An Investigation of Classroom Situational Dimensions of Emotional and Behavioral Adjustment and Cognitive and Social Outcomes for Head Start Children

This study employed a developmental-ecological approach to investigate the relationship across the school year between early problems in preschool classroom situations and a comprehensive set of readiness competencies for urban, low-income children. Study I identified three reliable and unique underlying classroom situational dimensions where behavior problems occurred: Structured Learning, Peer Interaction, and Teacher Interaction situations. Boys and younger children evidenced more problematic behavior across all situations. Study II investigated the relationship between early problems in the situations and readiness outcomes. Early situational difficulties uniquely and differentially predicted lower peer social and classroom learning outcomes. In combination, both the type of behavior problem (what) and the situational problem (where) explained greater variance in the prediction of readiness outcomes, contributing to a more comprehensive understanding of developmental trajectories

Change in anxiety following successful and unsuccessful attempts at smoking cessation: cohort study

Background Despite a lack of empirical evidence, many smokers and health professionals believe that tobacco smoking reduces anxiety, which may deter smoking cessation. Aims The study aim was to assess whether successful smoking cessation or relapse to smoking after a quit attempt are associated with changes in anxiety. Method A total of 491 smokers attending National Health Service smoking cessation clinics in England were followed up 6 months after enrolment in a trial of pharmacogenetic tailoring of nicotine replacement therapy (ISRCTN14352545). Results There was a points difference of 11.8 (95% CI 7.7-16.0) in anxiety score 6 months after cessation between people who relapsed to smoking and people who attained abstinence. This reflected a three-point increase in anxiety from baseline for participants who relapsed and a nine-point decrease for participants who abstained. The increase in anxiety in those who relapsed was largest for those with a current diagnosis of psychiatric disorder and whose main reason for smoking was to cope with stress. The decrease in anxiety on abstinence was larger for these groups also. Conclusions People who achieve abstinence experience a marked reduction in anxiety whereas those who fail to quit experience a modest increase in the long term. These data contradict the assumption that smoking is a stress reliever, but suggest that failure of a quit attempt may generate anxiety

Fate of the Josephson effect in thin-film superconductors

The dc Josephson effect refers to the dissipationless electrical current -- the supercurrent -- that can be sustained across a weak link connecting two bulk superconductors. This effect is a probe of the fundamental nature of the superconducting state. Here, we analyze the case of two superconducting thin films connected by a point contact. Remarkably, the Josephson effect is absent at nonzero temperature, and the resistance across the contact is nonzero. Moreover, the point contact resistance is found to vary with temperature in a nearly activated fashion, with a UNIVERSAL energy barrier determined only by the superfluid stiffness characterizing the films, an angle characterizing the geometry, and whether or not the Coulomb interaction between Cooper pairs is screened. This behavior reflects the subtle nature of the superconductivity in two-dimensional thin films, and should be testable in detail by future experiments.Comment: 16 + 8 pages. 1 figure, 1 tabl

Determination of intracellular glutathione and glutathione disulfide using high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection

Measurement of glutathione (GSH) and glutathione disulfide (GSSG) is a crucial tool to assess cellular redox state. Herein we report a direct approach to determine intracellular GSH based on a rapid chromatographic separation coupled with acidic potassium permanganate chemiluminescence detection, which was extended to GSSG by incorporating thiol blocking and disulfide bond reduction. Importantly, this simple procedure avoids derivatisation of GSH (thus minimising auto-oxidation) and overcomes problems encountered when deriving the concentration of GSSG from &lsquo;total GSH&rsquo;. The linear range and limit of detection for both analytes were 7.5 &times; 10&minus;7 to 1 &times; 10&minus;5 M, and 5 &times; 10&minus;7 M, respectively. GSH and GSSG were determined in cultured muscle cells treated for 24 h with glucose oxidase (0, 15, 30, 100, 250 and 500 mU mL&minus;1), which exposed them to a continuous source of reactive oxygen species (ROS). Both analyte concentrations were greater in myotubes treated with 100 or 250 mU mL&minus;1 glucose oxidase (compared to untreated controls), but were significantly lower in myotubes treated with 500 mU mL&minus;1 (p &lt; 0.05), which was rationalised by considering measurements of H2O2 and cell viability. However, the GSH/GSSG ratio in myotubes treated with 100, 250 and 500 mU mL&minus;1 glucose oxidase exhibited a dose-dependent decrease that reflected the increase in intracellular ROS.<br /

Patients with TNF Receptor Associated Periodic Syndrome (TRAPS) are hypersensitive to Toll‐like receptor 9 stimulation

Tumour necrosis factor receptor‐associated periodic syndrome (TRAPS) is an hereditary autoinflammatory disorder characterised by recurrent episodes of fever and inflammation. It is associated with autosomal dominant mutations in TNFRSF1A, which encodes tumour necrosis factor receptor‐1 (TNFR1). Our aim was to understand the influence of TRAPS mutations on the response to stimulation of the pattern recognition receptor TLR9. Peripheral blood mononuclear cells (PBMCs) and serum were isolated from TRAPS patients and healthy controls: Serum levels of fifteen pro‐inflammatory cytokines were measured to assess the initial inflammatory status. IL‐1β, IL‐6, IL‐8, IL17, IL22, TNF‐α, VEGF, IFN‐γ, MCP‐1 and TGF‐β were significantly elevated in TRAPS patients sera, consistent with constitutive inflammation. Stimulation of PBMCs with TLR9 ligand (ODN2006) triggered significantly greater upregulation of pro‐inflammatory signalling intermediates (TRAF3, IRAK2, TOLLIP, TRAF6, pTAK, TAB2, pTAB2, IRF7, RIP, NF‐kB p65, pNF‐κB p65, and MEK1/2) in TRAPS patients’ PBMCs. This upregulation of proinflammatory signalling intermediates and raised serum cytokines occurred despite concurrent anakinra treatment and no overt clinical symptoms at time of sampling. These novel findings further demonstrate the wide‐ranging nature of the dysregulation of innate immune responses underlying the pathology of TRAPS and highlights the need for novel pathway‐specific therapeutic treatments for this disease

Increasing the Yield of Irish Brown Crab (Cancer pagurus) during Processing without Adversely Affecting Shelf-Life

During the processing of Irish Brown Crab (Cancer pagurus), protein and moisture are released and losses up to 10% (by weight) are common. The objective of this study was to investigate the use of clean label ingredients to reduce this loss, without adversely affecting shelf-life or promoting the growth of spoilage bacteria. Following preliminary studies, 5% (w/v) sodium caseinate (SC) and (5%, w/v) potato starch (PS), with and without (0.5%, w/v) ascorbic acid (AA) were selected. Ninety crabs (30 per treatment) were soaked and boiled in water (control 1), AA (control 2), SC, PS, SC plus AA, or PS plus AA and analyzed for cook loss as well as pH, aw, water holding capacity (WHC), and microbial shelf-life (total viable count (TVC), total Enterobacteriaceae count (TEC), and spoilage bacteria) during 28 days storage at 4 ◦ C. On average, 11.1% of the control 1 weight was lost during processing. This was reduced to 8.0% when treated with AA (control 2) and to 3.5%, 4.7%, 5.8%, and 2.3% with SC, PS, SC plus AA, and PS plus AA, respectively. None of these treatments negatively impacted on shelf-life and similar growth curves were observed for TVC, TEC, Pseudomonas spp., Clostridium spp., lactic acid bacteria (LAB), and hydrogen disulphide producing bacteria, regardless of treatment. It was therefore concluded that, subject to sensory evaluation and validation under commercial conditions, these natural ingredients could be used to substantially increase the yield and hence commercial value of crab meat, without adversely affecting shelf-life.Department of Agriculture, Food and the Marin

PP2A inhibition overcomes acquired resistance to HER2 targeted therapy

Background: HER2 targeted therapies including trastuzumab and more recently lapatinib have significantly improved the prognosis for HER2 positive breast cancer patients. However, resistance to these agents is a significant clinical problem. Although several mechanisms have been proposed for resistance to trastuzumab, the mechanisms of lapatinib resistance remain largely unknown. In this study we generated new models of acquired resistance to HER2 targeted therapy and investigated mechanisms of resistance using phospho-proteomic profiling. Results: Long-term continuous exposure of SKBR3 cells to low dose lapatinib established a cell line, SKBR3-L, which is resistant to both lapatinib and trastuzumab. Phospho-proteomic profiling and immunoblotting revealed significant alterations in phospho-proteins involved in key signaling pathways and molecular events. In particular, phosphorylation of eukaryotic elongation factor 2 (eEF2), which inactivates eEF2, was significantly decreased in SKBR3-L cells compared to the parental SKBR3 cells. SKBR3-L cells exhibited significantly increased activity of protein phosphatase 2A (PP2A), a phosphatase that dephosphorylates eEF2. SKBR3-L cells showed increased sensitivity to PP2A inhibition, with okadaic acid, compared to SKBR3 cells. PP2A inhibition significantly enhanced response to lapatinib in both the SKBR3 and SKBR3-L cells. Furthermore, treatment of SKBR3 parental cells with the PP2A activator, FTY720, decreased sensitivity to lapatinib. The alteration in eEF2 phosphorylation, PP2A activity and sensitivity to okadaic acid were also observed in a second HER2 positive cell line model of acquired lapatinib resistance, HCC1954-L. Conclusions: Our data suggests that decreased eEF2 phosphorylation, mediated by increased PP2A activity, contributes to resistance to HER2 inhibition and may provide novel targets for therapeutic intervention in HER2 positive breast cancer which is resistant to HER2 targeted therapies

The Global Epidemiological Transition in Cardiovascular Diseases:Unrecognised Impact of Endemic Infections on Peripheral Artery Disease

An epidemiological transition in the prevalence of peripheral artery disease (PAD) is taking place especially in low- and middle-income countries (LMICs) where an ageing population and adoption of western lifestyles are associated with an increase in PAD. We discuss the limited evidence which suggests that infection, potentially mediated by inflammation, may be a risk factor for PAD, and show by means of an ecological analysis that country-level prevalence of the major endemic infections of HIV, tuberculosis and malaria are associated with the prevalence of PAD. While further research is required, we propose that scientists and health authorities pay more attention to the interplay between communicable and non-communicable diseases, and we suggest that limiting the occurrence of endemic infections might have some effect on slowing the epidemiological transition in PAD

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

Interleukin‐22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110834/1/imm12414.pd