Self-harm and suicidal behaviors in children: perspectives of mental health clinicians.

OBJECTIVE: Presentations for self-harm and suicidal behaviors are increasing in children and young people, although less is known about these presentations in children aged 12 years and under. This study aims to understand how mental health clinicians in public health services conceptualize, identify and respond to self-harm and suicidal behaviors in children. METHODS: 26 mental health clinicians provided their perspectives through interviews or focus groups. Participant responses were analyzed using reflexive thematic analysis. RESULTS: Mental health clinicians described how self-harm and suicidal behaviors may present differently in children compared with adolescents, particularly with the methods used. Using developmentally appropriate language and including parents or carers when screening for self-harm and suicidal behaviors was recommended by clinicians. The inclusion of parents or carers throughout the treatment process was important for clinicians, including helping parents understand their child's behavior and manage their own distress. Clinicians also highlighted the benefit of collaborating with schools to support children, yet noted primary school staff require training in responding to child self-harm and suicidal behavior. The limited services available for children 12 years and under including emergency care services, was identified as a problem. CONCLUSIONS: Findings highlight the importance of timely assessment and interventions which include mental health and medical clinicians, parents, carers, and school staff to support children with self-harm and suicidal behaviors.

Mind-mindedness and preschool children's behavioral difficulties: The moderating role of maternal parenting distress.

Mind-mindedness (MM) is a caregiver's tendency to appreciate their infant's internal mental states. This longitudinal study investigated whether maternal MM (10 months) was linked with children's later behavioral problems (51 months) and the moderating role of maternal parenting distress (PD; 36 months) in a sample of 91 mother-infant dyads. Appropriate MM comments were coded from video-recorded, semi-structured play interactions between mothers and their infants; PD was obtained from maternal completion of the PD subscale of the Parenting Stress Index - Short Form (PSI-SF); and child internalizing and externalizing behavior problems were gathered from maternal report on the Strengths and Difficulties Questionnaire (SDQ). Moderated regression analyses revealed higher early appropriate MM was associated with significantly fewer internalizing emotional problems at 51 months among mothers with lower PD at 36 months, and higher early appropriate MM was associated with lower conduct problems at 51 months in mothers with higher PD at 36 months. Findings demonstrated the importance of considering nuanced contexts such as at-risk mothers and differential presentations of child difficulties in the analysis of the relationship between MM and child behavioral difficulties and the development of MM interventions.

Antenatal mind-mindedness and its relationship to maternal-fetal attachment in pregnant women.

In this study, researchers aimed to investigate whether a relationship exists between maternal-fetal attachment (MFA) and antenatal mind-mindedness in a sample of Australian pregnant women (n = 43). Participants completed the Maternal Fetal Attachment Scale (MFAS) in their second and third trimester, and a modified 'describe your baby' interview with the inclusion of general prompts as a measure of antenatal mind-mindedness in their third trimester. Positive correlations were observed between mental comments, but not total predictions, made by women during the modified antenatal mind-mindedness task and MFAS scores at the second and third trimesters. An average of 6.07 total predictions and 1.30 mental predictions were made before prompts, increasing to 17.65 total comments and 6.58 mental comments after prompts. Prompts within the mind-mindedness task resulted in 42 participants making at least one mental prediction (M = 6.58). Our findings provide the first evidence for a relationship between MFA and antenatal mind-mindedness, and highlight the importance of considering mind-mindedness during pregnancy in the developing bond from mother to baby.

What aspects of mindfulness and emotion regulation underpin self-harm in individuals with borderline personality disorder?

BACKGROUND: Self-harm presents significant risk for individuals with borderline personality disorder (BPD). Both self-harm and BPD are associated with deficits in mindfulness and emotion dysregulation. Previous research suggests that thought suppression and emotional inexpressivity may underpin self-harm in people with BPD, suggesting potential links to self-harm functions common for those with BPD. More research is needed to strengthen our understanding of this relationship. AIMS: This study examines how BPD symptoms, mindfulness, emotion dysregulation and self-harm functions are related. METHODS: Australian community outpatients diagnosed with BPD (N = 110) completed measures of mindfulness, emotion dysregulation and self-harm functions. Serial mediation analyses were conducted to examine relationships between variables. RESULTS: BPD symptoms, chronic emptiness, mindfulness skills, describing and non-reacting, emotion dysregulation areas of emotion regulation strategies and poor emotional clarity were associated with recent self-harm. Various combinations of describing, strategies and clarity mediated the path between emptiness and self-harm functions more likely to be endorsed by individuals with a diagnosis of BPD. Describing was associated with all but anti-suicide function, while strategies was associated with all but anti-dissociation. CONCLUSION: The study highlights how individuals with BPD experiencing chronic emptiness may benefit from treatment targeting describing skills and adaptive emotion regulation strategies.

Overexpression and surface localization of HPRT in prostate cancer provides a potential target for cancer specific antibody mediated cellular cytotoxicity.

We chose to evaluate Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) as a possible biomarker for prostate cancer due to its involvement in nucleotide synthesis and cell cycle progression. We utilized two prostate cancer cell lines (PC3 and DU145) along with patient tissue and knockdowns to evaluate overall HPRT expression. The surface localization of HPRT was determined utilizing flow cytometry, confocal microscopy, and scanning electron microscopy followed by ADCC to evaluate targeting potential. We found significant upregulation of HPRT within malignant samples with approximately 47% of patients had elevated levels of HPRT compared to normal controls. We also observed a significant association between HPRT and the plasma membrane of DU145 cells (p = 0.0004), but found no presence on PC3 cells (p = 0.14). This was confirmed with scanning electron microscopy and confocal microscopy. ADCC experiments were performed to determine whether HPRT could be used as a target antigen for selective cell-mediated killing. We found that DU145 cells treated with HPRT antibodies had a significantly higher incidence of cell death than both isotype treated samples and PC3 cells treated with the same concentrations of HPRT antibody. Finally, we determined that p53 had a significant impact on HPRT expression both internally and on the surface of cancer cells. These results suggest HPRT as a possible biomarker target for the treatment of patients with prostate cancer.

Living with pathological narcissism: core conflictual relational themes within intimate relationships.

BACKGROUND: Pathological narcissism is a severe mental health condition that includes disturbances in interpersonal functioning. Interpersonal difficulties by those affected include aggressive, domineering, cold and coercive behaviours which often result in strong negative reactions from others. We sought to examine the moment-to-moment patterns that emerge within close relationships between intimate partners and family members. METHODS: Participants (N = 15) were romantic partners (73.3%) and family members (26.6%) in a close and long-term relationship (+ 10 years) with an individual with pathological narcissism. Participants told verbatim relationship narratives involving five narrative interactions with their relative with pathological narcissism and five narrative interactions with others. Transcripts were coded using the using Core Conflictual Relationship Theme method. Participants also completed three versions of the Relationship Questionnaire, reporting on 1. their relationship style 'in general', 2. their relationship style 'with their relative' and 3. the relationship style of their relative. RESULTS: A total of 133 relationship episodes were analysed, comprising 783 components (wishes, responses of others and responses of self). While the identified wishes (e.g., for love, for support) were consistent between relative and non-relative narratives, there was significantly higher disharmony and lower harmony in narratives involving relatives with pathological narcissism. Described disharmony in these relationships involved the relative's rejecting, subjugating and attacking behaviours, and participants rejecting and withdrawing behaviours. There was a prominent deactivation of participants attachment system when interacting with their relative with pathological narcissism, endorsing predominately dismissing relationship styles. Individuals with pathological narcissism were similarly rated as predominately dismissing. CONCLUSIONS: Together, these results reflect the cycles of interpersonal dysfunction for individuals with pathological narcissism and their partners and family members. Treatment implications point to the risk of therapists withdrawing and dismissing a patient with high pathological narcissism in the countertransference. Strategies to monitor and manage these core relational themes in treatment remain a challenge.

Personal agency and borderline personality disorder: a longitudinal study of outcomes.

BACKGROUND: Low personal agency is the concept of attributing successes and failures to external factors rather than personal characteristics. Previous research supported links between low personal agency and symptoms of borderline personality disorder (BPD). The present research followed patients in an outpatient dialectical behavioural therapy (DBT) group from intake to 12 months follow up to examine the impact of personal agency on outcome. METHODS: Patients (N = 57, age 18-72, 91.5% female) were assessed at intake, after three months of DBT treatment, and 12 months follow up on measures of symptoms and personal agency. Three separate measures were used to assess treatment outcomes: the BPD Checklist, the Personality Inventory for DSM-5 (PID-5), and the Mental Health Inventory (MHI-5). RESULTS: Mixed model analyses found BPD symptoms significantly reduced as a result of DBT treatment and were maintained at follow-up. However, 47% of participants continued to meet BPD criteria 12 months later, despite treatment. Regression analyses indicated that low personal agency at intake was associated with higher BPD symptom severity at post-treatment and 12 month follow up. In addition, low personal agency at intake was associated with greater levels of negative affectivity at post-treatment. Personal agency did not relate to levels of depression and anxiety. CONCLUSIONS: Despite the reductions in BPD symptomology, personal agency did not significantly change over time. Those with lower agency at intake continued to do more poorly at follow up. We speculate that poor outcomes may be contributed to by patients' lack of engagement in recovery due to poor agency and an external locus of control. As such, therapeutic approaches, like DBT, may require additional strategies to appropriately target low personal agency. Further research is needed to understand if other treatment protocols may facilitate positive change in personal agency.

The role of pregnancy acceptability in maternal mental health and bonding during pregnancy.

BACKGROUND: Pregnancy is an important time for women's mental health and marks the foundations of the emerging bond between mother and baby. This study aimed to investigate the role of pregnancy acceptability and intendedness in maternal mental health and bonding during pregnancy. METHODS: Data were collected from a community sample of 116 Australian pregnant women (M = 29.54, SD = 5.31) through a series of self-report questionnaires pertaining to mental health and antenatal bonding. RESULTS: Lower pregnancy acceptability was correlated with higher depression, anxiety and total distress, lower physical and environmental quality of life and lower antenatal bonding. Women who reported their pregnancy was intended reported higher physical quality of life than those who reported their pregnancy was unintended. The relationship between total distress and antenatal bonding was moderated by women's degree of pregnancy acceptability (low versus high). For women with low acceptability, higher distress was associated with lower bonding, but there was no such association for women with high pregnancy acceptability. The moderation model examining associations between distress and pregnancy acceptability explained 15% of the variance in antenatal bonding scores. CONCLUSION: Consideration of women's appraisal of their pregnancy acceptability may provide a valuable framework for identifying individuals who may be at risk for mental health and bonding difficulties.

Non-response to psychotherapy for borderline personality disorder: A systematic review.

HIGHLIGHT: This is the first systematic review to investigate non-response to psychotherapy for borderline personality disorder. BACKGROUND: Psychotherapy is the recommended treatment for borderline personality disorder. While systematic reviews have demonstrated the effectiveness of psychotherapy for borderline personality disorder, effect sizes remain small and influenced by bias. Furthermore, the proportion of people who do not respond to treatment is seldom reported or analysed. OBJECTIVE: To obtain an informed estimate of the proportion of people who do not respond to psychotherapy for borderline personality disorder. METHODS: Systematic searches of five databases, PubMed, Web of Science, Scopus, PsycINFO and the Cochrane Library, occurred in November 2020. Inclusion criteria: participants diagnosed with borderline personality disorder, treated with psychotherapy and data reporting either (a) the proportion of the sample that experienced 'reliable change' or (b) the percentage of sample that no longer met criteria for borderline personality disorder at conclusion of therapy. Exclusion criteria: studies published prior to 1980 or not in English. Of the 19,517 studies identified, 28 met inclusion criteria. RESULTS: Twenty-eight studies were included in the review comprising a total of 2436 participants. Average treatment duration was 11 months using well-known evidence-based approaches. Approximately half did not respond to treatment; M = 48.80% (SD = 22.77). LIMITATIONS: Data regarding within sample variability and non-response are seldom reported. Methods of reporting data on dosage and comorbidities were highly divergent which precluded the ability to conduct predictive analyses. Other limitations include lack of sensitivity analysis, and studies published in English only. CONCLUSION: Results of this review suggest that a large proportion of people are not responding to psychotherapy for borderline personality disorder and that factors relating to non-response are both elusive and inconsistently reported. Novel, tailored or enhanced interventions are needed to improve outcomes for individuals not responding to current established treatments.

Human pregnancy zone protein stabilizes misfolded proteins including preeclampsia- and Alzheimer's-associated amyloid beta peptide.

Protein misfolding underlies the pathology of a large number of human disorders, many of which are age-related. An exception to this is preeclampsia, a leading cause of pregnancy-associated morbidity and mortality in which misfolded proteins accumulate in body fluids and the placenta. We demonstrate that pregnancy zone protein (PZP), which is dramatically elevated in maternal plasma during pregnancy, efficiently inhibits in vitro the aggregation of misfolded proteins, including the amyloid beta peptide (Aß) that is implicated in preeclampsia as well as with Alzheimer's disease. The mechanism by which this inhibition occurs involves the formation of stable complexes between PZP and monomeric Aß or small soluble Aß oligomers formed early in the aggregation pathway. The chaperone activity of PZP is more efficient than that of the closely related protein alpha-2-macroglobulin (α2M), although the chaperone activity of α2M is enhanced by inducing its dissociation into PZP-like dimers. By immunohistochemistry analysis, PZP is found primarily in extravillous trophoblasts in the placenta. In severe preeclampsia, PZP-positive extravillous trophoblasts are adjacent to extracellular plaques containing Aß, but PZP is not abundant within extracellular plaques. Our data support the conclusion that the up-regulation of PZP during pregnancy represents a major maternal adaptation that helps to maintain extracellular proteostasis during gestation in humans. We propose that overwhelming or disrupting the chaperone function of PZP could underlie the accumulation of misfolded proteins in vivo. Attempts to characterize extracellular proteostasis in pregnancy will potentially have broad-reaching significance for understanding disease-related protein misfolding.

Now and then: a ten-year comparison of young people in residential substance use disorder treatment receiving group dialectical behaviour therapy.

BACKGROUND: Reducing substance use in youth is a global health priority. We compared two cohorts from the same 12-week residential substance use disorder (SUD) facility over a 10 year period: Cohort A (2008-2009) and Cohort B (2018-2020). The essential components of the program remained the same with the primary treatment being dialectical behaviour therapy (DBT) plus residential milieu. METHODS: Young people in the current Cohort B (N = 100) versus historical Cohort A (N = 102) had a similar ratio of males (74 vs. 70%) but were slightly older (mean 20.6 vs. 19.5 years). Linear mixed models were used to model outcome measures (global psychiatric symptoms, substance use severity, and quality of life) longitudinally up to 12 months later. RESULTS: Baseline to end-of-treatment comparisons showed that the current Cohort B had overall higher levels of global psychiatric symptoms (d = 0.70), but both groups reduced psychiatric symptoms (Cohort A: d = 1.05; Cohort B: d = 0.61), and had comparable increases in confidence to resist substance use (d = 0.95). Longitudinal data from the current Cohort B showed significant decreases in substance use severity from baseline to 6-month follow-up (d = 1.83), which were sustained at 12-month follow-up (d = 0.94), and increases in quality of life from baseline to end-of-treatment (d = 0.83). CONCLUSIONS: We demonstrate how DBT plus milieu residential care for young people continues to show positive effects in a 10-year comparison. However, youth seeking treatment today compared to 10 years ago evidenced higher acuity of psychiatric symptoms reinforcing the importance of continuous improvement of psychological treatments. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: trial ID ACTRN12618000866202 , retrospectively registered on 22/05/2018, .

Evaluation of the upregulation and surface expression of hypoxanthine guanine phosphoribosyltransferase in acute lymphoblastic leukemia and Burkitt's B cell lymphoma.

BACKGROUND: The aim of this study is to determine whether Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) could be used as a biomarker for the diagnosis and treatment of B cell malignancies. With 4.3% of all new cancers diagnosed as Non-Hodgkin lymphoma, finding new biomarkers for the treatment of B cell cancers is an ongoing pursuit. HPRT is a nucleotide salvage pathway enzyme responsible for the synthesis of guanine and inosine throughout the cell cycle. METHODS: Raji cells were used for this analysis due to their high HPRT internal expression. Internal expression was evaluated utilizing western blotting and RNA sequencing. Surface localization was analyzed using flow cytometry, confocal microscopy, and membrane biotinylation. To determine the source of HPRT surface expression, a CRISPR knockdown of HPRT was generated and confirmed using western blotting. To determine clinical significance, patient blood samples were collected and analyzed for HPRT surface localization. RESULTS: We found surface localization of HPRT on both Raji cancer cells and in 77% of the malignant ALL samples analyzed and observed no significant expression in healthy cells. Surface expression was confirmed in Raji cells with confocal microscopy, where a direct overlap between HPRT specific antibodies and a membrane-specific dye was observed. HPRT was also detected in biotinylated membranes of Raji cells. Upon HPRT knockdown in Raji cells, we found a significant reduction in surface expression, which shows that the HPRT found on the surface originates from the cells themselves. Finally, we found that cells that had elevated levels of HPRT had a direct correlation to XRCC2, BRCA1, PIK3CA, MSH2, MSH6, WDYHV1, AK7, and BLMH expression and an inverse correlation to PRKD2, PTGS2, TCF7L2, CDH1, IL6R, MC1R, AMPD1, TLR6, and BAK1 expression. Of the 17 genes with significant correlation, 9 are involved in cellular proliferation and DNA synthesis, regulation, and repair. CONCLUSIONS: As a surface biomarker that is found on malignant cells and not on healthy cells, HPRT could be used as a surface antigen for targeted immunotherapy. In addition, the gene correlations show that HPRT may have an additional role in regulation of cancer proliferation that has not been previously discovered.

Novel monoclonal antibodies against thymidine kinase 1 and their potential use for the immunotargeting of lung, breast and colon cancer cells.

BACKGROUND: Thymidine kinase 1 (TK1) is a pyrimidine salvage pathway enzyme that is up-regulated in malignant tissues and elevated in the serum of cancer patients. While TK1 has been well established as a tumor biomarker, little has been done to explore its potential as a tumor target. Recently, we reported the membrane expression of TK1 on malignant cells, but not on normal cells. This study explores the possible use of monoclonal antibodies for the targeting of membrane associated TK1 in lung, breast, colon and prostate cancer cells. METHODS: We generated and evaluated a panel of monoclonal antibodies against six different epitopes exposed in the tetrameric form of TK1. Antibodies were developed with hybridoma technology and validated with Western blot, siRNA TK1 knockdown, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The therapeutic potential of the antibodies was evaluated in vitro in antibody-dependent cell-mediated-cytotoxicity (ADCC) experiments. RESULTS: Binding of the antibodies to TK1 was confirmed by Western blot in purified recombinant protein, cancer serum, and cell lysate. After a TK1 knockdown was performed, a reduction of TK1 expression was observed with five antibodies. Using indirect ELISA, we identified 3B2E11, 9C10, 7H2, 3B4, 8G2 among the most sensitive antibodies (LOD = 10.73-66.9 pg/ml). Surface expression of TK1 on the membrane of various cancer cell lines was analyzed with flow cytometry. Antibodies 8G2, 3B4, 7HD and 5F7G11 detected TK1 on the membrane of various cancer cell lines, including lung, prostate, colon and breast. No significant binding was detected on normal lymphocytes. Increased cytolysis of lung (~ 70%. p = 0.0001), breast (~ 70%, p = 0.0461) and colon (~ 50% p = 0.0216) cancer cells by effector cells was observed when anti-TK1 antibodies were added during ADCC experiments. CONCLUSIONS: The antibodies developed showed potential to be used to detect and target TK1 on the membrane of various tumor cells. The targeting of TK1 in malignant cells using monoclonal antibodies may be a feasible approach for the elimination of high TK1 expressing tumor cells.

Maternal perinatal mental health: Associations with bonding, mindfulness, and self-criticism at 18 months' postpartum.

The perinatal period is a time of significant transition for women, with changes in maternal mental health from pregnancy to 18 months' postpartum. This study specifically analyzes maternal self-criticism and mindfulness during pregnancy and at 18 months' postpartum, and their associations with bonding. A longitudinal study (30 weeks' gestation-18 months' postpartum) assessed 32 mother-infant dyads, examining changes in maternal depression, anxiety, self-criticism, and mindfulness. In addition, associations between maternal variables during pregnancy and bonding were investigated. Maternal depression and self-criticism significantly increased from pregnancy to postpartum. Maternal anxiety, self-criticism, and facets of mindfulness during pregnancy were also associated with mother-infant bonding at 18 months. Maternal mental health during pregnancy is subject to change postchildbirth. The lack of control and autonomy accompanying motherhood may result in an increase in self-criticism during this period. Such feelings may elevate a woman's vulnerability to postpartum depression and have consequences for later maternal bonding. Early identification of at-risk mothers is important to increase likelihood of positive outcomes.

Trasfondo: el período perinatal es un momento de significativa transición para las mujeres, con cambios en la salud mental materna a partir del embarazo hasta los 18 meses después del parto. Este estudio específicamente analiza la auto-crítica y la plena atención maternas durante el embarazo y a los 18 meses después del parto y sus asociaciones con la vinculación afectiva. Método: un estudio longitudinal (gestación de 30 semanas a 18 meses después del parto) evaluó a 32 díadas madre-infante por medio de examinar cambios en cuanto a depresión materna, ansiedad, auto-crítica y plena atención. Adicionalmente, se investigaron las asociaciones entre las variables maternas durante el embarazo y la vinculación afectiva. Resultados: la depresión materna y la auto-crítica aumentaron significativamente desde el embarazo hasta después del parto. También se asociaron la ansiedad materna, la auto-crítica y facetas de la plena atención durante el embarazo con la vinculación afectiva entre madre e infante a los 18 meses. Discusión: la salud mental materna durante el embarazo está sujeta a cambiar después del nacimiento del niño. La falta de control y autonomía que acompaña a la maternidad pudiera resultar en un aumento en la auto-crítica durante este período. Tales sentimientos pudieran incrementar la vulnerabilidad de una mujer con respecto a la depresión posterior al parto y tener consecuencias más tarde en la vinculación afectiva materna. Es importante la temprana identificación de madres bajo riesgo para aumentar la probabilidad de resultados positivos.

Contexte: La période périnatale est un moment de transition importante pour les femmes, avec des changements dans la santé mentale maternelle de la grossesse à 18 mois après la naissance. Cette étude analyse plus spécifiquement l'autocritique maternelle et la pleine conscience durant la grossesse et à 18 mois après la naissance, ainsi que leur lien avec la connexion. Méthode: Une étude longitudinale (30 semaine de grosses à 18 mois après la naissance) a évalué 32 dyades mère-nourrisson, en examinant les changements dans la dépression maternelle, l'anxiété, l'autocritique et la pleine conscience. De plus les liens entre les variables maternelles durant la grossesse et la connexion ont fait l'objet de la recherche. Résultats : La dépression maternelle et l'autocritique ont fortement augmenté de la grossesse à la période postpartum. L'anxiété maternelle, l'autocritique et les facettes de pleine conscience durant la grossesse étaient également liées à la connexion mère-nourrisson à 18 mois. Discussion: La santé mentale maternelle durant la grossesse peut changer après la naissance de l'enfant. Le manque de contrôle et d'autonomie qui accompagne la maternité peut résulter en une augmentation de l'autocritique durant cette période. De tels sentiments peuvent élever la vulnérabilité d'une femme à la dépression postpartum et avoir des conséquences sur la connexion maternelle ultérieure. Une identification précoce des mères à risque est importante afin d'augmenter les chances de résultats positifs.

Potential new biomarkers for endometrial cancer.

BACKGROUND: Incidence of endometrial cancer are rising both in the United States and worldwide. As endometrial cancer becomes more prominent, the need to develop and characterize biomarkers for early stage diagnosis and the treatment of endometrial cancer has become an important priority. Several biomarkers currently used to diagnose endometrial cancer are directly related to obesity. Although epigenetic and mutational biomarkers have been identified and have resulted in treatment options for patients with specific aberrations, many tumors do not harbor those specific aberrations. A promising alternative is to determine biomarkers based on differential gene expression, which can be used to estimate prognosis. METHODS: We evaluated 589 patients to determine differential expression between normal and malignant patient samples. We then supplemented these evaluations with immunohistochemistry staining of endometrial tumors and normal tissues. Additionally, we used the Library of Integrated Network-based Cellular Signatures to evaluate the effects of 1826 chemotherapy drugs on 26 cell lines to determine the effects of each drug on HPRT1 and AURKA expression. RESULTS: Expression of HPRT1, Jag2, AURKA, and PGK1 were elevated when compared to normal samples, and HPRT1 and PGK1 showed a stepwise elevation in expression that was significantly related to cancer grade. To determine the prognostic potential of these genes, we evaluated patient outcome and found that levels of both HPRT1 and AURKA were significantly correlated with overall patient survival. When evaluating drugs that had the most significant effect on lowering the expression of HPRT1 and AURKA, we found that Topo I and MEK inhibitors were most effective at reducing HPRT1 expression. Meanwhile, drugs that were effective at reducing AURKA expression were more diverse (MEK, Topo I, MELK, HDAC, etc.). The effects of these drugs on the expression of HPRT1 and AURKA provides insight into their role within cellular maintenance. CONCLUSIONS: Collectively, these data show that JAG2, AURKA, PGK1, and HRPT1 have the potential to be used independently as diagnostic, prognostic, or treatment biomarkers in endometrial cancer. Expression levels of these genes may provide physicians with insight into tumor aggressiveness and chemotherapy drugs that are well suited to individual patients.

Correction to: Membrane expression of thymidine kinase 1 and potential clinical relevance in lung, breast, and colorectal malignancies.

[This corrects the article DOI: 10.1186/s12935-018-0633-9.].

Evaluation of a brief intervention within a stepped care whole of service model for personality disorder.

BACKGROUND: Although there is growing evidence that stepped models of care are useful for providing appropriate, person centered care, there are very few studies applied to personality disorders. A brief, four session, psychological treatment intervention for personality disorder within a whole of service stepped care model was evaluated. The intervention stepped between acute emergency crisis mental health services and longer-term outpatient treatments. METHODS: Study 1 used service utilization data from 191 individuals referred to the brief intervention at a single community health site in a metropolitan health service. Proportions of individuals retained across the intervention and the referral pathways accessed following the intervention were examined. Study 2 examined 67 individuals referred to the brief intervention across 4 different sites in metropolitan health services. A range of measures of symptoms and quality of life were administered at the first and last session of the intervention. Effect sizes were calculated to examine mean changes across the course of the intervention. RESULTS: Study 1 found that 84.29% of individuals referred to the intervention attended at least 1 session, 60.21% attended 2 sessions or more and 41.89% attended 3 or more sessions. 13.61% of the sample required their care to be "stepped up" within the service, whereas 29.31% were referred to other treatment providers following referral to the intervention. Study 2 found a significant reduction in borderline personality disorder symptom severity and distress following the intervention, and an increase in quality of life. The largest reduction was found for suicidal ideation (d = 1.01). CONCLUSIONS: Brief psychological intervention was a useful step between acute services and longer-term treatments in this stepped model of care for personality disorder. Suicide risk and symptom severity reduced and quality of life improved, with only a small proportion of individuals requiring ongoing support from the health service following the intervention.

Membrane expression of thymidine kinase 1 and potential clinical relevance in lung, breast, and colorectal malignancies.

BACKGROUND: Lung, breast, and colorectal malignancies are the leading cause of cancer-related deaths in the world causing over 2.8 million cancer-related deaths yearly. Despite efforts to improve prevention methods, early detection, and treatments, survival rates for advanced stage lung, breast, and colon cancer remain low, indicating a critical need to identify cancer-specific biomarkers for early detection and treatment. Thymidine kinase 1 (TK1) is a nucleotide salvage pathway enzyme involved in cellular proliferation and considered an important tumor proliferation biomarker in the serum. In this study, we further characterized TK1's potential as a tumor biomarker and immunotherapeutic target and clinical relevance. METHODS: We assessed TK1 surface localization by flow cytometry and confocal microscopy in lung (NCI-H460, A549), breast (MDA-MB-231, MCF7), and colorectal (HT-29, SW620) cancer cell lines. We also isolated cell surface proteins from HT-29 cells and performed a western blot confirming the presence of TK1 on cell membrane protein fractions. To evaluate TK1's clinical relevance, we compared TK1 expression levels in normal and malignant tissue through flow cytometry and immunohistochemistry. We also analyzed RNA-Seq data from The Cancer Genome Atlas (TCGA) to assess differential expression of the TK1 gene in lung, breast, and colorectal cancer patients. RESULTS: We found significant expression of TK1 on the surface of NCI-H460, A549, MDA-MB-231, MCF7, and HT-29 cell lines and a strong association between TK1's localization with the membrane through confocal microscopy and Western blot. We found negligible TK1 surface expression in normal healthy tissue and significantly higher TK1 expression in malignant tissues. Patient data from TCGA revealed that the TK1 gene expression is upregulated in cancer patients compared to normal healthy patients. CONCLUSIONS: Our results show that TK1 localizes on the surface of lung, breast, and colorectal cell lines and is upregulated in malignant tissues and patients compared to healthy tissues and patients. We conclude that TK1 is a potential clinical biomarker for the treatment of lung, breast, and colorectal cancer.

TOP-DOWN AND BOTTOM-UP: THE ROLE OF SOCIAL INFORMATION PROCESSING AND MINDFULNESS AS PREDICTORS IN MATERNAL-INFANT INTERACTION.

The cross-generational transmission of attachment appears to reflect a complex interplay of factors, which have been challenging to identify. The current longitudinal study explored the maternal cognitive model of relationships through language use, maternal mindfulness, and attachment style assessed prenatally, as predictors of maternal response to distress and infant behavior at 6 months' postpartum. Infant behavior to the mother also was examined to provide an understanding of the evolving relationship. Thirty-two females were interviewed prenatally regarding social and family experiences. At 6 months' postpartum, each mother participated in a video-recorded session where she was asked to teach her infant a developmentally appropriate task. Videos were analyzed using the NCAST Teaching Protocol. Language use prenatally as well as the mindfulness facets (acting with awareness and describing) predicted the mothers' ability to respond to infant distress, indicating greater attunement. Infant's response to mother and clarity of cues also were predicted by maternal pronoun use. The study highlights the role of internal working models reflective of interpersonal beliefs, cognitive models, and current-moment awareness in maternal behavior. The effect of maternal language on infant behavior arguably indicates the infant's integration of maternal internal working models.

Personality disorder: A mental health priority area.

Personality disorders have received limited recognition as a public health priority, despite the publication of treatment guidelines and reviews showing effective treatments are available. Inclusive approaches to understanding and servicing personality disorder are required that integrate different service providers. This viewpoint paper identifies pertinent issues surrounding early intervention, treatment needs, consumer and carer experiences, and the need for accurate and representative data collection in personality disorder as starting points in mental health care reform.