One of the primary facets of borderline personality disorder (BPD) is behavioral dysregulation, a wide array of behaviors that are difficult to control and harmful to the individual. The purpose of this study was to explore the association between BPD and a variety of dysregulated behaviors, some of which have received little empirical attention. Using a large sample of individuals diagnosed with anorexia nervosa, 41 individuals diagnosed with BPD were compared to the rest of the sample on the presence of dysregulated behaviors using logistic regression analyses. Anorexia nervosa subtypes, age, and other Cluster B personality disorders were used as covariates. Results support an association between BPD and alcohol misuse, hitting someone/breaking things, provoking fights/ arguments, self-injury, overdosing, street drug use, binge-eating, impulsive spending, shoplifting/stealing and risky sexual behaviors. Differences between dichotomous and continuous measures of BPD yielded somewhat different results.
borderline personality disorder; behavioral dysregulation; substance abuse; anorexia nervosa
Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved.
We assessed the relation between season of birth and eating disorder symptoms and personality characteristics in a sample of 880 women with eating disorders and 580 controls from two Price Foundation Studies. Eating disorder symptoms were assessed using Structured Interview of Anorexic and Bulimic Disorders and the Structured Clinical Interview for DSM-IV. Personality traits were assessed using the Temperament and Character Inventory and the Frost Multidimensional Perfectionism Scale. Date of birth was obtained from a sociodemographic questionnaire.
No significant differences were observed 1) in season of birth across eating disorder subtypes and controls; nor 2) for any clinical or personality variables and season of birth. We found no evidence of season of birth variation in eating disorders symptoms or personality traits. Contributing to previous conflicting findings, the present results do not support a season of birth hypothesis for eating disorders.
anorexia nervosa; bulimia nervosa; eating disorders; season of birth
Patients with germline fumarate hydratase (FH) mutation are predisposed to develop aggressive kidney cancer with few treatment options and poor therapeutic outcomes. Activity of the proto-oncogene ABL1 is upregulated in FH-deficient kidney tumors and drives a metabolic and survival signaling network necessary to cope with impaired mitochondrial function and abnormal accumulation of intracellular fumarate. Excess fumarate indirectly stimulates ABL1 activity while restoration of wild-type FH abrogates both ABL1 activation and the cytotoxicity caused by ABL1 inhibition or knockdown. ABL1 upregulates aerobic glycolysis via the mTOR/HIF1α pathway and neutralizes fumarate-induced proteotoxic stress by promoting nuclear localization of the anti-oxidant response transcription factor NRF2. Our findings identify ABL1 as a pharmacologically tractable therapeutic target in glycolytically dependent, oxidatively stressed tumors.
vandetanib; ABL1; HLRCC; glycolysis; antioxidant response; NRF2
This study examined the association between restrictive eating behaviors and binge eating in anorexia nervosa (AN) using data collected in the natural environment. Women (N = 118) with DSM-IV full or sub-threshold AN reported eating disorder behaviors, including binge eating episodes, going ≥ 8 waking hours without eating, and skipping meals, during 2 weeks of ecological momentary assessment (EMA). Time-lagged generalized estimating equations tested the following hypotheses: 1) dietary restriction would predict binge eating while controlling for binge eating the previous day; 2) binge eating would predict restriction the subsequent day while controlling for restriction the previous day. After controlling for relevant covariates, the hypotheses were not supported; however, there appeared to be a cumulative effect of repeatedly going 8 consecutive hours without eating (i.e. fasting) on the risk of binge eating among individuals who recently engaged in binge eating. In addition, skipping meals was associated with a lower risk of same day binge eating. The relationship between binge eating and dietary restriction appears to be complex and may vary by type of restrictive eating behavior. Future research should aim to further clarify the nature of the interaction of binge eating and restrictive eating among individuals with AN in order to effectively eliminate these behaviors in treatment.
Binge eating; Restriction; Anorexia nervosa
A number of agents are used clinically to enhance the efficacy of radiotherapy today, many of which are cytotoxic chemotherapies. Agents that enhance radiation induced tumor cell killing or protect normal tissues from the deleterious effects of ionizing radiation are collectively termed radiation modifiers. A significant effort in radiobiological research is geared towards describing and testing radiation modifiers with the intent of enhancing the therapeutic effects of radiation while minimizing normal tissue toxicity. In this review, we discuss the characteristics of these agents, the testing required to translate these agents into clinical trials, and highlight some challenges in these efforts.
Evidence suggests that both obesity and binge eating disorder (BED) may be associated with deficits in cognitive functioning. The purpose of this study was to examine whether a lifetime history of BED would be associated with changes in several domains of cognitive functioning (attention, executive function, language, and memory) following bariatric surgery. Participants were 68 bariatric surgery patients who completed a computerized battery of cognitive tests within 30 days prior to undergoing surgery and again at a 12-month postoperative follow-up. Results revealed that on the whole, participants displayed improvements from baseline to follow-up in attention, executive function, and memory, even after controlling for diagnostic history of depression; no changes were observed for language. However, individuals with and without a history of BED did not differ in changes in body mass index or in the degree of improvement in cognitive functioning from baseline to follow-up. Such results suggest that a history of BED does not influence changes in cognitive functioning following bariatric surgery. Future research will be needed to further clarify the role of BED in predicting cognitive function over time.
cognition; obesity; bariatric surgery; binge eating disorder
Concerns that the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) may increase the risk of HIV acquisition in women led to questions on whether DMPA could reduce efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model to investigate the impact of prolonged DMPA on PrEP with FTC/TDF. Twelve pigtail macaques treated with DMPA were exposed vaginally to SHIV once a week for up to 5 months and received either placebo (n=6) or FTC/TDF (n=6). All control macaques were infected while the PrEP-treated animals remained protected (p=0.0007). This model suggests that women using DMPA will fully benefit from PrEP.
Depot-medroxyprogesterone acetate; injections; contraception; macaques; pre-exposure prophylaxis; simian HIV
Bariatric surgery is associated with cognitive benefits, but the nature of such gains may be variable across demographically and clinically diverse persons. Older adults achieve less weight loss and resolution of fewer medical comorbidities after surgery compared to younger patients, and are also at heightened risk for nutritional deficiencies. However, no study has examined the influence of age on cognitive improvements after bariatric surgery.
To determine the effects of age on cognitive function post-bariatric surgery.
95 participants enrolled in the Longitudinal Assessment for Bariatric Surgery completed a computerized cognitive test battery prior to bariatric surgery and at 12-weeks, and 12-months post-operatively.
Baseline cognitive impairments were common. Significant improvements were found in attention/executive function and memory abilities 12-weeks and 12-months after surgery. Age was not associated with baseline cognitive test performance. Separate multivariable regression analyses controlling for baseline attention/executive function and memory also showed that age was not a significant predictor of 12-week or 12-month performances in these domains (p > 0.05 for all).
The current study provides preliminary evidence suggesting that older age does not preclude post-bariatric surgery cognitive benefits. Prospective studies in more age diverse samples (i.e., up to 70 years) are needed to determine whether bariatric surgery can reduce risk of age-related neurological conditions like Alzheimer’s disease and stroke.
Obesity; bariatric surgery; cognitive function; age; older adults
Mitochondrial dysfunction is a common feature in neurodegeneration and aging. We identify mitochondrial dysfunction in xeroderma pigmentosum group A (XPA), a nucleotide excision DNA repair disorder with severe neurodegeneration, in silico and in vivo. XPA deficient cells show defective mitophagy with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD+-SIRT1-PGC-1α axis triggered by hyperactivation of the DNA damage sensor PARP1. This phenotype is rescued by PARP1 inhibition or by supplementation with NAD+ precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration. Our findings reveal a novel nuclear-mitochondrial cross-talk that is critical for the maintenance of mitochondrial health.
Recently we found that mice bearing subcutaneous non-metastatic tumors exhibited elevated levels of two types of complex DNA damage, i.e., double-strand breaks and oxidatively-induced clustered DNA lesions in various tissues throughout the body, both adjacent to and distant from the tumor site. This DNA damage was dependent on CCL2, a cytokine involved in the recruitment and activation of macrophages, suggesting that this systemic DNA damage was mediated via tumor-induced chronic inflammatory responses involving cytokines, activation of macrophages, and consequent free radical production. If free radicals are involved, then a diet containing an antioxidant may decrease the distant DNA damage.
Here we repeated our standard protocol in cohorts of two syngeneic tumor-bearing C57BL/6NCr mice that were on a Tempol-supplemented diet. We show that double-strand break and oxidatively-induced clustered DNA lesion levels were considerably decreased, about 2-3 fold, in the majority of tissues studied from the tumor-bearing mice fed the antioxidant Tempol compared to the control tumor-bearing mice. Similar results were also observed in nude mice suggesting that the Tempol effects are independent of functioning adaptive immunity.
This is the first in vivo study demonstrating the effect of a dietary antioxidant on abscopal DNA damage in tissues distant from a localized source of genotoxic stress. These findings may be important for understanding the mechanisms of genomic instability and carcinogenesis caused by chronic stress-induced systemic DNA damage and for developing preventative strategies.
Tumor-bearing mice; DNA damage; antioxidants; Tempol; non-targeted effects
The study was designed to develop a new screening instrument for pathological buying (PB), and to examine its psychometric properties in a large-scale sample. By using a facet theoretical approach and based on literature as well as on clinical experience, a 20-item Pathological Buying Screener (PBS) was developed and administered to a representative German sample (n = 2,539). Valid data were available from 2,403 participants who were subjects for three subsequent empirical studies. The first study explored the factor structure using exploratory factor analyses in a subsample of 498 participants. Based on factor loadings, a 13-item version with the two factors loss of control / consequences and excessive buying behavior was revealed. This two-factor model was confirmed in study 2 by confirmatory factor analysis performed on another subsample (n = 1,905). Study 3 investigated age and gender effects and convergent validity of the PBS using the Compulsive Buying Scale (CBS) in the full sample (N = 2,403). The total PBS score was adequately correlated with the CBS score. Hierarchical regression analyses with the CBS score as the dependent variable and the two PBS factors as the predictors indicated an own incremental validity of the two factors in participants ≤ 65 years. The reliability of the total score as well as of the two subscales was good to excellent. Overall, the PBS represents a useful measure for PB. Future studies are needed to replicate the two-factor structure in clinical samples and to define a valid cutoff for PB.
The mechanisms for improved cognitive function post-bariatric surgery are not well understood. Markers of kidney and liver function (i.e., cystatin C and alkaline phosphatase (ALP)) are elevated in obese individuals and associated with poor neurocognitive outcomes in other samples. Bariatric surgery can improve cystatin C and ALP levels, but no study has examined whether such changes correspond to post-operative cognitive benefits.
78 bariatric surgery patients completed a computerized cognitive test battery prior to and 12-months after surgery. All participants underwent an eight-hour fasting blood draw to quantify cystatin C and ALP concentrations.
Cognitive function improved after surgery. Cystatin C levels decreased at the 12-month follow-up; however, no changes were found in ALP concentrations. At baseline, higher cystatin C levels predicted worse attention/executive function, but no such effects emerged for ALP. Regression analyses controlling for possible medical and demographic confounds and baseline factors revealed that decreased ALP levels following surgery predicted better attention/executive function and memory abilities. Post-surgery changes in cystatin C did not correspond to cognitive improvements.
Decreased ALP levels predicted better cognition following bariatric surgery, suggesting improved liver function as a possible mechanism of post-operative cognitive benefits. Future studies with neuroimaging and longer follow-up periods are needed to determine whether bariatric surgery can decrease risk for adverse brain changes and dementia in severely obese persons via improved metabolic function.
Obesity; bariatric surgery; cognitive function; cystatin C; alkaline phosphatase; metabolic function
Background. Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood.
Methods. Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy.
Results. Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P = .04, by the log–rank test; relative risk, 2.5 [95% confidence interval, 1.1–5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P = .01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon γ, interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P ≤ .05, by the Wilcoxon test).
Conclusions. C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological assocations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention.
HIV risk; STI or STD; Chlamydia; Trichomonas; menstrual cycle; macaque; HIV susceptibility model
Nitroxides can ameliorate the toxic effects of radiation during cancer therapy. Nitroxides are paramagnetic and can be used in magnetic resonance imaging (MRI) and electron paramagnetic resonance imaging (EPRI) to monitor in vivo oxidative stress status. Compound 5 (3-(N-piperidinemethyl)-2, 2, 5, 5-tetramethyl-1-oxy-3-pyrroline) was found to be the most effective nitroxide radioprotector. An efficient synthesis for this promising radioprotector was developed.
Nitroxide; redox; radioprotector; MRI; EPRI
FTY720 has been shown to reduce inflammatory cytokines and immune cells in the genital mucosa of macaques. This pilot study examined the ability of FTY720 to inhibit HIV acquisition. Systemic treatment with FTY720 failed to prevent or delay vaginal SHIV transmission.
Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microarray analysis of vein grafts in a model of bilateral rabbit jugular vein graft revealed Cx43 as an early upregulated gene. Additional experiments conducted using an ex-vivo human saphenous veins perfusion system (EVPS) confirmed that Cx43 was rapidly increased in human veins subjected ex-vivo to arterial hemodynamics. Cx43 knock-down by RNA interference, or adenoviral-mediated overexpression, respectively inhibited or stimulated the proliferation of primary human VSMC in vitro. Furthermore, Cx blockade with carbenoxolone or the specific Cx43 inhibitory peptide 43gap26 prevented the burst in myointimal proliferation and IH formation in human saphenous veins. Our data demonstrated that Cx43 controls proliferation and the formation of IH after arterial engraftment.
The System for Continuous Observation of Rodents in Home-cage Environment (SCORHE) was developed to demonstrate the viability of compact and scalable designs for quantifying activity levels and behavior patterns for mice housed within a commercial ventilated cage rack. The SCORHE in-rack design provides day- and night-time monitoring with the consistency and convenience of the home-cage environment. The dual-video camera custom hardware design makes efficient use of space, does not require home-cage modification, and is animal-facility user-friendly. Given the system’s low cost and suitability for use in existing vivariums without modification to the animal husbandry procedures or housing setup, SCORHE opens up the potential for the wider use of automated video monitoring in animal facilities. SCORHE’s potential uses include day-to-day health monitoring, as well as advanced behavioral screening and ethology experiments, ranging from the assessment of the short- and long-term effects of experimental cancer treatments to the evaluation of mouse models. When used for phenotyping and animal model studies, SCORHE aims to eliminate the concerns often associated with many mouse-monitoring methods, such as circadian rhythm disruption, acclimation periods, lack of night-time measurements, and short monitoring periods. Custom software integrates two video streams to extract several mouse activity and behavior measures. Studies comparing the activity levels of ABCB5 knockout and HMGN1 overexpresser mice with their respective C57BL parental strains demonstrate SCORHE’s efficacy in characterizing the activity profiles for singly- and doubly-housed mice. Another study was conducted to demonstrate the ability of SCORHE to detect a change in activity resulting from administering a sedative.
Video monitoring; Home-cage behavior; Mouse behavior; Mouse activity profiling
A new bioresorbable polylactide/calcium phosphate composite with improved mechanical strengths and a more basic filler, tetracalcium phosphate (TTCP), was prepared by melt compounding. N-(2-aminoethyl)-3-aminoproplytrimethoxysilane (AEAPS) and pyromellitic dianhydride (PMDA) were used to improve the interfacial adhesion between TTCP and polylactide (PLA). While AEAPS improved the dispersion of TTCP in the matrix, PMDA might react with the terminal hydroxyl group of PLA and the amino group on the surface of AEAPS modified TTCP, which could further enhance the interfacial strength. The tensile strength was improved to 68.4 MPa for the PLA/TTCP-AEAPS composite from 51.5 MPa for the PLA/TTCP composite (20 wt% of TTCP). Dynamic mechanical analysis suggested that there was a 51 % improvement in storage modulus compared to that of PLA alone, when PMDA (0.2 wt% of PMDA) was incorporated into the PLA/TTCP-AEAPS composite (5 wt% of TTCP). Using this new bioresorbable PLA composite incorporated with a more basic filler for biomedical application, the inflammation and allergic effect resulted from the degraded acidic product are expected to be reduced.
polylactide; tetracalcium phosphate; mechanical properties; composite
Previous research has identified exercise identity and social physique anxiety as two independent factors that are associated with exercise dependence.
The purpose of our study was to investigate the unique and interactive effect of these two known correlates of exercise dependence in a sample of 1,766 female runners.
Regression analyses tested the main effects of exercise identity and social physique anxiety on exercise dependence. An interaction term was calculated to examine the potential moderating effect of social physique anxiety on the exercise identity and exercise dependence relationship.
Results indicate a main effect for exercise identity and social physique anxiety on exercise dependence; and the interaction of these factors explained exercise dependence scores beyond the independent effects. Thus, social physique anxiety acted as a moderator in the exercise identity and exercise dependence relationship.
Our results indicate that individuals who strongly identify themselves as an exerciser and also endorse a high degree of social physique anxiety may be at risk for developing exercise dependence.
Our study supports previous research which has examined factors that may contribute to the development of exercise dependence and also suggests a previously unknown moderating relationship for social physique anxiety on exercise dependence.
exercise dependence; exercise identity; social physique anxiety; eating disorders
The goal of this study was to examine associations between dimensions of emotion dysregulation and eating disorder (ED) symptoms in bulimia nervosa (BN). This investigation used baseline data from a BN treatment study that included 80 adults (90% women) with full or subthreshold BN. Participants completed the Difficulties in Emotion Regulation Scale (DERS) and the Eating Disorders Examination (EDE) interview. The EDE global score was significantly correlated with the DERS total score, as well as several DERS subscales: Nonacceptance, Impulse, and Strategies. Further, the DERS Goals subscale was found to be uniquely associated with frequency of purging and driven exercise, although none of the subscales were associated with frequency of objective binge eating. Findings indicate that emotion dysregulation is associated with ED symptoms in BN, suggesting the utility of interventions that address emotion regulation skills deficits in the treatment of the disorder.
emotion regulation; affect regulation; emotion; bulimia nervosa
Growing evidence indicates that both positive and negative emotion potentially influence the development and maintenance of anorexia nervosa, through both positive and negative reinforcement of weight loss activities. Such reactive emotional experience may be characterized by frequent and intense fluctuations in emotion, a construct known as “emotional instability.” The purpose of this study was to investigate the association between positive emotional instability and weight loss activities in anorexia nervosa, and to investigate the synergistic effects of positive and negative emotional instability on promoting weight loss activities. Using ecological momentary assessment methods, 118 participants with anorexia nervosa reported their emotional experiences and behaviors at least six times daily over 2 weeks using a portable digital device. Using generalized linear modeling, results indicated that high levels of both positive and negative emotional instability, and the interaction between the two, were associated with more frequent weight-loss activities, beyond anorexia subtype and mean levels of emotional intensity. These findings indicate that when women with anorexia exhibit both high levels of both positive and negative emotional instability they are more prone to a variety of weight loss activities. The importance of addressing the role of both positive and negative emotion in anorexia treatment is discussed.
anorexia nervosa; positive emotion; emotional instability; purging; weighing
Three new species of Koonunga were discovered in surface and subterranean waters in southern Australia, and were defined using mtDNA analyses and morphology. The new species are: Koonunga hornei Leijs & King; K. tatiaraensis Leijs & King and K. allambiensis Leijs & King. Molecular clock analyses indicate that the divergence times of the species are older than the landscape that they currently inhabit. Different scenarios explaining this apparent discrepancy are discussed in the context of the palaeography of the area. A freshwater epigean origin for Koonunga is considered the most likely hypothesis, whereby some lineages made the transition to the subterranean environment within the last few million years influenced by significant climatic cooling/drying. We discuss the possibility that one stygobitic lineage secondarily regained some of its body pigmentation as adaptation to increased photic conditions after cave collapse and forming of cenotes during the last glacial maximum.
Protein restriction (PR) is important for the benefits of dietary restriction on longevity and stress resistance, but relevant nutrient sensors and downstream effectors in mammals remain poorly defined. We used PR-mediated protection from hepatic ischemia reperfusion injury to probe genetic requirements for evolutionarily conserved nutrient sensors GCN2 and mTORC1 in stress resistance. One week of PR reduced free amino acids and circulating growth factors, activating GCN2 and mTORC1 repressor TSC complex. However, while GCN2 was dispensable for PR-induced protection, hepatic TSC1 was required. PR improved hepatic insulin sensitivity in a TSC1-dependent manner prior to ischemia, facilitating increased pro-survival signaling and reduced apoptosis after reperfusion. These benefits were partially abrogated by pharmacological PI3K inhibition or genetic deletion of the insulin receptor in hepatocytes. In conclusion, improved insulin sensitivity upon short-term PR required TSC1, facilitated increased pro-survival signaling after injury, and contributed partially to PR-mediated resistance to clinically relevant ischemia reperfusion injury.
Although there are several recent reviews of the pre-operative factors that influence treatment outcome for bariatric surgery, commensurate efforts to identify and review the predictive validity of post-operative variables are lacking. This review describes the post-operative psychosocial predictors of weight loss in bariatric surgery. Results suggest empirical support for post-operative binge eating, uncontrolled eating/grazing, and presence of a depressive disorder as negative predictors of weight loss outcomes; whereas, adherence to dietary and physical activity guidelines emerged as positive predictors of weight loss. With the exception of depression, psychological comorbidities were not consistently associated with weight loss outcomes. Results highlight the need for post-operative assessment of disordered eating and depressive disorder, further research on the predictive value of post-operative psychosocial factors, and development of targeted interventions.
bariatric surgery; post-operative; psychopathology; psychosocial; weight loss