Impulse buying, Compulsive buying, Self-regulation, Consumer policy,

The aim of the study was to provide an overview of the effect of exercise interventions on subjective quality of life (QoL) across adult clinical populations and well people, and to systematically investigate the impact of the exercise setting, intensity and type on these outcomes. From a systematic search of six electronic databases, 56 original studies were extracted, reporting on 7937 sick and well people. A meta-analysis was conducted on change in QoL from pre- to post-intervention compared with outcomes from a no-exercise control group, using weighted (by the study's sample size) pooled mean effect sizes and a fixed-effects model. Significant differences in outcome were found when treatment purpose was compared; prevention/promotion (well populations), rehabilitation, or disease management. Three to 6 months post-baseline, a moderate positive effect of exercise interventions was found for overall QoL in rehabilitation patients, but no significant effect for well or disease management groups. However, physical and psychological QoL domains improved significantly relative to controls in well participants. Psychological QoL was significantly poorer relative to controls in the disease management group. This pattern of results persisted over 1 year. With some exceptions, better overall QoL was reported for light intensity exercise undertaken in group settings, with greater improvement in physical QoL following moderate intensity exercise. The implications for future health care practice and research are discussed.

Acceptance and commitment therapy (ACT) is a developing approach for chronic pain. The current study was designed to pilot test a brief, widely inclusive, local access format of ACT in a UK primary care setting. Seventy-three participants (68.5% women) were randomized to either ACT or treatment as usual (TAU). Many of the participants were aged 65 years or older (27.6%), were diagnosed with fibromyalgia (30.2%) and depression (40.3%), and had longstanding pain (median = 10 years). Standard clinical outcome measures included disability, depression, physical functioning, emotional functioning, and rated improvement. Process measures included pain-related and general psychological acceptance. The recruitment target was met within 6 months, and 72.9% of those allocated to ACT completed treatment. Immediately post treatment, relative to TAU, participants in ACT demonstrated lower depression and higher ratings of overall improvement. At a 3-month follow-up, again relative to TAU, those in ACT demonstrated lower disability, less depression, and significantly higher pain acceptance; d = .58, .59, and .64, respectively. Analyses based on intention-to-treat and on treatment “completers,” perhaps predictably, revealed more sobering and more encouraging results, respectively. A larger trial of ACT delivered in primary care, in the format employed here, appears feasible with some recommended adjustments in the methods used here (Trial registration: ISRCTN49827391).PerspectiveThis article presents a pilot randomized controlled trial of ACT for chronic pain in a primary care setting in the United Kingdom. Both positive clinical outcomes and ways to improve future trials are reported.

In most colorectal cancers, Wnt/β-catenin signaling is activated by loss-of-function mutations in the () gene and plays a critical role in tumorigenesis. Tankyrases poly(ADP-ribosyl)ate and destabilize Axins, a negative regulator of β-catenin, and upregulate β-catenin signaling. Tankyrase inhibitors downregulate β-catenin and are expected to be promising therapeutics for colorectal cancer. However, colorectal cancer cells are not always sensitive to tankyrase inhibitors, and predictive biomarkers for the drug sensitivity remain elusive. Here we demonstrate that the short-form mutations predict the sensitivity of colorectal cancer cells to tankyrase inhibitors. By using well-established colorectal cancer cell lines, we found that tankyrase inhibitors downregulated β-catenin in the drug-sensitive, but not resistant, colorectal cancer cells. The drug-sensitive cells showed higher Tcf/LEF transcriptional activity than the resistant cells and possessed "short" truncated APCs lacking all seven β-catenin-binding 20-amino acid repeats (20-AARs). In contrast, the drug-resistant cells possessed "long" APC retaining two or more 20-AARs. Knockdown of the long APCs with two 20-AARs increased β-catenin, Tcf/LEF transcriptional activity and its target gene expression. Under these conditions, tankyrase inhibitors were able to downregulate β-catenin in the resistant cells. These results indicate that the long APCs are hypomorphic mutants, whereas they exert a dominant-negative effect on Axin-dependent β-catenin degradation caused by tankyrase inhibitors. Finally, we established 16 patient-derived colorectal cancer cells and confirmed that the tankyrase inhibitor-responsive cells harbor the short-form APC mutations. These observations exemplify the predictive importance of mutations, the most common genetic alteration in colorectal cancers, for molecular targeted therapeutics..

An electronic cigarette (e-cigarette) is a product used to smoke aerosol by heating a solution of “e-liquid” that consists of propylene glycol (PG) and glycerol (GLY) containing nicotine and flavors. In this study, thermal decomposition products generated from three brands of e-cigarettes were determined at various electric power levels. When using neat PG or GLY instead of e-liquid, propylene oxide was detected only in the gas phase from PG and not detected from GLY. In contrast, glycidol was detected only from GLY and not from PG. Almost all of the glyoxal and acrolein was detected from GLY, but formaldehyde and methyl glyoxal were detected from both PG and GLY. Using commercially available e-liquids, the same results were obtained. Nearly all chemical compounds generated from e-cigarettes have a carbon number of 3 or less except for nicotine and flavors. We measured chemical compounds generated from e-cigarettes at various electric power levels (1–85 W). At an electric power of 10 W, the generation of chemical compounds was very low; however, when the electric power exceeded 40 W, it increased exponentially. As thermal decomposition products of e-liquid, acetaldehyde, acrolein, and propylene oxide mainly occur as gaseous matter, while glyoxal, methylglyoxal, and glycidol mainly occur as particulate matter. Formaldehyde exits in both gaseous and particulate matter forms. Thermal decomposition products can be divided into three groups: thermal decomposition products originating from PG and GLY, those originating from other sources, and those directly generated. Concentrations of these thermal decomposition products were mostly higher than those in traditional cigarettes. In particular, thermal decomposition products generated from one of the studied e-cigarettes were very high; e.g., formaldehyde reached 4400 μg/15 puffs at 50 W. E-cigarette users must know that hazardous substances are generated even within the recommended electric power limits.

Lentiviral vectors deliver transgenes efficiently to a wide range of neuronal cell types in the mammalian central nervous system. To drive gene expression, internal promoters are essential; however, the in vivo properties of promoters, such as their cell type specificity and gene expression activity, are not well known, especially in the nonhuman primate brain. Here, the properties of five ubiquitous promoters (murine stem cell virus [MSCV], cytomegalovirus [CMV], CMV early enhancer/chicken β-actin [CAG], human elongation factor-1α [EF-1α], and Rous sarcoma virus [RSV]) and two cell type-specific promoters (rat synapsin I and mouse α-calcium/calmodulin-dependent protein kinase II [CaMKIIα]) in rat and monkey motor cortices in vivo were characterized. Vesicular stomatitis virus G (VSV-G)-pseudotyped lentiviral vectors expressing enhanced green fluorescent protein (EGFP) under the control of the various promoters were prepared and injected into rat and monkey motor cortices. Immunohistochemical analysis revealed that all of the VSV-G-pseudotyped lentiviral vectors had strong endogenous neuronal tropisms in rat and monkey brains. Among the seven promoters, the CMV promoter showed modest expression in glial cells (9.4%) of the rat brain, whereas the five ubiquitous promoters (MSCV, CMV, CAG, EF-1α, and RSV) showed expression in glial cells (7.0-14.7%) in the monkey brain. Cell type-specific synapsin I and CaMKIIα promoters showed excitatory neuron-specific expression in the monkey brain (synapsin I, 99.7%; CaMKIIα, 100.0%), but their specificities for excitatory neurons were significantly lower in the rat brain (synapsin I, 94.6%; CaMKIIα, 93.7%). These findings could be useful in basic and clinical neuroscience research for the design of vectors that efficiently deliver and express transgenes into rat and monkey brains.

Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex. Although their anatomical connections and physiological response properties have been extensively studied, the causal role of their activity in behavioral, cognitive and autonomic functions is still unclear because PC activity cannot be selectively controlled. Here we developed a novel technique using optogenetics for selective and rapidly reversible manipulation of PC activity in vivo. We injected into rat cerebellar cortex lentiviruses expressing either the light-activated cationic channel channelrhodopsin-2 (ChR2) or light-driven chloride pump halorhodopsin (eNpHR) under the control of the PC-specific L7 promoter. Transgene expression was observed in most PCs (ChR2, 92.6%; eNpHR, 95.3%), as determined by immunohistochemical analysis. In vivo electrophysiological recordings showed that all light-responsive PCs in ChR2-transduced rats increased frequency of simple spike in response to blue laser illumination. Similarly, most light-responsive PCs (93.8%) in eNpHR-transduced rats decreased frequency of simple spike in response to orange laser illumination. We then applied these techniques to characterize the roles of rat cerebellar uvula, one of the cardiovascular regulatory regions in the cerebellum, in resting blood pressure (BP) regulation in anesthetized rats. ChR2-mediated photostimulation and eNpHR-mediated photoinhibition of the uvula had opposite effects on resting BP, inducing depressor and pressor responses, respectively. In contrast, manipulation of PC activity within the neighboring lobule VIII had no effect on BP. Blue and orange laser illumination onto PBS-injected lobule IX didn't affect BP, indicating the observed effects on BP were actually due to PC activation and inhibition. These results clearly demonstrate that the optogenetic method we developed here will provide a powerful way to elucidate a causal relationship between local PC activity and functions of the cerebellum.

Activation of Wnt/β-catenin signaling is essential for colorectal carcinogenesis. Tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, is a positive regulator of the Wnt/β-catenin signaling. Accordingly, tankyrase inhibitors are under preclinical development for colorectal cancer (CRC) therapy. However, Wnt-driven colorectal cancer cells are not equally sensitive to tankyrase inhibitors, and cellular factors that affect tankyrase inhibitor sensitivity remain elusive. Here, we established a tankyrase inhibitor-resistant cell line, 320-IWR, from Wnt/β-catenin-dependent CRC COLO-320DM cells. 320-IWR cells exhibited resistance to tankyrase inhibitors, IWR-1 and G007-LK, but remained sensitive to a PARP-1/2 inhibitor, olaparib, and several anti-CRC agents. In 320-IWR cells, nuclear localization of active β-catenin was decreased and expression of β-catenin target genes was constitutively repressed, suggesting that these cells repressed the Wnt/β-catenin signaling and were dependent on alternative proliferation pathways. 320-IWR cells exhibited upregulated mTOR signaling and were more sensitive to mTOR inhibition than the parental cells. Importantly, mTOR inhibition reversed resistance to tankyrase inhibitors and potentiated their anti-proliferative effects in 320-IWR cells as well as in CRC cell lines in which the mTOR pathway was intrinsically activated. These results indicate that mTOR signaling confers resistance to tankyrase inhibitors in CRC cells and suggest that the combination of tankyrase and mTOR inhibitors would be a useful therapeutic approach for a subset of CRCs.