Adverse childhood experiences, associated stressors and comorbidities in children and youth with fetal alcohol spectrum disorder across the justice and child protection settings in Western Australia.

BACKGROUND: Individuals with Fetal Alcohol Spectrum Disorder (FASD) are at risk of having adverse childhood experiences (ACEs), especially those with child protection and/or justice system involvement. The complex relationship between FASD and psychosocial vulnerabilities in the affected individual is an important clinical risk factor for comorbidity. This study (1) explored the ACEs and associated stressors in individuals with FASD; (2) investigated the association between ACEs and negative outcomes, i.e., justice/child protection system involvement; and (3) examined the relationship between ACEs and comorbid conditions such as mood and neurodevelopmental disorders. METHODS: Data were collected retrospectively via file review from diagnostic clinics in Western Australia. Life adversity was coded using a standardised ACEs questionnaire. A total of 211 participants (72% males) with FASD with a mean age of 11 years (range = 2-21) were included in the final sample. 70% of the total sample had been involved with the child protection system and 40% had trouble with the law. RESULTS: Exposure to drinking/substance misuse at home (70%) and domestic violence (52%) were the two most common ACEs across the total sample. In the entire cohort, 39% had four or more ACEs, indicating higher risks of poor health outcomes. Additional stressors recorded were disengagement from school (43%), transiency (19%), victims of bullying (12%), traumatic brain injury (9%) and homelessness (5%). ACEs such as drinking/substance misuse at home, emotional neglect and physical neglect were positively associated with child protection system involvement. Additionally, exposure to domestic violence was positively correlated with justice system involvement. Higher rates of life adversity in this clinical population were associated with an increased number of comorbidities. Specifically, those with FASD who had comorbidities such as attachment disorder, substance use disorder, and PTSD also reported higher ACEs scores. CONCLUSION: ACEs were common in this clinical population. Increased ACEs in this sample were associated with increased comorbidities and involvement with the child protection and/or justice system. This highlights that prevention, intervention and early diagnosis of FASD are important for at risk children to reduce the negative effects of ACEs.

Correction: Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.

[This corrects the article DOI: 10.1371/journal.pone.0283394.].

Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.

INTRODUCTION: Inclusion body myositis (IBM) is the most commonly acquired skeletal muscle disease of older adults involving both autoimmune attack and muscle degeneration. As exercise training can improve outcomes in IBM, this study assessed whether a combination of testosterone supplementation and exercise training would improve muscle strength, physical function and quality of life in men affected by IBM, more than exercise alone. METHODS: This pilot study was a single site randomised, double-blind, placebo-controlled, crossover study. Testosterone (exercise and testosterone cream) and placebo (exercise and placebo cream) were each delivered for 12 weeks, with a two-week wash-out between the two periods. The primary outcome measure was improvement in quadriceps isokinetic muscle strength. Secondary outcomes included assessment of isokinetic peak flexion force, walk capacity and patient reported outcomes, and other tests, comparing results between the placebo and testosterone arms. A 12-month Open Label Extension (OLE) was offered using the same outcome measures collected at 6 and 12-months. RESULTS: 14 men completed the trial. There were no significant improvements in quadriceps extension strength or lean body mass, nor any of the secondary outcomes. Improvement in the RAND Short Form 36 patient reported outcome questionnaire 'emotional wellbeing' sub-category was reported during the testosterone arm compared to the placebo arm (mean difference [95% CI]: 6.0 points, [95% CI 1.7,10.3]). The OLE demonstrated relative disease stability over the 12-month period but with a higher number of testosterone-related adverse events. CONCLUSIONS: Adding testosterone supplementation to exercise training did not significantly improve muscle strength or physical function over a 12-week intervention period, compared to exercise alone. However, the combination improved emotional well-being over this period, and relative stabilisation of disease was found during the 12-month OLE. A longer duration trial involving a larger group of participants is warranted.

The relationship between spider naevi & de novo arteriovenous malformations in chronic liver disease.

We report a patient with decompensated alcoholic liver cirrhosis (Child-Turcotte-Pugh class C) who developed a de novo left frontal cerebral AVM and a subcutaneous left temporal scalp spider naevus. Arteriovenous malformations (AVMs) are vascular abnormalities previously thought to be congenital in nature, although new research has revealed the potential for de novo AVM formation through a two-hit hypothesis. We propose that the oestrogen-rich environment seen in chronic liver disease could act as the second hit to allow for an angiogenic state favouring de novo AVM development. We also postulate that spider naevi are formed through a similar mechanism and may represent early-stage AVMs.

The impact of the 2022 Ukraine/Russian conflict on cancer clinical trials.

Since the invasion of Ukraine in February 2022, clinical trial conduct has become extremely challenging due to damage to the healthcare infrastructure and patient displacement. This current study aimed to estimate the number of cancer clinical trials at risk of impact from the conflict. A descriptive analysis and narrative review were completed using data from cancer clinical trials with sites in Russia or Ukraine using the 'clinical trials.gov' online database between February 2022 and May 2022. There were 508 clinical trials involving sites in Ukraine or Russia. Most were multinational studies (470 of 508; 93%). The majority of studies were phase 3 (344 of 508; 68%) and these also had the largest sample sizes (median 624, range 12-5637). The most common tumour types were lung (128 of 508; 25%), urogenital (94 of 508; 19%) and breast (78 of 508; 15%). A meaningful number of trials had curative intent (129 of 508; 25%). The most common intervention was immunotherapy-related (218 of 508; 43%), followed by other targeted therapy (185 of 508; 36%). Ukraine and Russia are both large centres for global clinical trial activity. The invasion of Ukraine may result in underpowering of international clinical trial results with loss of future recruitment sites for both countries.

Brain activations show association with subsequent endocrine responses to oral glucose challenge in a satiation-level dependent manner.

Aims: The communication between brain and peripheral homeostatic systems is a central element of ingestive control. We set out to explore which parts of the brain have strong functional connections to peripheral signalling molecules in a physiological context. It was hypothesised that associations can be found between endocrine response to glucose ingestion and preceding brain activity in dependence of the nutritional status of the body. Materials and methods: Young, healthy male participants underwent both a 38 â€‹h fasting and a control condition with standardized meals. On the second day of the experiment, participants underwent fMRI scanning followed by ingestion of glucose solution in both conditions. Subsequent endocrine responses relevant to energy metabolism were assessed. Associations between preceding brain activation and endocrine responses were examined. Results: In both fasting and non-fasting conditions, brain activity was associated with subsequent endocrine responses after glucose administration, but relevant brain areas differed substantially between the conditions. In the fasting condition relations between the caudate nucleus and the orbitofrontal regions with insulin and C-peptide were prevailing, whereas in the non-fasting condition associations between various brain regions and adiponectin and cortisol were the predominant significant outcome. Conclusion: Connections between endocrine response following a glucose challenge and prior brain activity suggests that the brain is playing an active role in the networks regulating food intake and associated endocrine signals. Further studies are needed to demonstrate causation.

Endocrine profile dataset of fasting and normally eating young, healthy men and following activation of brain areas involved in ingestive behaviour.

Data includes endocrine data (adiponectin, ACTH, cortisol, C-peptide, insulin and glucose) of a 38 hour fasting intervention and a control condition with standardised meals in young healthy male subjects. The data was collected using a within-design approach. The data of ten common bilateral regions of interest (ROIs) involved in ingestive behaviour are included as fMRI percent signal change measurements of the amygdala, caudate nucleus, insula (classified into three regions), nucleus accumbens (NAcc), orbitofrontal cortex (OFC, classified into two different regions), pallidum, and lastly, the putamen. These measurements were performed whilst images of food were shown to participants during fMRI who would rate them on a scale from 1 to 8. Reaction times as well as each image's score are also included in the dataset. Endocrine data is especially useful as it is a well-controlled dataset of healthy young males in fasting and satiated conditions. Furthermore, this data can provide a physiological reference for experiments in patients with impaired glucose tolerance or metabolic syndrome. fMRI data may be useful as an extension of an existing dataset or for replication of the collected data.