A History of Trauma is Associated with Aggression, Depression, Non-Suicidal Self-Injury Behavior, and Suicide Ideation in First-Episode Psychosis.

The association between trauma and psychosis outcomes is well-established, and yet the impact of trauma on comorbid clinical symptoms-such as aggression, non-suicidal self-injury behavior (NSSIB), suicide ideation, and suicide behavior-for those with psychosis is unclear. To effectively treat those with first-episode psychosis (FEP) and a history of trauma, we need to understand the impact of trauma on their whole presentation. FEP participants were recruited from an Early Psychosis Program (N = 187, ages 12-35, 72.2% male). Clinicians gathered history of trauma, aggression, and suicide data, and rated current symptom severity and functioning. Data was coded using clinician rated measures, self-report measures, and retrospective clinical chart review. Regression analyses examined whether trauma was associated with a history of aggression, suicidal ideation, suicide behavior, NSSIB, symptoms, and functioning. Trauma was associated with aggression, aggression severity and type of aggression (aggression towards others). Trauma was also associated with depression severity, suicide ideation, most severe suicide ideation, and NSSIB. Trauma was not associated with suicide behavior, severity of suicide behavior or psychosocial functioning. Integrating trauma treatment into FEP care could reduce rates of depression, aggression, suicide ideation, and NSSIB for those with a history of trauma. To reduce suicide attempt occurrence and improve functioning, more research is needed

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Funder: Breast Cancer Now (BCN); doi: https://doi.org/10.13039/100009794Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2009-223175, HEALTH-F2-2009-223175Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada); doi: https://doi.org/10.13039/501100000024Funder: Quebec Breast cancer Foundation Genome QuebecFunder: U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM); doi: https://doi.org/10.13039/100000092Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))Funder: European Union’s Horizon 2020Funder: Deutsche Krebshilfe (German Cancer Aid); doi: https://doi.org/10.13039/501100005972Funder: BCAST - European Union’s Horizon 2020Funder: Breast Cancer Now; doi: https://doi.org/10.13039/501100007913Abstract: Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women

Psychotic Like Experiences are Associated with Suicide Ideation and Behavior in 9 to 10 Year Old Children in the United States

Those experiencing psychotic like experiences (PLEs) are at higher risk for suicide ideation and behavior. However, it is unclear if PLEs are related to suicide ideation and behavior in children, and whether other factors such as impulsivity or emotion dysregulation might moderate the relationship. We hypothesize that PLEs are associated with suicide ideation and behavior, with impulsivity and emotion dysregulation moderating this relationship, in middle childhood. History of PLEs, suicide ideation and behavior, depression, emotion dysregulation, and impulsivity were assessed for 10,624 children aged 9 to 10.9 years (47.8% female, 34.4% minority race, 20.0% Hispanic) as part of the Adolescent Brain Cognitive Development℠ study. Hypotheses about associations between variables were assessed using hierarchical linear modeling. PLEs were associated with suicide ideation and suicide behavior even when controlling for depression severity. Emotion dysregulation and impulsivity were also associated with suicide ideation and moderated the relationship between PLEs and suicide ideation. Variation in suicide ideation due to impulsivity and emotion dysregulation appears to be strongest when people are experiencing low levels to no PLEs. Only impulsivity and PLEs were associated with suicide behavior. Depression was associated with suicide ideation, but not suicide behavior. PLEs may be an important risk factor for suicide ideation and behavior in 9 to 10-year-old children, comparable to adult and adolescent populations. When considering prevention of suicidality, these data suggest that considering the relations between PLEs, impulsivity and emotion dysregulation may be important

A History of Trauma is Associated with Aggression, Depression, Non-Suicidal Self-Injury Behavior, and Suicide Ideation in First-Episode Psychosis

The association between trauma and psychosis outcomes is well-established, and yet the impact of trauma on comorbid clinical symptoms—such as aggression, non-suicidal self-injury behavior (NSSIB), suicide ideation, and suicide behavior—for those with psychosis is unclear. To effectively treat those with first-episode psychosis (FEP) and a history of trauma, we need to understand the impact of trauma on their whole presentation. FEP participants were recruited from an Early Psychosis Program (N = 187, ages 12–35, 72.2% male). Clinicians gathered history of trauma, aggression, and suicide data, and rated current symptom severity and functioning. Data was coded using clinician rated measures, self-report measures, and retrospective clinical chart review. Regression analyses examined whether trauma was associated with a history of aggression, suicidal ideation, suicide behavior, NSSIB, symptoms, and functioning. Trauma was associated with aggression, aggression severity and type of aggression (aggression towards others). Trauma was also associated with depression severity, suicide ideation, most severe suicide ideation, and NSSIB. Trauma was not associated with suicide behavior, severity of suicide behavior or psychosocial functioning. Integrating trauma treatment into FEP care could reduce rates of depression, aggression, suicide ideation, and NSSIB for those with a history of trauma. To reduce suicide attempt occurrence and improve functioning, more research is needed

Nanotechnology for a Sustainable Future: Addressing Global Challenges with the International Network4Sustainable Nanotechnology.

Nanotechnology has important roles to play in international efforts in sustainability. We discuss how current and future capabilities in nanotechnology align with and support the United Nations’ Sustainable Development Goals. We argue that, as a field, we can accelerate the progress toward these goals both directly through technological solutions and through our special interdisciplinary skills in communication and tackling difficult challenges. We discuss the roles of targeting solutions, technology translation, the circular economy, and a number of examples from national efforts around the world in reaching these goals. We have formed a network of leading nanocenters to address these challenges globally and seek to recruit others to join us

Systemic infusion of TLR3-ligand and IFN-α in patients with breast cancer reprograms local tumor microenvironments for selective CTL influx

Background Presence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts the effectiveness of cancer immunotherapies. The ability of toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory T cell (Treg)-attractants) in the TME, but not in healthy tissues, observed in our preclinical studies, suggested that their systemic application can reprogram local TMEs.Methods Six evaluable patients (33–69 years) with metastatic triple-negative breast cancer received six doses of systemic chemokine-modulating (CKM) regimen composed of TLR3 ligand (rintatolimod; 200 mg; intravenous), IFN-α2b (20 MU/m2; intravenous) and COX2 inhibitor (celecoxib; 2×200 mg; oral) over 2 weeks. The predetermined primary endpoint was the intratumoral change in the expression of CTL marker, CD8α, in the post-CKM versus pre-CKM tumor biopsies. Patients received follow-up pembrolizumab (200 mg, intravenously, every 3 weeks), starting 3–8 days after completion of CKM.Results Post-CKM biopsies showed selectively increased CTL markers CD8α (average 10.2-fold, median 5.5-fold, p=0.034) and granzyme B (GZMB; 6.1-fold, median 5.8-fold, p=0.02), but not FOXP3 (Treg marker) relative to HPRT1 expression, resulting in the increases in average CD8α/FOXP3 ratio and GZMB/FOXP3 ratio. CKM increased intratumoral CTL-attractants CCL5 and CXCL10, but not Treg-attractants CCL22 or CXCL12. In contrast, CD8+ T cells and their CXCR3+ subset showed transient decreases in blood. One clinical response (breast tumor autoamputation) and three stable diseases were observed. The patient with clinical response remains disease free, with a follow-up of 46 months as of data cut-off.Conclusions Short-term systemic CKM selectively increases CTL numbers and CTL/Treg ratios in the TME, while transiently decreasing CTL numbers in the blood. Transient effects of CKM suggest that its simultaneous application with checkpoint blockade and other forms of immunotherapy may be needed for optimal outcomes

Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease

Low serum magnesium has been associated with kidney function decline in persons with diabetes as well as cardiovascular disease in the general population. Since the association of serum magnesium with incident kidney disease in the general population is unknown, we assessed this in 13,226 participants (aged 45 to 65) in the Atherosclerosis Risk in Communities study with baseline estimated glomerular filtration rate of at least 60 ml/min/1.73m2 in years 1987–89 and followed through 2010. The risks for incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) associated with baseline total serum magnesium levels were evaluated using Cox regression. There were 1,965 CKD and 208 ESRD events during a median follow-up of 21 years. In adjusted analysis, low serum magnesium levels (0.7mmol/L or less) had significant associations with incident CKD and ESRD compared with the highest quartile with adjusted hazard ratio of 1.58 (95% CI: 1.35–1.87) for CKD and 2.39 (95% CI: 1.61–3.56) for ESRD. These associations remained significant after excluding users of diuretics and across subgroups stratified by hypertension, diabetes, and self-reported race. Thus, in a large sample of middle-aged adults, low total serum magnesium was independently associated with incident CKD and ESRD. Further studies are needed to determine whether modification of serum magnesium levels might alter subsequent incident kidney disease rates