Performance Deficits of NK1 Receptor Knockout Mice in the 5-Choice Serial Reaction-Time Task: Effects of d-Amphetamine, Stress and Time of Day

Background: The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon.Methods and Results: The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning.Conclusion: In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Squamous Cell Carcinoma of the Skin and Coal Tar Creosote Exposure in a Railroad Worker

A 50-year-old male railroad worker presented to his primary care physician with an erythematous, tender skin lesion on the right knee; a biopsy of this lesion revealed squamous cell carcinoma in situ. The site of the lesion was sun-protected but had been associated with 30 years of creosote-soaked clothing. In this article, we review dermal and other malignancies associated with creosote, along with creosote occupational exposures and exposure limits. This is a unique case, given the lack of other, potentially confounding, polyaromatic hydrocarbons and the sun-protected location of the lesion

The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wildtype mice in the 5 Choice Serial Reaction Time Task

Genetically-altered mice, lacking functional NK1 receptors (NK1R-/-), express abnormal behaviours that are prominent in Attention Deficit Hyperactivity Disorder: namely, inattentiveness and impulsivity (indicated by their greater %omissions and premature responses in the 5 Choice Serial Reaction Time Task: ‘5 CSRTT’) and locomotor hyperactivity. Here, we investigated how behaviour in the 5 CSRTT is affected by repeated testing and whether the abnormalities expressed by NK1R-/- mice are mimicked by treating wildtypes with an NK1R antagonist (L 733060 or RP 67580; 5 or 10 mg/kg). Repeated testing with a variable (VITI) or fixed, prolonged (LITI) intertrial interval reduced %omissions. Premature responses also declined, but only in NK1R /- mice in the VITI test. By contrast, perseveration increased in both genotypes. RP 67580 (10 mg/kg) increased the %omissions in both genotypes in the VITI, an action which cannot be attributed to NK1R antagonism. Neither drug affected perseveration. However, for premature responses, the profile of the response suggests that the low and high doses of RP 67580 (VITI) and L 733060 (LITI) have opposing effects on this behaviour. We infer that the effect of NK1R antagonists in the 5 CSRTT is confounded by animals’ test experience and non-specific drug effects at sites other than NK1R, possibly L type Ca2+v channels

Unique contributions to the scalar bispectrum in `just enough inflation'

A scalar field rolling down a potential with a large initial velocity results in inflation of a finite duration. Such a scenario suppresses the scalar power on large scales improving the fit to the cosmological data. We find that the scenario leads to a hitherto unexplored situation wherein the boundary terms dominate the contributions to the scalar bispectrum over the bulk terms. We show that the consistency relation governing the non-Gaussianity parameter $f_{_{\rm NL}}$ is violated on large scales and that the contributions at the initial time can substantially enhance the value of $f_{_{\rm NL}}$.Comment: v1: 5 pages, 4 figure

Relevance and quality of climate planning for large and medium-sized cities of the Tropics

In the last seven years, the number of plans with climate measures for tropical cities has increased 2.3 times compared to the previous seven years as a result of the initiatives of central and local governments, multi-bilateral development aid and development banks. The plans matter in achieving the 11th United Nations’ Sustainable development goal. Therefore, the objective of this chapter is to ascertain the relevance and quality of climate planning in large and medium-sized cities in the Tropics. The chapter proposes and applies the QCPI-Quality of Climate Plans Index, consisting of 10 indicators (characterization of climate, number, quantification, relevance, potential impact, cost, funding sources, timetable and responsibility of measures, implementation monitoring and reporting). It is revealed that 338 tropical cities currently have a local development, emergency, master, mitigation, adaptation, risk reduction plan or a resilience or smart city strategy. These tools were unquestionably more common in large cities, especially in OCDE and BRICS countries, while they were rare in Developing Countries. Local development plans (Municipal development, general, comprehensive) were the most common in medium-sized cities, along with those with the lowest quality, while stand-alone strategies and plans (resilience, mitigation, sustainable, adaptation), applied mostly in big cities, present much higher quality

Designing a physical activity parenting course : parental views on recruitment, content and delivery

Background Many children do not engage in sufficient levels of physical activity (PA) and spend too much time screen-viewing (SV). High levels of SV (e.g. watching TV, playing video games and surfing the internet) and low levels of PA have been associated with adverse health outcomes. Parenting courses may hold promise as an intervention medium to change children’s PA and SV. The current study was formative work conducted to design a new parenting programme to increase children’s PA and reduce their SV. Specifically, we focussed on interest in a course, desired content and delivery style, barriers and facilitators to participation and opinions on control group provision. Methods In-depth telephone interviews were conducted with thirty two parents (29 female) of 6–8 year olds. Data were analysed thematically. An anonymous online survey was also completed by 750 parents of 6–8 year old children and descriptive statistics calculated. Results Interview participants were interested in a parenting course because they wanted general parenting advice and ideas to help their children be physically active. Parents indicated that they would benefit from knowing how to quantify their child’s PA and SV levels. Parents wanted practical ideas of alternatives to SV. Most parents would be unable to attend unless childcare was provided. Schools were perceived to be a trusted source of information about parenting courses and the optimal recruitment location. In terms of delivery style, the majority of parents stated they would prefer a group-based approach that provided opportunities for peer learning and support with professional input. Survey participants reported the timing of classes and the provision of childcare were essential factors that would affect participation. In terms of designing an intervention, the most preferred control group option was the opportunity to attend the same course at a later date. Conclusions Parents are interested in PA/SV parenting courses but the provision of child care is essential for attendance. Recruitment is likely to be facilitated via trusted sources. Parents want practical advice on how to overcome barriers and suggest advice is provided in a mutually supportive group experience with expert input

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al

A population-based cohort study of HRT use and breast cancer in southern Sweden

The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25–65 when interviewed in 1990–92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93–1.04). There was a small excess of breast cancer with 434 observed and 387.69 expected (SIR = 1.12, 95% CI 1.02–1.23). Among about 3 663 ever users of HRT, there was no increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86–1.12) but a significant excess of breast cancer (SIR = 1.35, 95% CI 1.09–1.64) compared with never users (SIR = 1.07, 95% CI 0.96–1.19). Breast cancer increased with increasing duration of use and for 48–120 months use the SIR was 1.92 (95% CI 1.32–2.70). There was no significant interaction with family history of breast cancer although an independent additive effect was suggested between HRT use and family history. In a Cox regression model time to breast cancer in relation to duration of HRT use was analysed adjusting for age at menarche, age at menopause, age at first full term pregnancy, parity and age at diagnosis. A significantly higher risk was seen for longer duration of HRT use compared with never users. No increased risk is seen in women beyond 5 years after stopping HRT. There was no interaction between previous use of oral contraceptives and later HRT use. © 2001 Cancer Research Campaign http://www.bjcancer.co

Rethinking the patient: using Burden of Treatment Theory to understand the changing dynamics of illness

<b>Background</b> In this article we outline Burden of Treatment Theory, a new model of the relationship between sick people, their social networks, and healthcare services. Health services face the challenge of growing populations with long-term and life-limiting conditions, they have responded to this by delegating to sick people and their networks routine work aimed at managing symptoms, and at retarding - and sometimes preventing - disease progression. This is the new proactive work of patient-hood for which patients are increasingly accountable: founded on ideas about self-care, self-empowerment, and self-actualization, and on new technologies and treatment modalities which can be shifted from the clinic into the community. These place new demands on sick people, which they may experience as burdens of treatment.<p></p> <b>Discussion</b> As the burdens accumulate some patients are overwhelmed, and the consequences are likely to be poor healthcare outcomes for individual patients, increasing strain on caregivers, and rising demand and costs of healthcare services. In the face of these challenges we need to better understand the resources that patients draw upon as they respond to the demands of both burdens of illness and burdens of treatment, and the ways that resources interact with healthcare utilization.<p></p> <b>Summary</b> Burden of Treatment Theory is oriented to understanding how capacity for action interacts with the work that stems from healthcare. Burden of Treatment Theory is a structural model that focuses on the work that patients and their networks do. It thus helps us understand variations in healthcare utilization and adherence in different healthcare settings and clinical contexts

Electron quantum metamaterials in van der Waals heterostructures

In recent decades, scientists have developed the means to engineer synthetic periodic arrays with feature sizes below the wavelength of light. When such features are appropriately structured, electromagnetic radiation can be manipulated in unusual ways, resulting in optical metamaterials whose function is directly controlled through nanoscale structure. Nature, too, has adopted such techniques -- for example in the unique coloring of butterfly wings -- to manipulate photons as they propagate through nanoscale periodic assemblies. In this Perspective, we highlight the intriguing potential of designer sub-electron wavelength (as well as wavelength-scale) structuring of electronic matter, which affords a new range of synthetic quantum metamaterials with unconventional responses. Driven by experimental developments in stacking atomically layered heterostructures -- e.g., mechanical pick-up/transfer assembly -- atomic scale registrations and structures can be readily tuned over distances smaller than characteristic electronic length-scales (such as electron wavelength, screening length, and electron mean free path). Yet electronic metamaterials promise far richer categories of behavior than those found in conventional optical metamaterial technologies. This is because unlike photons that scarcely interact with each other, electrons in subwavelength structured metamaterials are charged, and strongly interact. As a result, an enormous variety of emergent phenomena can be expected, and radically new classes of interacting quantum metamaterials designed