The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. METHODS: The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. RESULTS: There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. CONCLUSIONS: The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. FUNDING: This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).

Targeting the chromatin binding of exportin-1 disrupts NFAT and T cell activation.

Exportin-1 (XPO1/CRM1) plays a central role in the nuclear-to-cytoplasmic transport of hundreds of proteins and contributes to other cellular processes, such as centrosome duplication. Small molecules targeting XPO1 induce cytotoxicity, and selinexor was approved by the Food and Drug Administration in 2019 as a cancer chemotherapy for relapsed multiple myeloma. Here, we describe a cell-type-dependent chromatin-binding function for XPO1 that is essential for the chromatin occupancy of NFAT transcription factors and thus the appropriate activation of T cells. Additionally, we establish a class of XPO1-targeting small molecules capable of disrupting the chromatin binding of XPO1 without perturbing nuclear export or inducing cytotoxicity. This work defines a broad transcription regulatory role for XPO1 that is essential for T cell activation as well as a new class of XPO1 modulators to enable therapeutic targeting of XPO1 beyond oncology including in T cell-driven autoimmune disorders.

Effectiveness of anterior repositioning splint versus other occlusal splints in the management of temporomandibular joint disc displacement with reduction: A meta-analysis.

BACKGROUND: Disc displacement with reduction (DDwR) is among the common disc disorders of temporomandibular joint (TMJ), which can be managed conservatively by splint therapy. Anterior repositioning splint (ARS) is the most commonly prescribed splint by dental practitioners, but not getting a normal disc-condyle relationship always and other side effects lead to need of comparing with other occlusal splints. This review will help in informed decision-making by clinicians in choosing an appropriate splint type for patients. AIM: The aim is to compare the effectiveness of ARS in the management of DDwR with other occlusal splints for TMJ and muscle pain, TMJ noise, any adverse effects, regaining normal disc-condyle relationship. MATERIALS AND METHODS: We followed published protocol in the International prospective register of systematic reviews. Databases were searched till May 2023 using different search strategies as per the database. Title and abstract screening, followed by full-text screening and data extraction with risk of bias, was done by two independent reviewers in Covidence. Outcomes were reported as risk ratio (RR) or mean difference (MD) for dichotomous or continuous outcomes, respectively, using RevMan 5.4 (Review Manager 5.4) software. We used a random effect model for statistical analysis. Certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation Guideline Development Tool (GRADEpro GDT) software. RESULTS: A total of 1145 reports were found from a database search. After screening, four studies were included for systematic reviews. Other occlusal splints reported were sagittal vertical extrusion device and mandibular ARS, full hard stabilization splint of canine or centric stabilization type. Data of only two studies could be used for meta-analysis having 30 participants received ARS and 40 received other occlusal splints. We did not find evidence of any difference between ARS and other occlusal splints for TMJ clicking in short term (RR 1.25, 95% confidence interval [CI] 0.91-1.72) but a small difference in favor of other occlusal splint in long term (RR 2.40, 95% CI 1.04-5.55). No evidence of any difference was found between both treatments for TMJ pain in short term (MD-5.68, 95% CI-17.31-5.95) and long term (MD 0.00, 95% CI-2.86-2.86) and muscle pain in short term. The certainty of evidence for comparison of two treatments for different outcomes was of low or very low level. CONCLUSION: Evidence is uncertain that other occlusal splints reduced TMJ clicking slightly in comparison to ARS. For the remaining outcomes, no evidence of any difference was found between the two splints and it may be biased due to selection bias, inadequate blinding of participants, and outcome assessor.

Changes in Early Childhood Irritability and Its Association With Depressive Symptoms and Self-Harm During Adolescence in a Nationally Representative United Kingdom Birth Cohort.

OBJECTIVE: This study aimed to investigate longitudinal associations between changes in early childhood irritability, and depressive symptoms and self-harm at 14 years. METHOD: We used data from 7,225 children in a UK-based general population birth cohort. Childhood irritability was measured at 3, 5, and 7 years using 4 items from 2 questionnaires (the Children's Social Behaviour Questionnaire [CSBQ] and the Strengths and Difficulties Questionnaire [SDQ]). Participants reported depressive symptoms via the short Mood and Feelings Questionnaire (sMFQ) and self-harm via a single-item question, at 14 years. We used multilevel models to calculate within-child change in irritability between 3 and 7 years and examined associations between irritability, and depressive symptoms and self-harm at 14 years using linear and logistic regression models, respectively. We adjusted for child and family sociodemographic/economic characteristics, mental health difficulties, and child cognitive development. RESULTS: Irritability at ages 5 and 7 years was positively associated with depressive symptoms and self-harm at age 14 years. Irritability that remained high between 3 and 7 years was associated with depressive symptoms and self-harm at 14 years in unadjusted (depressive symptoms: ß coefficient = 0.22, 95 % CI = 0.08-0.37, p = .003; self-harm: odds ratio = 1.09, 95 % CI = 1.01-1.16, p = .019) and adjusted models (depressive symptoms: ß coefficient = 0.31, 95 % CI = 0.17-0.45, p < .001; self-harm: odds ratio = 1.12, 95 % CI = 1.0.4-1.19, p = .004). Results were similar in imputed samples. CONCLUSION: Children with irritability that remains high between 3 and 7 years are more likely to report higher depressive symptoms and self-harm during adolescence. These findings support early intervention for children with high irritability and universal interventions in managing irritability for parents of preschool-aged children.

Treatment of an Ill-Fitting Complete Dental Prosthesis with Digital Sensor Device: A Case Report.

Complete edentulism is one of the most common problems encountered by geriatric individuals. With advanced aging, despite attempts made to retain natural dentition, loss of entire teeth is yet observed. For precise denture fabrication, a digital sensor device was used during the making procedure. The use of sensor device aided in better appreciation and more retentiveness of denture.

Mental health impact of autism on families of children with intellectual and developmental disabilities of genetic origin.

Background: Many children with an intellectual or developmental disability (IDD) have associated autism spectrum disorders (ASD), as well as an increased risk of mental health difficulties. In a cohort with IDD of genetic aetiology, we tested the hypothesis that excess risk attached to those with ASD + IDD, in terms of both children's mental health and parental psychological distress. Methods: Participants with a copy number variant or single nucleotide variant (5-19 years) were recruited via UK National Health Service. 1904 caregivers competed an online assessment of child mental health and reported on their own psychological wellbeing. We used regression to examine the association between IDD with and without co-occurring ASD, and co-occurring mental health difficulties, as well as with parental psychological distress. We adjusted for children's sex, developmental level, physical health, and socio-economic deprivation. Results: Of the 1904 participants with IDD, 701 (36.8%) had co-occurring ASD. Children with both IDD and ASD were at higher risk of associated disorders than those with IDD alone (ADHD: OR = 1.84, 95% confidence interval [CI] 1.46-2.32, p < 0.0001; emotional disorders: OR = 1.85, 95%CI 1.36-2.5, p < 0.0001; disruptive behaviour disorders: OR = 1.79, 95%CI 1.36-2.37, p < 0.0001). The severity of associated symptoms was also greater in those with ASD (hyperactivity: B = 0.25, 95%CI 0.07-0.34, p = 0.006; emotional difficulties: B = 0.91, 95%CI 0.67 to 1.14, p < 0.0001; conduct problems: B = 0.25, 95%CI 0.05 to 0.46, p = 0.013). Parents of children with IDD and ASD also reported greater psychological distress than those with IDD alone (ß = 0.1, 95% CI 0.85 to 2.21, p < 0.0001). Specifically, in those with ASD, symptoms of hyperactivity (ß = 0.13, 95% CI 0.29-0.63, p < 0.0001), emotional difficulties (ß = 0.15, 95% CI 0.26-0.51, p < 0.0001) and conduct difficulties (ß = 0.07, 95% CI 0.07-0.37, p < 0.004) all significantly contributed to parental psychological distress. Conclusions: Among children with IDD of genetic aetiology, one third have co-occurring ASD. Not only do those with co-occurring ASD present with a wider range of associated mental health disorders and more severe mental health difficulties than those with IDD alone, but their parents also experience more psychological distress. Our findings suggest that the additional mental health and behavioural symptoms in those with ASD contributed to the degree of parental psychological distress.

Differences in quality of life and patient satisfaction between complete denture occlusion schemes: A parallel randomized control trial.

STATEMENT OF PROBLEM: Bilateral balanced occlusion has been advocated over nonbalanced occlusion for improved removable complete denture stability and function. However, assessments of quality of life and patient satisfaction studies between the 2 occlusion schemes are lacking. PURPOSE: The objective of this parallel randomized control trial was to determine the difference in quality of life and patient satisfaction between the nonbalanced and bilaterally balanced occlusal schemes. MATERIAL AND METHODS: Sixty participants were included in the parallel randomized control trial of nonbalanced and bilaterally balanced complete dentures. Thirty were recruited into each group with definitive inclusion and exclusion criteria as per the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Quality of life was estimated from the oral health quality of life (Oral Health Impact profile) for edentulous patients questionnaire, and patient satisfaction was analyzed from a visual analog scale. The estimation was made at 0, 3, and 6 months after denture insertion. The data were statistically analyzed with the Friedman, Mann-Whitney, and t test (α=.05). RESULTS: The mean ±standard deviation Oral Health Impact profile score was 60.81 ±8.87 for nonbalanced dentures and 64.12 ±8.98 for bilaterally balanced dentures. The mean ±standard deviation visual analog scale score was 2.84 ±0.28 for nonbalanced dentures and 2.90 ±0.31 for bilaterally balanced dentures. The Mann-Whitney and t test indicated nonsignificant differences between the 2 groups and at different time intervals for Oral Health Impact profile and visual analog scale scores (P>.05). CONCLUSIONS: The study detected no significant differences between the 2 occlusal schemes in quality of life or patient satisfaction.

The art of managing various ocular defects in different clinical scenarios: A case series.

The absence of eye and irradiation post-enucleation may result in problems like dryness of the eye sockets, itching and crusting. This may lead to poor prosthesis adaptation and a lack of patient acceptance of the prosthesis. To combat the most common problem of dryness, patients are advised artificial tears to use as teardrops or ocular prostheses along with a tear reservoir. This case series describes methods of fabricating ocular prosthesis indicated in different scenarios: the modified stock ocular and a custom-made ocular prosthesis when tearing secretion is enough in the eye socket and an ocular prosthesis with a tear reservoir in cases showing reduced tear secretion. A novel technique of fabricating hollow lightweight ocular prostheses having the sustained prolonged release of artificial tears has been described.

Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE, a UK national cohort study.

BACKGROUND: Children with intellectual disability frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aim to determine the effect of genomics, inheritance, and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared with the general population. METHODS: IMAGINE is a prospective cohort study using online mental health and medical assessments in a cohort of 3407 UK participants with intellectual disability and pathogenic genomic variants as identified by the UK's National Health Service (NHS). Our study is on a subset of these participants, including all children aged 4-19 years. We collected diagnostic genomic reports from NHS records and asked primary caregivers to provide an assessment of their child using the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), the Adaptive Behaviour Assessment System 3 (ABAS-3), and a medical history questionnaire. Each child was assigned a rank based on their postcode using the index of multiple deprivation (IMD). We compared the IMAGINE cohort with the 2017 National Survey of Children's Mental Health in England. The main outcomes of interest were mental health and neurodevelopment according to the DAWBA and SDQ. FINDINGS: We recruited 2770 children from the IMAGINE study between Oct 1, 2014 and June 30, 2019, of whom 2397 (86·5%) had a basic assessment of their mental health completed by their families and 1277 (46·1%) completed a medical history questionnaire. The mean age of participants was 9·2 years (SD 3·9); 1339 (55·9%) were boys and 1058 (44·1%) were girls. 355 (27·8%) of 1277 reported a seizure disorder and 814 (63·7%) reported movement or co-ordination problems. 1771 (73·9%) of 2397 participants had a pathogenic copy number variant (CNV) and 626 (26·1%) had a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk (RR) of co-occurring neuropsychiatric diagnoses, compared with the English national population, was high: autism spectrum disorder RR 29·2 (95% CI 23·9-36·5), ADHD RR 13·5 (95% CI 11·1-16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas than those with a de novo variant. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV. INTERPRETATION: Children with genomic variants and intellectual disability are at an increased risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk. Early genomic investigations of children with intellectual disability could facilitate the identification of the most vulnerable children. Additionally, harnessing parental expertise using online DAWBA assessments could rapidly identify children with exceptional needs to child mental health services. FUNDING: UK Medical Research Council and Medical Research Foundation.

Inhibition of SC4MOL and HSD17B7 shifts cellular sterol composition and promotes oligodendrocyte formation.

While the cholesterol biosynthesis pathway has been extensively studied, recent work has forged new links between inhibition of specific sterol pathway enzymes, accumulation of their unique sterol substrates, and biological areas as diverse as cancer, immunology, and neurodegenerative disease. We recently reported that dozens of small molecules enhance formation of oligodendrocytes, a glial cell type lost in multiple sclerosis, by inhibiting CYP51, Sterol 14-reductase, or EBP and inducing cellular accumulation of their 8,9-unsaturated sterol substrates. Several adjacent pathway enzymes also have 8,9-unsaturated sterol substrates but have not yet been evaluated as potential targets for oligodendrocyte formation or in many other biological contexts, in part due to a lack of available small-molecule probes. Here, we show that genetic suppression of SC4MOL or HSD17B7 increases the formation of oligodendrocytes. Additionally, we have identified and optimized multiple potent new series of SC4MOL and HSD17B7 inhibitors and shown that these small molecules enhance oligodendrocyte formation. SC4MOL inhibitor CW4142 induced accumulation of SC4MOL's sterol substrates in mouse brain and represents an in vivo probe of SC4MOL activity. Mechanistically, the cellular accumulation of these 8,9-unsaturated sterols represents a central driver of enhanced oligodendrocyte formation, as exogenous addition of purified SC4MOL and HSD17B7 substrates but not their 8,9-saturated analogs promotes OPC differentiation. Our work validates SC4MOL and HSD17B7 as novel targets for promoting oligodendrocyte formation, underlines a broad role for 8,9-unsaturated sterols as enhancers of oligodendrocyte formation, and establishes the first high-quality small molecules targeting SC4MOL and HSD17B7 as novel tools for probing diverse areas of biology.

Risk-taking to obtain reward: sex differences and associations with emotional and depressive symptoms in a nationally representative cohort of UK adolescents.

BACKGROUND: Cognitive mechanisms that characterize or precede depressive symptoms are poorly understood. We investigated cross-sectional and longitudinal associations between risk taking to obtain reward and adolescent depressive symptoms in a large prospective cohort, using the Cambridge Gambling Task (CGT). We also explored sex differences. METHODS: The Millennium Cohort Study (MCS) is an ongoing UK study, following the lives of 19 000 individuals born 2000/02. The CGT was completed at ages 11 (n = 12 355) and 14 (n = 10 578). Our main exposure was the proportion of points gambled, when the odds of winning were above chance (risk-taking to obtain reward). Outcomes were emotional symptoms (Strengths and Difficulties Questionnaire, SDQ) at age 11 and depressive symptoms (short Mood and Feelings Questionnaire, sMFQ) at age 14. We calculated cross-sectional and longitudinal associations, using linear regressions. RESULTS: In univariable models, there was evidence of cross-sectional associations between risk-taking and SDQ/sMFQ scores, but these associations disappeared after we adjusted for sex. Longitudinally, there was weak evidence of an association between risk-taking and depressive symptoms in females only [a 20-point increase in risk-taking at age 11 was associated with a reduction of 0.31 sMFQ points at age 14 (95% CI -0.60 to -0.02)]. At both time-points, females were less risk-taking than males. CONCLUSIONS: We found no convincing evidence of a relationship between risk-taking to obtain reward and depressive symptoms. There were large sex differences in risk-taking, but these do not appear to contribute to the female preponderance of depressive symptoms in adolescence.

Association of Emotion Regulation Trajectories in Childhood With Anorexia Nervosa and Atypical Anorexia Nervosa in Early Adolescence.

Importance: People with anorexia nervosa often experience difficulties regulating their emotions. There is no longitudinal evidence as to whether these differences are already present in childhood or when they begin to emerge. Objective: To investigate the association between emotion regulation trajectories from 3 to 7 years of age and symptoms of anorexia nervosa and atypical anorexia nervosa in adolescence. Design, Setting, and Participants: This cohort study included all children with complete exposure data in the Millennium Cohort Study, a UK general population birth cohort. Data were acquired from June 2001 to March 2016 and analyzed from June to November 2020. Exposures: Mothers reported on their children's emotion regulation skills at 3, 5, and 7 years of age using the Children's Social Behavior Questionnaire. Multilevel models were used to derive early childhood emotion regulation scores (ie, predicted intercept) and within-child changes in emotion regulation scores from 3 to 7 years of age (ie, predicted slope). Main Outcome and Measures: Symptoms consistent with a DSM-5 diagnosis of anorexia nervosa or atypical anorexia nervosa at 14 years of age, defined using a range of questions relative to body image, weight perception, and dieting behaviors (hereinafter referred to as broad anorexia nervosa). Univariable and multivariable logistic regression models tested the association between exposures and outcome. Regression models were adjusted for child and family sociodemographic and socioeconomic characteristics and mental health difficulties, prenatal and perinatal factors, child's cognitive development, and maternal attachment. Results: A total of 15 896 participants (85.7% of total sample; 51.0% boys; 84.5% White individuals) had complete data on the exposure and were included in the main analyses. Among those with complete exposure and outcome data (9912 of the analytical sample [62.4%]), 97 participants (1.0%; 86 [88.7%] girls and 85 [87.6%] White individuals) had symptoms consistent with a diagnosis of broad anorexia nervosa at 14 years of age. No evidence suggested that children with lower emotion regulation ability at 3 years of age had greater odds of later reporting symptoms of broad anorexia nervosa (odds ratio [OR], 1.21; 95% CI, 0.91-1.63). However, children whose emotion regulation skills did not improve over childhood and who had greater problems regulating emotions at 7 years of age had higher odds of having broad anorexia nervosa at 14 years of age (OR, 1.45; 95% CI, 1.16-1.83). Conclusions and Relevance: These findings suggest that difficulties in developing age-appropriate emotion regulation skills in childhood are associated with experiencing broad anorexia nervosa in adolescence. Interventions to support the development of emotion regulation skills across childhood may help reduce the incidence of anorexia nervosa.

Clinical and social factors associated with involuntary psychiatric hospitalisation in children and adolescents: a systematic review, meta-analysis, and narrative synthesis.

BACKGROUND: Disparities in involuntary psychiatric hospitalisation between population subgroups have been identified in adults, but little is known about the factors associated with involuntary hospitalisation in children or adolescents. We did a systematic review, meta-analysis, and narrative synthesis to investigate the social and clinical factors associated with involuntary psychiatric hospitalisation among children and adolescents. METHODS: We searched MEDLINE, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials for studies of any type up to July 22, 2020, that compared the characteristics of voluntary and involuntary psychiatric inpatients (mean age of sample ≤18 years). We synthesised results using random effects meta-analysis on unadjusted data and by narrative synthesis. Heterogeneity between studies was calculated using I2. This study is registered on PROSPERO, CRD42020099892. FINDINGS: 23 studies from 11 countries were included in the systematic review and narrative synthesis, of which 19 studies (n=31 212) were included in the meta-analysis. On meta-analysis, involuntary rather than voluntary hospitalisation of minors was associated with a diagnosis of psychosis (eight studies; odds ratio 3·63, 95% CI 2·43-5·44, p<0·0001), substance misuse (five studies; 1·87, 1·05-3·30, p=0·032), or intellectual disability (four studies; 3·33, 1·33-8·34, p=0·010), as well as presenting with a perceived risk of harm to self (eight studies; 2·05, 1·15-3·64, p=0·015) or to others (five studies; 2·37, 1·39-4·03, p=0·0015). Involuntary hospitalisation was also found to be associated with being aged 12 years or older (three studies; 3·57, 1·46-8·73, p=0·0052) and being from a Black rather than a White ethnic group (three studies; 2·72, 1·88-3·95, p<0·0001). There was substantial between-study heterogeneity for most factors included in the meta-analysis (I2 from 51·3% to 92·3%). Narrative synthesis found that more severe illness and poorer global functioning was associated with involuntary hospitalisation. INTERPRETATION: Over-representation of involuntary psychiatric hospitalisation in certain groups might begin in childhood, potentially establishing a cycle of inequality that continues into adulthood. Further research into the systemic factors underlying these health-care inequalities and the barriers to accessing less coercive psychiatric treatment is urgently required, with specific consideration of racial and ethnic factors. FUNDING: UK National Institute for Health Research and Wellcome Trust.

Deterministic and probabilistic health risk assessment for exposure to non-steroidal anti-inflammatory drugs in an Indian river.

This study presents deterministic and probabilistic human health risk assessment using Monte Carlo simulations on exposure to an Indian river, Kaveri, which has been contaminated by non-steroidal anti-inflammatory drugs (NSAIDs). The NSAIDs of concern are naproxen, ibuprofen, aspirin, ketoprofen, and diclofenac. We have considered three exposure scenarios (water ingestion, dermal exposure, and fish ingestion) for four different age groups (0-5, 6-10, 11-18, and 19-70 years). Deterministic risk assessment revealed teenagers to be the most sensitive receptors and water ingestion to be the most crucial pathway contributing to maximum health risk (79 to 86%). Based on the results of Monte Carlo simulations, it was found that the probability of exceeding the deterministic mean risks ranged from 17 to 39% for different exposure routes. High end risk estimates such as 95th percentiles and maximum values of HQ for the entire population did not exceed the USEPA allowable risk. This implies that the NSAIDs at the detected concentrations in the Kaveri river may not pose adverse health effects even in the worst-case scenario. Among the five NSAIDs, diclofenac was found to be the major contributor for health risk. Moreover, the concentration of diclofenac was just one order less than the estimated site-specific threshold concentrations. From sensitivity analysis, the most and the least impactful parameters were found to be water ingestion rate and fish ingestion rate respectively.

Cam morphology is associated with MRI-defined cartilage defects and labral tears: a case-control study of 237 young adult football players with and without hip and groin pain.

OBJECTIVE: Football players are at risk of developing hip osteoarthritis (OA). Cam morphology (present in almost two of every three football players) may explain this heightened risk, but there is limited research on its role in hip OA development in younger athletes. Knowledge of this relationship will advance our understanding of the aetiology of hip OA in football players. We aimed to study the relationship between cam morphology size and MRI-defined cartilage defects and labral tears, and if this relationship differs by symptomatic state in young adult football players. METHODS: For this case-control study, 182 (288 hips) symptomatic (hip and/or groin pain >6 months and positive flexion-adduction-internal-rotation (FADIR) test) and 55 (110 hips) pain-free football players (soccer or Australian football) underwent anteroposterior and Dunn 45° radiographs, and 3-Tesla MRI. Cam morphology size was defined using alpha angle, and cartilage defects and labral tears were scored semiquantitatively. Presence, location and score (severity) of cartilage defects and labral tears were determined. Each participant completed the International Hip Outcome Tool 33 and Copenhagen Hip and Groin Outcome Score. RESULTS: Greater alpha angle was associated with cartilage defects (OR 1.03, 95% CI 1.01 to 1.04) and labral tears (OR 1.02, 95% CI 1.01 to 1.04). Greater alpha angle was associated with superolateral cartilage defects (OR 1.03, 95% CI 1.02 to 1.05) and superior labral tears (OR 1.03, 95% CI 1.02 to 1.05). The association of alpha angle with MRI-defined cartilage defects and labral tears was no greater in football players with symptoms than in those without (p=0.189-0.937). CONCLUSION: Cam morphology size was associated with cartilage defects and labral tears in young adult football players with and without pain. This study provides evidence that cam morphology may contribute to the high prevalence of hip OA in football players. Prospective studies of football players are now needed to establish if cam morphology causes progression of cartilage defects and labral tears and development of hip OA.

Salpingovesical fistula mimicking an enterovaginal fistula.

Fallopian tube fistula with the bladder can mimic an enterovaginal fistula. A 34-year-old woman presented with continuous urinary incontinence after hysterectomy. A cystogram confirmed a vesicovaginal fistula and a possible additional intestinal communication. Further imaging, however, ruled out an enterovaginal fistula and diagnosed a fallopian tube prolapse with salpingovesicovaginal fistula. This case demonstrates the importance of multiple imaging modalities in identifying and clearly delineating the anatomy of gynecologic fistulous connections. The case illustrates the fact that while salpingovesical fistula is a rare complication of hysterectomy, it is an important consideration in one's differential diagnosis.

Maternal perinatal depressive symptoms and offspring psychotic experiences at 18 years of age: a longitudinal study.

BACKGROUND: Evidence exists that maternal depression in the perinatal period has an adverse effect on a range of early childhood outcomes and increases the risk of offspring depression during adolescence. However, the association between maternal depression during the perinatal period and offspring psychotic experiences has not been investigated. We aimed to investigate whether there is an association between maternal antenatal or postnatal depression and offspring psychotic experiences at 18 years of age. METHODS: This longitudinal study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort, which recruited 14 541 pregnant women with an estimated delivery date between April 1, 1991, and Dec 31, 1992. Perinatal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS); offspring psychotic experiences at 18 years of age were measured using the Psychosis-Like Symptom Interview. Offspring of mothers with complete data on maternal perinatal depression measures, and complete data on outcome (psychotic experiences) and confounding variables were included in the main analysis. For the main analysis, we used logistic regression to examine the associations between maternal depression (antenatal and postnatal) and offspring psychotic experiences at the age of 18 years. We used biprobit regression to model the association between maternal antenatal depression and the two offspring outcomes (psychotic experiences and depression) at 18 years of age jointly. FINDINGS: 3067 offspring for whom data were available on maternal perinatal depression and offspring psychotic experiences aged 18 years were included in analyses. Maternal antenatal depressive symptoms were associated with offspring psychotic experiences at 18 years of age, with an unadjusted odds ratio (OR) of 1·38 (95% CI 1·18-1·61, p=0·0001) and after adjustment for confounders, an OR of 1·26 (1·06-1·49, p=0·0074). Maternal antenatal depressive symptoms were associated with both offspring psychotic experiences at the age of 18 years (n=2830, OR for a 5-point increase in EPDS score: 1·32 [95% CI 1·16-1·51], p<0·0001) and offspring depression at 18 years (OR for a 5-point increase in EPDS score: 1·18 [1·03-1·34], p=0·016). From joint modelling, there was no evidence that the association between maternal antenatal depression and offspring psychotic experiences differed in strength compared with offspring depression (p=0·19). INTERPRETATION: The offspring of mothers who experience depression in the perinatal period are more likely to report psychotic experiences at 18 years of age. If the association is found to be causal, it would strengthen the case for identifying and treating maternal depression during and after pregnancy. FUNDING: UK Medical Research Council and the Wellcome Trust.

Computer-Aided Detection AI Reduces Interreader Variability in Grading Hip Abnormalities With MRI.

BACKGROUND: Accurate interpretation of hip MRI is time-intensive and difficult, prone to inter- and intrareviewer variability, and lacks a universally accepted grading scale to evaluate morphological abnormalities. PURPOSE: To 1) develop and evaluate a deep-learning-based model for binary classification of hip osteoarthritis (OA) morphological abnormalities on MR images, and 2) develop an artificial intelligence (AI)-based assist tool to find if using the model predictions improves interreader agreement in hip grading. STUDY TYPE: Retrospective study aimed to evaluate a technical development. POPULATION: A total of 764 MRI volumes (364 patients) obtained from two studies (242 patients from LASEM [FORCe] and 122 patients from UCSF), split into a 65-25-10% train, validation, test set for network training. FIELD STRENGTH/SEQUENCE: 3T MRI, 2D T2 FSE, PD SPAIR. ASSESSMENT: Automatic binary classification of cartilage lesions, bone marrow edema-like lesions, and subchondral cyst-like lesions using the MRNet, interreader agreement before and after using network predictions. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve, area under curve (AUC), specificity and sensitivity, and balanced accuracy. RESULTS: For cartilage lesions, bone marrow edema-like lesions and subchondral cyst-like lesions the AUCs were: 0.80 (95% confidence interval [CI] 0.65, 0.95), 0.84 (95% CI 0.67, 1.00), and 0.77 (95% CI 0.66, 0.85), respectively. The sensitivity and specificity of the radiologist for binary classification were: 0.79 (95% CI 0.65, 0.93) and 0.80 (95% CI 0.59, 1.02), 0.40 (95% CI -0.02, 0.83) and 0.72 (95% CI 0.59, 0.86), 0.75 (95% CI 0.45, 1.05) and 0.88 (95% CI 0.77, 0.98). The interreader balanced accuracy increased from 53%, 71% and 56% to 60%, 73% and 68% after using the network predictions and saliency maps. DATA CONCLUSION: We have shown that a deep-learning approach achieved high performance in clinical classification tasks on hip MR images, and that using the predictions from the deep-learning model improved the interreader agreement in all pathologies. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;52:1163-1172.

Trauma-informed care for adult survivors of developmental trauma with psychotic and dissociative symptoms: a systematic review of intervention studies.

Developmental trauma is associated with an increased risk of psychosis and predicts poor prognosis. Despite this association, little is known about which treatments work best for survivors of developmental trauma with psychosis. We sought to do the first review, to our knowledge, to investigate treatments for people with psychotic and dissociative symptoms who have a history of developmental trauma. We searched MEDLINE, PsychINFO, and Google Scholar for studies reporting psychological and pharmacological treatments of psychotic or dissociative symptoms in adult survivors of developmental trauma. We identified 24 studies, most of which investigated various modalities of psychotherapy with two case reports of pharmacological treatments. There is preliminary evidence in favour of third wave cognitive therapies. However, because of low methodological quality and reporting in most of the studies found, it remains unknown which treatments are most effective in this clinical group. Nonetheless, our findings of potential treatment targets, including emotion regulation, acceptance, interpersonal skills, trauma re-processing, and the integration of dissociated ego states, could guide future work in this area. Methodologically rigorous studies are needed to enable clinicians and patients to collaboratively form evidence-based treatment plans. Our Review is registered with PROSPERO, number CRD42018104533.

Liquid crystal display electrode-assisted bio-electroperoxone treatment train for the abatement of organic contaminants in a pharmaceutical wastewater.

Pharmaceutical contaminants present in wastewaters cause severe health hazards among chronically exposed population. Emerging pharmaceutically active contaminants pose a serious challenge to conventional treatment technologies. Employing advanced treatment technologies for the abatement of such contaminants is usually energy-intensive. In this study, a complex pharmaceutical wastewater from a pharmaceutical industry in California, USA, was treated by employing a novel bio-electrochemical treatment train system. Labeled "Bio-electroperoxone," our proposed system comprises (i) an electrically bound biofilm reactor (EBBR) that accelerates bacterial adhesion for the removal of biodegradable and persistent organics and (ii) an electroperoxone reactor that removes recalcitrant organics with minimal energy uptake. The EBBR comprises a platinum-coated titanium cathode and a conductive nematic liquid crystal display electrode (NLCE) obtained from electronic waste that serves as the anode. Characterization of functional groups, morphology, and elemental mapping of NLCE were carried out to explain mechanisms for rapid biofilm attachment. The concomitant electroperoxone reactor comprises a platinum-coated titanium (Pt-Ti) anode and a reticulated vitreous carbon (RVC) cathode that catalyzes the two-electron reduction of oxygen to form in situ H2O2. The bio-electroperoxone system (i) inactivated 99.99% of the micro-organisms, removed (ii) 92.20% of the color, (iii) 84.72% of the total suspended solids, and (iv) 89% of the total organic carbon (TOC). Possible mechanisms for the degradation of organic contaminants are elucidated. Bio-electroperoxone thus paves the way for an efficient and sustainable approach for the efficient removal of both biodegradable and recalcitrant, persistent organic contaminants from pharmaceutical and possibly other complex wastewaters.