individual variation in early literacy skills in kindergarten children with intellectual disabilities

Publication date: January 2018
Source:Research in Developmental Disabilities, Volume 72
Author(s): Arjan van Tilborg, Eliane Segers, Hans van Balkom, Ludo Verhoeven
In the present study, we investigated (i) to what extent the early literacy skills (phonological awareness, letter knowledge, and word decoding) along with cognitive (nonverbal reasoning, attention, phonological short-term memory, sequential memory, executive functioning) and linguistic (auditory discrimination, rapid naming, articulation, vocabulary) precursor measures of 53 six-year old children with intellectual disabilities (ID) differ from a group of 74 peers with normal language acquisition (NLA) and (ii) whether the individual variation of early literacy skills in the two groups to the same extent can be explained from the precursor measures. Results showed that children with ID scored below the NLA group on all literacy and precursor measures. Structural equation modeling evidenced that in the children with NLA early literacy was directly predicted by phonological awareness, PSTM and vocabulary, with nonverbal reasoning and auditory discrimination also predicting phonological awareness. In children with ID however, the variation in word decoding was predicted by letter knowledge and nonverbal reasoning, whereas letter knowledge was predicted by rapid naming, which on its turn was predicted by attentional skills. It can be concluded phonological awareness plays a differential role in the early literacy skills of children with and without ID. As a consequence, the arrears in phonological awareness in children with ID might put them on hold in gaining proper access to literacy acquisition.What this paper addsThis paper adds to the theoretical knowledge base on literacy acquisition in a special population, namely children with intellectual disabilities (ID). It addresses factors that influence early literacy learning, which have not been investigated thoroughly in this special and specific group. Furthermore, the children are not tested solely on literacy, but also on cognitive measures that may influence literacy acquisition. Whereas most research in ID focuses on groups with specific syndromes/etiologies, this paper takes a varied group of children with ID into account. The paper also adds to educational insights, since the findings imply that children with ID are able to use phonological pathways in learning to read. Educators could teach these children phonics-based literacy skills tailored to their individual learning needs.



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Feasibility and validity of a tool for identification of people with intellectual disabilities in need of palliative care (PALLI)

Publication date: January 2018
Source:Research in Developmental Disabilities, Volume 72
Author(s): C. Vrijmoeth, C.M. Groot, M.G.M. Christians, W.J.J. Assendelft, D.A.M. Festen, C.C.D. van der Rijt, H.M.J. van Schrojenstein Lantman-de Valk, K.C.P. Vissers, M.A. Echteld
BackgroundThere is a need for a specific tool that supports healthcare professionals in timely identifying people with intellectual disabilities (ID) in need of palliative care. Therefore, we developed PALLI: a tool for screening deteriorating health, indicative of a limited life expectancy.AimsWe evaluated feasibility, construct validity and predictive validity of PALLI.Methods190 people with ID likely to be in need of palliative care were included. Physicians and daily care professionals (DCPs) completed PALLI and provided information on health outcomes at baseline, after 5–6 months and after 10–12 months. Linear Mixed Models and Generalized Linear Mixed Models were used to test validity.ResultsFeasibility was adequate: physicians and DCPs were able to answer most items with 'yes' or 'no' and within a short amount of time. Construct validity was promising: a higher PALLI score at baseline was related to a higher level of decline in health, a higher symptom burden, a lower quality of life and more ADL-dependency at baseline. Predictive validity: only a higher physician-reported PALLI score at baseline significantly increased risk of death within 12 months.ConclusionsPALLI shows promising feasibility and validity and has potential as a tool for timely identifying people with ID who may benefit from palliative care.



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The effect of the KTP laser on smear layer and temperature change: an in vitro study

Abstract

The purpose of this study was to evaluate the effects of potassium-titanyl-phosphate (KTP) laser irradiation on smear layer removal and temperature changes of the root surfaces. Two hundred four extracted single-root human premolars were included. The canals were instrumented and divided into two main groups: group A (smear layer examination n:119) and group B (temperature change examination n:85). Each group was divided into subgroups (n:17) according to the different five laser power settings: A1, B1: 1 W–5.33 J/cm²; A2, B2: 1.5 W–7.52 J/cm²; A3, B3: 2 W–10.3 J/cm²; A4, B4: 3 W–15.5 J/cm², A5, B5: 4 W–20.1 J/cm2, A6: positive control no laser irradiation-irrigated 2 mL for 2 min 2.5% NaOCl + 2 mL distilled water and A7: negative control groups no laser irradiation irrigated 2 mL for 2 min 17% EDTA + 2 mL for 2 min 2.5% NaOCl + 2 mL distilled water. The temperature elevations were measured with an infrared thermographic camera and smear layer examined by scanning electron microscope. According to Kruskal-Wallis and Tukey's tests, in all groups the highest smear scores were in the apical third. In all areas, there were statistically significant differences between negative control group (17% EDTA) and all other groups (p < 0.05). The highest smear scores were determined in 1 W KTP laser and positive control (2.5% NaOCl) groups. Statistically, in all thirds, the differences the 3 W and 4 W KTP laser groups between each other and all other groups were significant (p < 0.05). After the end of the use of the laser, increase in temperature values in all groups were found to be below 10 °C in 20 s.

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A micro-plate colorimetric assay for rapid determination of trace zinc in animal feed, pet food and drinking water by ion masking and statistical partitioning correction

Publication date: 15 April 2018
Source:Food Chemistry, Volume 245
Author(s): Jiayi Wang, Yiming Niu, Chi Zhang, Yiqiang Chen
A new micro-plate colorimetric assay was developed for rapid determination of zinc in animal feed, pet food and drinking water. Zinc ion was extracted from sample by trichloroacetic acid and then reacted with 2-(5-Bromo-2-pyridylazo)-5-[N-propyl-N-(3-sulfopropyl)amino]phenol (5-Br-PAPS) to form a Zn-PAPS complex to be detected by a micro-plate reader at 552 nm. An ion masking formula including salicylaldoxime, deferoxamine and sodium citrate were screened and applied to exclude the interference from other heavy metals and a partitioning correction approach was proposed to eliminate the matrix effect derived from feed sample. The entire procedure can be completed within 40 min and the detection range was 0.038–8.0 μg mL⁻¹ zinc in buffer solution. Moreover, the analysis in real samples revealed the consistency of results by this assay and those by atomic absorption spectrometry analysis. These features highlighted the possibility for this proposed assay to be used for rapid determination of zinc in complex samples.



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The age-related slow increase in amyloid pathology in APP.V717I mice activates microglia, but does not alter hippocampal neurogenesis

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61
Author(s): Lianne Hoeijmakers, Gideon F. Meerhoff, Janneke W. de Vries, Silvie R. Ruigrok, Anne-Marie van Dam, Fred van Leuven, Aniko Korosi, Paul J. Lucassen
In Alzheimer's disease, the hippocampus is characterized by abundant deposition of amyloid peptides (amyloid β [Aβ]) and neuroinflammation. Adult hippocampal neurogenesis (AHN) is a form of plasticity that contributes to cognition and can be influenced by either or both pathology and neuroinflammation. Their interaction has been studied before in rapidly progressing transgenic mouse models with strong overexpression of amyloid precursor protein (APP) and/or presenilin 1. So far, changes in AHN and neuroinflammation remain poorly characterized in slower progressing models at advanced age, which approach more closely sporadic Alzheimer's disease. Here, we analyzed 10- to 26-month-old APP.V717I mice for possible correlations between Aβ pathology, microglia, and AHN. The age-related increase in amyloid pathology was closely paralleled by microglial CD68 upregulation, which was largely absent in age-matched wild-type littermates. Notably, aging reduced the AHN marker doublecortin, but not calretinin, to a similar extent in wild-type and APP.V717I mice between 10 and 26 months. This demonstrates that AHN is influenced by advanced age in the APP.V717I mouse model, but not by Aβ and microglial activation.



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The aging rat retina: from function to anatomy

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61
Author(s): Francisco M. Nadal-Nicolás, Manuel Vidal-Sanz, Marta Agudo-Barriuso
In healthy beings, age is the ultimate reason of cellular malfunction and death. In the rat retina, age causes a functional decline and loss of specific neuronal populations. In this regard, controversial conclusions have been reported for the innermost retina. Here, we have studied the albino and pigmented retina for the duration of the rat life-span. Independent of age (21 days–22 months), the electroretinographic recordings and the volume of the retina and its layers are smaller in albinos. Functionally, aging causes in both strains a loss of cone- and rod-mediated responses. Anatomically, cell density decreases with age because the retina grows linearly with time; no cell loss is observed in the ganglion cell layer; and only in the pigmented rat, there is a decrease in cone photoreceptors. In old animals of both strains, there is gliosis in the superior colliculi and a diminution of the area innervated by retinal ganglion cells. In conclusion, this work provides the basis for further studies linking senescence to neurodegenerative retinal diseases.



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Anxiety-like behavior as an early endophenotype in the TgF344-AD rat model of Alzheimer's disease

Publication date: January 2018
Source:Neurobiology of Aging, Volume 61
Author(s): Nathan S. Pentkowski, Laura E. Berkowitz, Shannon M. Thompson, Emma N. Drake, Carlos R. Olguin, Benjamin J. Clark
Alzheimer's disease (AD) is characterized by progressive cognitive decline and the presence of aggregates of amyloid beta (plaques) and hyperphosphorylated tau (tangles). Early diagnosis through neuropsychological testing is difficult due to comorbidity of symptoms between AD and other types of dementia. As a result, there is a need to identify the range of behavioral phenotypes expressed in AD. In the present study, we utilized a transgenic rat (TgF344-AD) model that bears the mutated amyloid precursor protein as well as presenilin-1 genes, resulting in progressive plaque and tangle pathogenesis throughout the cortex. We tested young adult male and female TgF344-AD rats in a spatial memory task in the Morris water maze and for anxiety-like behavior in the elevated plus-maze. Results indicated that regardless of sex, TgF344-AD rats exhibited increased anxiety-like behavior in the elevated plus-maze, which occurred without significant deficits in the spatial memory. Together, these results indicate that enhanced anxiety-like behavior represents an early-stage behavioral marker in the TgF344-AD rat model.



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Thermodynamics, ecology and evolutionary biology: A bridge over troubled water or common ground?

Publication date: November 2017
Source:Acta Oecologica, Volume 85
Author(s): Keith R. Skene
This paper addresses a key issue confronting ecological and evolutionary biology, namely the challenge of a cohesive approach to these fields given significant differences in the concepts and foundations of their study. Yet these two areas of scientific research are paramount in terms addressing the spatial and temporal dynamics and distribution of diversity, an understanding of which is needed if we are to resolve the current crisis facing the biosphere. The importance of understanding how nature responds to change is now of essential rather than of metaphysical interest as our planet struggles with increasing anthropogenic damage. Ecology and evolutionary biology can no longer remain disjointed. While some progress has been made in terms of synthetic thinking across these areas, this has often been in terms of bridge building, where thinking in one aspect is extended over to the other side. We review these bridges and the success or otherwise of such efforts. This paper then suggests that in order to move from a descriptive to a mechanistic understanding of the biosphere, we may need to re-evaluate our approach to the studies of ecology and evolutionary biology, finding a common denominator that will enable us to address the critical issues facing us, particularly in terms of understanding what drives change, what determines tempo and how communities function. Common ground, we argue, is essential if we are to comprehend how resilience operates in the natural world and how diversification can counter increasing extinction rates. This paper suggests that thermodynamics may provide a bridge between ecology and evolutionary biology, and that this will enable us to move forward with otherwise intractable problems.



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How do patch quality and spatial context affect invertebrate communities in a natural moss microlandscape?

Publication date: November 2017
Source:Acta Oecologica, Volume 85
Author(s): Hendrik Trekels, Mario Driesen, Bram Vanschoenwinkel
Globally, moss associated invertebrates remain poorly studied and it is largely unknown to what extent their diversity is driven by local environmental conditions or the landscape context. Here, we investigated small scale drivers of invertebrate communities in a moss landscape in a temperate forest in Western Europe. By comparing replicate quadrats of 5 different moss species in a continuous moss landscape, we found that mosses differed in invertebrate density and community composition. Although, in general, richness was similar among moss species, some invertebrate taxa were significantly linked to certain moss species. Only moss biomass and not relative moisture content could explain differences in invertebrate densities among moss species. Second, we focused on invertebrate communities associated with the locally common moss species Kindbergia praelonga in isolated moss patches on dead tree trunks to look at effects of patch size, quality, heterogeneity and connectivity on invertebrate communities. Invertebrate richness was higher in patches under closed canopies than under more open canopies, presumably due to the higher input of leaf litter and/or lower evaporation. In addition, increased numbers of other moss species in the same patch seemed to promote invertebrate richness in K. praelonga, possibly due to mass effects. Since invertebrate richness was unaffected by patch size and isolation, dispersal was probably not limiting in this system with patches separated by tens of meters, or stochastic extinctions may be uncommon. Overall, we conclude that invertebrate composition in moss patches may not only depend on local patch conditions, in a particular moss species, but also on the presence of other moss species in the direct vicinity.



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Refuse dumps from leaf-cutting ant nests reduce the intensity of above-ground competition among neighboring plants in a Patagonian steppe

Publication date: November 2017
Source:Acta Oecologica, Volume 85
Author(s): Alejandro G. Farji-Brener, María Natalia Lescano
In arid environments, the high availability of sunlight due to the scarcity of trees suggests that plant competition take place mainly belowground for water and nutrients. However, the occurrence of soil disturbances that increase nutrient availability and thereby promote plant growth may enhance shoot competition between neighboring plants. We conducted a greenhouse experiment to evaluate the influence of the enriched soil patches generated by the leaf-cutting ant, Acromyrmex lobicornis, on the performance of the alien forb Carduus thoermeri (Asteraceae) under different intraspecific competition scenarios. Our results showed that substrate type and competition scenario affected mainly aboveground plant growth. As expected, plants growing without neighbors and in nutrient-rich ant refuse dumps showed more aboveground biomass than plants growing with neighbors and in nutrient-poor steppe soils. However, aboveground competition was more intense in nutrient-poor substrates: plants under shoot and full competition growing in the nutrient-rich ant refuse dumps showed higher biomass than those growing on steppe soils. Belowground biomass was similar among focal plants growing under different substrate type. Our results support the traditional view that increments in resource availability reduce competition intensity. Moreover, the fact that seedlings in this sunny habitat mainly compete aboveground illustrates how limiting factors may be scale-dependent and change in importance as plants grow.



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Modeling impacts of human footprint and soil variability on the potential distribution of invasive plant species in different biomes

Publication date: November 2017
Source:Acta Oecologica, Volume 85
Author(s): Ji-Zhong Wan, Chun-Jing Wang, Fei-Hai Yu
Human footprint and soil variability may be important in shaping the spread of invasive plant species (IPS). However, until now, there is little knowledge on how human footprint and soil variability affect the potential distribution of IPS in different biomes. We used Maxent modeling to project the potential distribution of 29 IPS with wide distributions and long introduction histories in China based on various combinations of climatic correlates, soil characteristics and human footprint. Then, we evaluated the relative importance of each type of environmental variables (climate, soil and human footprint) as well as the difference in range and similarity of the potential distribution of IPS between different biomes. Human footprint and soil variables contributed to the prediction of the potential distribution of IPS, and different types of biomes had varying responses and degrees of impacts from the tested variables. Human footprint and soil variability had the highest tendency to increase the potential distribution of IPS in Montane Grasslands and Shrublands. We propose to integrate the assessment in impacts of human footprint and soil variability on the potential distribution of IPS in different biomes into the prevention and control of plant invasion.



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Polyactin A is a novel and potent immunological adjuvant for peptide-based cancer vaccine

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Wei Wang, Yanqin Li, Yawen Wang, Shuting Ren, Yiping Li, Bing Wang
Synthetic peptide cancer vaccines are poorly immunogenic sub-unit vaccines and thus essentially need adjuvants in their formulations to increase the efficacy by enhancing the peptide-specific immune response. However, aluminum-based compounds are almost dependent for clinical use at present. Therefore, the increasing use of peptide-based vaccines makes the need for novel and potent adjuvants. Polyactin A (PAA) has been used for the clinical treatment of impaired immunity in China for over 30years. To figure out the adjuvant effects of PAA for E75 peptide breast cancer vaccine (Her2 p369-p377), the generation of mature dendritic cells (DCs) from peripheral blood monocytes (PBMCs) cultured with PAA, IL-4 and TNF-α was assessed by morphologic features and the expressions of special surface markers using flow cytometry. Then the functional features of PBMCs-derived DCs cultured with PAA, IL-4 and TNF-α were investigated by inducing E75-specific cytotoxicity. Finally, C57BL/6-Tg(HLA-A2.1)1Enge/J transgenic mice were immunized with E75 and various amounts of PAA, and splenic lymphocyte proliferation and the IFN-γ level were determined. The results showed that PAA, just like granulocyte-macrophage colony stimulating factor, with IL-4 and TNF-α efficiently induced mature DCs from PBMCs, and these DCs could trigger a potent E75 peptide-specific CD8⁺ T-cell response in vitro. Immunization with E75 and PAA significantly increased positive rates of CD4⁺ and CD8⁺ T lymphocytes, and enhanced splenocytes proliferation and levels of IFN-γ in splenocytes when induced by E75. Our results indicated that PAA could efficiently induce E75-specific immunologic responses in vitro and in vivo. Therefore, PAA possesses potent adjuvant effect on peptide-based cancer vaccine. Our study provides a safe, effective and novel adjuvant for clinical use.



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Vertical distributions and source identification of the radionuclides 239Pu and 240Pu in the sediments of the Liao River estuary, China

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): Kexin Zhang, Shaoming Pan, Zhiyong Liu, Guosheng Li, Yihong Xu, Yongpei Hao
Activity concentration of plutonium (Pu) and its isotopic compositions are extensively used for measuring transport processes of Pu and identifying its source. We investigated the spatial distribution characteristics of ^239+240Pu activity concentrations and ²⁴⁰Pu/²³⁹Pu atom ratio in several sediment cores collected from the Liao River coastal zone. Additionally, we calculated the ^239+240Pu inventories and based on the ²⁴⁰Pu/²³⁹Pu atom ratio to trace Pu source. The activity concentrations of ^239+240Pu in surface sediments of the Liao River estuary ranged between 0.103 ± 0.008 and 0.978 ± 0.035 mBq/g, with an average of 0.294 ± 0.024 mBq/g. The ²⁴⁰Pu/²³⁹Pu atom ratios, ranging from 0.173 ± 0.047 to 0.215 ± 0.061 (mean: 0.188 ± 0.049 (1σ)), were consistent with global fallout value, which indicates the global atmospheric fallout is the main source of Pu in sediment cores from the both sides of Liao River estuary. As for the tidal flat core LT-2, the mean ²⁴⁰Pu/²³⁹Pu atom ratio, slightly higher than that of the global fallout value, was 0.217 ± 0.050. Such pattern of Pu isotopic compositions indicated that Pu on the tidal flat in the Liao River estuary is sourced from a combination of global fallout and close-in fallout from the PPG by ocean currents transporting. And by using a two end-member mixing model, the results indicate the relative contribution of the PPG close-in fallout to core LT-2 is round 27% and 73% can be attributed to global fallout and river input. Therefore, these results clearly indicate that the direct global fallout is the main source of Pu in the Liao River estuary.

Graphical abstract

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Sources of inflow and nature of redistribution of 90Sr in the salt lakes of the Crimea

Publication date: Available online 5 November 2017
Source:Journal of Environmental Radioactivity
Author(s): N.Yu. Mirzoyeva, S.I. Arkhipova, N.V. Kravchenko
At the first time for the period after the Chernobyl NPP accident the nature of the redistribution of the ⁹⁰Sr concentrations in components of the ecosystems of the salt lakes of the Crimea were identified and described. Concentration of ⁹⁰Sr in water of the salt lakes depends on the sources of the inflow this radionuclide into aquatic ecosystems and salinity level of lakes water. Until April 2014 the flow of the Dnieper river water through the Northern-Crimean canal was more important factor of contamination of salt lakes of the Crimea by ⁹⁰Sr, than atmospheric fallout of this radionuclide after the Chernobyl NPP accident. Concentrations of ⁹⁰Sr in water of the salt lakes of the Crimea exceeded 2.4–156.5 times its concentrations in their bottom sediments. The ⁹⁰Sr dose commitments to hydrophytes, which were sampled from the salt lakes of the Crimea have not reached values which could impact them during entire the after-accident period.



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To prep or not to prep - that is the question: A randomized trial on the use of anti-flatulent medication as part of bowel preparation for patients having image-guided external-beam radiotherapy to the prostate

Publication date: Available online 4 November 2017
Source:Practical Radiation Oncology
Author(s): Merrylee McGuffin, Naila Devji, Lyann Kehoe, Anne Carty, Steve Russell, Lisa Di Prospero, Carlo DeAngelis, Alex Kiss, Danny Vesprini, Andrew Loblaw, Laura D'Alimonte
IntroductionRadiation therapy is a standard treatment option for prostate cancer. With growing use of escalated doses and tighter margins, procedures to limit rectal size variation are needed to reduce prostate motion, increase treatment accuracy and minimize rectal toxicity. This prospective study was done to determine whether the introduction of an anti-flatulent medication would decrease rectal distention at CT simulation and throughout a course of radiation therapy.Methods and MaterialsPatients undergoing a radical course of radiotherapy to the prostate/prostate bed were eligible to participate. Participants were randomly assigned to the intervention arm (anti-flatulent medication) or the control arm (no medication). For each participant, the number of CT simulation rescans was recorded. Rectal diameters were measured on CT simulation and treatment CBCT scans. Acute rectal toxicities were assessed at baseline and weekly using NCI CTCAE v4.0. Chi-square analysis was used to compare the number of participants requiring a rescan in each study arm. Change in rectal diameter over time was assessed using repeated measures ANOVA.ResultsA total of 78 patients participated, with equal numbers assigned to each study arm. There was no significant difference between arms in the number of participants requiring a CT simulation rescan (p=0.5551). There was no significant variation in rectal diameter between arms (p=0.8999). However, there was a significant effect of time (p=0.0017) and a significant interaction effect between study arm and time on rectal diameter (p=0.0141). No acute rectal toxicities above grade 2 were reported.ConclusionsThe addition of anti-flatulent medication did not affect the frequency of CT simulation rescans. Both time and the interaction between study arm and time had a statistically significant effect on rectal diameter, though neither finding was clinically significant. Instead, standardized bowel preparation education developed for this study may have been sufficient to limit rectal size variation.



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Multiple myeloma and a mischievous pacemaker: A teaching case involving irradiation of a cardiovascular implantable electronic device

Publication date: Available online 4 November 2017
Source:Practical Radiation Oncology
Author(s): Shane Lloyd, Olivier Morin, Isaac Whitman, David Raleigh, Shannon Fogh, Paul Menzel




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Clinical log data analysis for assessing the accuracy of the CyberKnife fiducial-free lung tumor tracking system

Publication date: Available online 4 November 2017
Source:Practical Radiation Oncology
Author(s): Masao Nakayama, Hideki Nishimura, Hiroshi Mayahara, Masaki Nakamura, Kazuyuki Uehara, Shinji Tsudou, Aya Harada, Hiroaki Akasaka, Ryohei Sasaki
PurposeThe CyberKnife Xsight Lung Tracking (XLT) and 1-View tracking systems can synchronize beam targeting to a visible lung tumor with respiratory motion during irradiation without requiring internal fiducial markers. The systems utilize a correlation model that relates external marker positions to tumor positions as well as a prediction model that predicts the target's future position. In this study, the correlation and prediction model uncertainties related to the CyberKnife fiducial-free tumor tracking system were evaluated using clinical log data.Methods and materialsData from 211 fractions in 42 patients with lung tumors were analyzed. Log files produced by the CyberKnife Synchrony system were acquired after each treatment; the mean correlation and prediction errors for each patient were calculated. Additionally, we examined the tracking tumor-related parameters and analyzed the relationships between the model errors and tracking tumor-related parameters.ResultsThe overall means ± standard deviations (SDs) of the correlation errors were 0.70±0.43mm, 0.36±0.16mm, 0.44±0.22mm, and 0.95±0.43mm for the superior–inferior (SI), left–right (LR), anterior–posterior (AP), and radial directions, respectively. The overall means ± SDs of the prediction errors were 0.13±0.11mm, 0.03±0.02mm, 0.03±0.02mm, and 0.14±0.11mm for the SI, LR, AP, and radial directions, respectively. There were no significant differences in these errors between the XLT and 1-View tracking methods. The tumor motion amplitude was moderately associated with the correlation error and strongly related to the prediction error in the SI and radial directions.ConclusionsClinical log data analysis can be used to determine the necessary margin sizes in treatment plans to compensate for correlation and prediction errors in the CyberKnife fiducial-free lung tumor tracking system. The tumor motion amplitude may facilitate margin determination.



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Towards consensus reporting of radiation-induced liver toxicity in the treatment of primary liver malignancies: defining clinically relevant endpoints

Publication date: Available online 4 November 2017
Source:Practical Radiation Oncology
Author(s): Tobias R. Chapman, Stephen R. Bowen, Stephanie K. Schaub, Rosanna H. Yeung, Sharon W. Kwan, James O. Park, Lei Yu, William P. Harris, Guy E. Johnson, Iris W. Liou, Matthew J. Nyflot, Smith Apisarnthanarax
Background and PurposeTo define the most clinically relevant "non-classic" radiation-induced liver disease (ncRILD) endpoints in cirrhotic patients receiving stereotactic body radiotherapy (SBRT) or proton beam therapy (PBT) for primary liver cancer.Material and MethodsWe retrospectively collected pre-treatment, detailed toxicity (≤6 months post-treatment), and outcomes data from 48 patients. Deaths were examined for association with RILD. Univariate (UA) and multivariate (MA) Cox models defined significant predictors of overall survival (OS)/RILD-specific survival (RILD-SS).ResultsWith median follow-up of 13 months, 23 patients (48%) had an increase in CP score (≥2, 25%) and three (6%) had ≥G3 transaminase elevation. Of 18 deaths, 6 were potentially ascribed to RILD. On UA, CP score increases of ≥1, ≥2 and CP class change predicted OS, as did ≥G3 AST elevation and ≥1 CTCAE AST toxicity grade change. On MA, CP score increase of ≥2 and ≥1 CTCAE AST toxicity grade change were the strongest independent ncRILD predictors of OS. For RILD-SS, CP score increases of ≥2, ≥G3 CTCAE ALT and ≥G2 bilirubin elevations were predictive.ConclusionsIncreased CP score of ≥2 strongly predicts of both OS and RILD-SS, and should be reported in future studies along with transaminase elevations, which are also predictive of outcomes.



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Circle of Gratitude

Publication date: Available online 4 November 2017
Source:Practical Radiation Oncology
Author(s): Christian Molerin




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Bowel and urinary quality of life after whole-pelvic versus prostate-only volumetric-modulated arc therapy for localized prostate cancer

Publication date: Available online 5 November 2017
Source:Practical Radiation Oncology
Author(s): Kentaro Ishii, Toshiko Yamanaga, Ryo Ogino, Yukinari Hosokawa, Shun Kishimoto, Ryuta Nakahara, Chiaki Shimada, Ryu Kawamorita, Takuhito Tada, Yoshiki Hayashi, Toshifumi Nakajima
PurposeThis study aimed to compare bowel and urinary health-related quality of life (HRQOL) between prostate-only (PO) volumetric-modulated arc therapy (VMAT) and whole-pelvic (WP) VMAT in patients with localized prostate cancer.Methods and MaterialsA total of 234 patients treated with definitive VMAT to 78Gy in 39 fractions were enrolled. Of these, 108 patients received PO-VMAT, and 126 patients received initial WP-VMAT to 46.8Gy in 26 fractions using a simultaneous integrated boost technique. HRQOL was prospectively assessed before radiotherapy (baseline), and 3, 6, 12, and 24months after treatment using the Expanded Prostate Cancer Index Composite (EPIC).ResultsBaseline HRQOL scores did not differ significantly between the two groups. No significant between-group differences in HRQOL change from baseline were observed for all bowel and urinary EPIC domains. The proportion of patients showing a clinically relevant decrease in bowel and urinary HRQOL scores from baseline was similar between the groups throughout the follow-up period. An analysis of individual HRQOL items showed that patients undergoing WP-VMAT were more likely to report moderate/big problems with bloody stools (P=.039) and overall bowel problems (P=.008) than those undergoing PO-VMAT at 12months. However, there was no significant between-group difference in any individual items at 24months.ConclusionsBowel and urinary HRQOL is largely similar for patients receiving PO-VMAT and WP-VMAT during 24months of follow-up, with the only differences seen in responses to specific bowel HRQOL items at 12months.



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Radiation-Induced Undifferentiated Pleomorphic Sarcoma of the Heart: A Case Report

Publication date: Available online 4 November 2017
Source:Practical Radiation Oncology
Author(s): Alexander K. Tsai, Melissa AL. Vyfhuis, Martha Francis, Fikru Merechi, Allen P. Burke, William F. Regine




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LAMPs: Shedding Light on Cancer Biology

Publication date: Available online 4 November 2017
Source:Seminars in Oncology
Author(s): Federica Alessandrini, Laura Pezzè, Yari Ciribilli
Lysosomes are important cytoplasmic organelles whose critical functions in cells are increasingly being understood. In particular, despite the long-standing accepted concept about the role of lysosomes as cellular machineries solely assigned to degradation, it has been demonstrated that they play active roles in homeostasis and even in cancer biology. Indeed, it is now well documented that during the process of cellular transformation and cancer progression lysosomes are changing localization, composition and volume and, through the release of their enzymes, lysosomes can also enhance cancer aggressiveness. LAMPs, Lysosome Associated Membrane Proteins, represent a family of glycosylated proteins present predominantly on the membrane of lysosomes whose expression can vary among different tissues, suggesting a separation of functions. In this review we focus on the functions and roles of the different LAMP family members with a particular emphasis on cancer progression and metastatic spread. LAMP proteins are involved in many different aspects of cell biology and can influence cellular processes such as phagocytosis, autophagy, lipid transport and aging. Interestingly, for all the five members identified so far, LAMP1, LAMP2, LAMP3, CD68/Macrosialin/LAMP4 and BAD-LAMP/LAMP5, a role in cancer has been suggested. While this is well documented for LAMP1 and LAMP2, the involvement of the other three proteins in cancer progression and aggressiveness has recently been proposed and remains to be elucidated. Here we present different examples about how LAMP proteins can influence and support tumor growth and metastatic spread, emphasizing the impact of each single member of the family.



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Downregulation of BDH2 modulates iron homeostasis and promotes DNA demethylation in CD4+ T cells of systemic lupus erythematosus

Publication date: Available online 4 November 2017
Source:Clinical Immunology
Author(s): Ming Zhao, Meng-ying Li, Xiao-fei Gao, Su-jie Jia, Ke-qin Gao, Yin Zhou, Hui-hui Zhang, Yi Huang, Jing Wang, Hai-jing Wu, Qian-jin Lu
DNA hypomethylation plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Here we investigated whether 3-hydroxy butyrate dehydrogenase 2 (BDH2), a modulator of intracellular iron homeostasis, was involved in regulating DNA hypomethylation and hyper-hydroxymethylation in lupus CD4⁺ T cells. Our results showed that BDH2 expression was decreased, intracellular iron was increased, global DNA hydroxymethylation level was elevated, while methylation level was reduced in lupus CD4⁺ T cells compared with healthy controls. The decreased BDH2 contributed to DNA hyper-hydroxymethylation and hypomethylation via increasing intracellular iron in CD4⁺ T cells, which led to overexpression of immune related genes. Moreover, we showed that BDH2 was the target gene of miR-21. miR-21 promoted DNA demethylation in CD4⁺ T cells through inhibiting BDH2 expression. Our data demonstrated that the dysregulation of iron homeostasis in CD4⁺ T cells induced by BDH2 deficiency contributes to DNA demethylation and self-reactive T cells in SLE.



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On Denny-Brown’s ‘spastic dystonia’ - what is it and what causes it?

Publication date: Available online 4 November 2017
Source:Clinical Neurophysiology
Author(s): Jakob Lorentzen, Maud Pradines, Jean-Michel Gracies, Jens Bo Nielsen
In this review, we will work around two simple definitions of two different entities, which most often co-exist in patients with lesions to central motor pathways: Spasticity is "Enhanced excitability of velocity-dependent responses to phasic stretch at rest",(Gracies, 2005) which will not be the subject of this review. Spastic dystonia is tonic, chronic, involuntary muscle contraction in the absence of any stretch or any voluntary command. Spastic dystonia is a much less well understood entity that will be the subject this review.Denny-Brown (1966) observed involuntary sustained muscle activity in monkeys with lesions restricted to the motor cortices . He further observed that such involuntary muscle activity persisted following abolition of sensory input to the spinal cord and concluded that a central mechanism rather than exaggerated stretch reflex activity had to be involved. He coined the term spastic dystonia to describe this involuntary tonic activity in the context of otherwise exaggerated stretch reflexes. Sustained involuntary muscle activity in the absence of any stretch or any voluntary command contributes to burdensome and disabling body deformities in patients with spastic paresis. Yet, little has been done since Denny-Brown's studies to determine the pathophysiology of this non- stretch or effort related sustained involuntary muscle activity following motor lesions and there is a clear need for research studies in order to improve current therapy.The purpose of the present review is to discuss some of the possible mechanisms that may be involved in the hope that this may guide future research. We discuss the existence of persistent inward currents in spinal motoneurones and present the evidence that the channels involved may be upregulated following central motor lesions. We also discuss a possible contribution from alterations in synaptic inputs from surviving or abnormally branched sensory and descending fibres leading to over-activity and lack of motor coordination. We finally discuss evidence of alterations in motor cortical representational maps and basal ganglia lesions.



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Wheat yield responses to stomatal uptake of ozone: Peak vs rising background ozone conditions

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Harry Harmens, Felicity Hayes, Gina Mills, Katrina Sharps, Stephanie Osborne, Håkan Pleijel
Recent decades have seen a changing temporal profile of ground-level ozone (O3) in Europe. While peaks in O3 concentrations during summer months have been declining in amplitude, the background concentration has gradually increased as a result of the hemispheric transport of O3 precursors from other world regions. Ground-level O3 is known to adversely affect O3-sensitive vegetation, including reducing the yield of O3-sensitive crops such as common wheat (Triticum aestivum L.). The reduction in wheat yield has been shown to be linearly related to the phytotoxic O3 dose above a flux threshold of Y (PODY) accumulated over a specific period. In the current study, we tested whether the flux-effect relationships for wheat yield and 1,000-grain weight were affected by the temporal profile of O3 exposure. A modern wheat cultivar (Skyfall) was exposed to eight different realistic O3 profiles repeated weekly: four profiles with increasing background O3 concentrations (ca. 30–60 ppb) including small peaks and four profiles with increasing O3 peak concentrations (ca. 35–110 ppb). Both wheat yield and 1,000-grain weight declined linearly with increasingPODY. The slope of the flux-effect relationships was not affected significantly by the profile of O3 exposure. Hence, flux-effect relationships developed for wheat based on exposure to enhanced peak O3 concentrations are also valid for the changing European O3 profile with higher background and lower peak concentrations. The current study also shows that the modern wheat cultivar Skyfall is more sensitive to O3 than European wheat varieties tested for O3 sensitivity in the 1980s and 1990s.

Graphical abstract

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Ghrelin suppresses cardiac fibrosis of post-myocardial infarction heart failure rats by adjusting the activinA-follistatin imbalance

Publication date: Available online 4 November 2017
Source:Peptides
Author(s): Chunyan Yang, Jinsha Liu, Kai Liu, Beibei Du, Kaiyao Shi, Mei Ding, Bing Li, Ping Yang
Ghrelin, a growth hormone–releasing peptide, potentially improves cardiac function, but the mechanisms remain unclear. In the study, the rat heart failure (HF) model was established by ligating the left anterior descending coronary artery (LAD) and treated with ghrelin (100μg/kg, subcutaneous injection, bid); neonatal rat cardiomyocytes were cultured and stimulated with Ang II (0.1μM) and ghrelin(0.1μM) to explore the underlying mechanism of ghrelin in myocardial remodeling. Hemodynamic changes and serum brain natriuretic peptide (BNP) concentrations were measured to assess cardiac function. Left ventricular mass index (LVMI), hematoxylin and eosin (H&E) staining, and Masson's trichrome staining were performed to evaluate myocardial fibrosis. Interestingly, ghrelin significantly improved cardiac function by inhibiting fibrous tissue proliferation. To further explore the mechanisms by which ghrelin interferes with myocardial fibrosis, the levels of activin A (Act A) and its blocker-follistatin (FS) were examined by immunohistochemistry; Act A levels were significantly increased in the myocardial infarction (MI), and ghrelin administeration downregulated Act A expression. In contrast, FS expression showed no significant change in all experimental groups. Furthermore, ghrelin decreased Ang II-induced Act A expression with no effect on FS expression in primary rat cardiomyocytes in vitro (real-time quantitative PCR and ELISA). Thus, ghrelin corrected the Act A/FS imbalance. Finally, Act A treated cultured primary rat cardiac fibroblasts (CFs) showed increased proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay] and enhanced expressions of type I and type III collagen (Col I and Col III) (real-time quantitative PCR). These data suggest that ghrelin inhibits myocardial fibrosis, attenuates left ventricular remodeling, and eventually improves cardiac function by adjusting Act A/FS imbalance.



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A longitudinal examination of event-related potentials sensitive to monetary reward and loss feedback from late childhood to middle adolescence

Publication date: Available online 4 November 2017
Source:International Journal of Psychophysiology
Author(s): Autumn Kujawa, Ashley Carroll, Emma Mumper, Dahlia Mukherjee, Ellen Kessel, Thomas Olino, Greg Hajcak, Daniel N. Klein
Brain regions involved in reward processing undergo developmental changes from childhood to adolescence, and alterations in reward-related brain function are thought to contribute to the development of psychopathology. Event-related potentials (ERPs), such as the reward positivity (RewP) component, are valid measures of reward responsiveness that are easily assessed across development and provide insight into temporal dynamics of reward processing. Little work has systematically examined developmental changes in ERPs sensitive to reward. In this longitudinal study of 75 youth assessed 3 times across 6years, we used principal components analyses (PCA) to differentiate ERPs sensitive to monetary reward and loss feedback in late childhood, early adolescence, and middle adolescence. We then tested reliability of, and developmental changes in, ERPs. A greater number of ERP components differentiated reward and loss feedback in late childhood compared to adolescence, but components in childhood accounted for only a small proportion of variance. A component consistent with RewP was the only one to consistently emerge at each of the 3 assessments. RewP demonstrated acceptable reliability, particularly from early to middle adolescence, though reliability estimates varied depending on scoring approaches and developmental periods. The magnitude of the RewP component did not significantly change across time. Results provide insight into developmental changes in the structure of ERPs sensitive to reward, and support RewP as a consistently observed and relatively stable measure of reward responsiveness, particularly across adolescence.



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Heart rate variability mediates the link between rumination and depressive symptoms: A longitudinal study

Publication date: Available online 5 November 2017
Source:International Journal of Psychophysiology
Author(s): Luca Carnevali, Julian F. Thayer, Jos F. Brosschot, Cristina Ottaviani
Ruminative thinking about negative feelings has been prospectively associated with increases in depressive symptoms and heightened risk for new onsets of major depression. One putative pathophysiological mechanism underlying this link might be represented by autonomic nervous system dysfunction. The objective of this longitudinal study was to evaluate the interplay between rumination, autonomic function (as revealed by heart rate variability (HRV) analysis), and depressive symptoms in healthy young subjects, over a three-year period. Rumination and depressive symptoms were evaluated in twenty-two women and twenty men at three assessment points (Time 0, 1 and 2) by the score on the Ruminative Response Scale, and the Center for Epidemiological Studies Depression Scale, respectively. Vagally-mediated HRV was assessed in a laboratory session (Time 0) and in two ambulatory sessions at Time 1 and Time 2 (~13 and 34months after Time 0, respectively). Ruminative thinking was found to be (i) a stable trait characteristic, (ii) more prevalent in women than men, and (iii) positively correlated with depressive symptoms. Moreover, resting HRV was negatively correlated with both rumination and depressive symptoms. Finally, HRV at Time 1 mediated the relationship between rumination at Time 0 and depressive symptoms at Time 2. We conclude that autonomic dysfunction, specifically low vagal tone, may be prospectively implicated in the generation of depressive symptoms in a non-clinical setting.



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Mucus models to evaluate the diffusion of drugs and particles

Publication date: Available online 5 November 2017
Source:Advanced Drug Delivery Reviews
Author(s): Jaclyn Y. Lock, Taylor Carlson, Rebecca L. Carrier
Mucus is a complex hydrogel that acts as a natural barrier to drug delivery at different mucosal surfaces including the respiratory, gastrointestinal, and vaginal tracts. To elucidate the role mucus plays in drug delivery, different in vitro, in vivo, and ex vivo mucus models and techniques have been utilized. Drug and drug carrier diffusion can be studied using various techniques in either isolated mucus gels or mucus present on cell cultures and tissues. The species, age, and potential disease state of the animal from which mucus is derived can all impact mucus composition and structure, and therefore impact drug and drug carrier diffusion. This review provides an overview of the techniques used to characterize drug and drug carrier diffusion, and discusses the advantages and disadvantages of the different models available to highlight the information they can afford.

Graphical abstract

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Do all roads lead to the Rome? The glycation perspective!

Publication date: Available online 4 November 2017
Source:Seminars in Cancer Biology
Author(s): Saheem Ahmad, Firoz Akhter, Uzma Shahab, Zeeshan Rafi, Mohd. Sajid Khan, Rabia Nabi, Mohd Salman Khan, Khurshid Ahmad, Jalaluddin Mohammad Ashraf, Moinuddin
Oxidative, carbonyl, and glycative stress have gained substantial attention recently for their alleged influence on cancer progression. Oxidative stress can trigger variable transcription factors, such as nuclear factor erythroid-2-related factor (Nrf2), nuclear factor kappa B (NF-κB), protein-53 (p-53), activating protein-1 (AP-1), hypoxia-inducible factor-1α (HIF-1α), β-catenin/Wnt and peroxisome proliferator-activated receptor-γ (PPAR-γ). Activated transcription factors can lead to approximately 500 different alterations in gene expression, and can alter expression patterns of inflammatory cytokines, growth factors, regulatory cell cycle molecules, and anti-inflammatory molecules. These alterations of gene expression can induce a normal cell to become a tumor cell.Glycative stress resulting from advanced glycation end products (AGEs) and reactive dicarbonyls can significantly affect cancer progression. AGEs are fashioned from the multifaceted chemical reaction of reducing sugars with a compound containing an amino group. AGEs bind to and trigger the receptor for AGEs (RAGE) through AGE-RAGE interaction, which is a major modulator of inflammation allied tumors. Dicarbonyls like, GO (glyoxal), MG (methylglyoxal) and 3-DG (3-deoxyglucosone) fashioned throughout lipid peroxidation, glycolysis, and protein degradation are viewed as key precursors of AGEs. These dicarbonyls lead to the carbonyl stress in living organisms, possibly resulting in carbonyl impairment of proteins, carbohydrates, DNA, and lipoproteins. The damage caused by carbonyls results in numerous lesions, some of which are involved in cancer pathogenesis. In this review, the effects of oxidative, carbonyl and glycative stress on cancer initiation and progression are thoroughly discussed, including probable signaling pathways and the effects on tumorigenesis.



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Natural killer cells play an essential role in resolution of antigen-induced inflammation in mice

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Osk U.U. Anuforo, Stefania P. Bjarnarson, Hulda S. Jonasdottir, Martin Giera, Ingibjorg Hardardottir, Jona Freysdottir
This study examined whether NK cells are important for resolution of antigen-induced inflammation. C57BL/6 mice were immunized twice with methylated BSA (mBSA) and inflammation induced by intraperitoneal injection of mBSA. Mice were injected intravenously with anti-asialo GM1 (αASGM1) or a control antibody 24h prior to peritonitis induction and peritoneal exudate collected at different time points. Expression of surface molecules and apoptosis on peritoneal cells was determined by flow cytometry and concentration of chemokines, cytokines, soluble cytokine receptors and lipid mediators by ELISA and LC–MS/MS. Apoptosis in parathymic lymph nodes and spleens was determined by TUNEL staining. Mice administered αASGM1 had lower peritoneal NK cell numbers and a higher number of peritoneal neutrophils 12h after induction of inflammation than control mice. The number of neutrophils was still high in the αASGM1 treated mice when their number had returned to baseline levels in the control mice, 48h after induction of inflammation. Peritoneal concentrations of the neutrophil regulators G-CSF and IL-12p40 were higher at 12h in the αASGM1 treated mice than in the control mice, whereas concentrations of lipid mediators implicated in resolution of inflammation, i.e. LXA4 and PGE2, were lower. Reduced apoptosis was detected in peritoneal neutrophils as well as in draining lymph nodes and spleens from the αASGM1 treated mice compared with that in the control mice. In addition, αASGM1 treated mice had lower number of peritoneal NK cells expressing NKp46 and NKG2D, receptors implicated in NK cell-induced neutrophil apoptosis. Furthermore, αASGM1 treatment completely blocked the increase in CD27⁺ NK cells that occurred in control mice following induction of inflammation, but CD27⁺ NK cells have been suggested to have a regulatory role. These results indicate a crucial role for NK cells in resolution of antigen-induced inflammation and suggest their importance in tempering neutrophil recruitment and maintaining neutrophil apoptosis.



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Traitement du lupus érythémateux par le bélimumab en pratique courante : étude rétrospective de 15 malades

Publication date: Available online 4 November 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): E. Garval, J.-L. Pennaforte, R. Jaussaud, A. Servettaz, P. Bernard, Z. Reguiai
IntroductionLe bélimumab (anticorps monoclonal anti-BLyS) a été récemment commercialisé dans le traitement du lupus érythémateux (LE) systémique. Le but de cette étude était d'en décrire l'efficacité, la tolérance, l'impact sur les paramètres sérologiques du LE et le rôle d'épargne des traitements de fond en pratique courante.Malades et méthodesCette étude rétrospective menée au CHU de Reims incluait tous les malades atteints de LE traités par bélimumab entre 2012 et 2016. L'efficacité du traitement était évaluée sur l'évolution clinique, la normalisation des concentrations d'anticorps anti-DNA et de complément, et l'épargne des autres traitements du LE.RésultatsUne réponse thérapeutique était obtenue chez 9 des 15 malades inclus (60 %), à type de rémission partielle pour 8 d'entre eux. La concentration médiane d'anti-DNA était de 50UI/mL (4 à 50) et celle de C3 sérique de 0,82g/L (0,36 à 1,23) à l'instauration du bélimumab, versus respectivement 25,5UI/mL (2 à 50) et 0,89g/L (0,34 à 1,22) à la date des dernières nouvelles (DDN), sans modification significative (respectivement p=0,12 et p=0,45). La posologie médiane de prednisone à l'instauration du bélimumab passait de 9,5mg/j (0 à 18) à 6mg/j (0 à 20) à la DDN. Huit malades (53 %) ont présenté des effets secondaires, toujours minimes.ConclusionLe bélimumab a eu chez 15 malades une efficacité modérée et une faible toxicité ; il a permis une épargne cortisonique modérée, en vue de limiter les effets secondaires de la corticothérapie au long cours.BackgroundBelimumab (an anti-BLyS monoclonal antibody) was recently approved for the treatment of systemic lupus erythematosus (SLE). The aim of the study was to describe efficacy and safety of the drug as well as its impact on serologic parameters and the role of long-term systemic sparing of treatment in clinical practice in LE.Patients and methodsWe conducted a retrospective study at Reims University Hospital between 2012 and 2016 including consecutive patients with LE treated with belimumab. Efficacy was evaluated in terms of clinical progression, and normalisation of laboratory factors (anti-DNA antibody and C3 serum levels) and sparing of associated long-term systemic therapies for LE.ResultsAmong the 15 patients included, a therapeutic response was obtained in 9 patients (60%), with partial remission in 8 of 9 cases. The median titre of anti-DNA antibody was 50IU/mL (range: 4–50) and the median C3 level was 0.82g/L (range: 0.36–1.23) before initiation of belimumab, vs. 25.5IU/mL (range: 2–50) and 0.89g/L (range: 0.34–1.22) at the last evaluation, respectively, without significant modification (P=0.12 and P=0.45). The median dose of prednisone at the time of the first belimumab infusion was reduced from 9.5mg/day (range: 0–18) to 6mg/day (range: 0–20) at the last clinical evaluation. Eight patients (53%) experienced adverse events, and these were very slight or moderate in all cases.ConclusionBelimumab appears to be an effective and well-tolerated treatment for moderately severe systemic LE, allowing sparing of maintenance corticosteroid therapy in order to decrease its frequent adverse events.



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A novel rat model of brachial plexus injury with nerve root stumps

Publication date: Available online 4 November 2017
Source:Journal of Neuroscience Methods
Author(s): Jintao Fang, Jiantao Yang, Yi Yang, Liang Li, Bengang Qin, Wenting He, Liwei Yan, Gang Chen, Zhehui Tu, Xiaolin Liu, Liqiang Gu
BackgroundThe C5-C6 nerve roots are usually spared from avulsion after brachial plexus injury (BPI) and thus can be used as donors for nerve grafting. To date, there are no appropriate animal models to evaluate spared nerve root stumps. Hence, the aim of this study was to establish and evaluate a rat model with spared nerve root stumps in BPI.New methodIn rupture group, the proximal parts of C5-T1 nerve roots were held with the surrounding muscles and the distal parts were pulled by a sudden force after the brachial plexus was fully exposed, and the results were compared with those of sham group. To validate the model, the lengths of C5-T1 spared nerve root stumps were measured and the histologies of the shortest one and the corresponding spinal cord were evaluated.ResultsC5 nerve root stump was found to be the shortest. Histology findings demonstrated that the nerve fibers became more irregular and the continuity decreased; numbers and diameters of myelinated axons and thickness of myelin sheaths significantly decreased over time. The survival of motoneurons was reduced, and the death of motoneurons may be related to the apoptotic process.Comparison with existing method(s)Our model could successfully create BPI model with nerve root stumps by traction, which could simulate injury mechanisms. While other models involve root avulsion or rupturing by distal nerve transection.ConclusionsThis model would be suitable for evaluating nerve root stumps and testing new therapeutic strategies for neuroprotection through nerve root stumps in the future.



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A New Rat-Compatible Robotic Framework for Spatial Navigation Behavioral Experiments

Publication date: Available online 4 November 2017
Source:Journal of Neuroscience Methods
Author(s): Sam Gianelli, Bruce Harland, Jean-Marc Fellous
BackgroundUnderstanding the neural substrate of information encoding and processing requires a precise control of the animal's behavior. Most of what has been learned from the rodent navigational system results from relatively simple tasks in which the movements of the animal is controlled by corridors or walkways, passive movements, treadmills or virtual reality environments. While a lot has been and continues to be learned from these types of experiments, recent evidence has shown that such artificial constraints may have significant consequences on the functioning of the neural circuits of spatial navigation.New methodsWe present a novel and alternative approach for effectively controlling the precise direction and speed of movement of the animal in an ethologically realistic environment, using a small robot (Sphero).ResultsWe describe the robotic framework and demonstrate its use in replicating pre-programmed or rat-recorded paths. We show that the robot can control the movement of a rat in order to produce specific trajectories and speeds. We demonstrate that the robot can be used to aid the rat in learning a spatial memory task in a large and complex environment. We show that dorsal hippocampal CA1 place cells do not remap when the rat is following the robot.Comparison with Existing Method(s): Our framework only involves positive motivation and has been tested together with wireless electrophysiology in large and complex environments.ConclusionsOur robotic framework can be used to design novel tasks and experiments in which electrophysiological recordings would be largely devoid of maze or task-dependent artifacts.



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Dual trajectories of breakfast eating and fruit and vegetable intake over a 5-year follow-up period among economically disadvantaged children: Gender differences

Publication date: 1 February 2018
Source:Appetite, Volume 121
Author(s): Chun-Yuan Chen, Yi-Chen Hsiao
Breakfast eating (BE) seems to be cross-sectionally associated with fruit and vegetable intake (FVI). To date, gender differences in any codevelopment between BE and FVI, as well as their associated factors, have not been examined. The objectives of this study were (1) to identify dual trajectories of BE and FVI among economically disadvantaged boys and girls; and (2) to examine potential associated factors of identified dual trajectories by gender. Children from economically disadvantaged families were enrolled in this prospective multicity study of the Taiwan Database of Children and Youth in Poverty between July 6 and October 31, 2009 and followed up biannually (2009, 2011, and 2013). One thousand one children (50.2% girls, mean ages at each time point being 9.1, 11.2 and 13.1 years, respectively; 49.8% boys, 9.0, 11.0 and 13.0 years) who completed at least two of the three assessments were included. Dual trajectories of BE and FVI over a 5-year follow-up period were identified as the outcome variables of interest by using mainly group-based dual trajectory modeling. Nine potential associated factors were then examined using logistic regression models. Two distinct dual trajectories of BE and FVI were identified among the girls: longitudinally irregular (68.8%) and shift to irregular (31.2%). Two distinct dual trajectories of BE and FVI were identified among the boys: longitudinally irregular (90.2%) and consistently regular (9.8%). Age was the significantly associated factor for boys. The findings confirmed a heterogeneous codevelopment between BE and FVI that may indicate different underlying mechanisms. Most children with a longitudinally irregular BE pattern had a similar pattern of FVI. Future research should comprehensively explore the gender differences in the determinants of codevelopment between BE and FVI.



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Can preoperative nasal cultures of Staphylococcus aureus predict infectious complications or outcomes following repair of fracture nonunion?

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Can preoperative nasal cultures of Staphylococcus aureus predict infectious complications or outcomes following repair of fracture nonunion?

J Infect Public Health. 2017 Oct 31;:

Authors: Taormina DP, Konda SR, Liporace FA, Egol KA

Abstract
INTRODUCTION: Much has been studied with reference to methicillin resistant Staphylococcus aureus (MRSA) and methicillin sensitive S. aureus (MSSA) colonization and associated outcomes and comorbidities. In the area of Orthopedic surgery, literature predominantly comes from the field of arthroplasty. Little is known about outcomes of fracture and Orthopedic trauma patients in the setting of S. aureus colonization. We believe that MRSA/MSSA colonization in and of itself may be a weak marker for generally poor protoplasm, potentially with complex medical history including previous hospitalization or rehab placement. This milieu of risk factors may or may not contribute to poorer outcomes after fracture and fracture nonunion surgery. The purpose of this study is to determine if nasal swabbing for S. aureus (MRSA or MSSA) carriage can predict operative culture, complications, or outcomes following fracture nonunion surgery.
METHODS: Sixty-two consecutive patients undergoing surgery for fracture nonunion were prospectively followed. Data analyses were performed using grouped MRSA and MSSA carriers (Staphylococcus carriers: SC). Outcomes analyzed included time to healing, need for additional surgery, and persistent nonunion.
RESULTS: Twenty-six percent of patients (16/62) were identified as MSSA carriers, an additional 6.5% (4/62) carried MRSA. Follow-up of at least 12-months was obtained on 90% (56/62) of patients. White blood cell counts, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values did not differ between SCs and non-carriers pre-operatively. Carriers were just as likely as non-carriers to culture positively for any pathogen at the time of surgery. Although SC's were three times as likely as non-carriers to grow S. aureus (15% vs. 5%), this difference did not reach statistical significance (p=0.3). Post-operative wound complications, antibiotic use, pain at follow-up and progression to healing did not differ between groups.
CONCLUSIONS: Ultimately, pre-operative nasal swabbing for S. aureus is a simple and non-invasive diagnostic tool with prognostic implications in patients undergoing fracture nonunion surgery. This study found that MRSA and MSSA colonized patients with fracture nonunion of long bones do not have an increased association with positive cultures or a predisposition towards greater post-operative infectious complications.

PMID: 29100874 [PubMed - as supplied by publisher]

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Sensitivity of a prompt-gamma slit-camera to detect range shifts for proton treatment verification

Publication date: Available online 4 November 2017
Source:Radiotherapy and Oncology
Author(s): Lena Nenoff, Marlen Priegnitz, Guillaume Janssens, Johannes Petzoldt, Patrick Wohlfahrt, Anna Trezza, Julien Smeets, Guntram Pausch, Christian Richter
Background and purposeA prompt-gamma imaging (PGI) slit-camera was recently applied successfully in clinical proton treatments using pencil beam scanning (PBS) and double scattering (DS). However, its full capability under clinical conditions has still to be systematically evaluated. Here, the performance of the slit-camera is systematically assessed in well-defined error scenarios using realistic treatment deliveries to an anthropomorphic head phantom.Materials and methodsThe sensitivity and accuracy to detect introduced global and local range shifts with the slit-camera was investigated in PBS and DS irradiations. For PBS, measured PGI information of shifted geometries were compared spot-wise with un-shifted PGI information derived from either a reference measurement or a treatment-plan-based simulation. Furthermore, for DS and PBS the integral PGI signal of the whole field was evaluated.ResultsDeviations from the treatment plan were detected with an accuracy better than 2 mm in PBS. The PGI simulation accuracy was well below 1 mm. Interfractional comparisons are more affected by measurement noise. The field-integral PGI sum signal allows the detection of global shifts in DS.ConclusionsDetection of global and local range shifts under close-to-clinical conditions is possible with the PGI slit-camera. Especially for PBS, high sensitivity and high accuracy in shift detection were found.



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Association between Fruit and Vegetable Consumption and Risk of Hypertension in Middle-Aged and Older Korean Adults

Publication date: Available online 4 November 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Jiwon Kim, Jihye Kim
BackgroundHigh fruit and vegetable (F/V) intake may be beneficial for hypertension prevention. However, a prospective association has not been investigated in a Korean population, and differences exist between typical diets in Korea and those of Western populations.ObjectiveThe aim of this prospective study was to investigate the association between F/V intake and risk of incident hypertension in middle-aged and older Korean adults using the data from the Korean Genome and Epidemiology Study (KoGES).DesignThe KoGES is a large community-based cohort study of Korean adults aged 40 to 69 years, which began in May 2001. Questionnaires on demographic information and lifestyle factors were completed at baseline. Anthropometrics and biochemical measurements were conducted biennially. Fruit and vegetable consumption was assessed with a semiquantitative food frequency questionnaire. Hypertension was defined as a systolic blood pressure≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.Participants and settingA total of 4,257 participants (2,085 men, 2,172 women) without hypertension at baseline were evaluated.Main outcome measuresThe primary outcome was incident hypertension.Statistical analysis performedMultivariate Cox proportional hazard models were used to examine hazard ratios (HRs) and 95% CIs for incident hypertension according to F/V consumption.ResultsDuring the 8-year follow-up, 1,158 participants (606 men and 552 women) developed hypertension. Among men, frequent fruit consumers (≥4 servings/day) had a 56% lower risk of incident hypertension than did infrequent consumers (<1 serving/day) (HR=0.44, 95% CI=0.32 to 0.60, P for trend <0.0001). Among women, frequent fruit consumers had a 67% lower risk of incident hypertension than did infrequent consumers (HR=0.33, 95% CI=0.24 to 0.45, P for trend <0.0001), after adjustment for potential confounders. However, there was no association between vegetable consumption and risk of incident hypertension in either men or women.ConclusionA higher intake of fruit was prospectively associated with a lower risk of incident hypertension in middle-aged and older Korean adults, regardless of sex.



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Cytomegalovirus reactivation in patients with refractory checkpoint inhibitor-induced colitis

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Cindy Franklin, Isabelle Rooms, Melanie Fiedler, Henning Reis, Laura Milsch, Saskia Herz, Elisabeth Livingstone, Lisa Zimmer, Kurt Werner Schmid, Ulf Dittmer, Dirk Schadendorf, Bastian Schilling
ObjectivesImmune checkpoint inhibitors can cause severe immune-related adverse events, with immune-related diarrhea and colitis (irColitis) being among the most frequent ones. While the majority of patients with irColitis respond well to corticosteroid treatment ± other immunomodulatory drugs such as infliximab, some patients do not show resolution of their symptoms. In the present study, we analysed the frequency of therapy-refractory irColitis, the underlying cause, and useful diagnostic approaches.MethodsBetween 2006 and 2016, 370 patients with metastatic malignant melanoma were treated with checkpoint inhibitors at the Department of Dermatology at the University Hospital Essen. All patients were identified for whom diarrhea and/or colitis was documented in the digital patient records. Patients who did not respond to standard immunosuppressive therapy within 2 weeks were classified as refractory. Demographic and clinical data of all patients were collected.ResultsWe identified 41 patients with irColitis, the majority occurring during treatment with ipilimumab. Amongst these, 5 (12.2%) were refractory to standard immunomodulatory treatment with corticosteroids and infliximab. Therapy-refractory cases tended to show more severe inflammation in colonic biopsies (p = 0.04). In all therapy-refractory cases cytomegalovirus (CMV) was detectable. CMV-DNA in colonic biopsies and in plasma was significantly more often detectable in therapy-refractory cases (in colonic biopsies p = 0.005, in plasma: p = 0.002). Presence of serum CMV IgM and positive immunohistochemical stainings of colon biopsies for CMV were also associated with refractory colitis (p=0.021; p = 0.053).ConclusionsThis report on CMV reactivation during management of checkpoint inhibitor-induced colitis emphasises the need for repetitive diagnostic measures in treatment-refractory irColitis.



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Recurrence dynamics of breast cancer according to baseline body mass index

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Elia Biganzoli, Christine Desmedt, Marco Fornili, Evandro de Azambuja, Nathalie Cornez, Fernand Ries, Marie-Thérèse Closon-Dejardin, Joseph Kerger, Christian Focan, Angelo Di Leo, Jean-Marie Nogaret, Christos Sotiriou, Martine Piccart, Romano Demicheli
BackgroundIn cancer follow-up, in addition to the evaluation of survival probabilities, there is a fundamental need of assessing recurrence dynamics for optimal disease management. Although the time-dependent effect of the oestrogen receptor (ER) status of the tumour has already been described, so far no factor has proven to disentangle the multi-peak behaviour observed for breast cancer recurrences. Here, we aimed at investigating whether adiposity at diagnosis, reflected by increased patient's body mass index (BMI), could be associated with breast cancer recurrence patterns over time after primary cancer therapy.MethodsWe retrieved BMI from 734 of 777 patients with node-positive breast cancer from a phase III randomised clinical trial, which compared different chemotherapy regimens and had a median follow-up of 15.4 years. Cumulative incidence estimation as well as piecewise exponential models were carried out to estimate the distant recurrence dynamics, in all patients, as well as in subgroups based on the ER status, with the ER-positive group being further split according to the menopausal status.ResultsIn patients with ER-negative breast cancer, time-dependent analyses revealed that the hazard of late relapses could mainly be attributed to the overweight and obese patients. Within the subgroup of premenopausal patients with ER-positive tumours, obesity was associated with an early high narrow peak of distant recurrences followed by another main peak after 5 years of follow-up. The risk for overweight patients was intermediate between obese and normal-weight patients. In the postmenopausal subgroup of patients with ER-positive tumours, the distant recurrence rate was significantly more elevated in the overweight patients compared to the other BMI categories, and a second late peak of recurrences was also observed for the obese patients.ConclusionThese results demonstrate that the patient's BMI at diagnosis is associated with cancer recurrence dynamics. Patient adiposity should therefore be central to the exploration of late adjuvant treatment modalities.



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The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: Exploratory analyses of AFFIRM and PREVAIL studies

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Tomasz M. Beer, Kurt Miller, Bertrand Tombal, David Cella, De Phung, Stefan Holmstrom, Cristina Ivanescu, Konstantina Skaltsa, Shevani Naidoo
BackgroundOur exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC).MethodsHRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Multivariate analyses evaluated the prognostic significance of baseline and time-dependent scores after adjusting for treatment and clinical/demographic variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) represented the hazard of rPFS or OS per minimally important difference (MID) score change in HRQoL variables.ResultsIn baseline and time-dependent multivariate analyses, OS was independently associated with multiple HRQoL measures across both studies. In time-dependent analyses, a 10-point (upper bound of MID range) increase (improvement) in FACT-P total score was associated with reductions in mortality risk of 19% in AFFIRM (HR 0.81 [95% CI 0.78–0.84]) and 21% in PREVAIL (HR 0.79 [0.76–0.83]). For baseline analyses, a 10-point increase in FACT-P total score was associated with reductions in mortality risk of 12% (HR 0.88 [0.84–0.93]) and 10% (HR 0.90 [0.86–0.95]) in AFFIRM and PREVAIL, respectively. rPFS was associated with a subset of HRQoL domains in both studies.ConclusionSeveral baseline HRQoL domains were prognostic for rPFS and OS in patients with mCRPC, and this association was maintained during treatment, indicating that changes in HRQoL are informative for patients' expected survival.



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Is post-mastectomy radiation therapy contributive in pN0-1mi breast cancer patients? Results of a French multi-centric cohort

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Violaine Forissier, Agnès Tallet, Monique Cohen, Jean-Marc Classe, Fabien Reyal, Nicolas Chopin, Chafika Mazouni, Pierre Gimbergues, Emile Daraï, Pierre Emmanuel Colombo, Pierre Azuar, Eric Lambaudie, Gilles Houvenaeghel
AimTo assess the value of post-mastectomy radiation therapy (PMRT) to breast cancer (BC) patients with no or minimal lymph node (LN) involvement.Materials and methodsWe retrospectively analysed a French multi-centric cohort of 4283 patients treated by mastectomy and axillary dissection, with or without PMRT, between 1980 and 2013. Practices were analysed for three treatment periods (1980–1999, 2000–2005 and 2006–2013). The impact of PMRT on loco-regional recurrence (LRR), disease-free survival (DFS), BC-specific survival and overall survival was assessed in pN0-1mi patients using multivariate analyses (logistic regression and Cox model). It was subsequently assessed based on the number of clinicopathological recurrence-risk factors, generating a prognostic index (French-PMRT index), to isolate a pN0-1mi patients subgroup that might derive a benefit from PMRT. We tested the accuracy of the Cambridge-PMRT (c-PMRT) index to discriminate between patients with significantly different outcomes and the value of PMRT in each c-PMRT prognostic group.ResultsMore than half of the pN0-1mi patients of our cohort underwent PMRT, which almost significantly improved LRR-free survival and DFS. Matching pN0-1mi patients based on the number of clinicopathologic recurrence-risk factors identified a higher risk subpopulation (≥3 recurrence-risk factors), but PMRT did not improve patient outcomes. Although the c-PMRT index had the potential to predict patient outcomes, its use did not help in making the decision of whether or not to use PMRT.ConclusionWe failed to isolate a subgroup of early BC patients without LN involvement suitable for PMRT, despite studying a large cohort.



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Response rate as a potential surrogate for survival and efficacy in patients treated with novel immune checkpoint inhibitors: A meta-regression of randomised prospective studies

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Giandomenico Roviello, Fabrice Andre, Sergio Venturini, Barbara Pistilli, Giuseppe Curigliano, Massimo Cristofanilli, Pietro Rosellini, Daniele Generali
IntroductionTo assess the role of the tumour response rate (RR) after immune checkpoint inhibitors–based therapy as a potential surrogate end-point of progression-free survival (PFS) and overall survival (OS) in patients with solid tumours, we performed a trial-based meta-regression of randomised studies comparing different immune checkpoint inhibitors–based treatments.MethodsThe systematic literature search included the electronic databases and the proceedings of oncologic meetings. Treatment effects on PFS and OS were expressed as hazard ratios (HRs); treatment effects on RR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome.ResultsTwenty-four trials, for a total of 11,894 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for PFS or the log(HR) for OS on the log(OR) for RR demonstrated weak associations (R² = 0.47; 95% confidence interval [CI], 0.03–0.77; P = 0.001; and R² = 0.32; 95% CI, 0.02–0.76; P = 0.01, respectively). The pre-planned analyses stratifying trials according to different type of disease and different mechanism of action of immune checkpoint inhibitors showed a very weak association of the RR with the OS for non–small cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyte–associated antigen 4 checkpoint inhibitors.ConclusionThe results of the trial-based meta-regression analysis indicated a weak correlation between RR and OS, supporting future investigations to assess the surrogacy of RR in the patient treated with immune checkpoint inhibitors.



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