Localization and functional characterization of the alternative oxidase in Naegleria.

The alternative oxidase (AOX) is a protein involved in supporting enzymatic reactions of the Krebs cycle in instances when the canonical (cytochrome-mediated) respiratory chain has been inhibited, while allowing for the maintenance of cell growth and necessary metabolic processes for survival. Among eukaryotes, alternative oxidases have dispersed distribution and are found in plants, fungi, and protists, including Naegleria ssp. Naegleria species are free-living unicellular amoeboflagellates and include the pathogenic species of N. fowleri, the so-called "brain-eating amoeba." Using a multidisciplinary approach, we aimed to understand the evolution, localization, and function of AOX and the role that plays in Naegleria's biology. Our analyses suggest that AOX was present in last common ancestor of the genus and structure prediction showed that all functional residues are also present in Naegleria species. Using cellular and biochemical techniques, we also functionally characterize N. gruberi's AOX in its mitochondria, and we demonstrate that its inactivation affects its proliferation. Consequently, we discuss the benefits of the presence of this protein in Naegleria species, along with its potential pathogenicity role in N. fowleri. We predict that our findings will spearhead new explorations to understand the cell biology, metabolism, and evolution of Naegleria and other free-living relatives.

Proteomic analysis of dietary restriction in yeast reveals a role for Hsp26 in replicative lifespan extension.

Dietary restriction (DR) has been shown to increase lifespan in organisms ranging from yeast to mammals. This suggests that the underlying mechanisms may be evolutionarily conserved. Indeed, upstream signalling pathways, such as TOR, are strongly linked to DR-induced longevity in various organisms. However, the downstream effector proteins that ultimately mediate lifespan extension are less clear. To shed light on this, we used a proteomic approach on budding yeast. Our reasoning was that analysis of proteome-wide changes in response to DR might enable the identification of proteins that mediate its physiological effects, including replicative lifespan extension. Of over 2500 proteins we identified by liquid chromatography-mass spectrometry, 183 were significantly altered in expression by at least 3-fold in response to DR. Most of these proteins were mitochondrial and/or had clear links to respiration and metabolism. Indeed, direct analysis of oxygen consumption confirmed that mitochondrial respiration was increased several-fold in response to DR. In addition, several key proteins involved in mating, including Ste2 and Ste6, were down-regulated by DR. Consistent with this, shmoo formation in response to α-factor pheromone was reduced by DR, thus confirming the inhibitory effect of DR on yeast mating. Finally, we found that Hsp26, a member of the conserved small heat shock protein (sHSP) family, was up-regulated by DR and that overexpression of Hsp26 extended yeast replicative lifespan. As overexpression of sHSPs in Caenorhabditis elegans and Drosophila has previously been shown to extend lifespan, our data on yeast Hsp26 suggest that sHSPs may be universally conserved effectors of longevity.

Country-level correlates of the Dark Triad traits in 49 countries.

OBJECTIVES: The Dark Triad traits (i.e., narcissism, psychopathy, Machiavellianism) capture individual differences in aversive personality to complement work on other taxonomies, such as the Big Five traits. However, the literature on the Dark Triad traits relies mostly on samples from English-speaking (i.e., Westernized) countries. We broadened the scope of this literature by sampling from a wider array of countries. METHOD: We drew on data from 49 countries (N = 11,723; 65.8% female; AgeMean  = 21.53) to examine how an extensive net of country-level variables in economic status (e.g., Human Development Index), social relations (e.g., gender equality), political orientations (e.g., democracy), and cultural values (e.g., embeddedness) relate to country-level rates of the Dark Triad traits, as well as variance in the magnitude of sex differences in them. RESULTS: Narcissism was especially sensitive to country-level variables. Countries with more embedded and hierarchical cultural systems were more narcissistic. Also, sex differences in narcissism were larger in more developed societies: Women were less likely to be narcissistic in developed (vs. less developed) countries. CONCLUSIONS: We discuss the results based on evolutionary and social role models of personality and sex differences. That higher country-level narcissism was more common in less developed countries, whereas sex differences in narcissism were larger in more developed countries, is more consistent with evolutionary than social role models.

The patient and clinician experience of informed consent for surgery: a systematic review of the qualitative evidence.

BACKGROUND: Informed consent is an integral component of good medical practice. Many researchers have investigated measures to improve the quality of informed consent, but it is not clear which techniques work best and why. To address this problem, we propose developing a core outcome set (COS) to evaluate interventions designed to improve the consent process for surgery in adult patients with capacity. Part of this process involves reviewing existing research that has reported what is important to patients and doctors in the informed consent process. METHODS: This qualitative synthesis comprises four phases: identification of published papers and determining their relevance; appraisal of the quality of the papers; identification and summary of the key findings from each paper while determining the definitiveness of each finding against the primary data; comparison of key themes between papers such that findings are linked across studies. RESULTS: Searches of bibliographic databases returned 11,073 titles. Of these, 16 studies met the inclusion criteria. Studies were published between 1996 and 2016 and included a total of 367 patients and 74 health care providers. Thirteen studies collected data using in-depth interviews and constant comparison was the most common means of qualitative analysis. A total of 94 findings were extracted from the primary papers and divided into 17 categories and ultimately 6 synthesised findings related to: patient characteristics, knowledge, communication, the model patient, trust and decision making. CONCLUSIONS: This qualitative meta-aggregation is the first to examine the issue of informed consent for surgery. It has revealed several outcomes deemed important to capture by patients and clinicians when evaluating the quality of a consent process. Some of these outcomes have not been examined previously in research comparing methods for informed consent. This review is an important step in the development of a COS to evaluate interventions designed to improve the consent process for surgery. REGISTRATION: The study protocol was registered on the international prospective register for systematic reviews (PROSPERO ID: CRD42017077101).

Prognosis following surgical resection versus local excision of stage pT1 colorectal cancer: A population-based cohort study.

AIMS: To evaluate patient management following stage pT1 colorectal cancer (CRC) diagnosis, and to determine if surgical resection improved outcome compared with local excision, within a population-based study. METHODS: Data were collected from the Northern Ireland Cancer Registry. Cases of stage pT1 CRC diagnosed from 2007 to 2012 were identified. Analyses were conducted using Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cancer-specific and all-cause mortality for individuals undergoing formal surgery versus local excision. RESULTS: 394 patients with pT1 CRC were included. Of these, 37.1% were treated by local resection, 36.8% had biopsy followed by surgery and 26.1% had local excision followed by surgery. There were 60 deaths over a mean 4.8 years of follow-up, including 10 CRC-specific deaths. An additional 12 patients had a CRC recurrence or metastases during follow-up. Of the CRC-specific deaths or recurrences, 27.3% had local excision only. Individuals treated by formal surgery did not have a reduced risk of CRC-specific death (adjusted HR = 1.51, 95% CI 0.29, 7.89), but did have a reduced risk of all-cause mortality (adjusted HR = 0.51 95% CI 0.30, 0.87) compared with those undergoing local excision only. CONCLUSIONS: Patients with stage pT1 CRC undergoing formal surgery had a reduced risk of all-cause mortality compared with those treated by local excision only. However, this was not explained by a reduced risk of recurrence/disease-free survival or CRC death, and suggests that the observed benefits may simply reflect selection of a healthier patient population in the formal surgery group.

Development and Validation of the Praise, Indulgence, and Status Parenting Scale.

The overarching aim of this study was to develop and validate a new scale (i.e., the Praise, Indulgence, and Status Parenting Scale [PISPS]) to measure modern parenting practices and behaviors consistent with instilling ideals of specialness (i.e., the notion that one is special), self-esteem, and status in children. In 2 studies on emerging adults (Study 1: N = 582, M age = 19.46; Study 2: N = 464, M age = 19.58), the PISPS was developed and validated using classical test theory (Study 1) and further refined using item-response theory (Study 2). Results from both studies indicated a 3-factor structure with factors differentially linked with correlates of interest including parenting strategies, self-esteem, narcissism, entitlement, and internalizing symptoms. Study 3 further validated the PISPS in a sample of parents (N = 638, M age = 35.79) reporting on their parenting and their child's emotion regulation and symptoms of psychopathology. Overall, findings support the PISPS, its psychometric properties, and its unique contribution to child symptoms.

The potential of respiration inhibition as a new approach to combat human fungal pathogens.

The respiratory chain has been proposed as an attractive target for the development of new therapies to tackle human fungal pathogens. This arises from the presence of fungal-specific electron transport chain components and links between respiration and the control of virulence traits in several pathogenic species. However, as the physiological roles of mitochondria remain largely undetermined with respect to pathogenesis, its value as a potential new drug target remains to be determined. The use of respiration inhibitors as fungicides is well developed but has been hampered by the emergence of rapid resistance to current inhibitors. In addition, recent data suggest that adaptation of the human fungal pathogen, Candida albicans, to respiration inhibitors can enhance virulence traits such as yeast-to-hypha transition and cell wall organisation. We conclude that although respiration holds promise as a target for the development of new therapies to treat human fungal infections, we require a more detailed understanding of the role that mitochondria play in stress adaption and virulence.

Exploring the structure of narcissism: Toward an integrated solution.

OBJECTIVE: Despite decades of work on narcissism, there remain many active areas of exploration and debate including a clear and consensual description of its underlying components. Understanding narcissism's factor structure is necessary for the precise measurement and investigation of specific psychological and behavioral processes. The aim of the current study was to explore the structure of narcissism by examining it at varying hierarchical levels. METHOD: Participants recruited from Amazon's Mechanical Turk (N = 591) completed 303 narcissism items encompassing 46 narcissism scales and subscales. Criterion variables measuring the five-factor model, self-esteem, aggression, and externalizing behavior were also collected. RESULTS: A series of factor analyses reveal the factor structure of narcissism at a range of specificities. No more than five meaningful factors (i.e., Grandiosity, Neuroticism, Antagonism, Distrustful Self-reliance, Attention-seeking) were identified and the most parsimonious model appears to be a three-factor structure. Narcissism scales that effectively capture each of the identified factors are identified. Factors diverged in their associations with criterion variables. CONCLUSIONS: A three-factor model (i.e., Agentic Extraversion, Narcissistic Neuroticism, Self-centered Antagonism) seems to be the most parsimonious conceptualization. Larger factor solutions are discussed, but future research will be necessary to determine the value of these increasingly narrow factors.

Using Item Response Theory to Develop a 60-Item Representation of the NEO PI-R Using the International Personality Item Pool: Development of the IPIP-NEO-60.

Given advantages of freely available and modifiable measures, an increase in the use of measures developed from the International Personality Item Pool (IPIP), including the 300-item representation of the Revised NEO Personality Inventory (NEO PI-R; Costa & McCrae, 1992a ) has occurred. The focus of this study was to use item response theory to develop a 60-item, IPIP-based measure of the Five-Factor Model (FFM) that provides equal representation of the FFM facets and to test the reliability and convergent and criterion validity of this measure compared to the NEO Five Factor Inventory (NEO-FFI). In an undergraduate sample (n = 359), scores from the NEO-FFI and IPIP-NEO-60 demonstrated good reliability and convergent validity with the NEO PI-R and IPIP-NEO-300. Additionally, across criterion variables in the undergraduate sample as well as a community-based sample (n = 757), the NEO-FFI and IPIP-NEO-60 demonstrated similar nomological networks across a wide range of external variables (rICC = .96). Finally, as expected, in an MTurk sample the IPIP-NEO-60 demonstrated advantages over the Big Five Inventory-2 (Soto & John, 2017 ; n = 342) with regard to the Agreeableness domain content. The results suggest strong reliability and validity of the IPIP-NEO-60 scores.

Media Use Is Linked to Lower Psychological Well-Being: Evidence from Three Datasets.

Adolescents spend a substantial and increasing amount of time using digital media (smartphones, computers, social media, gaming, Internet), but existing studies do not agree on whether time spent on digital media is associated with lower psychological well-being (including happiness, general well-being, and indicators of low well-being such as depression, suicidal ideation, and suicide attempts). Across three large surveys of adolescents in two countries (n = 221,096), light users (<1 h a day) of digital media reported substantially higher psychological well-being than heavy users (5+ hours a day). Datasets initially presented as supporting opposite conclusions produced similar effect sizes when analyzed using the same strategy. Heavy users (vs. light) of digital media were 48% to 171% more likely to be unhappy, to be in low in well-being, or to have suicide risk factors such as depression, suicidal ideation, or past suicide attempts. Heavy users (vs. light) were twice as likely to report having attempted suicide. Light users (rather than non- or moderate users) were highest in well-being, and for most digital media use the largest drop in well-being occurred between moderate use and heavy use. The limitations of using percent variance explained as a gauge of practical impact are discussed.

Inappropriate expression of the translation elongation factor 1A disrupts genome stability and metabolism.

The translation elongation factor eEF1A is one of the most abundant proteins found within cells, and its role within protein synthesis is well documented. Levels of eEF1A are tightly controlled, with inappropriate expression linked to oncogenesis. However, the mechanisms by which increased eEF1A expression alters cell behaviour are unknown. Our analyses in yeast suggest that elevation of eEF1A levels leads to stabilisation of the spindle pole body and changes in nuclear organisation. Elevation of the eEF1A2 isoform also leads to altered nuclear morphology in cultured human cells, suggesting a conserved role in maintaining genome stability. Gene expression and metabolomic analyses reveal that the level of eEF1A is crucial for the maintenance of metabolism and amino acid levels in yeast, most likely because of its role in the control of vacuole function. Increased eEF1A2 levels trigger lysosome biogenesis in cultured human cells, also suggesting a conserved role within metabolic control mechanisms. Taken together, our data suggest that the control of eEF1A levels is important for the maintenance of a number of cell functions beyond translation and that its de-regulation might contribute to its oncogenic properties.

New links between SOD1 and metabolic dysfunction from a yeast model of amyotrophic lateral sclerosis.

A number of genes have been linked to familial forms of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Over 150 mutations within the gene encoding superoxide dismutase 1 (SOD1) have been implicated in ALS, but why such mutations lead to ALS-associated cellular dysfunction is unclear. In this study, we identify how ALS-linked SOD1 mutations lead to changes in the cellular health of the yeast Saccharomyces cerevisiae We find that it is not the accumulation of aggregates but the loss of Sod1 protein stability that drives cellular dysfunction. The toxic effect of Sod1 instability does not correlate with a loss of mitochondrial function or increased production of reactive oxygen species, but instead prevents acidification of the vacuole, perturbs metabolic regulation and promotes senescence. Central to the toxic gain-of-function seen with the SOD1 mutants examined was an inability to regulate amino acid biosynthesis. We also report that leucine supplementation results in an improvement in motor function in a Caenorhabditis elegans model of ALS. Our data suggest that metabolic dysfunction plays an important role in Sod1-mediated toxicity in both the yeast and worm models of ALS.

Lipotoxicty in yeast: a focus on plasma membrane signalling and membrane contact sites.

Lipotoxicity is a pathophysiological process triggered by lipid overload. In metazoans, lipotoxicity is characterised by the ectopic deposition of lipids on organs other than adipose tissue. This leads to organ dysfunction, cell death, and is intimately linked to lipid-associated diseases such as cardiac dysfunction, atherosclerosis, stroke, hepatosteatosis, cancer and the metabolic syndrome. The molecules involved in eliciting lipotoxicity include FAs and their acyl-CoA derivatives, triacylglycerol (TG), diacylglycerol (DG), ceramides, acyl-carnitines and phospholipids. However, the cellular transport of toxic lipids through membrane contact sites (MCS) and vesicular mechanisms as well as lipid metabolism that progress lipotoxicity to the onset of disease are not entirely understood. Yeast has proven a useful model organism to study the molecular mechanisms of lipotoxicity. Recently, the Rim101 pathway, which senses alkaline pH and the lipid status at the plasmamembrane, has been connected to lipotoxicity. In this review article, we summarise recent research advances on the Rim101 pathway and MCS in the context of lipotoxicity in yeast and present a perspective for future research directions.

Ratings of affective and interpersonal tendencies differ for grandiose and vulnerable narcissism: A replication and extension of Gore and Widiger (2016).

OBJECTIVE: Theoretical conceptions of narcissism have long been characterized by two seemingly opposing poles: grandiosity and vulnerability. The goal of the current study was to investigate the extent to which traits associated with one profile are perceived to co-occur with the other within an individual. METHOD: Lay raters (N = 862; 56% female; 80% Caucasian; Mage = 37) recruited from Amazon's MTurk were assigned to one of four conditions in which they rated how often a series of narcissistic traits were displayed by a prototypical grandiose narcissist, a vulnerable narcissist, a close friend, or themselves. Vulnerable narcissism items were specifically worded to assess internalizing- versus externalizing-based emotional responses. RESULTS: Results suggest that grandiosely narcissistic individuals are seen as responding angrily to ego-threatening situations, whereas vulnerably narcissistic individuals are seen as responding with a broader array of negative emotions, including anger, sadness, and shame. In contrast, vulnerably narcissistic individuals were not rated as consistently demonstrating behaviors, attitudes, or cognitions associated with grandiose narcissism. CONCLUSIONS: Grandiose and vulnerable narcissistic individuals both exhibit anger in response to ego threat, but sadness/shame responses are more characteristic of vulnerable narcissism.

Vulnerable Narcissism Is (Mostly) a Disorder of Neuroticism.

OBJECTIVE: Increasing attention has been paid to the distinction between the dimensions of narcissistic grandiosity and vulnerability. We examine the degree to which basic traits underlie vulnerable narcissism, with a particular emphasis on the importance of Neuroticism and Agreeableness. METHOD: Across four samples (undergraduate, online community, clinical-community), we conduct dominance analyses to partition the variance predicted in vulnerable narcissism by the Five-Factor Model personality domains, as well as compare the empirical profiles generated by vulnerable narcissism and Neuroticism. RESULTS: These analyses demonstrate that the lion's share of variance is explained by Neuroticism (65%) and Agreeableness (19%). Similarity analyses were also conducted in which the extent to which vulnerable narcissism and Neuroticism share similar empirical networks was tested using an array of criteria, including self-, informant, and thin slice ratings of personality; interview-based ratings of personality disorder and pathological traits; and self-ratings of adverse events and functional outcomes. The empirical correlates of vulnerable narcissism and Neuroticism were nearly identical (MrICC = .94). Partial analyses demonstrated that the variance in vulnerable narcissism not shared with Neuroticism is largely specific to disagreeableness-related traits such as distrustfulness and grandiosity. CONCLUSIONS: These findings demonstrate the parsimony of using basic personality to study personality pathology and have implications for how vulnerable narcissism might be approached clinically.

A scoping review to explore how universal design for learning is described and implemented by rehabilitation health professionals in school settings.

BACKGROUND: Universal design for learning (UDL) is a framework that provides guidelines to support children with diverse needs in the classroom and promotes inclusion of all children. Although UDL is recognized as a promising approach for school-based rehabilitation health professionals (RHPs), there are no studies that synthesize evidence on the use of UDL by RHPs in the school setting. Therefore, the research question for this study is: How is UDL described and implemented in school settings by RHPs? This study specifically examined literature from occupational therapy, physiotherapy, and speech-language pathology. METHODS: A scoping review was completed to (a) summarize how UDL is described in the rehabilitation literature, (b) summarize the recommended and reported role of RHPs in the delivery of UDL, and (c) identify gaps in the evidence base. CINAHL, Embase, MEDLINE, PsychINFO, Sociological Abstracts, Web of Science, and ERIC electronic databases were searched. Numerical summaries and theoretical thematic analysis were used to describe the data both quantitatively and qualitatively. RESULTS: Inclusion criteria were achieved for 45 of the 3,998 screened documents. Most of the included documents lacked a definition of UDL. Analysis suggested that speech-language pathologists and occupational therapists implement UDL in a variety of ways within the school setting. No physiotherapy literature was found, and limited high-level empirical research has been conducted within rehabilitation. CONCLUSION: This scoping review provides a broad understanding of how RHPs describe and implement UDL-aligned services in school settings. UDL is a promising framework that provides RHPs with guidance on how to support children with diverse needs in the classroom, with the overall aim to promote inclusion of all children. There is a need for further research to determine the effectiveness of UDL as implemented by RHPs and to examine the role of physiotherapists in using UDL-type services.

A Comparison of the Nomological Networks Associated With Forced-Choice and Likert Formats of the Narcissistic Personality Inventory.

The Narcissistic Personality Inventory (NPI) is one of the most popular measures of narcissism. However, its use of a forced-choice response set might negatively affect some of its psychometric properties. The purpose of this research was to compare a Likert version of the NPI, in which only the narcissistic response of each pair was given, to the original NPI, in 3 samples of participants (N = 1,109). To this end, we compared the nomological networks of the forced-choice and Likert formats of the NPI in relation to alternative measures of narcissism, narcissistic personality disorder, entitlement, self-esteem, general personality traits (reported by self and informants), interpersonal styles, and general pathological traits included in the DSM-5. The Likert format NPI-total and subscales-manifested similar construct validity to the original forced-choice format across all criteria with only minor differences that seem to be due mainly to the increased reliability and variability found in the Likert NPI Entitlement/Exploitativeness subscale. These results provide evidence that a version of the NPI that employs a Likert format can justifiably be used in place of the original.

Assessment of Rapid-Blood-Culture-Identification Result Interpretation and Antibiotic Prescribing Practices.

Rapid pathogen identification can alter antibiotic prescribing practices if interpreted correctly. Microbiology reporting can be difficult to understand, and new technology has made it more challenging. Nebraska Medicine recently implemented the BioFire FilmArray blood culture identification panel (BCID) coupled with stewardship-based education on interpretation. Physician BCID result interpretation and prescribing were assessed via an electronic survey, with a response rate of 40.8% (156/382 surveys). Seven questions required respondents to interpret BCID results, identify the most likely pathogen, and then choose therapy based on the results. The tallied correct responses resulted in a knowledge score. General linear models evaluated the effect of role, specialty, and utilization of the BCID interpretation guide on the mean knowledge score. The specialties of the respondents included 55.7% internal medicine, 19.7% family medicine, and 24.6% other. Roles included 41.1% residents, 5.0% fellows, and 53.9% faculty. Most reported that they reviewed antimicrobial susceptibility results (89.4%) and adjusted therapy accordingly (81.6%), while only 60% stated that they adjusted therapy based on BCID results. The correct response rates ranged from 52 to 86% for the interpretation questions. The most common errors included misinterpretation of Enterobacteriaceae and Staphylococcus genus results. Neither role nor specialty was associated with total knowledge score in multivariate analysis (P = 0.13 and 0.47, respectively). In conclusion, physician interpretation of BCID results is suboptimal and can result in ineffective treatment or missed opportunity to narrow therapy. With the implementation of new technology, improved reporting practices of BCID results with clinical decision support tools providing interpretation guidance available at the point of care is recommended.

Controversies in Narcissism.

There has been a surge in interest in and research on narcissism and narcissistic personality disorder (NPD). Despite or because of this increased attention, there are several areas of substantial debate that surround the construct, including descriptions of grandiose and vulnerable dimensions or variants, questions regarding the existence of a consensual description, central versus peripheral features of narcissism, distinctions between normal and pathological narcissism, possible etiological factors, the role of self-esteem in narcissism, where narcissism should be studied, how it can be assessed, and its representation in diagnostic nosologies. We suggest that a failure to distinguish between grandiose (i.e., overtly immodest, self-centered, entitled, domineering) and vulnerable (e.g., self-centered, distrustful, neurotic, introverted) presentations of narcissism has led to a less cohesive and coherent literature and that trait-based models of personality and personality disorder can bring greater clarity to many of these important debates.

A study of the relationship between resilience, burnout and coping strategies in doctors.

PURPOSE OF THE STUDY: The aim of this study was to measure resilience, coping and professional quality of life in doctors. STUDY DESIGN: A cross-sectional study using an online questionnaire in a single National Health Service trust, including both primary and secondary care doctors. RESULTS: 283 doctors were included. Mean resilience was 68.9, higher than population norms. 100 (37%) doctors had high burnout, 194 (72%) doctors had high secondary traumatic stress and 64 (24%) had low compassion satisfaction. Burnout was positively associated with low resilience, low compassion satisfaction, high secondary traumatic stress and more frequent use of maladaptive coping mechanisms, including self-blame, behavioural disengagement and substance use. Non-clinical issues in the workplace were the main factor perceived to cause low resilience in doctors. CONCLUSIONS: Despite high levels of resilience, doctors had high levels of burnout and secondary traumatic stress. Doctors suffering from burnout were more likely to use maladaptive coping mechanisms. As doctors already have high resilience, improving personal resilience further may not offer much benefit to professional quality of life. A national study of professional Quality of Life, Coping And REsilience, which we are proposing to undertake, will for the first time assess the UK and Ireland medical workforce in this regard and guide future targeted interventions to improve professional quality of life.