Major Trauma Triage Tool Study (MATTS) expert consensus-derived injury assessment tool.

Introduction: Major trauma centre (MTC) care has been associated with improved outcomes for injured patients. English ambulance services and trauma networks currently use a range of triage tools to select patients for bypass to MTCs. A standardised national triage tool may improve triage accuracy, cost-effectiveness and the reproducibility of decision-making. Methods: We conducted an expert consensus process to derive and develop a major trauma triage tool for use in English trauma networks. A web-based Delphi survey was conducted to identify and confirm candidate triage tool predictors of major trauma. Facilitated roundtable consensus meetings were convened to confirm the proposed triage tool's purpose, target diagnostic threshold, scope, intended population and structure, as well as the individual triage tool predictors and cut points. Public and patient involvement (PPI) focus groups were held to ensure triage tool acceptability to service users. Results: The Delphi survey reached consensus on nine triage variables in two domains, from 109 candidate variables after three rounds. Following a review of the relevant evidence during the consensus meetings, iterative rounds of discussion achieved consensus on the following aspects of the triage tool: reference standard, scope, target diagnostic accuracy and intended population. A three-step tool comprising physiology, anatomical injury and clinical judgement domains, with triage variables assessed in parallel, was recommended. The triage tool was received favourably by PPI focus groups. Conclusions: This paper presents a new expert consensus derived major trauma triage tool with defined purpose, scope, intended population, structure, constituent variables, variable definitions and thresholds. Prospective evaluation is required to determine clinical and cost-effectiveness, acceptability and usability.

Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?

BACKGROUND: In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements. OBJECTIVES: The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians. RESULTS: Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency. CONCLUSION: The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses.

Plain language titleExcess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?Plain language summaryIt has been known for many decades that high doses of the B vitamin supplement, folic acid, can alleviate the anemia of vitamin B12 deficiency, at least temporarily. However, by alleviating the anemia, such folic acid supplements were said to "mask" the underlying vitamin B12 deficiency, thus allowing neurological damage to continue or possibly be exacerbated. Consequently, treating vitamin B12 deficiency with high dose folic acid was discontinued in the 1970s. The issue of whether folic acid supplements can exacerbate vitamin B12 deficiency reemerged in the 1990s with folic acid fortification of cereals and grains in the United States and Canada (and now in over 80 countries around the world) to prevent spina bifida and other birth defects. This narrative review summarizes the results of studies that have assessed the relationships between folic acid and folate and vitamin B12 status in patients and in populations. A recent hypothesis on how folic acid might exacerbate vitamin B12 deficiency is summarized, and recommendations to clinicians are made for increased vigilance in assessing vitamin B12 status in certain groups at risk of vitamin B12 deficiency, including older adults, people with gastrointestinal issues and other factors that cause vitamin B12 malabsorption, people with unexplained neurological problems, and people who follow vegan or vegetarian diets which are naturally low in vitamin B12.

Kinetic and Spectroscopic Investigation of the Y157F and C93G/Y157F Variants of Cysteine Dioxygenase: Dissecting the Roles of the Second-Sphere Residues C93 and Y157.

In mammals, l-cysteine (Cys) homeostasis is maintained by the mononuclear nonheme iron enzyme cysteine dioxygenase (CDO), which oxidizes Cys to cysteine sulfinic acid. CDO contains a rare post-translational modification, involving the formation of a thioether cross-link between a Cys residue at position 93 (Mus musculus CDO numbering) and a nearby tyrosine at position 157 (Cys-Tyr cross-link). As-isolated CDO contains both the cross-linked and non-cross-linked isoforms, and formation of the Cys-Tyr cross-link during repeated enzyme turnover increases CDO's catalytic efficiency by ∼10-fold. Interestingly, while the C93G CDO variant lacks the Cys-Tyr cross-link, it is similarly active as cross-linked wild-type (WT) CDO. Alternatively, the Y157F CDO variant, which also lacks the cross-link but maintains the free thiolate at position 93, exhibits a drastically reduced catalytic efficiency. These observations suggest that the untethered thiolate moiety of C93 is detrimental to CDO activity and/or that Y157 is essential for catalysis. To further assess the roles of residues C93 and Y157, we performed a spectroscopic and kinetic characterization of Y157F CDO and the newly designed C93G/Y157F CDO variant. Our results provide evidence that the non-cross-linked C93 thiolate stabilizes a water at the sixth coordination site of Cys-bound Y157F Fe(II)CDO. A water is also present, though more weakly coordinated, in Cys-bound C93G/Y157F Fe(II)CDO. The presence of a water molecule, which must be displaced by cosubstrate O2, likely makes a significant contribution to the ∼15-fold and ∼7-fold reduced catalytic efficiencies of the Y157F and C93G/Y157F CDO variants, respectively, relative to cross-linked WT CDO.

Development and Validation of the Five-Factor Borderline Inventory-Super Short Form and Screener.

The Five-Factor Borderline Inventory (FFBI) and FFBI-Short Form (FFBI-SF) are 120-item and 48-item measures that assess the underlying maladaptive personality traits of borderline personality disorder (BPD). The purpose of this study was to develop a super short form (FFBI-SSF) and an FFBI-Screener to facilitate the use of dimensional trait measures for BPD. Using item response theory analyses, the 48-item measure was reduced to 22 items using a large undergraduate sample (N = 1300) and then retested using a Mechanical Turk sample (N = 602), demonstrating strong replicability. IRT was again used to further reduce the measure from 22 items to four items to provide a brief screening tool. Correlations of the FFBI-SSF and Screener with measures of BPD-related variables were compared across five samples (N = 919, 204, 580, 281, and 488). Overall, the FFBI-SSF showed similar relations to the FFBI-SF at the full scale and domain-level scales, while the FFBI-screener demonstrated similar relations at the full scale level. This super short form and screener may best be used in large-scale research studies or as part of a screening tool in clinical settings.

The influence of an agricultural intervention on social capital and water insecurity coping strategies: Qualitative evidence from female smallholder farmers living with HIV in western Kenya.

Background: Greater social capital is associated with positive health outcomes and better HIV management. The ways by which social capital may influence household water insecurity (HHWI), a critical determinant of health among persons living with HIV, remain underexplored. Further, despite the importance of reliable water access and use for health and agricultural productivity, few studies have described the strategies smallholder farmers living with HIV use to manage water insecurity. Objective: We qualitatively explored how an agricultural intervention (provision of a treadle pump for irrigation) influenced HHWI coping strategies through its impacts on social capital among smallholder farmers living with HIV in western Kenya. Method: In 2018, we purposively recruited participants from the Shamba Maisha study, a randomized agricultural intervention (NCT02815579) that provided irrigation pumps to improve treatment outcomes and food security among smallholder farmers living with HIV in western Kenya (n = 42). Participants shared their experiences with water insecurity through go-along and photo-elicitation interviews. Data were thematically analyzed using inductively developed codes. Results: Participants described diverse strategies for coping with agricultural water insecurity. Dimensions of social capital such as feelings of belonging, connectedness, and trust influenced the use of the treadle water pump and other water access behaviors. For instance, participants reported borrowing or sharing water pumps with friends and neighbors if they felt they had a good rapport. In addition, participants indicated a willingness to engage in collective activities, such as supporting the operation of the irrigation pump during planting, when they felt sufficiently connected to a larger group. Overall, individuals in the intervention arm described greater social cohesion, reciprocity, and community connectedness than those in the control arm. Conclusion: The impact of an agricultural intervention on water access and use was described as being modified by social capital among female smallholder farmers living with HIV. Findings suggest that social capital may create an enabling environment for implementing strategies that improve the management and reduce the burden of HIV. Measuring these strategies and their associations with HIV outcomes may strengthen our understanding of resilience among female smallholder farmers living with HIV. The development of a coping strategies index and its use in a longitudinal study could help to identify pathways through which social capital influences health and the effectiveness of livelihood interventions.

Construction of Risk Prediction Model of Type 2 Diabetic Kidney Disease Based on Deep Learning.

Background: This study aimed to develop a diabetic kidney disease (DKD) prediction model using long short term memory (LSTM) neural network and evaluate its performance using accuracy, precision, recall, and area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Methods: The study identified DKD risk factors through literature review and physician focus group, and collected 7 years of data from 6,040 type 2 diabetes mellitus patients based on the risk factors. Pytorch was used to build the LSTM neural network, with 70% of the data used for training and the other 30% for testing. Three models were established to examine the impact of glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP), and pulse pressure (PP) variabilities on the model's performance. Results: The developed model achieved an accuracy of 83% and an AUC of 0.83. When the risk factor of HbA1c variability, SBP variability, or PP variability was removed one by one, the accuracy of each model was significantly lower than that of the optimal model, with an accuracy of 78% (P<0.001), 79% (P<0.001), and 81% (P<0.001), respectively. The AUC of ROC was also significantly lower for each model, with values of 0.72 (P<0.001), 0.75 (P<0.001), and 0.77 (P<0.05). Conclusion: The developed DKD risk predictive model using LSTM neural networks demonstrated high accuracy and AUC value. When HbA1c, SBP, and PP variabilities were added to the model as featured characteristics, the model's performance was greatly improved.

Differentiation of regulatory myeloid and T-cells from adult human hematopoietic stem cells after allogeneic stimulation.

Introduction: Donor hematopoietic stem cell (DHSC) infusions are increasingly being studied in transplant patients for tolerance induction. Methods: To analyze the fate of infused DHSCs in patients, we developed an in vitro culture system utilizing CD34+DHSCs stimulated with irradiated allogeneic cells in cytokine supplemented medium long-term. Results: Flow cytometric analyses revealed loss of the CD34 marker and an increase in CD33+ myeloid and CD3+ T-cell proportion by 10.4% and 72.7%, respectively, after 21 days in culture. T-cells primarily expressed TcR-αß and were of both CD4+ and CD8+ subsets. Approximately 80% of CD3+ T cells lacked expression of the co-stimulatory receptor CD28. The CD4+ compartment was predominated by CD4+CD25+CD127-FOXP3+ Tregs (>50% CD4+CD127- compartment) with <1% of all leukocytes exhibiting a CD4+CD127+ phenotype. Molecular analyses for T-cell receptor excision circles showed recent and increased numbers of TcR rearrangements in generated T cells over time suggesting de novo differentiation from DHSCs. CD33+ myeloid cells mostly expressed HLA-DR, but lacked expression of co-stimulatory receptors CD80 and CD83. When studied as modulators in primary mixed lymphocyte reactions where the cells used to stimulate the DHSC were used as responders, the DHSC-lines and their purified CD8+, CD4+, CD33+ and linage negative subsets inhibited the responses in a dose-dependent and non-specific fashion. The CD8+ cell-mediated inhibition was due to direct lysis of responder cells. Discussion: Extrapolation of these results into the clinical situation would suggest that DHSC infusions into transplant recipients may generate multiple subsets of donor "chimeric" cells and promote recipient Treg development that could regulate the anti-donor immune response in the periphery. These studies have also indicated that T cell maturation can occur in vitro in response to allogeneic stimulation without the pre-requisite of a thymic-like environment or NOTCH signaling stimulatory cell line.

Testing whether the relations between sex and psychopathology are accounted for by structural morphometry in ABCD.

Sex differences in psychopathology are well-established, with females demonstrating higher rates of internalizing (INT) psychopathology and males demonstrating higher rates of externalizing (EXT) psychopathology. Using two waves of data from the Adolescent Brain Cognitive Development Study (N = 6,778 at each wave), the current study tested whether the relations between sex and psychopathology might be accounted for by structural brain differences. In general, we found robust, relatively consistent relations between sex and structural morphometry across waves. Relatively few morphometric brain variables were significantly related to INT or EXT across waves, however, with very small effect sizes when present. Next, we tested the extent to which each morphometric brain variable could account for the associations of sex with INT and EXT psychopathology. We found a total of 26 brain regions that accounted for significant portions of the associations between sex and psychopathology across both waves (almost all related to EXT), although the effects present were very small. The current evidence suggests that in children aged 9-12, multiple whole-brain and regional brain variables appear to statistically account for small portions of the sex-psychopathology links, especially for externalizing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability - Sickle Cell Data Collection Program, 11 States, 2016-2020.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle ß-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

Perioperative Insulin Pump Therapy Decreases Readmission Risk and Improves Outcomes in Patients with Diabetes.

OBJECTIVE: To evaluate the impact of temporary insulin pump use during hospitalization on glycemia, postoperative complications, and cost/utilization in perioperative patients with diabetes. METHODS: Patients (n=159) with type 2 diabetes and hospitalized for elective surgery were recruited from three hospitals. Subjects were categorized into the insulin pump group and the multiple daily subcutaneous insulin injection group according to their treatment therapy. Data were collected at admission, discharge, and 3 months post-discharge. RESULTS: Subjects in the CSII group who were still on insulin therapy transitioned from CSII to MDII; however, their daily insulin dosages were lower than those in the MDII group (15.31±10.98 U/d vs. 23.48±17.02 U/d, P=0.015) after discharge. In terms of medical costs, the CSII group had significantly higher hospitalization costs than the MDII group (112.36±103.43 thousand RMB vs. 82.65±77.98 thousand RMB, P=0.043). After 3 months, the CSII group had significantly lower outpatient costs than the MDII group (3.17±0.94 thousand RMB vs. 3.98±1.76 thousand RMB, P ˂ 0.001). In the MDII group, 10 patients reported severe postoperative complications requiring re-hospitalization; there were no similar reports in the CSII group. CONCLUSION: Temporary use of insulin pump therapy for perioperative patients with diabetes results in a reduction in blood glucose and blood glucose fluctuation during hospitalization, HbA1c, and the risk of postoperative complication and readmission, thus significantly decreasing costs in this complex patient cohort. Further work is needed to better understand indications for utilizing pump therapy based on diabetes phenotype and the complexity of planned surgical intervention.

Exploring the structure of fearlessness using self-report measures.

OBJECTIVE: The present study examined the hierarchical structure of self-reported fearlessness and compared this structure to external criterion measures. BACKGROUND: Fearlessness is often discussed in relation to clinical and personality research. However, there is a paucity of research focusing on its empirical structure, in particular with self-report measures. METHOD: Using a preregistered analytical approach, we employed Goldberg's 2006 "bass-ackward" factor analysis on self-reported trait fear and fearlessness items to uncover the hierarchical structure of the construct. The final sample consisted of 619 participants and 562 informants. RESULTS: By assessing fit statistics and interpretability of the factors, we found a six-factor model fit the data best. The six-factor solution emerged as comprehensive and included components labeled Assertiveness, Low Anxiety, Sociability, Recklessness, Openness to Action, and Adventurousness. Criterion variables measuring boldness, fear, anxiety, psychopathy, basic personality traits, and impulsivity, were correlated with the factor scores at each factor level of the model. Conclusions The findings from this study elucidate how trait fearlessness unfolds at varying levels and how these factors relate to and diverge from various outcomes.

Momentary assessment of the relations between narcissistic traits, interpersonal behaviors, and aggression.

INTRODUCTION: This study explores the associations among narcissistic traits, interpersonal behaviors, and aggression using repeated, situation-based measurement. We examine narcissism's relations with aggression across three levels of its theorized hierarchy (level 1: narcissism; level 2: grandiose vs. vulnerable narcissism; level 3: antagonism, agentic extraversion, and narcissistic neuroticism). METHODS: Using an experience-sampling approach, the current study examined the effects of narcissism and its finer-grained components on daily affective experiences and aggressive behaviors in the context of interpersonal interactions. Data were collected from 477 undergraduate students who were instructed to complete four prompts a day for ten consecutive days. RESULTS: Narcissism at the global construct level positively predicted multiple indices of episodic aggression (i.e., aggressive temper, aggressive urge, verbal aggression). At the dual-dimension level, grandiose narcissism specifically predicted aggression, and then at the trifurcated level, interpersonal antagonism predicted aggression by itself and in interaction with event-level negative affect. Negative affect consistently exhibited both within- and between-person effects on aggression. CONCLUSION: In real-life social interactions, narcissism dimensions differentially affect the way individuals experience social interactions and process negative affect, and thus in both research and clinical practice, narcissism is best assessed as a heterogeneous, multidimensional construct.

Comparing Brief Measures of Narcissism-Internal Consistency, Validity, and Coverage.

Many measures, varying in breadth and length, have been constructed to measure narcissism. In recent years, super-short forms have become popular in research settings. Although brief measures hold some advantages, their brevity can come at psychometric costs. Participants recruited from Amazon's Mechanical Turk (N = 473) completed long and brief narcissism measures and criterion measures in a randomized order. Short forms were examined and compared to long forms in terms of their completion times and psychometric properties. Generally, the short forms demonstrated adequate internal consistency, variable convergence with each other, mostly moderate to strong convergence with long forms, and appropriate convergence with external criteria. These findings suggest that some short forms may be used when efficiency of survey administration is particularly important without significant psychometric cost. We discuss the advantages and disadvantages of the brief measures and make recommendations for which to use depending on the priorities of a given study.

Examining the structure of personality dysfunction.

Personality impairment is a core feature of personality disorders in both current (i.e., Diagnostic and Statistical Manual of Mental Disorders, fifth edition [DSM-5] personality disorders, International Classification of Diseases,11th revision personality disorders) and emerging (i.e., DSM-5's alternative model of personality disorders) models of psychopathology. Yet, despite its importance within clinical nosology, attempts to identify its optimal lower-order structure have yielded inconsistent findings. Given its presence in diagnostic models, it is important to better understand its empirical structure across a variety of instantiations. To the degree that impairment is multifaceted, various factors may have different nomological networks and varied implications for assessment, diagnosis, and treatment. Therefore, participants were recruited from two large public universities in the present preregistered study (N = 574) to explore the construct's structure with exploratory "bass-ackward" factor analyses at the item level. Participants completed over 250 items from six commonly used measures of personality dysfunction. Criterion variables in its nomological network were also collected (e.g., general and pathological personality traits, internalizing/externalizing behavior, and personality disorders) using both self- and informant-reports. These factor analyses identified four lower-order facets of impairment (i.e., negative self-regard, disagreeableness, intimacy problems, and lack of direction), all of which showed moderate to strong overlap with traits from both general and pathological models of personality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Associations between food insecurity and child and parental physical, nutritional, psychosocial and economic well-being globally during the first 1000 days: A scoping review.

Food insecurity affects billions of individuals annually and contributes to myriad poor health outcomes. Experiences of food insecurity may be particularly harmful during the first 1000 days, but literature on the topic has not been synthesized. We therefore aimed to characterize all available studies examining associations between food insecurity and nutritional, psychosocial, physical and economic well-being among parents and children during this period. We implemented a standardized search strategy across 11 databases. Four researchers screened 10,257 articles, 120 of which met the inclusion criteria. Most studies were conducted in Sub-Saharan Africa (43.3%), followed by North America (20.8%). Studies were primarily quantitative (95.8%), cross-sectional (70.0%) and focused on women (pregnant or post-partum, 48.3%) or women and children (15.8%). Physical health outcomes were the most investigated (n = 87 studies), followed by nutritional (n = 69), psychosocial (n = 35) and economic well-being (n = 2). The most studied associations were between food insecurity and stunting (n = 15), maternal depression (n = 12), child dietary diversity (n = 7) and maternal body mass index (n = 6). The strength of evidence for the observed associations varied across populations as well as within and between examined outcomes. We recommend that future studies recruit more diverse study populations, consider temporality of relationships, use instruments that facilitate cross-site comparisons, measure individual-level food insecurity and outcomes most likely to be impacted by food insecurity, evaluate contextual factors that may modify the effects of food insecurity and employ analytic techniques that permit assessment of causal pathways.

The structure of aggressive personality.

OBJECTIVE: We sought to factor analyze a broad array of aggression measures to identify a comprehensive, coherent factor structure for this construct. BACKGROUND: Measures and models of trait aggression have multiplied to the point of incoherence. METHOD: In Study 1, a diverse sample of 922 undergraduates completed a battery of items acquired from 42 self-report aggression questionnaires. In Study 2, we administered a curated item pool to another diverse sample of 1447 undergraduates, alongside criterion measures. RESULTS: We curated an initial item pool of 734 items down to 289 items that exhibited sufficient variability, were not redundant with other items, and possessed strong loadings onto a central 'trait aggression' factor. These remaining items were best characterized by a six-factor structure, which captured relational, angry, violent, retaliatory, intimate partner, and alcohol forms of aggression. We estimated their hierarchical structure, correlations with their original aggression scales, Five Factor Model trait dimensions, impulsivity facets, and found them to be robust to gender composition and the inclusion of alcohol-naive and intimate-partner-naive participants. CONCLUSIONS: This factor structure mostly supported widely-accepted models of aggressive personality that focus on its overt and relational forms and reactive functions, though proactive aggression only loosely emerged as a distinct entity. We retained the final items as the Comprehensive Aggression Scale (CAS).

RNF8 ubiquitylation of XRN2 facilitates R-loop resolution and restrains genomic instability in BRCA1 mutant cells.

Breast cancer linked with BRCA1/2 mutations commonly recur and resist current therapies, including PARP inhibitors. Given the lack of effective targeted therapies for BRCA1-mutant cancers, we sought to identify novel targets to selectively kill these cancers. Here, we report that loss of RNF8 significantly protects Brca1-mutant mice against mammary tumorigenesis. RNF8 deficiency in human BRCA1-mutant breast cancer cells was found to promote R-loop accumulation and replication fork instability, leading to increased DNA damage, senescence, and synthetic lethality. Mechanistically, RNF8 interacts with XRN2, which is crucial for transcription termination and R-loop resolution. We report that RNF8 ubiquitylates XRN2 to facilitate its recruitment to R-loop-prone genomic loci and that RNF8 deficiency in BRCA1-mutant breast cancer cells decreases XRN2 occupancy at R-loop-prone sites, thereby promoting R-loop accumulation, transcription-replication collisions, excessive genomic instability, and cancer cell death. Collectively, our work identifies a synthetic lethal interaction between RNF8 and BRCA1, which is mediated by a pathological accumulation of R-loops.

Is Personality Pathology Ego-Syntonic? Self- and Meta-Perception of Maladaptive Personality Traits.

Research has challenged the assumption that personality pathology is "ego-syntonic" or perceived favorably and consistent with one's self-image. The present study employed a community sample (n = 401) to examine relations between self-rated maladaptive personality and liking of maladaptive traits in self and others as well as meta-perception of personality pathology (i.e., how likable participants believe others find maladaptive traits). In general, individuals with higher self-rated maladaptive traits provided higher ratings of the likability of these traits in themselves and others. However, as hypothesized, comparison of liking ratings for high scorers and the rest of the sample revealed that individuals who score high on most pathological personality traits do not "like" these traits (or rate others as "liking" them) but simply dislike them less. Results support a dimensional view of ego-syntonicity.

Folic acid supplementation in a mouse model of diabetes in pregnancy alters insulin sensitivity in female mice and beta cell mass in offspring.

Epidemiological studies have reported discrepant findings on the relationship between folic acid intake during pregnancy and risk for gestational diabetes mellitus (GDM). To begin to understand how folic acid impacts metabolic health during pregnancy, we determined the effects of excess folic acid supplementation (5× recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL/6J) model of diet-induced diabetes in pregnancy (western diet) and control mice, we show that folic acid supplementation improved insulin sensitivity in the female mice fed the western diet and worsened insulin sensitivity in control mice. We found no unmetabolized folic acid in liver from supplemented mice suggesting the metabolic effects of folic acid supplementation are not due to unmetabolized folic acid. Male fetal (gestational day 18.5) offspring from folic acid supplemented dams (western and control) had greater beta cell mass and density than those from unsupplemented dams; this was not observed in female offspring. Differential sex-specific hepatic gene expression profiles were observed in the fetal offspring from supplemented dams but this differed between western and controls. Our findings suggest that folic acid supplementation affects insulin sensitivity in female mice, but is dependent on their metabolic phenotype and has sex-specific effects on offspring pancreas and liver.