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Allogeneic cell therapy as a means to break immunotolerance to solid tumors is increasingly used for cancer treatment. To investigate cellular alloimmune responses in a human tumor model, primary cultures were established from renal cell carcinoma (RCC) tissues of 56 patients. In three patients with stable RCC line and human leukocyte antigen (HLA)-identical sibling donor available, allogeneic and autologous RCC reactivities were compared using mixed lymphocyte/tumor cell cultures (MLTC). Responding lymphocytes were exclusively CD8+ T cells, whereas CD4+ T cells or natural killer cells were never observed. Sibling MLTC populations showed higher proliferative and cytolytic antitumor responses compared with their autologous counterparts. The allo-MLTC responders originated from the CD8+ CD62L(high)+ peripheral blood subpopulation containing naive precursor and central memory T cells. Limiting dilution cloning failed to establish CTL clones from autologous MLTCs or tumor-infiltrating lymphocytes. In contrast, a broad panel of RCC-reactive CTL clones was expanded from each allogeneic MLTC. These sibling CTL clones either recognized exclusively the original RCC tumor line or cross-reacted with nonmalignant kidney cells of patient origin. A minority of CTL clones also recognized patient-derived hematopoietic cells or other allogeneic tumor targets. The MHC-restricting alleles for RCC-reactive sibling CTL clones included HLA-A2, HLA-A3, HLA-A11, HLA-A24, and HLA-B7. In one sibling donor-RCC pair, strongly proliferative CD3+CD16+CD57+ CTL clones with non-HLA-restricted antitumor reactivity were established. Our results show superior tumor-reactive CD8 responses of matched allogeneic compared with autologous T cells. These data encourage the generation of antitumor T-cell products from HLA-identical siblings and their potential use in adoptive immunotherapy of metastatic RCC patients. (Cancer Res 2006; 66(23): 11447-54)

Supplementary Figure Legends 1-2 from Superior Antitumor In vitro Responses of Allogeneic Matched Sibling Compared with Autologous Patient CD8+ T Cells

Supplementary Figure 2 from Superior Antitumor In vitro Responses of Allogeneic Matched Sibling Compared with Autologous Patient CD8+ T Cells

This chapter examines three criminological perspectives through a gender lens. The first part is dedicated to crime and gender. This chapter presents official data of reported and convicted persons in European countries, discussing crime trends and the different involvement of sexes in certain criminal offences. Further, this chapter points to possible differences in the ethology of crime from a gender perspective at three levels: individual; family, and social. The second section deals with gender and criminal victimization, with special attention dedicated to issues of domestic violence and sexual crimes. The third section of this chapter analyses the penal policy of the courts. Data is presented on sentencing practices in European countries, with an emphasis on certain criminal offences. Besides data on imprisonment, attention is paid to other penal sanctions. This section of the text further explains possible factors related to the different sentencing of women and men. They are divided into two categories: the first is those mainly related to socio-economic characteristics and crime committed; the second is those that reflect courts as gender institutions. Finally, this chapter gives explanations of different treatments of trans offenders in the criminal justice system.

Violence against women lacks geographical boundaries, although research demonstrates higher rates of such violence in rural areas compared to urban areas. The repeated and systematic intimate partner violence (IPV) is especially problematic in isolated areas. This study aims to investigate how repeated and systematic IPV, was handled by the criminal justice system in rural areas in Sweden and how risk and victim vulnerability factors were related to recidivism in this longitudinal prospective study. The sample consisted of alleged perpetrators of repeated and systematic IPV who had been either reported, charged, or convicted of repeated and systematic IPV defined according to the Swedish Law Gross Violation of a Woman’s Integrity targeting such violence, in two rural Swedish police districts during 2011–2014 (N = 258). Results demonstrated that 30% of IPV perpetrators were charged with the Gross violation offense and 5% were charged for other IPV-related offenses. The conviction for the Gross violation offense was 11% and 24% for other IPV-related offenses. 56% were not charged or convicted of any IPV-related offenses. Perpetrators convicted of the Gross Violation offense were more likely to receive longer prison sentences than perpetrators convicted of other IPV-related offenses. Victim cooperation in the police investigation increased the likelihood for prosecution with 7.3 times and for a conviction with 6.1 times. In terms of recidivism 24% engaged in IPV towards the same victim and another 27% recidivated into general criminality. Recidivists had higher summary risk ratings and more individual risk factors than non-recidivists, such as general criminality, employment problems and mental health problems, and victim vulnerability factors including personal problems. To reduce re-victimization, risk and vulnerability factors and supporting victims to cooperate in the police investigation should be considered when forming risk management strategies to protect victims of repeated and systematic IPV in such rural areas.

This study aimed to describe and compare arrested and non-arrested male intimate partner violence (IPV) perpetrators, in terms of individual characteristics and variables related to the IPV incident, in a sample of 628 perpetrators reported to the Swedish police. We also explored recidivism rates in relation to arrest within the total sample, as well as among subtypes of partner violent men (i.e. generally violent [GV] and partner only [PO] violent). The perpetrators in this longitudinal study were reported to the police for male-to-female perpetrated IPV and subjected to a structured violence risk assessment between 2011 and 2014. The results showed that arrested perpetrators were more likely to be reported for severe forms of IPV, being assessed by the police post-arrest with a higher risk for recidivism, and being more likely to be prosecuted for the reported IPV incident. There was also a significant interaction effect between subtypes and arrest for IPV recidivism within 12 months post-arrest. Among those perpetrators who were arrested, GV perpetrators were more than four times as likely as PO violent perpetrators to recidivate in IPV. The results of this study highlight the importance of differentiating between subtypes when examining the impact of sanctions on IPV recidivism.

Forensic psychiatric patients’ low educational attainment is a strong predictor for recidivism. However, there is a lack of studies on the educational background among women admitted to forensic psychiatric care. The study aimed to investigate the educational background among women within a high secure forensic psychiatric setting. A mixed-method design was applied. Data were collected from registers, including medical records, forensic psychiatric investigations, and verdicts (n = 93), and by conducting interviews (n = 61) with women admitted to forensic psychiatric care in Sweden. The women’s education length varied between 5 and 18 years. According to interviews and registers, more than 70% of the women were found to have some school-related problems. In the interviews, some women associated school with conflicts, loneliness, and learning difficulties. Others explained how their disadvantageous home environment and many school changes affected their learning and problems developing and maintaining social relationships. Women with a neurodevelopmental disorder were to a higher degree documented with school-related problems than women without such disorders (97% vs. 63%). The educational attainment varied among the women, and consequently, their educational needs were heterogeneous. Therefore, they should be offered tailored education and vocational support to have an increased prerequisite for adjusting to and participating in society.

We previously demonstrated that a common dietary protein component, wheat amylase trypsin inhibitors (ATI), stimulate intestinal macrophages and dendritic cells via toll like receptor 4. Activation of these intestinal myeloid cells elicits an inflammatory signal that is propagated to mesenteric lymph nodes, and that can facilitate extraintestinal inflammation. Mice were fed a well-defined high fat diet, with (HFD/ATI) or without (HFD) nutritionally irrelevant amounts of ATI. Mice on HFD/ATI developed only mild signs of intestinal inflammation and myeloid cell activation but displayed significantly higher serum triglycerides and transaminases compared to mice on HFD alone. Moreover, they showed increased visceral and liver fat, and a higher insulin resistance. ATI feeding promoted liver and adipose tissue inflammation, with M1-type macrophage polarization and infiltration, and enhanced liver fibrogenesis. Gluten, the major protein component of wheat, did not induce these pathologies. Therefore, wheat ATI ingestion in minute quantities comparable to human daily wheat consumption exacerbated features of the metabolic syndrome and non-alcoholic steatohepatitis, despite its irrelevant caloric value.

Epithelial-to-mesenchymal transition (EMT) renders epithelial cells migratory properties. While epigenetic and splicing changes have been implicated in EMT, the mechanisms governing their crosstalk remain poorly understood. Here we discovered that a C2H2 zinc finger protein, ZNF827, is strongly induced during various contexts of EMT, including in brain development and breast cancer metastasis, and is required for the molecular and phenotypic changes underlying EMT in these processes. Mechanistically, ZNF827 mediated these responses by orchestrating a large-scale remodelling of the splicing landscape by recruiting HDAC1 for epigenetic modulation of distinct genomic loci, thereby slowing RNA polymerase II progression and altering the splicing of genes encoding key EMT regulators in cis. Our findings reveal an unprecedented complexity of crosstalk between epigenetic landscape and splicing programme in governing EMT and identify ZNF827 as a master regulator coupling these processes during EMT in brain development and breast cancer metastasis.

Dysregulated mammalian target of rapamycin (mTOR) activity is associated with various neurodevelopmental disorders ranging from idiopathic autism spectrum disorders to syndromes caused by single gene defects. This suggests that maintaining mTOR activity levels in a physiological range is essential for brain development and functioning. Upon activation, mTOR regulates a variety of cellular processes such as cell growth, autophagy and metabolism. On a molecular level, however, the consequences of mTOR activation in the brain are not well understood.Low levels of cholesterol are associated with a wide variety of neurodevelopmental disorders. We here describe numerous genes of the sterol/cholesterol biosynthesis pathway to be transcriptionally regulated by mTOR complex 1 (mTORC1) signaling in vitro in primary neurons and in vivo in the developing cerebral cortex of the mouse. We find that these genes are shared targets of the transcription factors SREBP, SP1 and NF-Y. Prenatal as well as postnatal mTORC1 inhibition downregulated expression of these genes which directly translated into reduced cholesterol levels pointing towards a substantial metabolic function of the mTORC1 signaling cascade. Altogether, our results indicate that mTORC1 is an essential transcriptional regulator of the expression of sterol/cholesterol biosynthesis genes in the developing brain. Altered expression of these genes may be an important factor contributing to the pathogenesis of neurodevelopmental disorders associated with dysregulated mTOR signaling.

Purpose and aim: Out from the sparse literature on risk assessment for violence committed by women the Female Additional Manual (FAM) was developed to be a complement to the HCR-20v2. The aim of th...

Human death receptors control apoptotic events during cell differentiation, cell homeostasis and the elimination of damaged or infected cells. Receptor activation involves ligand-induced structural reorganizations of preformed receptor trimers. Here we show that the death receptor transmembrane domains only have a weak intrinsic tendency to homo-oligomerize within a membrane, and thus these domains potentially do not significantly contribute to receptor trimerization. However, mutation of Pro183 in the human CD95/Fas receptor transmembrane helix results in a dramatically increased interaction propensity, as shown by genetic assays. The increased interaction of the transmembrane domain is coupled with a decreased ligand-sensitivity of cells expressing the Fas receptor, and thus in a decreased number of apoptotic events. Mutation of Pro183 likely results in a substantial rearrangement of the self-associated Fas receptor transmembrane trimer, which likely abolishes further signaling of the apoptotic signal but may activate other signaling pathways. Our study shows that formation of a stable Fas receptor transmembrane helix oligomer does not per se result in receptor activation.

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A lipid-protein autoimmunity target Several autoimmune diseases, including systemic lupus erythematosus and primary antiphospholipid syndrome, are characterized by the presence of antiphospholipid antibodies (aPLs). These molecules can activate the complement and coagulation cascades, which contributes to pathologies such as thrombosis, stroke, and pregnancy complications. Müller-Calleja et al. found that endothelial protein C receptor (EPCR) in complex with lysobisphosphatidic acid (LBPA) is the cell-surface target for aPL and mediates its internalization (see the Perspective by Kaplan). aPL binding to EPCR-LBPA resulted in the activation of tissue factor–mediated coagulation and interferon-α production by dendritic cells. Interferon-α, in turn, fueled the expansion of B1a cells, which secrete aPLs. The specific blockade of this target in mice inhibited the development of aPL autoimmunity, offering hope for future therapies for these conditions. Science , this issue p. eaay1833 ; see also p. 1100

Mutations in the actively expressed, maternal allele of the imprinted KCNK9 gene cause Birk-Barel intellectual disability syndrome (BBIDS). Using a BBIDS mouse model, we identify here a partial rescue of the BBIDS-like behavioral and neuronal phenotypes mediated via residual expression from the paternal Kcnk9 (Kcnk9pat) allele. We further demonstrate that the second-generation HDAC inhibitor CI-994 induces enhanced expression from the paternally silenced Kcnk9 allele and leads to a full rescue of the behavioral phenotype suggesting CI-994 as a promising molecule for BBIDS therapy. Thus, these findings suggest a potential approach to improve cognitive dysfunction in a mouse model of an imprinting disorder., Birk-Barel intellectual disability is an imprinting syndrome due to maternally-only transmitted mutations of KCNK9/TASK3. Here authors are using a heterozygous deletion of the active maternal Kcnk9 allele to model the disease and show phenotypic rescue by HDAC inhibition.

Cancer is one of the major causes of death in both the USA and Europe. Molecular imaging is a novel field that is revolutionizing cancer management. It is based on the molecular signature of cells in order to study the human body both in normal and diseased conditions. The emergence of molecular imaging has been driven by the difficulties associated with cancer detection, particularly early-stage premalignant lesions which are often unnoticed as a result of minimal or no structural changes. Endoscopic surveillance is the standard method for early-stage cancer detection. In addition to recent major advancements in endoscopic instruments, significant progress has been achieved in the exploration of highly specific molecular probes and the combination of both will permit significant improvement of patient care. In this review, we provide an outline of the current status of endoscopic imaging and focus on recent applications of molecular imaging in gastrointestinal, hepatic and other cancers in the context of detection, targeted therapy and personalized medicine. As new imaging agents have the potential to broadly expand our cancer diagnostic capability, we will also present an overview of the main types of optical molecular probes with their pros and cons. We conclude by discussing the challenges and future prospects of the field.

The knowledge of same-sex intimate partner violence (IPV) is limited. This study aims to investigate the perception of seriousness of same-sex IPV. A vignette study was undertaken among 248 police students (69% males and 31% females) in Sweden. The vignettes portrayed an intimate partner relationship between two people and were available in four versions with the sex of the offender and victim being alternated. Perceptions of IPV were measured using the Opinions of Domestic Violence Scale (Ahmed et al., 2013). The results showed that regardless of gender, IPV was considered serious; however, same-sex IPV was perceived as less serious than victimization of a heterosexual female but more serious than victimization of a heterosexual male. Police interventions were found to be less needed for same-sex victims than for heterosexual female victims.

Restraining orders can be used as a risk management strategy to reduce the likelihood of intimate partner violence (IPV) re-victimisation. The aim of this study was to examine how prosecutors work ...

There is emerging recognition that positive or pro-social characteristics may lessen criminal propensity. There are now several adult and youth forensic instruments that include protective or stren...

Although an essential component of assisted reproductive technologies, ovarian stimulation, or superovulation, may interfere with the epigenetic reprogramming machinery during early embryogenesis and gametogenesis. To investigate the possible impact of superovulation particularly on the methylation reprogramming process directly after fertilization, we performed immunofluorescence staining of pronuclear (PN) stage embryos with antibodies against 5mC and 5hmC. PN stage embryos obtained by superovulation displayed an increased incidence of abnormal methylation and hydroxymethylation patterns in both maternal and paternal pronuclear DNA. Subsequent single-cell RT-qPCR analyses of the Tet1, Tet2, and Tet3 genes revealed no significant expression differences between PN stage embryos from spontaneously and superovulated matings that could be causative for the abnormal methylation and hydroxymethylation patterns. To analyze the possible contribution of TET-independent replication-associated demethylation mechanisms, we then determined the 5mC and 5hmC levels of PN stage mouse embryos using immunofluorescence analyses after inhibition of DNA replication with aphidicolin. Inhibition of DNA replication had no effect on abnormal methylation and hydroxymethylation patterns that still persisted in the superovulated group. Interestingly, the onset of DNA replication, which was also analyzed in these experiments, was remarkably delayed in the superovulated group. Our findings imply an impact of superovulation on both replication-dependent and -independent or yet unknown demethylation mechanisms in PN stage mouse embryos. In addition, they reveal for the first time a negative effect of superovulation on the initiation of DNA replication in PN stage mouse embryos.

The aim of this study was to compare antisocial and family-only intimate partner violence (IPV) perpetrators in terms of IPV recidivism rates, type of recidivism crime, and time to recidivism. A total sample of 628 perpetrators was categorized as antisocial ( n = 327) or family-only ( n = 301) based on general criminality. Results demonstrated that antisocial perpetrators recidivated to a larger extent than family-only perpetrators (27.2% vs. 12.9%). Antisocial perpetrators were more prone to recidivate in both physical and nonphysical violence. Of the perpetrators who recidivated, the majority did so within the first year after their index crime. However, antisocial perpetrators recidivated more than family-only perpetrators after the first year. Key findings consisted of the subtypes’ differing propensity to reoffend and their different critical time periods for recidivism. These findings suggest the need for different risk management strategies depending on perpetrator subtype to prevent future violence.

Purpose Police play an essential role in reducing harms associated with family violence by identifying people at increased risk of physical or mental health-related harm and linking them with support services. Yet police are often poorly trained and resourced to conduct the kind of assessments necessary to identify family violence cases presenting with increased risk. The paper aims to discuss this issue. Design/methodology/approach This paper describes a multi-project collaboration between law enforcement, forensic mental health, and academia that has over three years worked to improve risk assessment and management of family violence by police in Victoria, Australia. Findings Evaluation of existing risk assessment instruments used by the state-wide police force showed they were ineffective in predicting future police reports of family violence (AUC=0.54-0.56). However, the addition of forensic psychology expertise to specialist family violence teams increased the number of risk management strategies implemented by police, and suggested that the Brief Spousal Assault Form for the Evaluation of Risk assessment instrument may be appropriate for use by Australian police (AUC=0.63). Practical implications The practical implications of this study are as follows: police risk assessment procedures should be subject to independent evaluation to determine whether they are performing as intended; multidisciplinary collaboration within police units can improve police practice; drawing on expertise from agencies external to police offers a way to improve evidence-based policing, and structured professional judgement risk assessment can be used in policing contexts with appropriate training and support. Originality/value The paper describes an innovative collaboration between police, mental health, and academia that is leading to improved police practices in responding to family violence. It includes data from the first evaluation of an Australian risk assessment instrument for family violence, and describes methods of improving police systems for responding to family violence.

Self-injury and institutional violence are well-known characteristics of female forensic psychiatric patients, but research on patients' experiences of these behaviours is limited.The aim of the study was to investigate how female forensic psychiatric patients describe their self-injury and aggression.The authors performed qualitative in-depth interviews with 13 female forensic psychiatric inpatients. The interviews were analysed using thematic analysis.The analysis resulted in three themes describing the process of handling negative thoughts and emotions by using self-injury or aggression towards others and thereby experiencing satisfaction. Both self-injury and aggression were experienced as strategies for emotional regulation. The forensic psychiatric care was perceived as important for the women in developing less harmful strategies for coping with negative thoughts and emotions instead of injuring themselves or others.Self-injury and aggression are often risk-assessed separately, but results from the present study suggest that these behaviours need a more holistic approach.

Superoxide dismutases (SOD) are a group of enzymes that catalyze the dismutation of superoxide (O2−) radicals into molecular oxygen (O2) and H2O2 as a first line of defense against oxidative stress. Here, we show that glycine-functionalized copper(II) hydroxide nanoparticles (Gly-Cu(OH)2 NPs) are functional SOD mimics, whereas bulk Cu(OH)2 is insoluble in water and catalytically inactive. In contrast, Gly-Cu(OH)2 NPs form water-dispersible mesocrystals with a SOD-like activity that is larger than that of their natural CuZn enzyme counterpart. Based on this finding, we devised an application where Gly-Cu(OH)2 NPs were incorporated into cigarette filters. Cigarette smoke contains high concentrations of toxic reactive oxygen species (ROS, >1016 molecules per puff) including superoxide and reactive nitrogen species which lead to the development of chronic and degenerative diseases via oxidative damage and subsequent cell death. Embedded in cigarette filters Gly-Cu(OH)2 NPs efficiently removed ROS from smoke, thereby protecting lung cancer cell lines from cytotoxic effects. Their stability, ease of production and versatility make them a powerful tool for a wide range of applications in environmental chemistry, biotechnology and medicine.

Targeting antigen combined with adjuvants to hepatic antigen-presenting cells (APCs) is essential for the induction of intrahepatic T cellular immunity controlling and resolving viral infections of the liver. Intravenous injection of antigen-loaded nanoparticles is a promising approach for the delivery of antigens to liver APCs. Accordingly, polymeric nanocapsules (NCs) synthesized exclusively of hepatitis C virus non-structural protein 5A (NS5A) and the adjuvant monophosphoryl lipid A (MPLA) adsorbed to the nanocapsule surface were developed. Aim of the present study was the evaluation of the in vitro and in vivo behavior of MPLA-functionalized NS5A-NCs regarding the interaction with liver dendritic cells (DCs) and the potential to induce intrahepatic immune responses in a mouse model. Maturation of DCs was significantly increased by application of NS5A+MPLA-NCs compared to non-functionalized NS5A-NCs promoting a vigorous expression of CD40, CD80, CD86 and a strong secretion of the Th1-related cytokine IL-12. NS5A-NCs were preferentially deposited in DCs and Kupffer cells residing in the liver after intravenous administration. Immunization with NS5A-NCs induced intrahepatic antigen-specific CD4(+) T cellular immune responses determined by the secretion of IFNγ and IL-2. Furthermore, supplementation with MPLA induced significant levels of NS5A-specific antibodies. The application of polymeric nanocapsules synthesized exclusively out of antigen avoids the risk of unintended side effects caused by additional carrier substances. Functionalization with adjuvants like MPLA and the efficient targeting to liver-resident APCs inherits the potential for application of antigen nanocapsules in further vaccination approaches against pathogens affecting the liver.

The RNA-binding protein RBFOX1 is an important regulator of neuron development and neuronal excitability. Rbfox1 is a dosage-sensitive gene and in both mice and humans, decreased expression of Rbfox1 has been linked to neurodevelopmental disorders. Alternative promoters drive expression of Rbfox1 transcript isoforms that encode an identical protein. The tissue- and developmental stage-specific expression of these isoforms, as well as the underlying regulatory mechanisms, are, however, unclear. Here, we set out to capture all of the Rbfox1 transcript isoforms and identify transcriptional mechanisms that regulate brain-specific Rbfox1 expression. Isoform sequencing identified multiple alternative Rbfox1 transcript variants in the mouse cerebral cortex, including transcripts with novel first exons, alternatively spliced exons and 3'-truncations. Quantitative RT-PCR determined the expression of the alternative first exons in the developing cerebral cortex and different subregions of the juvenile brain. Alternative first exons were found to be highly stage- and subregion specific in their expression patterns suggesting that they fulfill specific functions during cortex development and in different brain regions. Using reporter assays we found that the promoter regions of the two first exons E1B and E1C/E1C.1 contain several functional E-boxes. Together, we provide an extensive picture of Rbfox1 isoform expression. We further identified important regulatory mechanisms that drive neuron-specific Rbfox1 expression. Thus, our study forms the basis for further research into the mechanisms that ensure physiological Rbfox1 expression in the brain. It also helps to understand why, in patients with neurodevelopmental disorders deletion of individual RBFOX1 transcript isoforms could affect brain function.

Background and purpose Excessive inflammation in sepsis causes microvascular thrombosis and thrombocytopenia associated with organ dysfunction and high mortality. The present studies aimed to investigate whether inhibition of dipeptidyl peptidase-4 (DPP-4) and supplementation with glucagon-like peptide-1 (GLP-1) receptor agonists improved endotoxaemia-associated microvascular thrombosis via immunomodulatory effects. Experimental approach Endotoxaemia was induced in C57BL/6J mice by a single injection of LPS (17.5 mg kg-1 for survival and 10 mg kg-1 for all other studies). For survival studies, treatment was started 6 h after LPS injection. For all other studies, drugs were injected 48 h before LPS treatment. Key results Mice treated with LPS alone showed severe thrombocytopenia, microvascular thrombosis in the pulmonary circulation (fluorescence imaging), increased LDH activity, endothelial dysfunction and increased markers of inflammation in aorta and whole blood (leukocyte-dependent oxidative burst, nitrosyl-iron haemoglobin, a marker of nitrosative stress, and expression of inducible NOS). Treatment with the DPP-4 inhibitor linagliptin or the GLP-1 receptor agonist liraglutide, as well as genetic deletion of DPP-4 (DPP4-/- mice) improved all these parameters. In GLP-1 receptor-deficient mice, both linagliptin and liraglutide lost their beneficial effects and improvement of prognosis. Incubation of platelets and cultured monocytes (containing GLP-1 receptor protein) with GLP-1 receptor agonists inhibited the monocytic oxidative burst and platelet activation, with a GLP-1 receptor-dependent elevation of cAMP levels and PKA activation. Conclusions and implications GLP-1 receptor activation in platelets by linagliptin and liraglutide strongly attenuated endotoxaemia-induced microvascular thrombosis and mortality by a cAMP/PKA-dependent mechanism, preventing systemic inflammation, vascular dysfunction and end organ damage. Linked articles This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.

Inpatient aggression among female forensic psychiatric patients has been shown to be associated with self-harm, that is considered to be a historical risk factor for violence. Research on associations between previous or current self-harm and different types of inpatient aggression is missing.The aim of this register study was to investigate the prevalence of self-harm and the type of inpatient aggression among female forensic psychiatric inpatients, and to study whether the patients' self-harm before and/or during forensic psychiatric care is a risk factor for inpatient aggression.Female forensic psychiatric patients (n = 130) from a high security hospital were included.The results showed that 88% of the female patients had self-harmed at least once during their life and 57% had been physically and/or verbally aggressive towards staff or other patients while in care at the hospital. Self-harm before admission to the current forensic psychiatric care or repeated self-harm were not significantly associated with inpatient aggression, whereas self-harm during care was significantly associated with physical and verbal aggression directed at staff.These results pointed towards self-harm being a dynamic risk factor rather than a historical risk factor for inpatient aggression among female forensic psychiatric patients. Whether self-harm is an individual risk factor or a part of the clinical risk factor 'Symptom of major mental illness' within the HCR-20V3 must be further explored among women. Thus, addressing self-harm committed by female patients during forensic psychiatric care seems to be important in risk assessments and the management of violence, especially in reducing violence against staff in high-security forensic psychiatric services.

Purpose – The purpose of this paper is to explore the relationship between psychopathic features as measured with the Psychopathy Checklist: Youth Version (PCL:YV) and behavioural and emotional functioning in young female offenders in custody. Design/methodology/approach – This is a quantitative interview study investigating the relationship with psychopathic traits, measured with the PCL:YV (Forth et al., 2003), and different psychological characteristics as well as AD/HD, self-harm, and childhood trauma in adolescent offenders across genders. Data were collected from a sample of 40 female and 40 male adolescents who were incarcerated in Victoria, Australia. Findings – Results indicated that the behavioural subscales of the PCL:YV were associated with externalising behaviours possibly underpinned by histories of abuse and substantiated child protection incidences. The presence of AD/HD was strongly associated with affective deficits suggesting that the PCL:YV may be identifying young females with AD/HD rather than core psychopathic traits. Findings also indicate that female-specific manifestations of manipulation are likely being misidentified as behavioural phenomena precluding clinical recognition as a core interpersonal trait. Significant dissimilarities with a young male comparison group were identified and are discussed within. Research limitations/implications – The sample size is very small and the results should be seen as an indication rather than generalising. Originality/value – Studies on female juvenile offenders is rare and this study adds to the literature on the construct of psychopathy and its relationship to psychosocial factors as well as associations with AD/HD, self-harm, and childhood trauma, among incarcerated adolescents.

Constitutive epimutations of tumor suppressor genes are increasingly considered as cancer predisposing factors equally to sequence mutations. In light of the emerging role of the microenvironment for cancer predisposition, initiation, and progression, we aimed to characterize the consequences of a BRCA1 epimutation in cells of mesenchymal origin. We performed a comprehensive molecular and cellular comparison of primary dermal fibroblasts taken from a monozygous twin pair discordant for recurrent cancers and BRCA1 epimutation, whose exceptional clinical case we previously reported in this journal. Comparative transcriptome analysis identified differential expression of extracellular matrix-related genes and pro-tumorigenic growth factors, such as collagens and CXC chemokines. Moreover, genes known to be key markers of so called cancer-associated fibroblasts (CAFs), such as ACTA2, FAP, PDPN, and TNC, were upregulated in fibroblasts of the affected twin (BRCA1mosMe) in comparison to those of the healthy twin (BRCA1wt). Further analyses detected CAF-typical cellular features, including an elevated growth rate, enhanced migration, altered actin architecture and increased production of ketone bodies in BRCA1mosMe fibroblasts compared to BRCA1wt fibroblasts. In addition, conditioned medium of BRCA1mosMe fibroblasts was more potent than conditioned medium of BRCA1wt fibroblasts to promote cell proliferation in an epithelial and a cancer cell line. Our data demonstrate, that a CAF-like state is not an exclusive feature of tumor-associated tissue but also exists in healthy tissue with tumor suppressor deficiency. The naturally occurring phenomenon of twin fibroblasts differing in their BRCA1 methylation status revealed to be a unique powerful tool for exploring tumor suppressor deficiency-related changes in healthy tissue, reinforcing their significance for cancer predisposition.

This study examined the convergent validity of 2 youth psychopathy instruments, the Psychopathy Checklist: Youth Version (PCL: YV) and the Youth Psychopathic Trait Inventory (YPI) and their relationship with problem behaviors and recidivism in an Australian sample of young offenders in custody. The PCL: YV demonstrated a capacity to identify severely antisocial youth; however, the tool was unable to differentiate between potentially psychopathic and nonpsychopathic antisocial youth. The YPI was receptive to a wide variety of problem behaviors which precluded the unique identification of core psychopathic traits in the sample. Both instruments were unable to meaningfully distinguish between recidivists and nonrecidivists. As such, the PCL: YV and the YPI demonstrate limited utility for antisocial young offenders in custody. Further research on the durability and developmental manifestation of psychopathy in adolescents is necessary before these instruments are employed in similar contexts. Implications for the clinical use of psychopathy measures are discussed.

Semi-structured interviews with 13 forensic psychiatric inpatients that had decreased their assessed risk of violence were analyzed using interpretive description. The main contribution from this study is a detailed description of patients' own strategies to avoid violence. Participants described having an ongoing inner dialog in which they encouraged themselves, thereby increasing their self-esteem and trying to accept their current situation. An unsafe and overcrowded ward with uninterested and nonchalant staff increased the risk of aggressive behavior. In the process of decreasing violence, the patients and the forensic psychiatric nursing staff interacted to create and maintain a safe environment.