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Objectives: Gut microbiota has been widely reported to be involved in systemic inflammation through microbial translocation and T cell activation in several diseases. In this work we aimed to investigate bacterial infiltration and epithelial impairment in the gut of patients with IBD-associated SpA (SpA-IBD), as well as the relationship of microbial translocation with immune system activation and their putative role in the pathogenesis of joint inflammation in IBD patients., Methods: Tight-junction proteins (TJPs) occludin and claudin-1/-4 and bacteria were assessed by real-time PCR analysis and immunohistochemical staining of the ileum. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPS), soluble CD14 (sCD14), sclerostin and anti-sclerostin antibodies (anti-sclerostin-IgG) were assayed with ELISAs and peripheral mononuclear blood cells with flow cytometry. LPS and sCD14 were used in vitro to stimulate a human osteoblast cell line., Results: Compared with IBD, ileal samples from SpA-IBD patients showed bacterial infiltration, epithelial damage and downregulation of TJPs. In sera, they showed higher serum levels of I-FABP, LPS, sCD14 (the latter correlating with sclerostin and anti-sclerostin-IgG) and higher CD80+/CD163+ and lower CD14+ mononuclear cells. In vitro experiments demonstrated that only the LPS and sCD14 synergic action downregulates sclerostin expression in osteoblast cells., Conclusion: SpA-IBD patients are characterized by gut epithelium impairment with consequent translocation of microbial products into the bloodstream, immune system activation and an increase of specific soluble biomarkers. These findings suggest that gut dysbiosis could be involved in the pathogenesis of SpA-IBD and it could hopefully prompt the use of these biomarkers in the follow-up and management of IBD patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In July 2018, the Arkansas Department of Health (ADH) was notified by hospital A of 3 patients with bloodstream infections (BSIs) with a rapidly growing nontuberculous Mycobacterium (NTM) species; on 5 September 2018, 6 additional BSIs were reported. All were among oncology patients at clinic A. We investigated to identify sources and to prevent further infections., Methods: ADH performed an onsite investigation at clinic A on 7 September 2018 and reviewed patient charts, obtained environmental samples, and cultured isolates. The isolates were sequenced (whole genome, 16S, rpoB) by the Centers for Disease Control and Prevention to determine species identity and relatedness., Results: By 31 December 2018, 52 of 151 (34%) oncology patients with chemotherapy ports accessed at clinic A during 22 March-12 September 2018 had NTM BSIs. Infected patients received significantly more saline flushes than uninfected patients (P < .001) during the risk period. NTM grew from 6 unused saline flushes compounded by clinic A. The identified species was novel and designated Mycobacterium FVL 201832. Isolates from patients and saline flushes were highly related by whole-genome sequencing, indicating a common source. Clinic A changed to prefilled saline flushes on 12 September as recommended., Conclusions: Mycobacterium FVL 201832 caused BSIs in oncology clinic patients. Laboratory data allowed investigators to rapidly link infections to contaminated saline flushes; cooperation between multiple institutions resulted in timely outbreak resolution. New state policies being considered because of this outbreak include adding extrapulmonary NTM to ADH's reportable disease list and providing more oversight to outpatient oncology clinics., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Although oxytocin administration influences behavior, its effects on peripheral oxytocin concentrations are mixed and derived from studies on healthy subjects. Additionally, trauma attenuates the behavioral effects of oxytocin, but it is unknown whether it also influences its effect on peripheral circulation. This study examined whether salivary oxytocin increased after oxytocin administration and whether trauma attenuated this effect. We conducted a randomized, double-blind, placebo-controlled, within-subjects study in 100 male adolescents living in residential youth care facilities. Participants self-administered intranasally 24 IU of oxytocin and placebo (one week later) and provided a saliva sample before and 15 min after administration. Salivary oxytocin increased significantly after oxytocin administration, but this effect might be inflated by exogenous oxytocin reaching the throat. Trauma did not moderate this effect. Our findings suggest that trauma did not attenuate the effect of oxytocin administration on salivary oxytocin, but more robust methodologies are recommended to draw more solid conclusions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Although dissociative symptoms are observed in several psychiatric disorders and linked to antisocial behavior and offending, the relation between dissociation and psychopathology or comorbidity has not been consistently investigated in residential youth yet. This brief report documented prevalence and comorbidity rates of several psychiatric disorders and examined their relation to dissociation in residential youth. The study included 100 male adolescents ( M age = 16.51) admitted to residential youth care facilities. Psychopathology was assessed with the Mini International Neuropsychiatric Interview for children and adolescents (MINI-KID) and dissociation was measured with the Adolescent Dissociative Experiences Scale (A-DES). Externalizing problems (conduct disorder, oppositional defiant disorder, attention deficit hyperactivity disorder) were the most prevalent (81%) followed by substance abuse/dependence (71%), manic/hypomanic symptoms (40%), anxiety (35%), and depression (33%). High comorbidity was also observed in externalizing problems with alcohol/substance abuse/dependence (67%), manic/hypomanic symptoms (35%), depression (31%), and anxiety (30%). Logistic regression analyses revealed a significant link between dissociation and externalizing problems, depression, and manic/hypomanic symptoms, as well as comorbid externalizing problems and depression or manic/hypomanic symptoms. The findings highlight the need to assess dissociation in order to better understand the multifaceted individual profile of residential youth and incorporate it in the treatment plan.

Neurobiological models propose reactive aggression as a failure in emotion regulation, caused by an imbalance between prefrontal cortical control and excessive bottom-up signals of negative affect by limbic regions, including the amygdala. Therefore, we hypothesize a negative correlation between PFC and amygdala activity (pre/post resting-state scans) in violent offenders. In this study resting-state fMRI was administered before and after an emotion (anger and happiness) provocation or engagement task within 18 male violent offenders scoring high on reactive aggression, and 18 male non-offender controls. Research in emotional pre/post resting-state showed altered connectivity by task performance. Therefore, bilateral amygdala region of interest (ROI) whole brain functional connectivity analysis tested dynamic change differences between pre and post resting-state connectivity between groups. Self-reported anger showed a positive significant relationship with medial prefrontal cortex activity in the pre-task scan and significantly increased during the emotion task in both the violent and control group. Imaging results showed a significant decrease in amygdala - medial prefrontal functional connectivity in the violent offenders and an increase in the non-offender controls after the emotion task. The opposite pattern was found for amygdala connectivity with the (para) limbic regions: violent offenders showed increased connectivity and non-offender controls showed decreased connectivity. The present results indicate that reactive aggression might stem from a focus on emotion processing, as indicated by an increase in limbic functional connectivity. The combination of a focus on emotion, along with a lack of medial prefrontal cortex regulation, has the potential to grow out of control e.g. in reactive aggression.

Previous research has revealed a positive effect of oxytocin administration on several social behaviors especially in individuals with social-affective deficits. However, it is still unknown whether intranasal oxytocin administration (OT-IN) can be beneficial to residential youth who exhibit severe social-affective impairments. We conducted a randomized, double-blind, placebo-controlled, within-subjects, sequential study to examine the effect of OT-IN on empathy and emotion recognition in 100 male adolescents living in residential youth care facilities. We also explored the moderating role of callous-unemotional traits, trauma, and dissociation in the oxytocin effect. Participants self-administered one dose of 24 IU of oxytocin or placebo and performed experimental tasks on empathy and emotion recognition before and after the administration. The same procedure was performed one week later with the other substance. We found that empathy was increased after oxytocin administration compared to placebo and this effect was specific to individuals with high callous-unemotional traits. There was no effect of OT-IN on the overall emotion recognition, but there was a positive effect on accuracy of fear recognition. Trauma and dissociation did not moderate the oxytocin effect on empathy or emotion recognition. Our findings provided evidence of a beneficial effect of OT-IN on empathy and fear recognition in residential youth. We propose that a combination of OT-IN and psychological interventions merits further exploration, as it might be a novel promising direction for more tailored approaches and better treatment outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inconsistent findings have been found on the relation between oxytocin levels and psychopathy or callous-unemotional (CU) traits in humans, potentially because the role of trauma in oxytocin secretion and the distinction between primary and secondary psychopathy have been overlooked so far. Primary psychopathy has a stronger biological background, whereas secondary psychopathy mainly develops due to environmental adversity, such as childhood trauma. This study investigated the interaction effects of CU traits and childhood trauma on daily salivary oxytocin levels in 57 males living in residential youth care facilities. Participants provided six saliva samples (morning, afternoon, and evening for two consecutive days) and completed self-report questionnaires on CU traits and childhood trauma. A mean daily oxytocin and an oxytocin pattern across the day were examined. A significant interaction between CU traits and one trauma category (emotional neglect) on mean daily oxytocin was observed, demonstrating that subjects with high CU traits and low levels of emotional neglect (primary psychopathy) exhibited lower daily oxytocin secretion compared to subjects with high CU traits and high levels of emotional neglect (secondary psychopathy). There were no significant interactions with the other trauma types or in daily oxytocin patterns. Our findings provided a first insight into the potentially distinct oxytocin concentrations in primary and secondary psychopathy, suggesting that primary psychopathy might be linked to lower daily oxytocin output. Future longitudinal studies are required to unravel the developmental patterns of oxytocin secretion and determine whether lower oxytocin output might be a biomarker of primary psychopathy., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although the oxytocin receptor gene (OXTR) is involved in aggression and social affiliation, it has not been examined in gene-environment interaction studies. This longitudinal study examined the effect of genetic variants in OXTR and its gene-environment interaction with perceived deviant peer affiliation in the trajectories of antisocial behavior in 323 adolescents (182 males) from 13 to 18 years. Annual assessments of reactive and proactive aggression, delinquency, and friends' delinquency, as well as DNA at age 17 were collected. Gene-based tests yielded no main effect of OXTR, but revealed a significant gene-environment interaction in proactive aggression and delinquency. Variation in the OXTR might affect the influence of deviant peer affiliation on antisocial behavior, contributing to a better understanding of individual differences in antisocial behavior.

Callous-unemotional (CU) traits are thought to characterize children exhibiting persistent and severe conduct problems (CPs). Reward and punishment sensitivity have often been investigated, yet executive function problems have mostly been studied in adults. Moreover, the level of co-occurring CPs is important to take into account. Therefore, the current study investigated differences in reward responsivity, punishment sensitivity, and executive functioning (EF) between four subgroups of general community boys ( N = 346, M age = 14.01 years, SD = 1.19): high CU/high CP, low CU/high CP, high CU/low CP, and low CU/low CP. Boys with high CU/high CP showed significantly more EF problems, but similar reward and punishment sensitivity as low CU/high CP boys. Boys with high CU/low CP did not differ from low CU/low CP boys. Severity of executive function problems appears to distinguish boys who show a combination of CU-traits and CPs from boys with CPs alone.

Although numerous studies have examined the neuroendocrinology of aggression, the findings are mixed and focused on cortisol and testosterone. We argue that past findings remain inconclusive partly because the key roles of oxytocin and trauma have not been systematically integrated yet. Oxytocin is associated with social behavior and interacts with cortisol and testosterone, whereas trauma is a crucial risk factor of aggression that strongly affects hormonal activity. In this review, we investigate the role of trauma in the hormonal interplay of cortisol, testosterone, and oxytocin in aggression during adolescence. We first discuss how these hormones interact with each other and how trauma influences these interactions and then we propose a model that highlights the role of trauma in the hormonal interplay in aggression. We suggest that the timing of trauma has a distinct effect on hormonal activity and it should be integrated into any comprehensive model. Current trauma is linked to different levels of oxytocin, cortisol, testosterone, and testosterone/cortisol ratio than childhood trauma, but this distinction is also influenced by gender and type of aggression. We conclude that in order to better understand the neuroendocrinology of aggression, it is crucial to incorporate the investigation of oxytocin and trauma in future research., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aggression and callous-unemotional (CU) traits are common problems in incarcerated delinquent youth. The present study was conducted to examine whether living group climate was associated with aggression and CU traits in late adolescent male offenders ( N = 156) in a German youth prison. A structural equation model was fitted to the data and showed associations between repression and reactive aggression and CU traits, but no associations between an open and supportive living group climate and aggression and CU traits. Previous research in Dutch youth prisons did not find a relation between repression and aggression, buta relation between a positive living group climate and less aggression. These different findings may reflect differences in the German and Dutch prison system. Implications for practice are discussed.

Anger and anger regulation problems that result in aggressive behaviour pose a serious problem for society. In this study we investigated differences in brain responses during anger provocation or anger engagement, as well as anger regulation or distraction from anger, and compared 16 male violent offenders to 18 non-offender controls. During an fMRI adapted provocation and regulation task participants were presented with angry, happy and neutral scenarios. Prior research on violent offenders indicates that a combination of increased limbic activity (involved in emotion), along with decreased prefrontal activity (involved in emotion regulation), is associated with reactive aggression. We found increased ventrolateral prefrontal activity during anger engagement in violent offenders, while decreased dorsolateral and ventrolateral prefrontal activity was found during anger distraction. This activity pattern was specific for anger. We found no exclusive pattern for happiness. In violent offenders, this suggests an increased need to regulate specifically during anger engagement and regulation difficulties when explicitly instructed to distract. The constant effort required for violent offenders to regulate anger might exhaust the necessary cognitive resources, resulting in a risk for self-control failure. Consequently, continuous provocation might ultimately contribute to reactive aggression.

Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a PIK3CA mutant human breast cancer cell. We identified 5 genes ( PIM2, ZAK, TACC1, ZFR, ZNF565 ) whose suppression induced cell death upon PI3K inhibition. We showed that small molecule inhibitors of the PIM2 and ZAK kinases synergize with PI3K inhibition. In addition, using a microscale implementable device to deliver either siRNAs or small molecule inhibitors in vivo, we showed that suppressing these 5 genes with PI3K inhibition induced tumor regression. These observations identify targets whose inhibition synergizes with PI3K inhibitors and nominate potential combination therapies involving PI3K inhibition.

The current study investigated the relationship between psychopathy and two concepts that hold a central position in conceptualizations of this disorder, being guilt and dominance. Both constructs were measured using explicit measures (i.e., self-report), as well as indirect assessment (i.e., the Single Category Implicit Association Test; Sc-IAT). Our sample consisted of 43 psychopathic offenders, 42 nonpsychopathic offenders, and 26 nonoffender controls. Although no overall group differences emerged, the lifestyle/antisocial traits of psychopathy (Factor 2) predicted reduced self-reported guilt on a dimensional level. As hypothesized, such a relationship was absent for the interpersonal/affective dimension of psychopathy (Factor 1). Psychopathy was unrelated to implicit self-guilt associations. Regarding dominance, psychopathy was not significantly associated with indirectly or explicitly assessed dominance. These findings are interpreted in the light of empirical knowledge on moral emotions, insight and response distortion in highly antisocial offenders., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study examined relationships between the self-conscious emotions of guilt and shame in both clinical ( N  = 104) and non-clinical ( N  = 477) (young) adolescents aged 11-18 years, who completed a questionnaire to assess perceived parental rearing behaviors (EMBU-C) and a scenario-based instrument to measure proneness to guilt and shame (SCEMAS). Results indicated that parental rearing dimensions were positively related to self-conscious emotions. Regarding the non-clinical sample, both favourable (emotional warmth) and unfavourable (rejection) paternal and maternal rearing dimensions were significant correlates of guilt- and shame-proneness. The results for the clinical sample were less conclusive: only maternal emotional warmth and rejection were found to be significantly associated with guilt and shame. Interestingly, no associations between any of the paternal rearing dimensions and self-conscious emotions emerged. Taken together, these results are in keeping with the notion that parental rearing factors are involved in the development of both adaptive and maladaptive self-conscious emotions in adolescents.

Morality deficits have been linked to callous-unemotional traits and externalizing problems in response to moral dilemmas, but these associations are still obscure in response to antisocial acts in adolescence. Limited evidence on young boys suggested that callous-unemotional traits and externalizing problems were associated with affective but not cognitive morality judgments. The present study investigated these associations in a community sample of 277 adolescents (M age  = 15.35, 64 % females). Adolescents with high callous-unemotional traits showed deficits in affective but not cognitive morality, indicating that they can identify the appropriate moral emotions in others, but experience deviant moral emotions when imagining themselves committing antisocial acts. Externalizing problems and male gender were also strongly related to deficits in affective morality, but they had smaller associations with deficits in cognitive morality too. Implications for treatment and the justice system are discussed.

Objective: The current study assessed the feasibility and effectiveness of a full-body-driven intervention videogame targeted at decreasing attention deficit hyperactivity disorder (ADHD) symptoms, specifically inattention, hyperactivity, impulsivity, and motor deficiency., Materials and Methods: The game was tested in a Dutch sample (N = 73) of school-aged children with elevated ADHD symptoms. Children assigned to the intervention condition played "Adventurous Dreaming Highflying Dragon," and those in the control condition played a comparable full-body-driven game without ADHD-focused training components. Games were played during six 15-minute sessions. Outcomes were teacher-rated ADHD symptoms and scores on neuropsychological tasks assessing motor skills, impulsivity, and sustained attention., Results: There was some indication of greater improvement in the intervention group in comparison to the control group in terms of teacher-rated ADHD symptoms. Both groups showed equal indication of improvement in fine motor skills, but no change was found in gross motor skills. Additionally, both groups showed a deterioration in number of hits (assessing sustained attention) on the go/no-go task. Last, the intervention group showed a greater increase in false alarms (assessing impulsivity) than the control group., Conclusion: Dragon seems promising as a game-based intervention for children with ADHD. Children who played Dragon improved in several areas with only a short amount of gameplay (1.5 hours in total), and their satisfaction with the game was high. For future research, it is recommended to further inspect Dragon's influence on impulsivity and gross motor skills. Furthermore, it is recommended to disentangle, examine, and evaluate specific properties of videogames that might lead to positive behavioral change.

Medulloblastoma is the most common childhood malignant brain tumor. The most lethal medulloblastoma subtype exhibits a high expression of the GABAA receptor α5 subunit gene and MYC amplification. New benzodiazepines have been synthesized to function as α5-GABAA receptor ligands. To compare their efficacy with that of standard-of-care treatments, we have employed a newly developed microscale implantable device that allows for high-throughput localized intratumor drug delivery and efficacy testing. Microdoses of each drug were delivered into small distinct regions of tumors, as confirmed by tissue mass spectrometry, and the local drug effect was determined by immunohistochemistry. We have identified a benzodiazepine derivative, KRM-II-08, as a new potent inhibitor in several α5-GABAA receptor expressing tumor models. This is the first instance of in vivo testing of several benzodiazepine derivatives and standard chemotherapeutic drugs within the same tumor. Obtaining high-throughput drug efficacy data within a native tumor microenvironment as detailed herein, prior to pharmacological optimization for bioavailability or safety and without systemic exposure or toxicity, may allow for rapid prioritization of drug candidates for further pharmacological optimization., Competing Interests: of Potential Conflicts of Interest None of the authors have any conflicts of interests to declare, except for Nathalie Agar who is a scientific advisor to BayesianDx and to inviCRO.

This study investigated whether executive dysfunction and impulsivity are both predictors of reactive aggression and is the first to use behavioral assessment of aggression in response to provocation by means of a personalized boxing body opponent bag giving harassing feedback. Aggressive behavior, self-reported aggression, executive functioning (ie, working memory, flexibility, and divided attention), and impulsivity dimensions (i.e., Sensation Seeking, Impulsive Decision Making, and [inadequate] Response Inhibition) were measured in 44 incarcerated psychiatric patients. Results show that both executive functioning (working memory) and impulsivity (Impulsive Decision Making) predicted self-reported reactive aggression, whereas Response Inhibition was the only predictor for reactive aggressive behavioral responses. The study suggests that Response Inhibition is a stronger predictor of reactive aggressive behavior than executive capacities of working memory, flexibility, and divided attention. Therefore, future research should investigate whether (inadequate) Response Inhibition could also be a valuable predictor for violent recidivism.

This study tested the predictive value of attentional bias, emotion recognition, automatic associations, and response inhibition, in the assessment of in-clinic violent incidents. Sixty-nine male forensic patients participated and completed an Emotional Stroop to measure attentional bias for threat and aggression, a Single Target - Implicit Association Task to assess automatic associations, a Graded Emotional Recognition Task to measure emotion recognition, and an Affective Go/NoGo to measure response inhibition. Violent incidents were derived from patient files and scored on severity level. The predictive value of level of psychopathy was tested with the Psychopathy Checklist - Revised (PCL-R). Generalized linear mixed model analyses showed that increased attention towards threat and aggression, difficulty recognizing sad faces and factor 2 of the PCL-R predicted the sum of violent incidents. Specifically, verbal aggression was predicted by increased attention towards threat and aggression, difficulty to recognize sad and happy faces, and PCL-R factor 2; physical aggression by decreased response inhibition, higher PCL-R factor 2 and lower PCL-R factor 1 scores; and aggression against property by difficulty recognizing angry faces. Findings indicate that cognitive tasks could be valuable in predicting aggression, thereby extending current knowledge on dynamic factors predicting aggressive behavior in forensic patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The current study investigated whether a multidimensional model could underlie impulsivity and its associations with various disorders in a forensic sample. Data were available from self-report and behavioral impulsivity instruments of 87 forensic patients. Principal component analysis (PCA) was used to derive a dimensional impulsivity model, and the relationship between and possible predictive validity of impulsivity dimensions for psychopathology was investigated using product moment correlations and regression analysis. A 3-dimensional model of impulsivity was derived, with factors labeled impulsive decision making, sensation seeking, and response inhibition. Impulsive decision making was a predictor for a history of drug dependence, the impulsive lifestyle facet of psychopathy, and antisocial personality disorder. Sensation seeking was not related to any psychopathology. Inadequate response inhibition was a predictor for drug dependence, psychopathy, and antisocial personality disorder. Given the importance of the concept of impulsivity with regard to forensic risk assessment, the current results replicated earlier impulsivity models and imply that impulsivity is a crucial target for diagnosis and interventions and underlines the importance to consider impulsivity as a multidimensional construct.

The life span of persons with HIV has been greatly extended over the past 30 years due to novel therapies. In the developed world and urban settings, this results in a lifespan rivaling the lifespan of a person without HIV. A retrospective study was conducted on 459 patients of an urban, academic medical center who died between 2005 and 2013 in a medium-sized US city. Using the established Cause of Death Project (CoDe) protocol, we measured multiple factors including comorbidities, risk behaviours, contributing and underlying causes of death. This study is one of the few US-based studies using this validated protocol. Among the deaths, 25.9% were sudden and 15.2% were unexpected. Almost one-fifth were related to AIDS-related infections; 47.5% related to non-AIDS causes; with the remainder unknown. Statistically significant increases in CD4 counts and decreasing viral loads were observed over the study period. There were no statistically significant differences observed by HIV risk behaviour, race, gender, age at death, or on antiretrovirals at death. In support of the existing literature, improved HIV management appears to reduce the AIDS-related attributable death among patients observed in this study., (© The Author(s) 2015.)

There is a strong link between personality disorders (PDs) and aggression. This is reflected in high prevalence rates of PD diagnoses in forensic samples, and in several diagnostic criteria of PDs directly referring to elevated levels of aggression. Aggression can stem from two distinct types of motivation; reactive or impulsive aggression that serves as a defensive reaction to provocation, and proactive or premeditated aggression used to gain extrinsic benefits. Although some clinical conditions like antisocial, borderline, and narcissistic PDs or PD traits, have been empirically linked to reactive and/or proactive aggression, the current study pioneers assessing the relationship between reactive and proactive aggression and traits of all 10 PDs. A mixed sample of patient and non-patient (N=238) participants were administered with the SCID II to assess the level of PD traits; they also completed the Reactive Proactive Questionnaire to determine levels of reactive and proactive aggression. Results showed that paranoid PD traits were positively related to reactive aggression, whereas proactive aggression was uniquely related to antisocial PD traits. This highlights the importance of differentiating between distinct motivations for aggression in PD samples., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to identify implicit cognitive predictors of aggressive behavior. Specifically, the predictive value of an attentional bias for aggressive stimuli and automatic association of the self and aggression was examined for reactive and proactive aggressive behavior in a non-clinical sample (N = 90). An Emotional Stroop Task was used to measure an attentional bias. With an idiographic Single-Target Implicit Association Test, automatic associations were assessed between words referring to the self (e.g., the participants' name) and words referring to aggression (e.g., fighting). The Taylor Aggression Paradigm (TAP) was used to measure reactive and proactive aggressive behavior. Furthermore, self-reported aggressiveness was assessed with the Reactive Proactive Aggression Questionnaire (RPQ). Results showed that heightened attentional interference for aggressive words significantly predicted more reactive aggression, while lower attentional bias towards aggressive words predicted higher levels of proactive aggression. A stronger self-aggression association resulted in more proactive aggression, but not reactive aggression. Self-reports on aggression did not additionally predict behavioral aggression. This implies that the cognitive tests employed in our study have the potential to discriminate between reactive and proactive aggression. Aggr. Behav. 41:51-64 2015. © 2014 Wiley Periodicals, Inc., (© 2014 Wiley Periodicals, Inc.)

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.

The present research expands our understanding of cognitive and affective morality by exploring associations with callous-unemotional (CU) traits and externalizing symptoms. Participants were 46 8- to 12-year-old boys from the community who completed the Affective Morality Index, the Youth Self-Report, and the Inventory of Callous-Unemotional Traits. A pattern of results was found indicating that in particular the combination of high CU traits and high externalizing symptoms was associated with lack of affective morality, and an increased perceived likelihood of recommitting antisocial acts (recidivism). The implications of these findings and suggestions for future research are discussed.

Unlabelled: Previous research revealed hypothalamic-pituitary-adrenal (HPA) axis abnormalities in relation to antisocial and aggressive behavior. Some evidence suggests that low cortisol levels may serve as a biological marker for a severe antisocial subgroup with pronounced callous-unemotional (CU) traits. Children displaying the combination of severe antisocial behavior and CU traits appear to be particularly at risk of developing adult psychopathy. Given the lack of studies on the relationship between cortisol levels and CU traits in antisocial adolescents, the current study investigates whether cortisol levels are uniquely associated with CU traits as compared to other psychopathy dimensions (i.e., narcissism and impulsivity). Detained antisocial adolescents (n=63) and a community comparison group (n=62) completed diaries and collected three saliva samples daily on two days, with compliance monitored electronically. Psychopathy dimensions were assessed through self-report questionnaires. Externalizing symptoms were assessed by structured clinical interview. Multilevel regression analyses indicated no differences in cortisol levels or diurnal slopes between the two groups. Overall, cortisol levels were not significantly related to psychopathy dimensions. However, greater impulsivity was associated with lower cortisol levels in the community sample, but not in the antisocial group., Conclusion: Results cast doubt on the notion of low cortisol levels as a biological marker for CU traits. Low basal cortisol levels appear to be more closely related to a general deficit in behavioral regulation. Implications for future research are discussed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This study reports reliability and validity of the Dutch Reactive-Proactive Aggression Questionnaire (RPQ). In total, 845 participants completed the RPQ along with other measures of aggression. Groups consisted of non-offender participants, criminal offenders, youngsters (age 6-18), and adults (age above 18). Test-retest stability in a subsample of 324 childhood arrestees was good (all ICC's > 0.41). A confirmatory factor analysis supported the same two-factor structure as in the original RPQ. Convergent validity was adequate (all r's > 0.16). Moreover, results demonstrated that the proactive and reactive subscales were differentially related to measurements of callousness and impulsiveness, respectively. Criterion validity was shown in that non-offender subjects demonstrated significantly lower RPQ scores than offender samples. Finally, construct validity was demonstrated in that violent offenders showed higher aggression scores than non-violent offenders. Proactive aggression showed different developmental trajectories within non-offender versus criminal samples, indicating that this form of aggression may be more pathological., (© 2013 Wiley Periodicals, Inc.)

Risk assessment is considered to be a key element in the prevention of recidivism among juvenile sex offenders (JSOs), often by imposing long-term consequences based on that assessment. The authors reviewed the literature on the predictive accuracy of six well-known risk assessment instruments used to appraise risk among JSOs: the Juvenile Sex Offender Assessment Protocol-II (J-SOAP-II), Juvenile Sexual Offence Recidivism Risk Assessment Tool-II (J-SORRAT-II), Estimate of Risk of Adolescent Sexual Offence Recidivism (ERASOR), Juvenile Risk Assessment Scale (JRAS), Structured Assessment of Violent Risk in Youth (SAVRY), and Hare Psychopathy Checklist:Youth Version (PCL:YV). Through a systematic search, 19 studies were reviewed. Studies showed differences in the predictive accuracies for general, violent, and sexual recidivism, and none of the instruments showed unequivocal positive results in predicting future offending. Not unexpectedly, the accuracy of the SAVRY and PCL:YV appeared to be weaker for sexual recidivism compared with specialized tools such as the J-SOAP-II or the ERASOR. Because of the rapid development of juveniles, it is questionable to impose long-term restrictions based on a risk assessment only. New challenges in improving risk assessment are discussed.

Reactive aggression (RA) refers to angry responses to provocation or frustration, while proactive aggression (PA) denotes nonemotional, instrumental, and unprovoked aggression. The current study examined personality-related and cognitive correlates of both aggressive types. Respectively, the predictive values of antisocial personality disorder (ASPD), and of hostile interpretation bias, which is the tendency to interpret ambiguous stimuli in a hostile manner, were studied. The sample consisted of n = 37 male adult patients with mixed diagnoses and n = 29 male nonpatients that responded to vignettes and pictures of ambiguous situations, using both open and closed answer formats. ASPD was assessed by means of the Structured Clinical Interview for DSM-IV Axis II disorders (SCID-II), and the Reactive Proactive Questionnaire (RPQ) measured RA and PA. Results showed that although both RA and PA types were predicted by ASPD traits, RA was additionally predicted by a hostile interpretation bias. These findings suggest that reducing hostile bias is a promising avenue for clinical treatment of ASPD-patients high in RA.

Research supports the validity of the dimensional approach to psychopathy in both children and adults. The occurrence of severe aggressive and antisocial behavior in combination with callous-unemotional traits (CU traits) designates a group of children that is particularly at risk to develop psychopathy. However, most studies did not investigate the role of the remaining psychopathy dimensions (i.e. narcissism and impulsivity) in comparison. The present text reviews the newest developments in the dimensional study of psychopathy in relation to cognition, behavior and affect in clinical and detained child and adolescent samples. Findings support the role of the callous-unemotional dimension (CU traits) in the development of psychopathy. Additionally, they also underscore the importance of the narcissistic and impulsive dimensions for the understanding of psychopathy in children and adolescents and for the identification of different psychopathy profiles. Understanding differential correlates of the underlying dimensions of psychopathy is an important step in formulating interventions for those most at risk., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Limited treatment options exist for patients who suffer from a painful bladder condition known as interstitial cystitis/bladder pain syndrome (IC/BPS). Whether given systemically (orally) or by short-duration (1 to 2 hours) exposure via intravesical instillation, therapeutic agents have exhibited poor efficacy because their concentrations in the bladder are low. A previous attempt to develop a drug delivery device for use in the bladder was unsuccessful, likely as a result of poor tolerability. A continuous lidocaine-releasing intravesical system (LiRIS) was designed to be retained in the bladder and release therapeutic amounts of the drug into urine over a period of 2 weeks. The device was tested in healthy volunteers and IC/BPS patients and was found to be well tolerated in both subject groups because of its small size and freedom of movement within the bladder. The 16 women with IC/BPS who were enrolled in the study met the National Institute of Diabetes and Digestive and Kidney Diseases criteria for bladder hemorrhages or Hunner's lesions. Subjects received either LiRIS 200 mg or LiRIS 650 mg for 2 weeks. Safety, efficacy, cystoscopic appearance of the bladder, and limited pharmacokinetic data were collected. Both doses were well tolerated, and clinically meaningful reductions were seen in pain, urgency, voiding frequency, and disease questionnaires. Cystoscopic examinations showed improvement on day 14 (day of removal) compared with day 1, including resolution of Hunner's lesions in five of six subjects with baseline lesions. Global response assessment showed an overall responder rate of 64% at day 14 and a sustained overall responder rate of 64% 2 weeks later. Extended follow-up suggests that the reduction in pain was maintained for several months after the device was removed.

Background: Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of tumour progression, including the later stages of invasion and metastasis. Genetic variants in the MMP genes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. We have investigated the association between the -735 C/T, the -1171 5A/6A, and the -1562 C/T polymorphisms in the MMP2, MMP3 and MMP9 genes, respectively, and the risk and survival of lung cancer., Methods: The case-control study includes 879 lung cancer patients and 803 controls from a Caucasian population in Spain (CAPUA study). Genotypes were determined by PCR-RFLP. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. The Kaplan-Meier method, long-rank test and Cox's were used for the survival analysis., Results: The MMP9 -1562 T/T genotype was associated with a statistically significant decreased risk of developing lung cancer (OR = 0.23; 95% CI: 0.06-0.85), whereas no association was found for the MMP2 -735 C/T and MMP3 -1171 5A/6A polymorphisms. The MMP2 -735 T/T genotype was statistically significantly associated with a decreased survival in non-small cell lung cancer (NSCLC) patients, identified as an independent prognosis factor of survival (hazard ratio (HR) = 1.79; 95% CI: 1.00-3.20). In contrast, no association was found between the MMP3 -1171 5A/6A and the MMP9 -1562 C/T polymorphisms and survival., Conclusions: These findings support the hypothesis that the MMP9 -1562 C/T polymorphism is associated with a protective effect against the development of lung cancer and suggest that the MMP2 -735 C/T polymorphism modify the length of survival in NSCLC patients.

Findings on executive functioning in psychopathy are inconsistent. Different associations between psychopathy dimensions and executive functioning might explain contradicting findings. This study examined the role of psychopathy dimensions and types of aggression in response inhibition among 117 male adolescents (53 antisocial delinquents and 64 controls). Participants completed a self-report measure of aggression and a GoNoGo task. Psychopathy dimensions were assessed using the Psychopathy Checklist: Youth Version. Although high scores on the antisocial dimension and reactive aggression were associated with poor response inhibition, the affective-interpersonal dimension, proactive aggression, and verbal intelligence (IQ) were related to better response inhibition (two-factor model). Associations with the affective-interpersonal dimensions did not reach significance. Exploratory analyses showed that affective and antisocial facets accounted for the obtained opposing associations of the affective-interpersonal and antisocial psychopathy dimensions with response inhibition. The interpersonal and lifestyle facets (four-facet model) were unrelated to response inhibition. Results could not be explained by Attention Deficit Hyperactivity Disorder (ADHD). Findings suggest differential associations between the psychopathy dimensions, types of aggression, and response inhibition. Therefore, a dimensional approach to psychopathy and related concepts, such as aggression, might strongly improve diagnostic procedures. Global scores could mask important differential associations., (© 2011 Wiley Periodicals, Inc.)

A new electro-thermally induced structural failure actuator (ETISFA) is introduced as an activation mechanism for on demand controlled drug delivery from a Micro-Electro-Mechanical-System (MEMS). The device architecture is based on a reservoir that is sealed by a silicon nitride membrane. The release mechanism consists of an electrical fuse constructed on the membrane. Activation causes thermal shock of the suspended membrane allowing the drugs inside of the reservoir to diffuse out into the region of interest. The effects of fuse width and thickness were explored by observing the extent to which the membrane was ruptured and the required energy input. Device design and optimization simulations of the opening mechanism are presented, as well as experimental data showing optimal energy consumption per fuse geometry. In vitro release experiments demonstrated repeatable release curves of mannitol-C(14) that precisely follow ideal first order release kinetics. Thermally induced structural failure was demonstrated as a feasible activation mechanism that holds great promise for controlled release in biomedical microdevices.

Adult psychopaths have deficits in emotional processing and inhibitory control, engage in morally inappropriate behavior, and generally fail to distinguish moral from conventional violations. These observations, together with a dominant tradition in the discipline which sees emotional processes as causally necessary for moral judgment, have led to the conclusion that psychopaths lack an understanding of moral rights and wrongs. We test an alternative explanation: psychopaths have normal understanding of right and wrong, but abnormal regulation of morally appropriate behavior. We presented psychopaths with moral dilemmas, contrasting their judgments with age- and sex-matched (i) healthy subjects and (ii) non-psychopathic, delinquents. Subjects in each group judged cases of personal harms (i.e. requiring physical contact) as less permissible than impersonal harms, even though both types of harms led to utilitarian gains. Importantly, however, psychopaths' pattern of judgments on different dilemmas was the same as those of the other subjects. These results force a rejection of the strong hypothesis that emotional processes are causally necessary for judgments of moral dilemmas, suggesting instead that psychopaths understand the distinction between right and wrong, but do not care about such knowledge, or the consequences that ensue from their morally inappropriate behavior.

The current study assesses whether patients and therapists report similar levels of schema modes, one of the central features in Schema-Focused Therapy. Patient's self-report and therapists' report on an abbreviated Schema Mode Inventory were compared in a sample of 92 patients with antisocial, borderline or cluster C personality disorder. Results indicate a markedly stronger self-therapist discrepancy in mode rating in antisocial patients than in borderline and cluster C patients. Compared to their therapists, ASPD-patients report less presence of most maladaptive modes, whereas there was no difference in adaptive modes. These findings underscore the importance for the use of alternative assessment methods of cognitive concepts in antisocial patients.

We introduce the first implantable drug delivery system based on MEMS (Micro-Electro-Mechanical-Systems) technology specifically designed as a platform for treatment in ambulatory emergency care. The device is named IRD(3) (implantable rapid drug delivery device) and allows rapid delivery of drugs. Vasopressin was used as a model drug for in vitro tests as it is a commonly used drug for cardiac resuscitation. Experimental results reveal that the IRD(3) provides an effective method for rapid delivery without significant drug degradation. Several medical uses and delivery modalities for IRD(3) are proposed.

Background: Anger is the main deregulated emotion in patients with antisocial personality disorder (ASPD). The aim of this study was to examine emotional, cognitive and physiological correlates of anger and compare these between ASPD patients with varying degree of psychopathy (PP) and control groups., Method: Assessment of the effect of anger induction on self-reported emotions and schema modes, psychophysiology and implicit reaction-time tasks measuring self-anger and aggressor-swearword associations. Participants (n=147) were patients with DSM-IV antisocial (n=21), borderline (n=45) and cluster C personality disorder (n=46) and non-patient controls (n=35)., Results: Groups did not differ in self-reported anger. ASPD patients displayed a decrease in heart rate and systolic blood pressure (SBP) and stronger implicit self-anger associations. ASPD patients scoring low on affective PP reported less negative emotions and displayed a greater decrease in diastolic blood pressure (DBP)., Conclusions: ASPD patients did not display a deviant self-reported anger but physiological hyporesponsivity and cognitive hyper-responsivity. This ASPD anger response might reflect a controlled predatory-like fight preparation.

Background: Matrix metalloproteases (MMPs) constitute a family of enzymes capable of degrading different components of the extracellular matrix and are implicated in the invasion of tumor cells through the basement membrane. Polymorphisms in MMP genes may result in changes in the expression of MMPs being associated with the development and progression of cancer. We have investigated the association between three polymorphisms (-1607 1G/2G, +17 C/G and -77 A/G) in the human collagenases MMP1, MMP8 and MMP13 and the risk of development or progression of lung cancer., Methods: A hospital-based case-control study was designed including 501 lung cancer patients and 510 controls matched. Genotypes were determined by PCR-RFLP. Results were analyzed using unconditional logistic regression, Cox's proportional hazard regression, and the Kaplan-Meier method., Results: The MMP1 and MMP13 promoter polymorphisms were not associated with lung cancer risk, while the C/G polymorphism in MMP8 was associated with a statistically significant decreased risk of developing lung cancer (ORadj = 0.65; 95%CI = 0.45-0.93). The Kaplan-Meier analysis showed that the polymorphisms in MMP1, MMP8 and MMP13 not seem to modify the overall survival. Multivariate analysis revealed that MMP1, MMP8 and MMP13 polymorphisms are not independent prognostic factors for overall survival., Conclusion: This study suggests that the polymorphism in MMP8 is associated with a decreased lung cancer risk, which can be used as a prognostic marker in lung cancer.

Summary: Polymorphisms in tumor suppressor genes might contribute to the individual susceptibility to develop different types of cancer. Alterations in genes involved in cell cycle regulation and apoptosis, as tumor suppressor gene TP53, can lead to malignant transformations increasing the risk of developing cancer. We have investigated effects of polymorphism Arg72Pro on lung cancer risk, focusing on smoking and histology. Our study is a hospital-based case-control study designed with 589 lung cancer patients mainly with squamous cell carcinoma (215), adenocarcinoma (156) and small cell carcinoma (90), and 582 control subjects, matched in ethnicity, age and gender. Genotypes were determined by PCR-RFLP and the results were analysed using multivariate unconditional logistic regression, adjusted for age, gender and smoking status. The analysis showed a statistically significant increase of lung cancer risk in Pro carriers (Arg/Pro and Pro/Pro) (adjusted OR=1.32; 95% CI=1.03-1.69), especially for ever smokers (adjusted OR=1.34; 95% CI=1.04-1.73), heavy smokers (adjusted OR=1.48; 95% CI=1.01-2.16) and smokers of exclusively black tobacco (adjusted OR=1.45; 95% CI=1.04-2.00). Moreover, Pro carriers present an increased risk of developing small cell lung cancer (adjusted OR=1.70; 95% CI=1.07-2.69) and cancer in stage IV for NSCLC (adjusted OR=1.56; 95% CI=1.07-2.27). Our results suggest that polymorphism Arg72Pro in tumor suppressor gene TP53 increases the risk of lung cancer. The effect is especially strong for small cell lung cancer (SCLC) and heavy smokers.

The current research addresses the psychometric and diagnostic qualities of the Supernormality Scale-Revised (SS-R), a self-report measurement. Supernormality is defined as the tendency to systematically deny the presence of common symptoms (e.g., intrusive thoughts). In study 1, the SS-R was administered to forensic patients (n = 63), psychiatric patients (n = 26), honestly responding students (n = 26), and students instructed to fake supernormality (n = 20). Findings indicated good test-retest stability, and adequate internal consistency. Furthermore, the SS-R showed overall good predictive and convergent validity. Moreover, the diagnostic accuracy was excellent (sensitivity and specificity being 0.80 and 0.92, respectively). In study 2, 115 (healthy) controls and 32 forensic patients completed the SS-R and the Psychopathic Personality Inventory (PPI) (J Pers Assess 1996;66:488), an instrument measuring psychopathy. Results showed again that the SS-R is a reliable and valid instrument. However, supernormality was not related to psychopathy as measured by the PPI.

The relationship between self-reported traumatic childhood experiences, cortisol levels, aggression, and psychopathy was investigated in prison inmates (n=47) and healthy controls (n=27). Besides questionnaires, a brief salivary diurnal profile was measured. Results show that criminals (both psychopaths and non-psychopaths) demonstrate more traumatic childhood experiences than the control group. Within the group of criminals, psychopaths showed the lowest diurnal cortisol concentrations, whereas the non-psychopaths demonstrated highest daily average cortisol (DAC) scores. High levels of aggression were related to traumatic childhood experiences in non-psychopaths and control participants, but not in psychopaths. Although psychopathic offenders demonstrated low levels of cortisol, high levels of childhood traumatic experiences and high levels of aggression, cortisol was not a mediating factor between childhood traumatic experiences and aggression. Implications of the finding that psychopathic offenders displayed lower and non-psychopaths showed higher daily cortisol levels are discussed.

The present study examined how acute dissociation, trait-like dissociative symptoms, and physiological reactivity relate to each other. Sixty-nine undergraduate students were exposed to 14 aversive auditory probes, while their skin conductance responses were measured. A combination of self-reported anxiety and trait-like dissociation was found to predict variability in peritraumatic dissociation levels induced by the aversive probes. Furthermore, high levels of acute dissociation were associated with faster habituation of skin conductance responding, while trait-like dissociation was unrelated to habituation. Interestingly, individuals who reported childhood trauma displayed elevated skin conductance responses. Our findings contribute to the growing body of evidence indicating that subjective feelings of acute dissociation have their objective concomitants, notably fast habituation of physiologic responses.

The current article addresses the psychometric qualities of the German Version of Gudjonsson's Blame Attribution Inventory (GBAI), a self-report scale for measuring attribution of blame for crime. The GBAI was administered to a criminal sample of forensic and criminal inmates (n=107). Findings indicate that the German version of the Gudjonsson Blame Attribution Inventory possesses acceptable test-retest stability and good internal consistency. Factor analysis reproduced the three basic dimensions of the GBAI: external attribution, mental-element attribution, and guilt-feeling attribution. Forensic patients had higher mental-element attribution and guilt-feeling attribution scores than the prison inmates. Interestingly, sexual offenders who were prisoners, showed the lowest guilt-feeling attribution, while sexual offenders who were forensic patients had the highest guilt-feeling attribution scores. Since earlier research reported a tendency of faking good in sexual offenders, we suggest that the forensic sexual offenders may demonstrate a social desirable response tendency in an attempt to gain sympathy and/or earlier parole. All in all, our data show that the German version of the GBAI is a valuable tool for measuring attributional styles of offenders.

Introduction: In the last years exotic snakebite envenomations are increasingly reported. These cases are difficult to manage because of the limited experience of European physicians in the treatment of bites from such venomous snakes; moreover, specific antivenoms are unevenly stocked and they are difficult to find in case of a medical emergency., Observation: A 39-year-old herpetologist was bitten in his right hand by a mexican moccasin (Agkistrodon bilineatus) at the workplace, and presented in the Emergency Department 19 hours later. At admission, clinical evaluation showed local necrosis, swelling involving the entire limb up to the trunk, and severe pain. The specific antidote, not stocked in Italy, was sought abroad; its finding and routeing up to spot delivery required 12 hours. The antivenom, given 32 hours after the bite with no adverse reactions, was only partially effective. The clinical course was characterized by extensive edema with rhabdomyolysis. The necrotic wound at the bite site required after several days surgical debridement, and eventually skin graft. At 3 months follow-up, motor impairment of his right hand fingers with functional disability was still present., Comments: The envenomation by Agkistrodon bilineatus has some clinical aspects in common with that by European viper species, although crotalid venom usually causes more severe manifestations. The antivenom supply from a foreign country may delay its administration. A specific legislation aimed to simplify antidotes importing procedures for professional snake handlers may improve antivenoms availability and allow their timely use, as soon as clinically indicated.

Reduced DNA repair capacity due to inherited polymorphisms may increase the susceptibility to smoking-related cancers. In this report, we investigate the relationship between xeroderma pigmentosum complementary group C poly (AT) insertion/deletion polymorphism (XPC-PAT) of the XPC gene and lung cancer risk in a hospital-based case-control study of 359 newly diagnosed lung cancer patients and 375 control subjects matched on age, sex, and catchment area. The XPC genotype was determined by PCR-RFLP, and the results were analyzed using logistic regression, adjusting for relevant covariates. We found that the frequency of the PAT+/+ genotype was higher in the cases (20.6%) than in the controls (14.1%; P = 0.057) and that the PAT+/+ subjects were at significantly increased risk for lung cancer [adjusted odds ratio (OR), 1.60; 95% confidence interval (95% CI), 1.01-2.55]. Stratified analysis revealed that the risk was higher in former smokers (OR, 2.15; 95% CI, 1.07-4.31) and older people (OR, 2.76; 95% CI, 1.02-7.51), although this probably occurs due to 63.4% of cases older than 73 years being ex-smokers. When stratified by histologic type, the variant genotype was associated with statistically significant increased risk for squamous cell carcinoma (OR, 1.93; 95% CI, 1.06-3.51). In conclusion, our findings support the hypothesis that PAT and intron 11 C/A XPC polymorphisms are linked in the Spanish population and may contribute to the risk of developing lung cancer probably due to a higher frequency of deletion of exon 12 and reduced DNA repair capacity of the XPC protein.