"I'm so dumb and worthless right now": factors associated with heightened momentary self-criticism in daily life.

Self-criticism is a trait associated with increased psychopathology, but self-criticism is also a personality state reflecting an action that people do in moments of time. In the current study, we explored factors associated with heightened self-criticism in daily life. Participants (N = 197) received five random prompts per day for one week on their mobile phones, where they reported their current affect (negative and positive affect), willpower self-efficacy, distress intolerance, degree of support and criticism from others, current context (location, activity, hunger, tiredness) and momentary self-criticism. We first demonstrated that self-criticism varies over time and across contexts, and is associated with heightened trait self-criticism. Then, using multilevel modelling, we explored the contextual factors associated with greater self-criticism. We found that self-criticism was higher when people were at home, and more tired. We also found higher self-criticism to be associated with greater negative and lower positive affect, greater distress intolerance, lower willpower and greater perceived criticism from others. In addition, self-criticism predicted subsequent distress intolerance, willpower and positive affect in lagged analyses. This study provides evidence that both environmental and psychological factors are associated with the dynamics of self-critical thoughts.

How Person-Centred Is Cardiac Rehabilitation in England? Using Bourdieu to Explore Socio-Cultural Influences and Personalisation.

The National Health Service (NHS) cardiac rehabilitation patient care pathway has remained largely unchanged for many years despite, on average, half of all eligible patients declining to engage. To investigate reasons for non-engagement, we explored the experiences of ten cardiac patients who participated in cardiac rehabilitation, dropped out, or declined, as well as experiences of seven people deemed significant others by participants. Our ethnographic study involved participant observations, repeat in-depth semi-structured interviews, and reflexive journaling. Reflexive thematic analysis was conducted, focusing on participants' lived experiences. Utilising Bourdieusian concepts of habitus, capital, and field, this article highlights how personal biography, material conditions, and dispositional inclinations combine to make cardiac health care decision-making individual and complex. Despite this, health professionals were not always attuned to specific circumstances arising from differences in patients' experiences and lifeworlds. By considering service improvement recommendations that acknowledge socio-cultural influences, cardiac rehabilitation can work towards providing patients and their significant others with more appropriate, personalised, and person-centred support.

Older adults' and service providers' experiences of a settings-based health promotion initiative in English football.

The study was undertaken to explore the experiences of older adults and service providers in a settings-based health promotion initiative in a football club. We conducted semi-structured interviews with 10 older adults attending an 'Extra Time Hub' (ETH) and two staff delivering the initiative. Our reflexive thematic analysis generated six themes. Findings revealed the brand of the sports club attracted some to join the ETH, but through partnerships with local agencies, the initiative was also successful in widening participation beyond older adults with an interest in football. Participants perceived that the ETH was beneficial for their mental health, helped them develop social connections, and promoted positive physical activity experiences. Moreover, the variety of pleasures derived from participation were also discussed. Our findings also illustrate the central role of staff in older adults' experiences of this form of health promotion. Overall, this study contributes to understandings of settings-based health promotion activities in sports clubs, and also demonstrates the potential for sports clubs to widen engagement with the local community through health promotion for older adults.

A Case of Acute Encephalopathy After the Initiation of FOLFOX Chemotherapy in a Patient With Colon Cancer.

Acute encephalopathy is a change in the level of consciousness where the underlying etiology can be difficult to diagnose, and thus, difficult to treat, especially in the context of multi-organ diseases. We report a case of acute encephalopathy in a patient with end-stage renal disease (ESRD) on hemodialysis, chronic hypotension, and a recent diagnosis of colon cancer who presented shortly after initiation of FOLFOX, a chemotherapy regimen for treatment of colorectal cancer comprised of folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin (eloxatin). We present a systematic approach to elucidate ambiguous causes of toxic-metabolic encephalopathy.

Emergency Department Nurses' Perceptions of Patient Substance Use, Impact on Sexual Assault Care, and Access to Follow-up Behavioral Health Resources.

INTRODUCTION: Patients may present to the emergency department for sexual assault care under the influence of drugs or alcohol. However, many emergency nurses are not prepared to meet their unique needs or aware of follow-up behavioral health resources. The purpose of this study was to (1) summarize current resources provided to patients and processes for referral to behavioral health services after sexual assault care, (2) explore emergency nurses' attitudes and behaviors toward patient substance use, and (3) explore nurses' perceptions of adjunct mobile health interventions for follow-up behavioral health care and describe anticipated barriers to use. METHODS: Fifteen emergency nurses participated in semi-structured qualitative interviews. RESULTS: Participants had mixed perceptions of patient intoxication during sexual assault care. They felt that conversations about substance use may be more appropriate after the ED visit. Participants recognized the opportunity to connect ED patients with substance use treatment or prevention resources but perceived that there are few local service providers. Most participants were not referring patients with substance use issues to behavioral health services after sexual assault care and said that their emergency departments did not have processes for referral to these services. Acceptability of mobile health for follow-up behavioral health care was high, but participants had concerns for patient privacy and internet access. Participants gave recommendations to improve referral practices and patient engagement with mobile health interventions. DISCUSSION: This study highlights the need for emergency nurses to consider patient intoxication during sexual assault care and opportunities to connect patients with resources post-assault.

Sex-dependent and ontogenetic effects of low dose ethanol on social behavioral deficits induced by mouse maternal separation.

Early life stress can induce lifelong emotional and social behavioral deficits that may in some cases be alleviated by drugs or alcohol. A model for early life stress, rodent maternal separation, recapitulates these behavioral sequelae, which are not limited to potentiated anxiety-like behavior, attenuated social motivation, and altered reward-seeking. Here we employed mouse maternal separation with early weaning (MSEW), consisting of pup-dam separation lasting 4-8 hours on postnatal days (PD) 2-16, with early weaning on PD 17. Prior MSEW studies have limited subjects by age or sex, so we more comprehensively investigated MSEW effects in both sexes, during adolescence and adulthood. We found universal effects of MSEW to include lifelong enhancement of anxiety-like and despair behavior, as well as deficits in social motivation. We also observed some sex-dependent effects of MSEW, namely that female MSEW mice exhibited social habituation to a greater degree than their male counterparts. Low dose ethanol administration had no major effects on the social behavior of non-stressed mice. But interestingly, MSEW-induced social habituation was counteracted by low dose ethanol in adolescent female mice, and potentiated in adolescent male mice. These effects were absent in adult animals, suggesting that ethanol may exert differential effects on the developing brain in such a manner to produce age-, sex-, and stress-dependent effects upon social behavior. Together, results indicate that MSEW reliably produces long-lasting impairments in emotional and social behaviors in both sexes and across the lifespan, but may exert more salient social behavioral effects on female animals.

Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice.

Trauma during critical periods of development can induce long-lasting adverse effects. To study neural aberrations resulting from early life stress (ELS), many studies utilize rodent maternal separation, whereby pups are intermittently deprived of maternal care necessary for proper development. This can produce adulthood behavioral deficits related to anxiety, reward, and social behavior. The bed nucleus of the stria terminalis (BNST) encodes aspects of anxiety-like and social behaviors, and also undergoes developmental maturation during the early postnatal period, rendering it vulnerable to effects of ELS. Mice underwent maternal separation (separation 4 hr/day during postnatal day (PD)2-5 and 8 hr/day on PD6-16) with early weaning on PD17, which induced behavioral deficits in adulthood performance on two-part social interaction task designed to test social motivation (choice between a same-sex novel conspecific or an empty cup) and social novelty preference (choice between the original-novel conspecific vs. a new-novel conspecific). We used chemogenetics to non-selectively silence or activate neurons in the BNST to examine its role in social motivation and social novelty preference, in mice with or without the history of ELS. Manipulation of BNST produced differing social behavior effects in non-stressed versus ELS mice; social motivation was decreased in non-stressed mice following BNST activation, but unchanged following BNST silencing, while ELS mice showed no change in social behavior after BNST activation, but exhibited enhancement of social motivation-for which they were deficient prior-following BNST silencing. Findings emphasize the BNST as a potential therapeutic target for social anxiety disorders instigated by childhood trauma.

Functions of mountain pine beetle cytochromes P450 CYP6DJ1, CYP6BW1 and CYP6BW3 in the oxidation of pine monoterpenes and diterpene resin acids.

The mountain pine beetle (MPB; Dendroctonus ponderosae) is a forest insect pest that attacks several different pine (Pinus) species in its native range of distribution in western North America. MPB are exposed for most of their life cycle to the chemical defenses of their hosts. These defenses are dominated by oleoresin secretions containing mostly various monoterpenes and diterpene resin acids (DRAs). Cytochrome P450 enzymes (P450s) of the MPB are thought to be involved in the metabolism of at least some of these defense compounds. Here we describe the cloning and characterization of three MPB P450s, CYP6DJ1, CYP6BW1 and CYP6BW3, and their functions in the oxidation of various monoterpenes and diterpene resin acids. CYP6DJ1 oxidizes the monoterpenes (+)-(4R)-limonene, (-)-(4S)-limonene and terpinolene and produces (4R,8R)-limonene-8,9-epoxide, (4R,8S)-limonene-8,9-epoxide, (4S,8S)-limonene-8,9-epoxide, (4S,8R)-limonene-8,9-epoxide, perilla alcohol and several unidentified oxidized compounds. These products of CYP6DJ1 were also identified in extracts of MPB treated with the same monoterpenes. CYP6BW1 and CYP6BW3 both oxidize the DRAs abietic acid, dehydroabietic acid, neoabietic acid, levopimaric acid, palustric acid, and isopimaric acid, producing hydroxylated and epoxidized DRAs. CYP6DJ1, CYP6BW1 and CYP6BW3 appear to contribute to the metabolism of oleoresin terpenes as part of the MPB's ability to cope with host defenses.

Functions of stone cells and oleoresin terpenes in the conifer defense syndrome.

Conifers depend on complex defense systems against herbivores. Stone cells (SC) and oleoresin are physical and chemical defenses of Sitka spruce that have been separately studied in previous work. Weevil oviposit at the tip of the previous year's apical shoot (PYAS). We investigated interactions between weevil larvae and trees in controlled oviposition experiments with resistant (R) and susceptible (S) Sitka spruce. R trees have an abundance of SC in the PYAS cortex. SC are mostly absent in S trees. R trees and S trees also differ in the composition of oleoresin terpenes. Transcriptomes of R and S trees revealed differences in long-term weevil-induced responses. Performance of larvae was significantly reduced on R trees compared with S trees under experimental conditions that mimicked natural oviposition behavior at apical shoot tips and may be attributed to the effects of SC. In oviposition experiments designed for larvae to feed below the area of highest SC abundance, larvae showed an unusual feeding behavior and oleoresin appeared to function as the major defense. The results support a role for both SC and oleoresin terpenes and possible synergies between these traits in the defense syndrome of weevil-resistant Sitka spruce.

Cell-type- and tissue-specific transcriptomes of the white spruce (Picea glauca) bark unmask fine-scale spatial patterns of constitutive and induced conifer defense.

Plant defenses often involve specialized cells and tissues. In conifers, specialized cells of the bark are important for defense against insects and pathogens. Using laser microdissection, we characterized the transcriptomes of cortical resin duct cells, phenolic cells and phloem of white spruce (Picea glauca) bark under constitutive and methyl jasmonate (MeJa)-induced conditions, and we compared these transcriptomes with the transcriptome of the bark tissue complex. Overall, ~3700 bark transcripts were differentially expressed in response to MeJa. Approximately 25% of transcripts were expressed in only one cell type, revealing cell specialization at the transcriptome level. MeJa caused cell-type-specific transcriptome responses and changed the overall patterns of cell-type-specific transcript accumulation. Comparison of transcriptomes of the conifer bark tissue complex and specialized cells resolved a masking effect inherent to transcriptome analysis of complex tissues, and showed the actual cell-type-specific transcriptome signatures. Characterization of cell-type-specific transcriptomes is critical to reveal the dynamic patterns of spatial and temporal display of constitutive and induced defense systems in a complex plant tissue or organ. This was demonstrated with the improved resolution of spatially restricted expression of sets of genes of secondary metabolism in the specialized cell types.

Function of Sitka spruce stone cells as a physical defence against white pine weevil.

Stone cells are a physical defence of conifers against stem feeding insects such as weevils and bark beetles. In Sitka spruce, abundance of stone cells in the cortex of apical shoot tips is associated with resistance to white pine weevil. However, the mode of action by which stone cells interfere with growth and development of weevil larvae is unknown. We developed a bioassay system for testing potential effects of stone cells, which were isolated from resistant trees, on weevil larvae. Bioassays using artificial diet and controlled amounts of stone cells focused on physical defence. We evaluated the effects of stone cells on establishment of neonate larvae, mandible wear and changes in relative growth rates of third instar larvae. Establishment of neonates and relative growth rates of third instars were significantly reduced by stone cells. Stone cells appeared to be indigestible by weevil larvae. Our results suggest that stone cells affect weevil establishment and development by forming a physical feeding barrier against neonate larvae at the site of oviposition, and by reducing access to nutrients in the cortex of resistant trees, which contain an abundance of stone cells in place of a more nutrient rich tissue in susceptible trees.

Auditing the socio-environmental determinants of motivation towards physical activity or sedentariness in work-aged adults: a qualitative study.

BACKGROUND: There is a lack of understanding of work aged adults' (30-60 years old) perspectives on the motivation of physical activity versus sedentariness. This study aims to: (1) identify which socio-environmental factors motivate physical activity and/or sedentary behavior, in adults aged 30-60 years; and (2) explore how these motivators interact and combine. METHOD: Fifteen work-aged adults who, were able to engage in physical activity (Mean age = 43.9 years; SD 9.6, range 31-59), participated in semi-structured interviews. Inductive content analysis was used to generate an inventory of socio-environmental factors and their specific influences on motivation towards physical activity or sedentariness. RESULTS: Key socio-environmental agents found to influence motivation included: Spouse/partner, parents, children, siblings, whole family, grandchildren, friends, work-mates, neighbors, strangers, team-mates and class-mates, instructors, health care professionals, employers, gyms and health companies, governments, media and social media, cultural norms, and the physical environment. Mechanisms fell into five broad themes of socio-environmental motivation for both physical activity and sedentariness: (1) competence and progress; (2) informational influences, (3) emotional influences, (4) pragmatics and logistics, and (5) relationships. Similar socio-environmental factors were frequently reported as able to motivate both activity and sedentariness. Likewise, individual categories of influence could also motivate both behaviors, depending on context. CONCLUSION: The findings of this paper 'unpack' theoretical concepts into specific and targeted behavioral recommendations. The data suggested no simple solutions for promoting physical activity or reducing sedentariness, but rather complex and interacting systems surrounding work-aged adults. Findings also suggest that health professionals should be encouraged to support adults' health by examining the socio-environmental motivational influences, or 'motivational atmosphere'.

Quantitative metabolome, proteome and transcriptome analysis of midgut and fat body tissues in the mountain pine beetle, Dendroctonus ponderosae Hopkins, and insights into pheromone biosynthesis.

Bark beetles (Coleoptera: Scolytinae) are pests of many forests around the world. The mountain pine beetle (MPB), Dendroctonus ponderosae Hopkins, is a significant pest of western North American pine forests. The MPB is able to overcome the defences of pine trees through pheromone-assisted aggregation that results in a mass attack of host trees. These pheromones, both male and female produced, are believed to be biosynthesized in the midgut and/or fat bodies of these insects. We used metabolite analysis, quantitative proteomics (iTRAQ) and transcriptomics (RNA-seq) to identify proteins and transcripts differentially expressed between sexes and between tissues when treated with juvenile hormone III. Juvenile hormone III induced frontalin biosynthesis in males and trans-verbenol biosynthesis in females, as well as affected the expression of many proteins and transcripts in sex- and tissue-specific ways. Based on these analyses, we identified candidate genes involved in the biosynthesis of frontalin, exo-brevicomin, and trans-verbenol pheromones.

Histology and cell wall biochemistry of stone cells in the physical defence of conifers against insects.

Conifers possess an array of physical and chemical defences against stem-boring insects. Stone cells provide a physical defence associated with resistance against bark beetles and weevils. In Sitka spruce (Picea sitchensis), abundance of stone cells in the cortex of apical shoots is positively correlated with resistance to white pine weevil (Pissodes strobi). We identified histological, biochemical and molecular differences in the stone cell phenotype of weevil resistant (R) or susceptible (S) Sitka spruce genotypes. R trees displayed significantly higher quantities of cortical stone cells near the apical shoot node, the primary site for weevil feeding. Lignin, cellulose, xylan and mannan were the most abundant components of stone cell secondary walls, respectively. Lignin composition of stone cells isolated from R trees contained a higher percentage of G-lignin compared with S trees. Transcript profiling revealed higher transcript abundance in the R genotype of coumarate 3-hydroxylase, a key monolignol biosynthetic gene. Developing stone cells in current year apical shoots incorporated fluorescent-tagged monolignol into the secondary cell wall, while mature stone cells of previous year apical shoots did not. Stone cell development is an ephemeral process, and fortification of shoot tips in R trees is an effective strategy against insect feeding.

Quantitative proteomic profiling of pleomorphic human sarcoma identifies CLIC1 as a dominant pro-oncogenic receptor expressed in diverse sarcoma types.

Sarcomas are rare forms of cancer with a high unmet clinical need that develop in connective tissue, such as muscle, bone, nerves, cartilage, and fat. The outcome for patients is poor, with surgery and postoperative radiotherapy the standard treatment for patients. A better understanding of the molecular pathology of sarcoma may allow for the development of novel therapeutics. There are dozens of sarcoma subtypes where there is a need for targetted therapeutics, with the most commonly studied including Ewing's sarcoma and osteosarcoma. Here we initiate a proteomics-based target-discovery program to define "dominant" pro-oncogenic signaling targets in the most common sarcoma in adults: high-grade pleiomorphic soft tissue sarcoma. We have carried out a proteome screen using tandem mass tag isobaric labeling on three high-grade undifferentiated pleomorphic sarcoma biopsies from different tissue sites. We identified the commonly dysregulated proteins within the three sarcomas and further validated the most penetrant receptor as CLIC1, using immunohistochemistry arising from two different population cohorts representing over 300 patients. The dominant expression of CLIC1 in a broad range of human sarcomas suggests that studying this relatively unexplored signaling pathway might provide new insights into disease mechanism and facilitate the development of new CLIC1 targeted therapeutics.

Frontalin pheromone biosynthesis in the mountain pine beetle, Dendroctonus ponderosae, and the role of isoprenyl diphosphate synthases.

The mountain pine beetle (Dendroctonus ponderosae Hopkins) is the most destructive pest of western North American pine forests. Adult males produce frontalin, an eight-carbon antiaggregation pheromone, via the mevalonate pathway, as part of several pheromones that initiate and modulate the mass attack of host trees. Frontalin acts as a pheromone, attractant, or kairomone in most Dendroctonus species, other insects, and even elephants. 6-Methylhept-6-en-2-one, a frontalin precursor, is hypothesized to originate from 10-carbon geranyl diphosphate (GPP), 15-carbon farnesyl diphosphate (FPP), or 20-carbon geranylgeranyl diphosphate (GGPP) via a dioxygenase- or cytochrome P450-mediated carbon-carbon bond cleavage. To investigate the role of isoprenyl diphosphate synthases in pheromone biosynthesis, we characterized a bifunctional GPP/FPP synthase and a GGPP synthase in the mountain pine beetle. The ratio of GPP to FPP produced by the GPP/FPP synthase was highly dependent on the ratio of the substrates isopentenyl diphosphate and dimethylallyl diphosphate used in the assay. Transcript levels in various tissues and life stages suggested that GGPP rather than GPP or FPP is used as a precursor to frontalin. Reduction of transcript levels by RNA interference of the isoprenyl diphosphate synthases identified GGPP synthase as having the largest effect on frontalin production, suggesting that frontalin is derived from a 20-carbon isoprenoid precursor rather than from the 10- or 15-carbon precursors.

CYP345E2, an antenna-specific cytochrome P450 from the mountain pine beetle, Dendroctonus ponderosae Hopkins, catalyses the oxidation of pine host monoterpene volatiles.

The mountain pine beetle (MPB, Dendroctonus ponderosae Hopkins) is a significant pest of western North American pine forests. This beetle responds to pheromones and host volatiles in order to mass attack and thus overcome the terpenoid chemical defences of its host. The ability of MPB antennae to rapidly process odorants is necessary to avoid odorant receptor saturation and thus the enzymes responsible for odorant clearance are an important aspect of host colonization. An antenna-specific cytochrome P450, DponCYP345E2, is the most highly expressed transcript in adult MPB antenna. In in vitro assays with recombinant enzyme, DponCYP345E2 used several pine host monoterpenes as substrates, including (+)-(3)-carene, (+)-ß-pinene, (-)-ß-pinene, (+)-limonene, (-)-limonene, (-)-camphene, (+)-α-pinene, (-)-α-pinene, and terpinolene. The substrates were epoxidized or hydroxylated, depending upon the substrate. To complement DponCYP345E2, we also functionally characterized the NADPH-dependent cytochrome P450 reductase and the cytochrome b5 from MPB. DponCYP345E2 is the first cytochrome P450 to be functionally characterized in insect olfaction and in MPB.

Transcriptome resources and functional characterization of monoterpene synthases for two host species of the mountain pine beetle, lodgepole pine (Pinus contorta) and jack pine (Pinus banksiana).

BACKGROUND: The mountain pine beetle (MPB, Dendroctonus ponderosae) epidemic has affected lodgepole pine (Pinus contorta) across an area of more than 18 million hectares of pine forests in western Canada, and is a threat to the boreal jack pine (Pinus banksiana) forest. Defence of pines against MPB and associated fungal pathogens, as well as other pests, involves oleoresin monoterpenes, which are biosynthesized by families of terpene synthases (TPSs). Volatile monoterpenes also serve as host recognition cues for MPB and as precursors for MPB pheromones. The genes responsible for terpene biosynthesis in jack pine and lodgepole pine were previously unknown. RESULTS: We report the generation and quality assessment of assembled transcriptome resources for lodgepole pine and jack pine using Sanger, Roche 454, and Illumina sequencing technologies. Assemblies revealed transcripts for approximately 20,000 - 30,000 genes from each species and assembly analyses led to the identification of candidate full-length prenyl transferase, TPS, and P450 genes of oleoresin biosynthesis. We cloned and functionally characterized, via expression of recombinant proteins in E. coli, nine different jack pine and eight different lodgepole pine mono-TPSs. The newly identified lodgepole pine and jack pine mono-TPSs include (+)-α-pinene synthases, (-)-α-pinene synthases, (-)-ß-pinene synthases, (+)-3-carene synthases, and (-)-ß-phellandrene synthases from each of the two species. CONCLUSION: In the absence of genome sequences, transcriptome assemblies are important for defence gene discovery in lodgepole pine and jack pine, as demonstrated here for the terpenoid pathway genes. The product profiles of the functionally annotated mono-TPSs described here can account for the major monoterpene metabolites identified in lodgepole pine and jack pine.