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BACKGROUND: A decreased physical fitness has been reported in patients and survivors of childhood cancer. This is influenced by the negative effects of the disease and the treatment of childhood cancer. Exercise training for adult cancer patients has frequently been reported to improve physical fitness. In recent years, literature on this subject has also become available for children and young adults with cancer, both during and after treatment. This is an update of the original review that was performed in 2011. OBJECTIVES: To evaluate the effect of a physical exercise training intervention on the physical fitness (i.e. aerobic capacity, muscle strength, or functional performance) of children with cancer within the first five years from their diagnosis (performed either during or after cancer treatment), compared to a control group of children with cancer who did not receive an exercise intervention.To determine whether physical exercise within the first five years of diagnosis has an effect on fatigue, anxiety, depression, self efficacy, and HRQoL and to determine whether there are any adverse effects of the intervention. SEARCH METHODS: We searched the electronic databases of Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and PEDro; ongoing trial registries and conference proceedings on 6 September 2011 and 11 November 2014. In addition, we performed a handsearch of reference lists. SELECTION CRITERIA: The review included randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that compared the effects of physical exercise training with no training, in people who were within the first five years of their diagnosis of childhood cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies meeting the inclusion criteria, performed the data extraction, and assessed the risk of bias using standardized forms. Study quality was rated by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria. MAIN RESULTS: Apart from the five studies in the original review, this update included one additional RCT. In total, the analysis included 171 participants, all during treatment for childhood acute lymphoblastic leukaemia (ALL).The duration of the training sessions ranged from 15 to 60 minutes per session. Both the type of intervention and intervention period varied in all the included studies. However, the control group always received usual care.All studies had methodological limitations, such as small numbers of participants, unclear randomization methods, and single-blind study designs in case of one RCT and all results were of moderate to very low quality (GRADE).Cardiorespiratory fitness was evaluated by the 9-minute run-walk test, timed up-and-down stairs test, the timed up-and-go time test, and the 20-m shuttle run test. Data of the 9-minute run-walk test and the timed up-and-down stairs test could be pooled. The combined 9-minute run-walk test results showed significant differences between the intervention and the control groups, in favour of the intervention group (standardized mean difference (SMD) 0.69; 95% confidence interval (CI) 0.02 to 1.35). Pooled data from the timed up-and-down stairs test showed no significant differences in cardiorespiratory fitness (SMD -0.54; 95% CI -1.77 to 0.70). However, there was considerable heterogeneity (I(2) = 84%) between the two studies on this outcome. The other two single-study outcomes, 20-m shuttle run test and the timed up-and-go test, also showed positive results for cardiorespiratory fitness in favour of the intervention group.Only one study assessed the effect of exercise on bone mineral density (total body), showing a statistically significant positive intervention effect (SMD 1.07; 95% CI 0.48 to 1.66). The pooled data on body mass index showed no statistically significant end-score difference between the intervention and control group (SMD 0.59; 95% CI -0.23 to 1.41).Three studies assessed flexibility. Two studies assessed ankle dorsiflexion. One study assessed active ankle dorsiflexion, while the other assessed passive ankle dorsiflexion. There were no statistically significant differences between the intervention and control group with the active ankle dorsiflexion test; however, in favour of the intervention group, they were found for passive ankle dorsiflexion (SMD 0.69; 95% CI 0.12 to 1.25). The third study assessed body flexibility using the sit-and-reach distance test, but identified no statistically significant difference between the intervention and control group.Three studies assessed muscle strength (knee, ankle, back and leg, and inspiratory muscle strength). Only the back and leg strength combination score showed statistically significant differences on the muscle strength end-score between the intervention and control group (SMD 1.41; 95% CI 0.71 to 2.11).Apart from one sub-scale of the cancer scale (Worries; P value = 0.03), none of the health-related quality of life scales showed a significant difference between both study groups on the end-score. For the other outcomes of fatigue, level of daily activity, and adverse events (all assessed in one study), there were no statistically significant differences between the intervention and control group.None of the included studies evaluated activity energy expenditure, time spent on exercise, anxiety and depression, or self efficacy as an outcome. AUTHORS' CONCLUSIONS: The effects of physical exercise training interventions for childhood cancer participants are not yet convincing. Possible reasons are the small numbers of participants and insufficient study designs, but it can also be that this type of intervention is not as effective as in adult cancer patients. However, the first results show some positive effects on physical fitness in the intervention group compared to the control group. There were positive intervention effects for body composition, flexibility, cardiorespiratory fitness, muscle strength, and health-related quality of life (cancer-related items). These were measured by some assessment methods, but not all. However, the quality of the evidence was low and these positive effects were not found for the other assessed outcomes, such as fatigue, level of daily activity, and adverse events. There is a need for more studies with comparable aims and interventions, using a higher number of participants that also include diagnoses other than ALL.

Background: Alzheimer's disease is a global health concern, and with no present cure, prevention is critical. Exposure to adverse childhood experiences may increase the risk of developing Alzheimer's disease. This systematic review was conducted to synthesize the evidence on the associations between adverse childhood experiences (<18 years) and the risk of Alzheimer's disease in adulthood. Methods: A search strategy was developed and conducted to identify articles investigating the associations between exposure to adverse childhood experiences and the onset of Alzheimer's disease by searching key databases (CINAHL, MEDLINE and PsycInfo). Two reviewers independently determined the eligibility of studies according to pre-determined criteria, and assessed the methodological quality using the US National Heart, Lung and Blood Institute 14-item checklist for observational cohort and cross-sectional studies, respectively. Due to limited studies, a descriptive synthesis was performed. The protocol for this review is published in BMJ Open and registered with PROSPERO (CRD42020191439). Results: Our search yielded 781 articles, of which three (two separate analyses from the same cohort study and one cross-sectional study) met the predetermined eligibility criteria. The methodological quality assessment yielded an overall mean score of 78.9% (range 66.6 - 84.6%). All studies found adverse childhood experiences were associated with an increased risk of Alzheimer's disease. However, there was a limited number of available studies to inform the synthesis. Conclusions: Adverse childhood experiences appear to be associated with an increased risk of Alzheimer's disease, although, further research is needed. Registration and Protocol: The protocol for this review is registered with PROSPERO (CRD42020191439) and published with BMJ Open (Corney et al., 2021).

Abstract Aim Adverse childhood experiences (ACEs) are associated with numerous adverse mental and physical health outcomes. While interest in routine screening for ACEs is growing, there is still significant opposition to universal screening. This review explores the feasibility of implementing routine screening for ACEs in primary care settings. Subject and methods We searched PubMed, CINAHL, and PsycINFO, reference-mined relevant reviews, and consulted with key experts (June 2020). Studies from 1970 to date evaluating screening for childhood trauma, adversity, and ACEs in a routine healthcare setting, reporting quantitative or qualitative data were eligible. The project is registered in Open Science Framework (osf.io/5wef8) and reporting follows PRISMA-ScR guidelines. Results Searches retrieved 1402 citations. Of 246 publications screened as full text, 43 studies met inclusion criteria. Studies evaluated provider burden, familiarity with ACEs, practice characteristics, barriers to screening, frequency of ACE inquiry, reported or desired training, patient comfort, and referrals to support services. Conclusions This review found that the following factors increase the likelihood that ACE screenings can be successfully integrated into healthcare settings: staff trainings that increase provider confidence and competence in administering screenings, accessible and robust mental health resources, and organizational support. Further research should examine the scalability and sustainability of universal screening.

Adverse childhood experiences (ACEs) have been implicated in a range of negative health outcomes in adulthood, including increased suicide mortality. In this study, we explored the relationship between ACEs and hospital-treated self-harm. Specifically, we investigated whether those who had a history of repeat self-harm reported more ACEs than those who had self-harmed for the first time. Patients (n = 189) admitted to two hospitals in Glasgow (UK) following first-time (n = 41) or repeated (n = 148) self-harm completed psychosocial measures. Univariate analyses revealed that those presenting with repeat self-harm reported higher depressive symptoms, anxiety symptoms, intent to die, and ACEs, and lower dependent attachment style. However, only ACEs, along with female gender and depressive symptoms, significantly differentiated between the repeat self-harm group and the first-time self-harm group in the multivariate model. Controlling for all other psychosocial variables, participants who reported 4+ ACEs were significantly more likely to be in the repeat self-harm group as compared to those who experienced 0–3 ACEs. This finding highlights the pernicious effect of exposure to multiple ACEs. Further research is urgently required to better understand the mechanisms that explain this relationship. Clinicians should be aware of the extent of the association between ACEs and repeat self-harm.

BACKGROUND: The well-established relationship between childhood adversity and psychosis is likely to involve other factors such as genetic variants that can help us to understand why not everyone exposed to adverse events develops psychotic symptoms later in life. AIMS: We investigated the influence of childhood abuse and neglect on positive and negative psychotic-like experiences in adulthood and the potential moderating effect of the BDNF-Val66Met polymorphism. METHOD: Psychotic-like experiences and childhood adversity were assessed in 533 individuals from the general population. RESULTS: Childhood abuse showed a strong independent effect on the positive dimension of psychotic-like experiences (β = 0.16, s.e. = 0.05, P = 0.002). Furthermore, this association was moderated by the BDNF-Val66Met polymorphism (β = 0.27, s.e. = 0.10, P = 0.004). CONCLUSIONS: Individuals exposed to childhood abuse are more likely to report positive psychotic-like experiences. Met carriers reported more positive psychotic-like experiences when exposed to childhood abuse than did individuals carrying the Val/Val genotype. Therefore, the observed gene-environment interaction effect may be partially responsible for individual variation in response to childhood abuse.

BACKGROUND: Studies demonstrating an association between childhood trauma and psychosis in adulthood have not systematically explored gender differences. AIMS: To investigate gender differences in the prevalence of childhood sexual and physical abuse among people with psychosis in comparison with healthy controls. METHOD: The Childhood Experiences of Care and Abuse Questionnaire was completed to elicit experiences of sexual and physical abuse during childhood in first-episode psychosis cases and population-based controls. RESULTS: Among women, those in the cases group were twice as likely to report either physical or sexual abuse compared with controls following adjustment for all confounders. In particular, the effect of physical abuse in women was stronger and more robust than that for sexual abuse. A similar trend was found for psychotic-like experiences in the female control group. No association was found in men. CONCLUSIONS: Reports of severe childhood physical or sexual abuse were associated with psychosis in women but not in men.

This document of the European Society of Human Genetics contains recommendations regarding responsible implementation of expanded carrier screening. Carrier screening is defined here as the detection of carrier status of recessive diseases in couples or persons who do not have an a priori increased risk of being a carrier based on their or their partners' personal or family history. Expanded carrier screening offers carrier screening for multiple autosomal and X-linked recessive disorders, facilitated by new genetic testing technologies, and allows testing of individuals regardless of ancestry or geographic origin. Carrier screening aims to identify couples who have an increased risk of having an affected child in order to facilitate informed reproductive decision making. In previous decades, carrier screening was typically performed for one or few relatively common recessive disorders associated with significant morbidity, reduced life-expectancy and often because of a considerable higher carrier frequency in a specific population for certain diseases. New genetic testing technologies enable the expansion of screening to multiple conditions, genes or sequence variants. Expanded carrier screening panels that have been introduced to date have been advertised and offered to health care professionals and the public on a commercial basis. This document discusses the challenges that expanded carrier screening might pose in the context of the lessons learnt from decades of population-based carrier screening and in the context of existing screening criteria. It aims to contribute to the public and professional discussion and to arrive at better clinical and laboratory practice guidelines.

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic-pituitary-adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1(F) NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10(-8), 5.18 × 10(-7) and 1.25 × 10(-9), respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology.