Cognitive stimulation as a mechanism linking socioeconomic status and neural function supporting working memory: a longitudinal fMRI study.

Childhood experiences of low socioeconomic status are associated with alterations in neural function in the frontoparietal network and ventral visual stream, which may drive differences in working memory. However, the specific features of low socioeconomic status environments that contribute to these disparities remain poorly understood. Here, we examined experiences of cognitive deprivation (i.e. decreased variety and complexity of experience), as opposed to experiences of threat (i.e. violence exposure), as a potential mechanism through which family income contributes to alterations in neural activation during working memory. As part of a longitudinal study, 148 youth between aged 10 and 13 years completed a visuospatial working memory fMRI task. Early childhood low income, chronicity of low income in early childhood, and current income-to-needs were associated with task-related activation in the ventral visual stream and frontoparietal network. The association of family income with decreased activation in the lateral occipital cortex and intraparietal sulcus during working memory was mediated by experiences of cognitive deprivation. Surprisingly, however, family income and deprivation were not significantly related to working memory performance, and only deprivation was associated with academic achievement in this sample. Taken together, these findings suggest that early life low income and associated cognitive deprivation are important factors in neural function supporting working memory.

Fabry Disease: Cardiac Implications and Molecular Mechanisms.

PURPOSE OF REVIEW: This review explores the interplay among metabolic dysfunction, oxidative stress, inflammation, and fibrosis in Fabry disease, focusing on their potential implications for cardiac involvement. We aim to discuss the biochemical processes that operate in parallel to sphingolipid accumulation and contribute to disease pathogenesis, emphasizing the importance of a comprehensive understanding of these processes. RECENT FINDINGS: Beyond sphingolipid accumulation, emerging studies have revealed that mitochondrial dysfunction, oxidative stress, and chronic inflammation could be significant contributors to Fabry disease and cardiac involvement. These factors promote cardiac remodeling and fibrosis and may predispose Fabry patients to conduction disturbances, ventricular arrhythmias, and heart failure. While current treatments, such as enzyme replacement therapy and pharmacological chaperones, address disease progression and symptoms, their effectiveness is limited. Our review uncovers the potential relationships among metabolic disturbances, oxidative stress, inflammation, and fibrosis in Fabry disease-related cardiac complications. Current findings suggest that beyond sphingolipid accumulation, other mechanisms may significantly contribute to disease pathogenesis. This prompts the exploration of innovative therapeutic strategies and underscores the importance of a holistic approach to understanding and managing Fabry disease.

Fatal Occupational Asthma in Cannabis Production - Massachusetts, 2022.

Multiple respiratory hazards have been identified in the cannabis cultivation and production industry, in which occupational asthma and work-related exacerbation of preexisting asthma have been reported. An employee working in a Massachusetts cannabis cultivation and processing facility experienced progressively worsening work-associated respiratory symptoms, which culminated in a fatal asthma attack in January 2022. This report represents findings of an Occupational Safety and Health Administration inspection, which included a worksite exposure assessment, coworker and next-of-kin interviews, medical record reviews, and collaboration with the Massachusetts Department of Public Health. Respiratory tract or skin symptoms were reported by four of 10 coworkers with similar job duties. Prevention is best achieved through a multifaceted approach, including controlling asthmagen exposures, such as cannabis dust, providing worker training, and conducting medical monitoring for occupational allergy. Evaluation of workers with new-onset or worsening asthma is essential, along with prompt diagnosis and medical management, which might include cessation of work and workers' compensation when relation to work exposures is identified. It is important to recognize that work in cannabis production is potentially causative.

Industry, occupation, and exposure history of mesothelioma patients in the U.S. National Mesothelioma Virtual Bank, 2006-2022.

BACKGROUND: Malignant mesothelioma is associated with environmental and occupational exposure to certain mineral fibers, especially asbestos. This study aims to examine work histories of mesothelioma patients and their survival time. METHOD: Using the NIOSH Industry and Occupation Computerized Coding System, we mapped occupations and industries recorded for 748 of 1444 patients in the U.S. National Mesothelioma Virtual Bank (NMVB) during the period 2006-2022. Descriptive and survival analyses were conducted. RESULTS: Among the 1023 industries recorded for those having mesothelioma, the most frequent cases were found for those in manufacturing (n = 225, 22.0%), construction (138, 13.5%), and education services (66, 6.5%); among the 924 occupation records, the most frequent cases were found for those in construction and extraction (174, 18.8%), production (145, 15.7%), and management (84, 9.1%). Males (583) or persons aged >40 years (658) at the time of diagnosis tended to have worked in industries traditionally associated with mesothelioma (e.g., construction), while females (163) or persons aged 20-40 years (27) tended to have worked in industries not traditionally associated with mesothelioma (e.g., health care). Asbestos, unknown substances, and chemical solvents were the most frequently reported exposure, with females most often reporting an unknown substance. A multi-variable Cox Hazard Regression analysis showed that significant prognostic factors associated with decreased survival in mesothelioma cases are sex (male) and work experience in utility-related industry, while factor associated with increased survival are epithelial or epithelioid histological type, prior history of surgery and immunotherapy, and industry experience in accommodation and food services. CONCLUSION: The NMVB has the potential of serving as a sentinel surveillance mechanism for identifying industries and occupations not traditionally associated with mesothelioma. Results indicate the importance of considering all potential sources of asbestos exposures including occupational, environmental, and extra-occupational exposures when evaluating mesothelioma patients and advising family members.

Importance of and Approach to Taking a History of Exposures to Occupational Respiratory Hazards.

Occupational respiratory diseases are caused by exposure to respiratory hazards at work. It is important to document those exposures and whether they are causing or exacerbating disease because these determinations can have important impacts on diagnosis, treatment, job restrictions, and eligibility for benefits. Without investigation, it is easy to miss clinically relevant exposures, especially in those with chronic diseases that can have work and nonwork causes. The first and most important step in identifying exposures to respiratory hazards at work is to take an appropriate history. For efficiency, this is a two-step process. An initial quick screening history is done by asking only a few questions. Follow-up questions are asked if there are positive responses to the screening questions or if an occupational etiology is suspected based on the clinical presentation. Electronic health records have promise for facilitating this process. Follow-up to the screening history may include additional questions, evaluating additional sources of information about workplace exposures, and medical testing. Radiographic findings or tests conducted on noninvasive samples or lung tissue can be used as biomarkers. Online resources can be used to learn more about exposures associated with occupations and industries and to see if investigations evaluating exposures were performed in the patient's own workplace. It is important to adhere to the patient's wishes about contacting the employer. With patient consent, the employer can be an important source of information about exposures and, if a problem exists, has an important role in taking corrective action. Consultation for challenging cases is available from a variety of professional and governmental entities. If a clinician identifies a significant public health issue, such as an occupational disease outbreak, it is important to notify relevant public health authorities so that steps can be taken to prevent additional exposures and appropriately care for those already exposed.

Child abuse and automatic emotion regulation in children and adolescents.

Child abuse is associated with elevated risk for psychopathology. The current study examined the role of automatic emotion regulation as a potential mechanism linking child abuse with internalizing psychopathology. A sample of 237 youth aged 8-16 years and their caregivers participated. Child abuse severity was assessed by self-report questionnaires, and automatic emotion regulation was assessed using an emotional Stroop task designed to measure adaptation to emotional conflict. A similar task without emotional stimuli was also administered to evaluate whether abuse was uniquely associated with emotion regulation, but not cognitive control applied in a nonemotional context. Internalizing psychopathology was assessed concurrently and at a 2-year longitudinal follow-up. Child abuse severity was associated with lower emotional conflict adaptation but was unrelated to cognitive control. Specifically, the severity of emotional and physical abuse, but not sexual abuse, were associated with lower emotional conflict adaptation. Emotional conflict adaptation was not associated with internalizing psychopathology prospectively. These findings suggest that childhood emotional and physical abuse, in particular, may influence automatic forms of emotion regulation. Future work exploring the socioemotional consequences of altered automatic emotion regulation among youth exposed to child abuse is clearly needed.

Vagal flexibility to negative emotions moderates the relations between environmental risk and adjustment problems in childhood.

Neurobiological and social-contextual influences shape children's adjustment, yet limited biopsychosocial studies have integrated temporal features when modeling physiological regulation of emotion. This study explored whether a common underlying pattern of non-linear change in respiratory sinus arrhythmia (RSA) across emotional scenarios characterized 4-6 year-old children's parasympathetic reactivity (N = 180). Additionally, we tested whether dynamic RSA reactivity was an index of neurobiological susceptibility or a diathesis in the association between socioeconomic status, authoritarian parenting, and the development of externalizing problems (EP) and internalizing problems over two years. There was a shared RSA pattern across all emotions, characterized by more initial RSA suppression and a subsequent return toward baseline, which we call vagal flexibility (VF). VF interacted with parenting to predict EP. More authoritarian parenting predicted increased EP two years later only when VF was low; conversely, when VF was very high, authoritarian mothers reported that their children had fewer EP. Altogether, children's patterns of dynamic RSA change to negative emotions can be characterized by a higher order factor, and the nature by which VF contributes to EP depends on maternal socialization practices, with low VF augmenting and high VF buffering children against the effects of authoritarian parenting.

Associations Between Structural Stigma and Psychopathology Among Early Adolescents.

OBJECTIVE: Ample evidence demonstrates that structural stigma - defined as societal-level conditions, cultural norms, and institutional policies and practices that constrain opportunities, resources, and well-being of stigmatized populations - is associated with psychopathology in adults from marginalized groups. Yet there is limited research on whether structural stigma is similarly associated with internalizing and externalizing symptoms among youth. METHOD: Structural stigma related to sex, sexual orientation, race, and Latinx ethnicity was measured using indicators of state-level policy and aggregated attitudes. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 10,414; M age = 12 years, SD = 0.66; 48% female, 6.8% lesbian, gay, and bisexual (LGB), 13.4% Black, 20% Latinx), we examined associations of structural stigma with internalizing and externalizing symptoms among female, LGB, Black, and Latinx youth. RESULTS: LGB youth living in higher (vs. lower) structural stigma states had elevated levels of internalizing and externalizing symptoms. In lower structural stigma states, there were no differences in externalizing symptoms between LGB and heterosexual youth. Similarly, Latinx youth and females living in higher (vs. lower) structural stigma states had elevated levels of externalizing symptoms. In lower structural stigma states, there were no differences in externalizing symptoms between Latinx youth and non-Latinx White youth. Structural stigma related to race was unrelated to internalizing or externalizing symptoms for Black youth. CONCLUSIONS: This study provides novel evidence that macro-level social environments, in the form of structural stigma, contribute to adverse mental health outcomes for marginalized youth and partly explain disparities in externalizing symptoms.

Exposure to Violence as an Environmental Pathway Linking Low Socioeconomic Status with Altered Neural Processing of Threat and Adolescent Psychopathology.

Low childhood socioeconomic status (SES) is associated with increased risk for psychopathology, in part because of heightened exposure to environmental adversity. Adverse experiences can be characterized along dimensions, including threat and deprivation, that contribute to psychopathology via distinct mechanisms. The current study investigated a neural mechanism through which threat and deprivation may contribute to socioeconomic disparities in psychopathology. Participants were 177 youths (83 girls) aged 10-13 years recruited from a cohort followed since the age of 3 years. SES was assessed using the income-to-needs ratio at the age of 3 years. At the age of 10-13 years, retrospective and current exposure to adverse experiences and symptoms of psychopathology were assessed. At this same time point, participants also completed a face processing task (passive viewing of fearful and neutral faces) during an fMRI scan. Lower childhood SES was associated with greater exposure to threat and deprivation experiences. Both threat and deprivation were associated with higher depression symptoms, whereas threat experiences were uniquely linked to posttraumatic stress disorder symptoms. Greater exposure to threat, but not deprivation, was associated with higher activation in dorsomedial pFC to fearful compared with neutral faces. The dorsomedial pFC is a hub of the default mode network thought to be involved in internally directed attention and cognition. Experiences of threat, but not deprivation, are associated with greater engagement of this region in response to threat cues. Threat-related adversity contributes to socioeconomic disparities in adolescent psychopathology through distinct mechanisms from deprivation.

Malignant Mesothelioma Mortality in Women - United States, 1999-2020.

Inhalation of asbestos fibers can cause malignant mesothelioma, a rapidly progressing and lethal cancer of the mesothelium, the thin layer of tissues surrounding internal organs in the chest and abdomen. Patients with malignant mesothelioma have a poor prognosis, with a median survival of 1 year from diagnosis. The estimated median interval from initial occupational asbestos exposure to death is 32 years (range = 13-70 years) (1). Occupational asbestos exposure is most often reported in men working in industries such as construction and manufacturing; however, women are also at risk for exposure to asbestos fibers, and limited data exist on longer-term trends in mesothelioma deaths among women. To characterize deaths associated with mesothelioma and temporal trends in mesothelioma mortality among women in the United States, CDC analyzed annual Multiple Cause of Death records from the National Vital Statistics System for 1999-2020, the most recent years for which complete data are available. The annual number of mesothelioma deaths among women increased significantly, from 489 in 1999 to 614 in 2020; however, the age-adjusted death rate per 1 million women declined significantly, from 4.83 in 1999 to 4.15 in 2020. The largest number of deaths was associated with the health care and social assistance industry (89; 15.7%) and homemaker occupation (129; 22.8%). Efforts to limit exposure to asbestos fibers, including among women, need to be maintained.

COVID-19 test positivity by occupation using the Delphi US COVID-19 trends and impact survey, September-November 2020.

BACKGROUND: The potential for work to be a risk factor for coronavirus disease 2019 (COVID-19) was recognized early in the pandemic based on the likelihood of work-related differences in exposures to COVID-19 in different occupations. Due to intense demands of the pandemic, implementation of recommendations to collect information on occupation in relation to COVID-19 has been uneven across the United States. The objective of this study was to investigate COVID-19 test positivity by occupation. METHODS: We analyzed data collected from September 8 to November 30, 2020, by the Delphi Group at Carnegie Mellon University US COVID-19 Trends and Impact Survey, offered daily to a random sample of US-based Facebook users aged 18 years or older, who were invited via a banner in their news feed. Our focus was ever testing positive for COVID-19 in respondents working outside the home for pay in the past 4 weeks. RESULTS: The major occupational groups of "Production", "Building and grounds cleaning and maintenance," "Construction and extraction," "Healthcare support," and "Food preparation and serving" had the five highest test positivity percentages (16.7%-14.4%). Highest detailed occupational categories (28.6%-19.1%) were "Massage therapist," "Food processing worker," "Bailiff, correctional officer, or jailer," "Funeral service worker," "First-line supervisor of production and operating workers," and "Nursing assistant or psychiatric aide." Differences in test positivity by occupation remained after adjustment for age, gender, and pre-existing medical conditions. CONCLUSION: Information on differences in test positivity by occupation can aid targeting of messaging for vaccination and testing and mitigation strategies for the current and future respiratory infection epidemics and pandemics. These results, obtained before availability of COVID-19 vaccines, can form a basis for comparison to evaluate impacts of vaccination and subsequent emergence of viral variants.

Neural connectivity biotypes: associations with internalizing problems throughout adolescence.

BACKGROUND: Neurophysiological patterns may distinguish which youth are at risk for the well-documented increase in internalizing symptoms during adolescence. Adolescents with internalizing problems exhibit altered resting-state functional connectivity (RSFC) of brain regions involved in socio-affective processing. Whether connectivity-based biotypes differentiate adolescents' levels of internalizing problems remains unknown. METHOD: Sixty-eight adolescents (37 females) reported on their internalizing problems at ages 14, 16, and 18 years. A resting-state functional neuroimaging scan was collected at age 16. Time-series data of 15 internalizing-relevant brain regions were entered into the Subgroup-Group Iterative Multi-Model Estimation program to identify subgroups based on RSFC maps. Associations between internalizing problems and connectivity-based biotypes were tested with regression analyses. RESULTS: Two connectivity-based biotypes were found: a Diffusely-connected biotype (N = 46), with long-range fronto-parietal paths, and a Hyper-connected biotype (N = 22), with paths between subcortical and medial frontal areas (e.g. affective and default-mode network regions). Higher levels of past (age 14) internalizing problems predicted a greater likelihood of belonging to the Hyper-connected biotype at age 16. The Hyper-connected biotype showed higher levels of concurrent problems (age 16) and future (age 18) internalizing problems. CONCLUSIONS: Differential patterns of RSFC among socio-affective brain regions were predicted by earlier internalizing problems and predicted future internalizing problems in adolescence. Measuring connectivity-based biotypes in adolescence may offer insight into which youth face an elevated risk for internalizing disorders during this critical developmental period.

Family Risk and Externalizing Problems in Chilean Children: Mediation by Harsh Parenting and Emotional Support.

Latent class analysis and multigroup mediation were used with 8,860 families in Chile to identify risk groups varying in socioeconomic status, family structure, and maternal depression, to determine whether profiles differed in children's development of externalizing problems (EP) from 35 to 61 months, and maternal parenting that predicted EP. Four groups were identified: one no-risk profile and three risk profiles, impoverished and undereducated, depressed and impoverished, and father-absent and impoverished. All classes differed in EP. Maternal emotional support and harsh parenting were differentially associated with the development of EP across the three risk groups, relative to the low-risk group. Thus, specific constellations of adversities differentially predicted children's EP and socialization processes mediating links between risk and EP. Implications are discussed.

Corporal Punishment and Elevated Neural Response to Threat in Children.

Spanking remains common around the world, despite evidence linking corporal punishment to detrimental child outcomes. This study tested whether children (Mage  = 11.60) who were spanked (N = 40) exhibited altered neural function in response to stimuli that suggest the presence of an environmental threat compared to children who were not spanked (N = 107). Children who were spanked exhibited greater activation in multiple regions of the medial and lateral prefrontal cortex (PFC), including dorsal anterior cingulate cortex, dorsomedial PFC, bilateral frontal pole, and left middle frontal gyrus in response to fearful relative to neutral faces compared to children who were not spanked. These findings suggest that spanking may alter neural responses to environmental threats in a manner similar to more severe forms of maltreatment.

High vagal tone and rapid extinction learning as potential transdiagnostic protective factors following childhood violence exposure.

Childhood exposure to violence is strongly associated with psychopathology. High resting respiratory sinus arrhythmia (RSA) is associated with lower levels of psychopathology in children exposed to violence. High RSA may help to protect against psychopathology by facilitating fear extinction learning, allowing more flexible autonomic responses to learned threat and safety cues. In this study, 165 youth (79 female, aged 9-17; 86 exposed to violence) completed assessments of violence exposure, RSA, and psychopathology, and a fear extinction learning task; 134 participants returned and completed psychopathology assessments 2 years later. Resting RSA moderated the longitudinal association of violence exposure with post-traumatic stress disorder (PTSD) symptoms and externalizing psychopathology, such that the association was weaker among youths with higher RSA. Higher skin conductance responses (SCR) during extinction learning to the threat cue (CS+) was associated with higher internalizing symptoms at follow-up and greater SCR to the safety cue (CS-) was associated with higher PTSD, internalizing, and externalizing symptoms, as well as the p-factor, controlling for baseline symptoms. Findings suggest that higher RSA may protect against emergence of psychopathology among children exposed to violence. Moreover, difficulty extinguishing learned threat responses and elevated autonomic responses to safety cues may be associated with risk for future psychopathology.

Direct replication of task-dependent neural activation patterns during sadness introspection in two independent adolescent samples.

Functional neuroimaging results need to replicate to inform sound models of human social cognition and its neural correlates. Introspection, the capacity to reflect on one's thoughts and feelings, is one process required for normative social cognition and emotional functioning. Engaging in introspection draws on a network of brain regions including medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), middle temporal gyri (MTG), and temporoparietal junction (TPJ). Maturation of these regions during adolescence mirrors the behavioral advances seen in adolescent social cognition, but the neural correlates of introspection in adolescence need to replicate to confirm their generalizability and role as a possible mechanism. The current study investigated whether reflecting upon one's own feelings of sadness would activate and replicate similar brain regions in two independent samples of adolescents. Participants included 156 adolescents (50% female) from the California Families Project and 119 adolescent girls from the Pittsburgh Girls Study of Emotion. All participants completed the Emotion Regulation Questionnaire (ERQ) and underwent a functional magnetic resonance imaging scan while completing the same facial emotion-processing task at age 16-17 years. Both samples showed similar whole-brain activation patterns when engaged in sadness introspection and when judging a nonemotional facial feature. Whole-brain activation was unrelated to ERQ scores in both samples. Neural responsivity to task manipulations replicated in regions recruited for socio-emotional (mPFC, PCC, MTG, TPJ) and attention (dorsolateral PFC, precentral gyri, superior occipital gyrus, superior parietal lobule) processing. These findings demonstrate robust replication of neural engagement during sadness introspection in two independent adolescent samples.

Mechanisms linking childhood trauma exposure and psychopathology: a transdiagnostic model of risk and resilience.

BACKGROUND: Transdiagnostic processes confer risk for multiple types of psychopathology and explain the co-occurrence of different disorders. For this reason, transdiagnostic processes provide ideal targets for early intervention and treatment. Childhood trauma exposure is associated with elevated risk for virtually all commonly occurring forms of psychopathology. We articulate a transdiagnostic model of the developmental mechanisms that explain the strong links between childhood trauma and psychopathology as well as protective factors that promote resilience against multiple forms of psychopathology. MAIN BODY: We present a model of transdiagnostic mechanisms spanning three broad domains: social information processing, emotional processing, and accelerated biological aging. Changes in social information processing that prioritize threat-related information-such as heightened perceptual sensitivity to threat, misclassification of negative and neutral emotions as anger, and attention biases towards threat-related cues-have been consistently observed in children who have experienced trauma. Patterns of emotional processing common in children exposed to trauma include elevated emotional reactivity to threat-related stimuli, low emotional awareness, and difficulties with emotional learning and emotion regulation. More recently, a pattern of accelerated aging across multiple biological metrics, including pubertal development and cellular aging, has been found in trauma-exposed children. Although these changes in social information processing, emotional responding, and the pace of biological aging reflect developmental adaptations that may promote safety and provide other benefits for children raised in dangerous environments, they have been consistently associated with the emergence of multiple forms of internalizing and externalizing psychopathology and explain the link between childhood trauma exposure and transdiagnostic psychopathology. Children with higher levels of social support, particularly from caregivers, are less likely to develop psychopathology following trauma exposure. Caregiver buffering of threat-related processing may be one mechanism explaining this protective effect. CONCLUSION: Childhood trauma exposure is a powerful transdiagnostic risk factor associated with elevated risk for multiple forms of psychopathology across development. Changes in threat-related social and emotional processing and accelerated biological aging serve as transdiagnostic mechanisms linking childhood trauma with psychopathology. These transdiagnostic mechanisms represent critical targets for early interventions aimed at preventing the emergence of psychopathology in children who have experienced trauma.

Girls' brain structural connectivity in late adolescence relates to history of depression symptoms.

BACKGROUND: Girls' depressive symptoms typically increase in adolescence, with individual differences in course and severity being key risk factors for impaired emotional functioning in young adulthood. Given the continued brain white matter (WM) maturation that occurs in adolescence, the present study tested whether structural connectivity patterns in late adolescence are associated with variation in the course of depression symptom severity throughout adolescence. METHOD: Participants were girls (N = 115) enrolled in a multiyear prospective cohort study of risk for depression. Initial depression severity (intercept) at age 10 and change in severity (linear slope) across ages 10-19 were examined in relation to WM tractography collected at age 19. Network-based statistic analyses were used to identify clusters showing variation in structural connectivity in association with depressive symptom intercept, slope, and their interaction. RESULTS: Higher initial depressive severity and steeper positive slope (separately) were associated with greater structural connectivity between temporal, subcortical socioaffective, and occipital regions. Intercept showed more connectivity associations than slope. The interaction effect indicated that higher initial symptom severity and a steeper negative slope (i.e., alleviating symptoms) were related to greater connectivity between cognitive control regions. Moderately severe symptoms that worsened over time were followed by greater connectivity between self-referential and cognitive regions (e.g., posterior cingulate and frontal gyrus). CONCLUSIONS: Higher depressive symptom severity in early adolescence and increasing symptom severity over time may forecast structural connectivity differences in late adolescence, particularly in pathways involving cognitive and emotion-processing regions. Understanding how clinical course relates to neurobiological correlates may inform new treatment approaches to adolescent depression.

Reduced hippocampal and amygdala volume as a mechanism underlying stress sensitization to depression following childhood trauma.

BACKGROUND: Stressful life events are more likely to trigger depression among individuals exposed to childhood adversity. However, the mechanisms underlying this stress sensitization remain largely unknown. Any such mechanism must be altered by childhood adversity and interact with recent stressful life events, magnifying their association with depression. AIM: This study investigated whether reduced hippocampal and amygdala volume are potential mechanisms underlying stress sensitization following childhood violence exposure. METHOD: A sample of 149 youth (aged 8-17 years), with (N = 75) and without (N = 74) exposure to physical abuse, sexual abuse, or domestic violence participated. Participants completed a structural MRI scan and assessments of depression. Approximately 2 years later, stressful life events were assessed along with depression symptoms in 120 participants (57 violence exposed). RESULTS: Childhood violence exposure was associated with smaller hippocampal and amygdala volume. Stressful life events occurring during the follow-up period predicted worsening depression over time, and this association was magnified among those with smaller hippocampal and amygdala volumes. Significant moderated mediation models revealed the indirect effects of violence exposure on increasing depression over time through hippocampal and amygdala volumes, particularly among youths who experienced more stressful life events. CONCLUSIONS: These results provide evidence for reduced hippocampal and amygdala volume as potential mechanisms of stress sensitization to depression following exposure to violence. More broadly, these patterns suggest that hippocampal and amygdala-mediated emotional and cognitive processes may confer vulnerability to stressful life events among children who have experienced violence.

Work-related adverse respiratory health outcomes at a machine manufacturing facility with a cluster of bronchiolitis, alveolar ductitis and emphysema (BADE).

OBJECTIVES: Four machine manufacturing facility workers had a novel occupational lung disease of uncertain aetiology characterised by lymphocytic bronchiolitis, alveolar ductitis and emphysema (BADE). We aimed to evaluate current workers' respiratory health in relation to job category and relative exposure to endotoxin, which is aerosolised from in-use metalworking fluid. METHODS: We offered a questionnaire and spirometry at baseline and 3.5 year follow-up. Endotoxin exposures were quantified for 16 production and non-production job groups. Forced expiratory volume in one second (FEV1) decline ≥10% was considered excessive. We examined SMRs compared with US adults, adjusted prevalence ratios (aPRs) for health outcomes by endotoxin exposure tertiles and predictors of excessive FEV1 decline. RESULTS: Among 388 (89%) baseline participants, SMRs were elevated for wheeze (2.5 (95% CI 2.1 to 3.0)), but not obstruction (0.5 (95% CI 0.3 to 1.1)). Mean endotoxin exposures (range: 0.09-28.4 EU/m3) were highest for machine shop jobs. Higher exposure was associated with exertional dyspnea (aPR=2.8 (95% CI 1.4 to 5.7)), but not lung function. Of 250 (64%) follow-up participants, 11 (4%) had excessive FEV1 decline (range: 403-2074 mL); 10 worked in production. Wheeze (aPR=3.6 (95% CI 1.1 to 12.1)) and medium (1.3-7.5 EU/m3) endotoxin exposure (aPR=10.5 (95% CI 1.3 to 83.1)) at baseline were associated with excessive decline. One production worker with excessive decline had BADE on subsequent lung biopsy. CONCLUSIONS: Lung function loss and BADE were associated with production work. Relationships with relative endotoxin exposure indicate work-related adverse respiratory health outcomes beyond the sentinel disease cluster, including an incident BADE case. Until causative factors and effective preventive strategies for BADE are determined, exposure minimisation and medical surveillance of affected workforces are recommended.