bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical activity and cannabis cessation
Authors: Irons Jessica G. , Babson Kimberly A. , Bergeria Cecilia L. , Bonn‐Miller Marcel O.
Published: March 2014

Background and Objectives

Based on recent empirical and theoretical work suggesting that physical activity (PA) activates many of the same physiological systems as cannabis, the present study sought to investigate the impact of PA level (ie, low [including none] vs. moderate/high) on a cannabis cessation attempt during the first 7 days post‐quit.

Methods

The present study was a 2 time‐point prospective study of 84 cannabis dependent military veterans (3 female) who responded to study flyers, within a Veterans Affairs Medical Center, seeking individuals interested in engaging in a self‐guided cessation attempt. All study measures were self‐report.

Results

Though no baseline differences between those with low and those with moderate/high levels of physical activity were observed, results revealed that participants who reported low levels of physical activity, versus moderate/high levels, were significantly more likely to report a cannabis lapse during the week following a quit attempt, particularly within the first 4 days of the cessation period. Further, individuals with low levels of PA were also more likely to report greater mean cannabis use during the first 4 days of the cessation period.

Conclusions and Scientific Significance

Findings suggest that early interventions aimed at increasing physical activity may be useful among individuals with cannabis dependence who are engaged in a cessation attempt. (Am J Addict 2014;23:485–492)
University Education Fees, Economic Rents and Distributive Justice
Authors: Lamont Julian
Published: March 2014

In this article I defend the claim that subsidies for university education should be substantially reduced. The normative justification for this conclusion derives from a theory of distributive justice called the Compensation Theory of Income Justice, which is most easily understood as a normative version of the positive economic theory of compensating differentials. Relying on the distinction between incentives and economic rents, and after considering two ‘received opinions’ about why large income differentials exist in modern societies, I note that substantial portions of above‐average incomes are likely to be artificial monopoly rents, rather than incentives or natural monopoly rents. Under the Compensation Theory of Income Justice the earning of artificial monopoly rents is not justified. Since subsidisation of university education fees increases lifetime artificial rents, the theory would recommend such subsidies be substantially reduced. I defend this conclusion against objections, the most notable of which is the view that university subsidies help to improve equality of opportunity to university education. I explain how it is possible to maintain the laudable aim of providing equality of opportunity while reducing the subsidisation and, as a consequence, the lifetime artificial rents.
Persistency of accuracy of genomic breeding values for different simulated pig breeding programs in developing countries
Authors: Akanno E.C. , Schenkel F.S. , Sargolzaei M. , Friendship R.M. , Robinson J.A.B.
Published: March 2014

Genetic improvement of pigs in tropical developing countries has focused on imported exotic populations which have been subjected to intensive selection with attendant high population‐wide linkage disequilibrium (LD). Presently, indigenous pig population with limited selection and low LD are being considered for improvement. Given that the infrastructure for genetic improvement using the conventional BLUP selection methods are lacking, a genome‐wide selection (GS) program was proposed for developing countries. A simulation study was conducted to evaluate the option of using 60 K SNP panel and observed amount of LD in the exotic and indigenous pig populations. Several scenarios were evaluated including different size and structure of training and validation populations, different selection methods and long‐term accuracy of GS in different population/breeding structures and traits. The training set included previously selected exotic population, unselected indigenous population and their crossbreds. Traits studied included number born alive (NBA), average daily gain (ADG) and back fat thickness (BFT). The ridge regression method was used to train the prediction model. The results showed that accuracies of genomic breeding values (GBVs) in the range of 0.30 (NBA) to 0.86 (BFT) in the validation population are expected if high density marker panels are utilized. The GS method improved accuracy of breeding values better than pedigree‐based approach for traits with low heritability and in young animals with no performance data. Crossbred training population performed better than purebreds when validation was in populations with similar or a different structure as in the training set. Genome‐wide selection holds promise for genetic improvement of pigs in the tropics.
TGF‐β cascade regulation by PPP1 and its interactors –impact on prostate cancer development and therapy
Authors: Korrodi‐Gregório Luís , Silva Joana Vieira , Santos‐Sousa Luís , Freitas Maria João , Felgueiras Juliana , Fardilha Margarida
Published: March 2014

Protein phosphorylation is a key mechanism by which normal and cancer cells regulate their main transduction pathways. Protein kinases and phosphatases are precisely orchestrated to achieve the (de)phosphorylation of candidate proteins. Indeed, cellular health is dependent on the fine‐tune of phosphorylation systems, which when deregulated lead to cancer. Transforming growth factor beta (TGF‐β) pathway involvement in the genesis of prostate cancer has long been established. Many of its members were shown to be hypo‐ or hyperphosphorylated during the process of malignancy. A major phosphatase that is responsible for the vast majority of the serine/threonine dephosphorylation is the phosphoprotein phosphatase 1 (PPP1). PPP1 has been associated with the dephosphorylation of several proteins involved in the TGF‐β cascade. This review will discuss the role of PPP1 in the regulation of several TGF‐β signalling members and how the subversion of this pathway is related to prostate cancer development. Furthermore, current challenges on the protein phosphatases field as new targets to cancer therapy will be addressed.
Working memory training in young children with ADHD: a randomized placebo‐controlled trial
Authors: van Dongen‐Boomsma Martine , Vollebregt Madelon A. , Buitelaar Jan K. , Slaats‐Willemse Dorine
Published: March 2014

Background

Until now, working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD; for young children with ADHD, no studies are available. To this end, a triple‐blind, randomized, placebo‐controlled study was designed to assess the efficacy of Cogmed Working Memory Training (CWMT) in young children with ADHD.

Methods

Fifty‐one children (5–7 years) with a DSM‐IV‐TR diagnosis of ADHD (without current psychotropic medication) were randomly assigned to the active (adaptive) or placebo (nonadaptive) training condition for 25 sessions during 5 weeks. The compliance criterion (>20 sessions) was met for 47 children. The primary outcome measure concerned the core behavioural symptoms of ADHD, measured with the ADHD Rating Scale IV (ADHD‐RS). Secondary outcome measures were neurocognitive functioning, daily executive functioning, and global clinical functioning. The influence of the increase in difficulty level (Index‐Improvement) for the treatment group was also analysed. Clinical trial registration information – ‘Working Memory Training in Young ADHD Children’; www.clinicaltrials.gov; NCT00819611.

Results

A significant improvement in favour of the active condition was found on a verbal working memory task (p = .041; adapted Digit Span WISC‐III, backward condition). However, it did not survive correction for multiple testing. No significant treatment effect on any of the primary or other secondary outcome measurements was found. The Index‐Improvement significantly contributed to ADHD‐RS and the Behavior Rating Inventory of Executive Function, both rated by the teacher, but revealed no significant group difference.

Conclusions

This study failed to find robust evidence for benefits of CMWT over the placebo training on behavioural symptoms, neurocognitive, daily executive, and global clinical functioning in young children with ADHD.
Improving child and parenting outcomes following paediatric acquired brain injury: a randomised controlled trial of Stepping Stones Triple P plus Acceptance and Commitment Therapy
Authors: Brown Felicity L. , Whittingham Koa , Boyd Roslyn N. , McKinlay Lynne , Sofronoff Kate
Published: March 2014

Background

Persistent behavioural difficulties are common following paediatric acquired brain injury (ABI). Parents and families also experience heightened stress, psychological symptoms and burden, and there is evidence of a reciprocal relationship between parent and child functioning, which may be mediated by the adoption of maladaptive parenting practices. Despite this, there is currently a paucity of research in family interventions in this population. The aim of this study was to determine the efficacy of Stepping Stones Triple P: Positive Parenting Program (SSTP), with an Acceptance and Commitment Therapy (ACT) workshop, in improving child outcomes and parenting practices following paediatric ABI.

Methods

Fifty‐nine parents of children (mean age 7 years, SD 3 years, 1 month; 35 males, 24 females) with ABI (Traumatic injuries 58%, Tumour 17%, Encephalitis or meningitis 15%, Cardiovascular accident 7%, Hypoxia 3%) who were evidencing at least mild behaviour problems were randomly assigned to treatment or care‐as‐usual conditions over 10 weeks. Mixed‐model repeated‐measures linear regression analyses were conducted to compare conditions from pre‐ to postintervention on child behavioural and emotional functioning (Eyberg Child Behavior Inventory, Strengths and Difficulties Questionnaire) and dysfunctional parenting style (Parenting Scale). Assessment of maintenance of change was conducted at a 6‐month follow‐up. The trial was registered on Australian New Zealand Clinical Trials Registry (ID: ACTRN12610001051033, www.anzctr.org.au).

Results

Significant time‐by‐condition interactions were identified on number and intensity of child behaviour problems, child emotional symptoms and parenting laxness and overreactivity, indicating significant improvements in the treatment condition, with medium‐to‐large effect sizes. Most improvements were maintained at 6 months.

Conclusions

Group parenting interventions incorporating Triple P and ACT may be efficacious in improving child and parenting outcomes following paediatric ABI.
Editorial Perspective: Assessing developmental risk in cultural context: the case of ‘left behind’ children in rural China
Authors: Ding Guodong , Bao Yixiao
Published: March 2014

The role of family factors in developmental risk is widely acknowledged in general child psychology and psychiatry. It is also well understood that rapid socio‐economic change can lead to stress on community and family systems that can place children at risk. However, the impact of these processes is likely to vary as a function of the cultural setting in which they occur. Since the reform and opening up policy started in the late 1970s, China has experienced unprecedented economic growth and urban development. The process of industrialization has accelerated rural reforms in China and increased agricultural productivity and freed agricultural labor. As a consequence large numbers of former rural laborers have headed into more urbanized areas, looking for better employment opportunities and sources of income, while having no choice but to leave their children living in rural hometowns. . This forms the background of “left behind” children in rural China. “Left behind” children are those under 18 years of age who live with a single parent or their extended family in rural areas while one or both of their parents are away seeking employment in urban settings. The purpose of this editorial perspective is to describe the Chinese “left behind” children phenomenon and to highlight the need for research to provide an evidence‐based component to the assessment of risks in any policy review.
Commentary: (How) does the experience of parental divorce in childhood contextualize adult development? Reflections on Fergusson et al. (2014)
Authors: Tasker Fiona
Published: March 2014

Fergusson, McLeod, and John Horwood (2014) have raised many interesting issues in their article considering the effects of parental separation/divorce in childhood on later adult partnership outcomes. In particular the article has contributed to our knowledge of the intergenerational transmission of marital instability. In my Commentary article I have: (a) situated the Christchurch Health and Development Study (CHDS) findings within the substantial body of literature on the intergenerational transmission of marital instability, (b) placed these findings within their sociocultural context, and (c) considered their clinical implications. I then consider the important role that the CHDS study has played in revealing the relative contributions of childhood family structure, social context, and family processes to patterns of intimate relationship formation in adulthood.
Development and validation of a clinical decision‐making aid for screening bowel symptoms in community pharmacies
Authors: Sriram Deepa , McManus Alexandra , Emmerton Lynne , Parsons Richard , Jiwa Moyez
Published: March 2014

Rationale, aims and objectives

Bowel symptoms are common, and community pharmacies are an ideal setting for health advice about these symptoms. The aim of this study was to develop and validate a questionnaire for use with adults presenting to community pharmacies with lower bowel symptoms. The purpose of the questionnaire was to stratify people into those requiring medical follow‐up for symptoms and those with self‐limiting symptoms.

Method

A self‐administered questionnaire, named the Jodi Lee test (JLT), was developed in three stages – review of the literature, questionnaire design and statistical validation – against a validated screening tool, the patient consultation questionnaire (PCQ), to assess the sensitivity and specificity of JLT. The questionnaire was developed to be simple, easy for all pharmacy staff to use and require no score calculation. Its application was designed to facilitate referral from pharmacy assistants to pharmacists and from pharmacists to medical practitioners.

Results

The questionnaire comprises eight questions. It has a Flesh–Kincaid reading score of 79.5. By considering different score thresholds on the PCQ, a receiver operator characteristic (ROC) curve was calculated to assess the effectiveness of the JLT. From a sample of 118 subjects, the area under the ROC curve was 0.94. At a threshold score of 30 on the PCQ, the sensitivity was 100%. The specificity was 65%.

Conclusion

The JLT has high sensitivity for identifying patients with symptoms of serious bowel disease. It is also likely to identify patients who have symptoms of relatively benign disease who would benefit from medical advice.
A qualitative assessment of provider perspectives on smoking cessation counselling
Authors: Champassak Sofie L. , Goggin Kathy , Finocchario‐Kessler Sarah , Farris Maghen , Ehtesham Maniza , Schoor Rachel , Catley Delwyn
Published: March 2014

Rationale, aims and objectives

Few studies have examined doctors' views about counselling unmotivated smokers. This study explored doctors' perceptions of useful strategies to motivate patients to quit, how receptive they felt patients were to these strategies, and the benefits and drawbacks of discussing smoking cessation with patients.

Methods

Fourteen semi‐structured qualitative interviews were conducted with doctors and resident doctors.

Results

Strategies reported by providers included: educating about the health risks of smoking, using ‘scare tactics’ to highlight the harmful effects and providing advice about how to quit. Providers believed that most patients were receptive to their strategies, but noted that they lacked feedback to know for sure. Providers saw the possibility of improving patients' health and decreasing overall health care costs as potential benefits, but cited the potential to damage rapport, competing priorities during already rushed visits and uncertainty about the effectiveness of their efforts as drawbacks that reduced their motivation to raise the issue with patients.

Conclusions

Doctors believe in the potential benefits of smoking cessation counselling but predominantly report focusing on enhancing patient's risk perceptions. They did not report attempting to use the wider array of recommended and empirically supported methods to counsel their patients. Providing doctors with increased training in motivational counselling and feedback about the efficacy their efforts or supplementing doctor care with behaviour change specialists would likely increase the benefits of counselling to patients.
Association Between Performance on Timed Up and Go Subtasks and Mild Cognitive Impairment: Further Insights into the Links Between Cognitive and Motor Function
Authors: Mirelman Anat , Weiss Aner , Buchman Aron S. , Bennett David A. , Giladi Nir , Hausdorff Jefferey M.
Published: March 2014

Objectives

To assess whether different Timed Up and Go (TUG) subtasks are affected differently in older adults with mild cognitive impairment (MCI) and are specific to different cognitive abilities.

Design

Cross‐sectional.

Setting

Community and home.

Participants

Older adults without dementia (N = 347; mean age 83.6 ± 3.5, 75% female, 19.3% with MCI) participating in the Rush Memory and Aging Project.

Measurements

Subjects wore a small, light‐weight sensor that measured acceleration and angular velocity while they performed the instrumented TUG (iTUG). Measures of iTUG were derived from four subtasks (walking, turning, sit‐to‐stand, stand‐to‐sit) and compared between participants with MCI and those with no cognitive impairment.

Results

Participants with no cognitive impairment and those with MCI did not differ in age (P = .90), sex (P = .80), years of education (P = .48) or time to complete the TUG (no cognitive impairment 7.6 ± 3.7 seconds; MCI 8.4 ± 3.7 seconds; P = .12). Participants with MCI had less walking consistency (P = .009), smaller pitch range during transitions (P = .005), lower angular velocity during turning (P = .04) and required more time to complete the turn‐to‐walk (P = .04). Gait consistency was correlated with perceptual speed (P = .01), and turning was correlated with perceptual speed (P = .02) and visual‐spatial abilities (P = .049).

Conclusion

Mild cognitive impairment is associated with impaired performance on iTUG subtasks that cannot be identified when simply measuring overall duration of performance. Distinctive iTUG tasks were related to particular cognitive domains, demonstrating the specificity of motor–cognitive interactions. Using a single sensor worn on the body for quantification of mobility may facilitate understanding of late‐life gait impairments and their interrelationship with cognitive decline.
“IDEAL” Aging Is Associated with Lower Resting Metabolic Rate: The Baltimore Longitudinal Study of Aging
Authors: Schrack Jennifer A. , Knuth Nicolas D. , Simonsick Eleanor M. , Ferrucci Luigi
Published: March 2014

Objectives

To assess the associations among age, health status, and resting metabolic rate (RMR) in a large population of older adults.

Design

Cross‐sectional analysis.

Setting

Community‐dwelling volunteers from the Baltimore Longitudinal Study of Aging (BLSA).

Participants

Persons aged 40 to 96 (mean 68.2 ± 11.0) who underwent a comprehensive physical examination, cognitive assessment, RMR testing, body composition assessment, and physical function testing during a 3‐day clinic visit (N = 420).

Measurements

Participants were assigned to Insight into the Determination of Exceptional Aging and Longevity (IDEAL) or non‐IDEAL categories based on health status. IDEAL participants were defined according to the absence of physical and cognitive impairments, chronic conditions and comorbidities, and blood profile abnormalities. A three‐stage linear regression model was used to assess the relationship between RMR and age, using IDEAL classification as a predictor and adjusting for sex and body composition.

Results

Resting metabolic rate averaged 1,512.4 ± 442.9 kcal/d and was lower with older age (β = −8.55, P < .001). After adjusting for age, sex, and body composition, RMR was 109.6 kcal/d lower in IDEAL than non‐IDEAL participants (P < .005).

Conclusion

Individuals who are fully functional and free of major medical conditions have lower RMR than those with disease and functional impairments. These findings suggest that health status plays a role in energy use and regulation independent of age and body composition and that elevated RMR may be a global biomarker of poor health in older persons.
Associations Between Observed In‐Home Behaviors and Self‐Reported Low Mood in Community‐Dwelling Older Adults
Authors: Thielke Stephen M. , Mattek Nora C. , Hayes Tamara L. , Dodge Hiroko H. , Quiñones Ana R. , Austin Daniel , Petersen Johanna , Kaye Jeffrey A.
Published: March 2014

Objectives

To ascertain the association between self‐report of low mood and unobtrusively measured behaviors (walking speed, time out of residence, frequency of room transitions, and computer use) in community‐dwelling older adults using novel monitoring technologies.

Design

Longitudinal cohort study of older adults whose homes were outfitted with activity sensors. Participants completed Internet‐based weekly health questionnaires with questions about mood.

Setting

Apartments and homes of older adults living in the Portland, Oregon, metropolitan area.

Participants

Adults, average age 84, followed for an average of 3.7 years (n = 157).

Measurements

Mood was assessed according to self‐report each week. Walking speed, time spent out of residence, and room transitions were estimated using data from sensors; computer use was measured by timing actual use. The association between global or weekly low mood and the four behavior measures was ascertained, adjusting for baseline characteristics.

Results

Eighteen thousand nine hundred sixty weekly observations of mood were analyzed; 2.6% involved low mood. Individuals who reported low mood more often had no average differences in any behavior parameters from those who reported low mood less often. During weeks when they reported low mood, participants spent significantly less time out of residence and on the computer but showed no change in walking speed or room transitions.

Conclusion

Low mood in these community‐dwelling older adults involved going out of the house less and using the computer less but no consistent changes in movements. Technologies to monitor in‐home behavior may have potential for research and clinical care.
Unilateral Lesion Increases Oestrogen Receptor α Expression in the Intact Side of the Ventromedial Hypothalamic Nucleus in Ovariectomised Rats
Authors: Shimogawa Y. , Maekawa F. , Yamanouchi K.
Published: March 2014

To determine the relationship between the right and left sides of the ventrolateral ventromedial hypothalamic nucleus (vlVMN) in regulating the expression of oestrogen receptor (ER)α, the unilateral vlVMN was lesioned and the number of ERα‐immunoreactive cells and the ERα mRNA level in the intact side of the vlVMN and arcuate nucleus (ARC) were measured in ovariectomised rats. Twenty‐four hours after lesioning, brain samples were collected for analysis of ERα expression by immunohistochemistry and the real‐time reverse transcriptase‐polymerase chain reaction. The number of ERα‐immunoreactive cells in the intact side of the vlVMN but not the ARC in the unilateral lesioned group was significantly higher than that in the control or sham‐lesioned group. Expression levels of ERα mRNA in the intact side of the vlVMN but not the ARC in unilateral lesioned rats were significantly higher than those in the sham‐lesioned group. Of transcript variants with alternative 5′‐untranslated regions (0S, 0N, 0, 0T and E1), the ERα 0 transcript level was significantly increased. These results indicate that unilateral damage of vlVMN induces an increase in ERα in the intact side by increasing ERα transcription in a promoter‐specific manner. The findings also suggest the existence of new neuroendocrine control system between the right and left sides for the expression of ERα in the vlVMN.
Use of self‐controlled designs in pharmacoepidemiology
Authors: Hallas J. , Pottegård A.
Published: March 2014

Self‐controlled observational study designs, such as the case–crossover design and the self‐controlled case series, are reviewed, and their respective rationale, strengths and limitations are compared. Although no single design is generally superior to the others, they share the trait of being robust towards confounders that are stable over time. The self‐controlled designs can be particularly useful when using secondary healthcare data for pharmacoepidemiological research and might be useful in screening for adverse drug effects. The main limitations of self‐controlled designs are that they are amenable only to transient effects; some may be inefficient with long‐term exposure; and they may be sensitive towards trends in exposure.
The acute promyelocytic leukaemia success story: curing leukaemia through targeted therapies
Authors: Rice K. L. , de Thé H.
Published: March 2014

The recent finding that almost all patients with acute promyelocytic leukaemia (APL) may be cured using a combination of retinoic acid (RA) and arsenic trioxide (As2O3) (N Engl J Med, 369, 2013 and 111) highlights the progress made in our understanding of APL pathogenesis and therapeutic approaches over the past 25 years. The study of APL has revealed many important lessons related to transcriptional control, nuclear organization, epigenetics and the role of proteolysis in biological control. Even more important has been the clinical demonstration that molecularly targeted therapy can eradicate disease.
The Capitalization of Insurance Premiums in House Prices
Authors: Nyce Charles , Dumm Randy E. , Sirmans G. Stacy , Smersh Greg
Published: March 2014

This study uses Miami‐Dade County, Florida home sales, and Citizens Property Insurance Corporation data for the period 2004 through 2009 to measure the capitalization effect of increases in premiums on house prices. Using hedonic pricing models, spatial autocorrelation models, and difference‐in‐differences models, we find that new information was conveyed to homeowners in the higher risk areas by the 2004/2005 storms and that consumers appear to use the insurance premium as a “risk signal.” We also find some support for the hypothesis that the risk of potential hurricane losses is communicated to potential homebuyers through windzone maps.
Molecular Characterization of Phytoplasmas Related to Apple Proliferation and Aster Yellows Groups Associated with Pear Decline Disease in Iran
Authors: Hashemi‐Tameh Mahdis , Bahar Masoud , Zirak Leila
Published: March 2014

Pear trees showing pear decline disease symptoms were observed in pear orchards in the centre and north of Iran. Detection of phytoplasmas using universal primer pair P1A/P7A followed by primer pair R16F2n/R16R2 in nested PCR confirmed association of phytoplasmas with diseased pear trees. However, PCR using group‐specific primer pairs R16(X)F1/R16(X)R1 and rp(I)F1A/rp(I)R1A showed that Iranian pear phytoplasmas are related to apple proliferation and aster yellows groups. Moreover, PCR results using primer pair ESFYf/ESFYr specific to 16SrX‐B subgroup indicated that ‘Ca. Phytoplasma prunorum’ is associated with pear decline disease in the north of Iran. RFLP analyses using HaeIII, HhaI, HinfI, HpaII and RsaI restriction enzymes confirmed the PCR results. Partial 16S rRNA, imp, rp and secY genes sequence analyses approved that ‘Ca. Phytoplasma pyri’ and ‘Ca. Phytoplasma asteris’ cause pear decline disease in the centre of Iran, whereas ‘Ca. Phytoplasma prunorum’ causes disease in the north of Iran. This is the first report of the association of ‘Ca. Phytoplasma asteris’ and ‘Ca. Phytoplasma prunorum’ with pear decline disease worldwide.
Accuracy and Reliability of Severity Estimates Using Linear or Logarithmic Disease Diagram Sets in True Colour or Black and White: a Study Case for Rice Brown Spot
Authors: Schwanck André Aguiar , Del Ponte Emerson Medeiros
Published: March 2014

Four disease diagram sets to aid in assessments of rice brown spot severity were developed and evaluated with regard to accuracy and reliability of the estimates. These sets had severity increments in a linear (LIN) or logarithmic (LOG) fashion with the diagrams depicted in true colour (COL) or black and white (BW). Ten inexperienced raters evaluated one of the sets, totalling forty raters. On each group of raters, the assessment was made first unaided and then aided with the respective diagram set. The minimum and the maximum severities of the diagram sets were 0.5 and 36%, respectively, and the five intermediate severity values were 6, 12, 18, 24 and 32% for the LIN diagram sets, and 1.8, 3.3, 6, 11 and 20% for the LOG sets. Overall agreement, measured by the Lin's concordance correlation coefficient (ρc), increased considerably when using the aid (unaided mean ρc = 0.53, aided mean ρc = 0.87) due to a strong reduction in the systematic bias, measured by the bias correction factor Cb (unaided mean Cb = 0.60, aided mean Cb = 0.95). All diagrams led to similar accuracy and precision, but a consistent overestimation was still observed when using the LIN sets, and variability for the absolute errors was higher for the LOG sets, compared with the LIN sets. Estimates using the diagram sets were more reliable based on the intraclass correlation (mean ρ = 0.79–0.86) compared with unaided estimates (mean ρ = 0.51–0.67). Raters exhibited preference for specific values, such as the ‘knots’ (10, 20, 30%, etc.), and the severity values represented in the diagrams, especially when using the LIN sets. The diagram sets similarly helped to improve accuracy and reliability of estimates of rice brown spot epidemics.
Melatonin reduces endothelin‐1 expression and secretion in colon cancer cells through the inactivation of FoxO‐1 and NF‐κβ
Authors: León Josefa , Casado Jorge , Jiménez Ruiz Sergio M. , Zurita María Sol , González‐Puga Cristina , Rejón Juan D. , Gila Ana , Muñoz de Rueda Paloma , Pavón Esther J. , Reiter Russel J. , Ruiz‐Extremera Angela , Salmerón Javier
Published: March 2014

Melatonin is an indoleamine that is synthesised from tryptophan under the control of the enzymes arylalkylamine N‐acetyltransferase (AA‐NAT) and acetylserotonin methyltransferase (ASMT). Melatonin inhibits colon cancer growth in both in vivo and in vitro models; however, a precise mechanism responsible for inhibiting tumour growth has not been clearly described. Endothelin‐1 (ET‐1) is a peptide that acts as a survival factor in colon cancer, inducing cell proliferation, protecting carcinoma cells from apoptosis and promoting angiogenesis. The data presented show that melatonin inhibits edn‐1 mRNA expression (the first step in ET‐1 synthesis), ECE‐1 protein expression and the release of ET‐1 from colorectal cancer cells in vitro. ET‐1 levels in cultured media present a similar inhibition pattern to that of edn‐1 mRNA expression despite the inhibition of ECE‐1 protein after melatonin treatment, which suggests that an endopeptidase other than ECE‐1 could be mainly responsible for ET‐1 synthesis. The inhibition of edn‐1 expression is due to an inactivation of FoxO1 and NF‐κβ transcription factors. FoxO1 inactivation is associated with an increased Src phosphorylation, due to elevated cAMP content and PKA activity, whereas NF‐κβ inactivation is associated with the blockade of Akt and ERK phosphorylation due to the inhibition of PKC activity after melatonin treatment. Melatonin also inhibits edn‐1 promoter activity regulated by FoxO1 and NF‐κβ. Finally, a significant correlation was observed between AA‐NAT and edn‐1 expression downregulation in human colorectal cancer tissues. In conclusion, melatonin may be useful in treating colon carcinoma in which the activation of ET‐1 plays a role in tumour growth and progression.
A review of metal‐catalyzed molecular damage: protection by melatonin
Authors: Romero Alejandro , Ramos Eva , de Los Ríos Cristóbal , Egea Javier , del Pino Javier , Reiter Russel J.
Published: March 2014

Metal exposure is associated with several toxic effects; herein, we review the toxicity mechanisms of cadmium, mercury, arsenic, lead, aluminum, chromium, iron, copper, nickel, cobalt, vanadium, and molybdenum as these processes relate to free radical generation. Free radicals can be generated in cells due to a wide variety of exogenous and endogenous processes, causing modifications in DNA bases, enhancing lipid peroxidation, and altering calcium and sulfhydryl homeostasis. Melatonin, an ubiquitous and pleiotropic molecule, exerts efficient protection against oxidative stress and ameliorates oxidative/nitrosative damage by a variety of mechanisms. Also, melatonin has a chelating property which may contribute in reducing metal‐induced toxicity as we postulate here. The aim of this review was to highlight the protective role of melatonin in counteracting metal‐induced free radical generation. Understanding the physicochemical insights of melatonin related to the free radical scavenging activity and the stimulation of antioxidative enzymes is of critical importance for the development of novel therapeutic strategies against the toxic action of these metals.
Unusual congenital pulmonary anomaly with presumed left lung hypoplasia in a young dog
Authors: Lee C. M. , Kim J. H. , Kang M. H. , Eom K. D. , Park H. M.
Published: March 2014

A seven‐month‐old, entire, male miniature schnauzer dog was referred with acute vomiting, inappetence and depression primarily as a result of a gastric foreign body (pine cones). During investigations, thoracic radiographs revealed increased volume of the right lung lobes, deviated cardiomediastinal structures and elevation of the heart from the sternum. Thoracic computed tomography revealed left cranial lung lobe hypoplasia and extension of the right cranial lung parenchyma across the midline to the left hemithorax. Branches of the right pulmonary vessels and bronchi also crossed the midline and extended to the left caudal lung lobe. These findings suggested that the right and left lungs were fused. In humans this finding is consistent with horseshoe lung, which is an uncommon congenital malformation. To the authors’ knowledge, this case represents the first report of such a pulmonary anomaly in a dog.
Effects of dietary sodium butyrate on hepatic biotransformation and pharmacokinetics of erythromycin in chickens
Authors: Csikó G. , Nagy G. , Mátis G. , Neogrády Z. , Kulcsár A. , Jerzsele Á. , Szekér K. , Gálfi P.
Published: March 2014

Butyrate, a commonly applied feed additive in poultry nutrition, can modify the expression of certain genes, including those encoding cytochrome P450 (CYP) enzymes. In comparative in vitro and in vivo experiments, the effect of butyrate on hepatic CYP genes was examined in primary cultures of chicken hepatocytes and in liver samples of chickens collected from animals that had been given butyrate as a feed additive. Moreover, the effect of butyrate on the biotransformation of erythromycin, a marker substance for the activity of enzymes of the CYP3A family, was investigated in vitro and in vivo. Butyrate increased the expression of the avian‐specific CYP2H1 both in vitro and in vivo. In contrast, the avian CYP3A37 expression was decreased in hepatocytes following butyrate exposure, but not in the in vivo model. CYP1A was suppressed by butyrate in the in vitro experiments, and overexpressed in vivo in butyrate‐fed animals. The concomitant incubation of hepatocytes with butyrate and erythromycin led to an increased CYP2H1 expression and a less pronounced inhibition of CYP3A37. In in vivo pharmacokinetic experiments, butyrate‐fed animals given a single i.m. injection of erythromycin, a slower absorption phase (longer Thalf‐abs and delayed Tmax) but a rapid elimination phase of this marker substrate was observed. Although these measurable differences were detected in the pharmacokinetics of erythromycin, it is unlikely that a concomitant application of sodium butyrate with erythromycin or other CYP substrates will cause clinically significant feed‐drug interaction in chickens.
Pharmacokinetics of gallium maltolate in Lawsonia intracellularis‐infected and uninfected rabbits
Authors: Sampieri F. , Alcorn J. , Allen A. L. , Clark C. R. , Vannucci F. A. , Pusterla N. , Mapes S. , Ball K. R. , Dowling P. M. , Thompson J. , Bernstein L. R. , Gebhart C. J. , Hamilton D. L.
Published: March 2014

Oral gallium maltolate (GaM) pharmacokinetics (PK) and intestinal tissue (IT) concentrations of elemental gallium ([Ga]) and iron ([Fe]) were investigated in a rabbit model of equine proliferative enteropathy (EPE). New Zealand white does (uninfected controls and EPE‐infected, n = 6/group) were given a single oral GaM dose (50 mg/kg). Serial blood samples were collected from 0 to 216 h post‐treatment (PT) and IT samples after euthanasia. Serology, qPCR, and immunohistochemistry confirmed, or excluded, EPE. Blood and IT [Ga] and [Fe] were determined using inductively coupled plasma–mass spectrometry. PK parameters were estimated through noncompartmental approaches. For all statistical comparisons on [Ga] and [Fe] α = 5%. The Ga log‐linear terminal phase rate constant was lower in EPE rabbits vs. uninfected controls [0.0116 ± 0.004 (SD) vs. 0.0171 ± 0.0028 per hour; P = 0.03]; but half‐life (59.4 ± 24.0 vs. 39.4 ± 10.8 h; P = 0.12); Cmax (0.50 ± 0.21 vs. 0.59 ± 0.42 μg/mL; P = 0.45); tmax (1.75 ± 0.41 vs. 0.9 ± 0.37 h; P = 0.20); and oral clearance (6.743 ± 1.887 vs. 7.208 ± 2.565 L/h; P = 0.74) were not. IT's [Ga] and [Fe] were higher (P < 0.0001) in controls. In conclusion, although infection reduces IT [Ga] and [Fe], a 48 h GaM dosing interval is appropriate for multidose studies in EPE rabbits.
n‐3 polyunsaturated fatty acids worsen inflammation and fibrosis in experimental nonalcoholic steatohepatitis
Authors: Provenzano Angela , Milani Stefano , Vizzutti Francesco , Delogu Wanda , Navari Nadia , Novo Erica , Maggiora Marina , Maurino Valter , Laffi Giacomo , Parola Maurizio , Marra Fabio
Published: March 2014

Background & Aims

n‐3 polyunsaturated fatty acids (PUFA) ameliorate fatty liver in experimental models, but their effects on inflammation and fibrosis during steatohepatitis are either controversial or lacking. We compared the effects of supplementation with olive oil (OO) alone or OO and n‐3 PUFA on the development and progression of experimental steatohepatitis.

Methods

Balb/C mice (≥5 mice/group) were fed a methionine‐ and choline‐deficient (MCD) diet or a control diet for 4 or 8 weeks. At the same time, mice were supplemented with n‐3 PUFA (eicosapentaenoic and docosahexahenoic acid, 25 mg together with 75 mg OO), or OO alone (100 mg), two times a week by intragastric gavage.

Results

After 8 weeks, mice on MCD/n‐3 had higher ALT levels compared to MCD/OO and more severe scores of inflammation, including a significant increase in the number of lipogranulomas (26.4 ± 8.4 vs. 5.1 ± 5 per field, P < 0.001). Intrahepatic expression of TNF‐α and CCL2 was higher in MCD/n‐3 mice at both time points. In addition, increased expression of the profibrogenic genes TIMP‐1 and TGF‐β, and more severe histological scores of fibrosis were evident in MCD/n‐3 mice. After 8 week of MCD diet, portal pressure was higher in mice receiving n‐3 than in those on OO alone (5.1 ± 1.4 vs. 7.0 ± 0.9 mmHg, P < 0.05). Analysis of hepatic fatty acid profile showed that supplementation resulted in effective incorporation of n‐3 PUFA.

Conclusions

In a murine model of steatohepatitis, supplementation with n‐3 PUFA and OO is associated with more severe necro‐inflammation and fibrosis than in mice treated with OO only.
The origins of crown group birds: molecules and fossils
Authors: Mayr Gerald
Published: March 2014

Knowledge of the evolutionary history of crown group birds (Neornithes) has significantly improved through emerging congruence among phylogenetic hypotheses and the description of numerous newPalaeogene stem group representatives. However, controversies still persist about the precise interrelationships of many extant and fossil taxa and about the timing of the diversification of the neornithine crown group. Using the example ofPhaethontiformes (tropicbirds) andPsittaciformes (parrots), it is shown how new sequence‐based phylogenies may shed light on the relationships of fossils with an unexpected character mosaic, and how such fossils can improve our understanding of character evolution in morphologically disparate avian taxa. The earliest occurrences of neornithine birds are plotted on a current phylogeny. As noted by previous authors, an extensive diversification of neornithine birds before the latestCretaceous is not supported by the fossil record, and the existence of essentially modern‐type representatives ofTelluraves (the clade including most arboreal birds) in theCretaceous, such as suggested from molecular calibrations, is highly unlikely.
Implications of the mesophyll conductance to CO2 for photosynthesis and water‐use efficiency during long‐term water stress and recovery in two contrasting Eucalyptus species
Authors: CANO F. JAVIER , LÓPEZ ROSANA , WARREN CHARLES R.
Published: March 2014

Water stress (WS) slows growth and photosynthesis (An), but most knowledge comes from short‐time studies that do not account for longer term acclimation processes that are especially relevant in tree species. Using two Eucalyptus species that contrast in drought tolerance, we induced moderate and severe water deficits by withholding water until stomatal conductance (gsw) decreased to two pre‐defined values for 24 d, WS was maintained at the target gsw for 29 d and then plants were re‐watered. Additionally, we developed new equations to simulate the effect on mesophyll conductance (gm) of accounting for the resistance to refixation of CO2. The diffusive limitations to CO2, dominated by the stomata, were the most important constraints to An. Full recovery of An was reached after re‐watering, characterized by quick recovery of gm and even higher biochemical capacity, in contrast to the slower recovery of gsw. The acclimation to long‐term WS led to decreased mesophyll and biochemical limitations, in contrast to studies in which stress was imposed more rapidly. Finally, we provide evidence that higher gm under WS contributes to higher intrinsic water‐use efficiency (iWUE) and reduces the leaf oxidative stress, highlighting the importance of gm as a target for breeding/genetic engineering.
Notch signaling in the pigmented epithelium of the anterior eye segment promotes ciliary body development at the expense of iris formation
Authors: Sarode Bhushan , Nowell Craig S. , Ihm JongEun , Kostic Corinne , Arsenijevic Yvan , Moulin Alexandre P. , Schorderet Daniel F. , Beermann Friedrich , Radtke Freddy
Published: March 2014

The ciliary body and iris are pigmented epithelial structures in the anterior eye segment that function to maintain correct intra‐ocular pressure and regulate exposure of the internal eye structures to light, respectively. The cellular and molecular factors that mediate the development of the ciliary body and iris from the ocular pigmented epithelium remain to be fully elucidated. Here, we have investigated the role of Notch signaling during the development of the anterior pigmented epithelium by using genetic loss‐ and gain‐of‐function approaches. Loss of canonical Notch signaling results in normal iris development but absence of the ciliary body. This causes progressive hypotony and over time leads to phthisis bulbi, a condition characterized by shrinkage of the eye and loss of structure/function. Conversely, Notch gain‐of‐function results in aniridia and profound ciliary body hyperplasia, which causes ocular hypertension and glaucoma‐like disease. Collectively, these data indicate that Notch signaling promotes ciliary body development at the expense of iris formation and reveals novel animal models of human ocular pathologies.
Metabotropic glutamate receptor 1 mediates melanocyte transformation via transactivation of insulin‐like growth factor 1 receptor
Authors: Teh Jessica L. F. , Shah Raj , Shin Seung‐Shick , Wen Yu , Mehnert Janice M. , Goydos James , Chen Suzie
Published: March 2014

Our laboratory previously described the oncogenic properties of metabotropic glutamate receptor 1 (mGluR1) in melanocytes. mGluR1 transformed immortalized mouse melanocytes in vitro and induced vigorous tumor formation in vivo. Subsequently, we observed the activation of PI3K/AKT in mGluR1‐mediated melanocytic tumorigenesis in vivo. In particular, we identified AKT2 being the predominant isoform contributing to the activation of AKT. Suppression of Grm1 or AKT2 using an inducible Tet‐R siRNA system resulted in a 60 or 30% reduction, respectively, in in vivo tumorigenesis. We show that simultaneous downregulation of Grm1 plus AKT2 results in a reduction of approximately 80% in tumor volumes, suggesting that both mGluR1 and AKT2 contribute to the tumorigenic phenotype in vivo. The discrepancy between the mild in vitro transformation characteristics and the aggressive in vivo tumorigenic phenotypes of these stable mGluR1‐melanocytic clones led us to investigate the possible involvement of other growth factors. Here, we highlight a potential crosstalk network between mGluR1 and tyrosine kinase, insulin‐like growth factor 1 receptor (IGF‐1R).
Targeted next generation sequencing identifies clinically actionable mutations in patients with melanoma
Authors: Jeck William R. , Parker Joel , Carson Craig C. , Shields Janiel M. , Sambade Maria J. , Peters Eldon C. , Burd Christin E. , Thomas Nancy E. , Chiang Derek Y. , Liu Wenjin , Eberhard David A. , Ollila David , Grilley‐Olson Juneko , Moschos Stergios , Neil Hayes D. , Sharpless Norman E.
Published: March 2014

Somatic sequencing of cancers has produced new insight into tumorigenesis, tumor heterogeneity, and disease progression, but the vast majority of genetic events identified are of indeterminate clinical significance. Here, we describe a NextGen sequencing approach to fully analyzing 248 genes, including all those of known clinical significance in melanoma. This strategy features solution capture of DNA followed by multiplexed, high‐throughput sequencing and was evaluated in 31 melanoma cell lines and 18 tumor tissues from patients with metastatic melanoma. Mutations in melanoma cell lines correlated with their sensitivity to corresponding small molecule inhibitors, confirming, for example, lapatinib sensitivity in ERBB4 mutant lines and identifying a novel activating mutation of BRAF. The latter event would not have been identified by clinical sequencing and was associated with responsiveness to a BRAF kinase inhibitor. This approach identified focal copy number changes of PTEN not found by standard methods, such as comparative genomic hybridization (CGH). Actionable mutations were found in 89% of the tumor tissues analyzed, 56% of which would not be identified by standard‐of‐care approaches. This work shows that targeted sequencing is an attractive approach for clinical use in melanoma.