Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 289
Filter
1.
Surg Pathol Clin ; 17(2): 193-202, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692804

ABSTRACT

Although silicosis has been an established disease with a recognized cause for more than 100 years, many workers continue to be exposed to silica and new outbreaks of disease continue to occur. This article describes some of the well-established and new exposures, including denim sandblasting, artificial stone cutting, and some forms of "coal worker's pneumoconiosis." The authors review the imaging and pathology of acute silicosis (silicoproteinosis), simple silicosis, and progressive massive fibrosis and summarize known and putative associations of silica exposure, including tuberculosis, lung cancer, connective tissue disease (especially systemic sclerosis), and vasculitis.


Subject(s)
Silicosis , Silicosis/pathology , Silicosis/diagnosis , Silicosis/etiology , Humans , Occupational Exposure/adverse effects , Silicon Dioxide/adverse effects
2.
Expert Rev Vaccines ; 23(1): 535-545, 2024.
Article in English | MEDLINE | ID: mdl-38664959

ABSTRACT

INTRODUCTION: Zebrafishes represent a proven model for human diseases and systems biology, exhibiting physiological and genetic similarities and having innate and adaptive immune systems. However, they are underexplored for human vaccinology, vaccine development, and testing. Here we summarize gaps and challenges. AREAS COVERED: Zebrafish models have four potential applications: 1) Vaccine safety: The past successes in using zebrafishes to test xenobiotics could extend to vaccine and adjuvant formulations for general safety or target organs due to the zebrafish embryos' optical transparency. 2) Innate immunity: The zebrafish offers refined ways to examine vaccine effects through signaling via Toll-like or NOD-like receptors in zebrafish myeloid cells. 3) Adaptive immunity: Zebrafishes produce IgM, IgD,and two IgZ immunoglobulins, but these are understudied, due to a lack of immunological reagents for challenge studies. 4) Systems vaccinology: Due to the availability of a well-referenced zebrafish genome, transcriptome, proteome, and epigenome, this model offers potential here. EXPERT OPINION: It remains unproven whether zebrafishes can be employed for testing and developing human vaccines. We are still at the hypothesis-generating stage, although it is possible to begin outlining experiments for this purpose. Through transgenic manipulation, zebrafish models could offer new paths for shaping animal models and systems vaccinology.


Subject(s)
Adaptive Immunity , Adjuvants, Immunologic , Immunity, Innate , Models, Animal , Vaccine Development , Vaccines , Zebrafish , Zebrafish/immunology , Animals , Adjuvants, Immunologic/administration & dosage , Humans , Vaccines/immunology , Vaccines/administration & dosage , Vaccinology/methods
3.
Article in English | MEDLINE | ID: mdl-38336872

ABSTRACT

OBJECTIVES: Interstitial lung disease (ILD) in connective tissue diseases (CTD) have highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality and immunosuppression response. METHODS: Patients with CTD-ILD had high-resolution chest computed tomography (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern (usual interstitial pneumonia [UIP]; non-specific interstitial pneumonia [NSIP]; organizing pneumonia [OP]; fibrotic hypersensitivity pneumonitis [fHP]; and other). Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. RESULTS: Of 645 CTD-ILD patients, the frequent CTDs were systemic sclerosis (n = 215), rheumatoid arthritis (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with UIP, FVC decline was slower for NSIP (1.1%/year, 95%CI 0.2, 1.9) and OP (3.5%/year, 95%CI 2.0, 4.9), and mortality was lower for NSIP (HR 0.65, 95%CI 0.45, 0.93) and OP (HR 0.18, 95%CI 0.05, 0.57), but higher in fHP (HR 1.58, 95%CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95%CI 1.4, 2.8), with no change for UIP or fHP. CONCLUSION: Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

4.
Psychoneuroendocrinology ; 159: 106668, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37944209

ABSTRACT

The COVID-19 pandemic generated significant life stress and increases in internalizing disorders. Moreover, COVID-related stressors disproportionately impacted women, consistent with outcomes showing a gender gap in stress-related disorders. Gender-related stress vulnerability emerges in adolescence alongside gender-specific changes in neuroendocrine signaling. Most research on the neuroendocrinology of stress-related disorders has focused on differences in the hypothalamic-pituitary-adrenal (HPA) axis effector hormone cortisol. More recent studies, however, emphasize dehydroepiandrosterone (DHEA), a neuroprotective and neuroactive hormone released concurrently with cortisol that balances its biobehavioral actions during stress. Notably, women show lower cortisol responses and higher DHEA responses to stress. However, lower cortisol and higher DHEA are associated with internalizing disorders in women, while those associations are opposite in men. Thus, gender-specific factors perhaps result in a neuroendocrine profile that places women at greater risk for stress-related disorders. The current study prospectively examined socially evaluated cold-pressor task (SECPT) induced neuroendocrine responses at age 15 and internalizing symptoms during the COVID-19 pandemic at age 21 in a cohort of 175 primarily Black low-socioeconomic status participants, while controlling for internalizing symptoms at age 15. The association between COVID-related stress and internalizing symptoms was not stronger in women. Lower DHEA-cortisol ratios were associated with a weaker relationship between COVID-related stress and internalizing symptoms in women, while higher ratios were associated with a weaker relationship in men. These findings suggest gender differences in the relationship between DHEA and cortisol and internalizing outcomes during a stressful period, and support differential neuroendocrine protective and risk pathways for young men and women.


Subject(s)
COVID-19 , Hydrocortisone , Male , Adolescent , Humans , Female , Young Adult , Adult , Hydrocortisone/metabolism , Pandemics , Stress, Psychological/metabolism , Hypothalamo-Hypophyseal System/metabolism , Pituitary-Adrenal System/metabolism , Psychophysiologic Disorders/metabolism , Saliva/metabolism , Dehydroepiandrosterone/metabolism
5.
Article in English | MEDLINE | ID: mdl-38141151

ABSTRACT

Although extant cross-sectional data suggest that parents have experienced numerous challenges (e.g., homeschooling, caregiver burden) and mental health consequences during the COVID-19 pandemic, longitudinal data are needed to confirm mental health changes relative to pre-pandemic levels and identify which specific pandemic-related changes most highly predict mental health during the pandemic. In two longitudinal subsamples (N = 299 and N = 175), we assessed change in anxiety, depression, and stress before and during the pandemic and whether the accumulation of pandemic-related changes predicted observed mental health changes. On average, parents reported increased depression and anxiety, but no significant changes in reported stress. Moreover, increased interpersonal conflict, difficulty managing work and caregiving responsibilities, and increased economic challenges were the types of pandemic-related changes that most strongly predicted worse mental health, highlighting that juggling caregiving responsibilities and economic concerns, along with the pandemic's impact on interpersonal family relationships are key predictors of worsening parental mental illness symptoms.

6.
Front Immunol ; 14: 1253648, 2023.
Article in English | MEDLINE | ID: mdl-37781403

ABSTRACT

Introduction: Invasion of the central nervous system (CNS) is the most serious consequence of Trypanosoma brucei infection, which causes sleeping sickness. Recent experimental data have revealed some more insights into the disease during the meningoencephalitic stage. However, detailed cellular processes befalling the CNS during the disease are poorly understood. Methods: To further address this issue, we implanted a cranial window on the cortex of B6.129P2(Cg)-Cx3cr1tm1Litt/J mice, infected them with Trypanosoma brucei expressing RFP via intraperitoneal injection, and monitored microglial cells and parasites longitudinally over 30 days using in vivo 2-photon imaging. We correlated the observed changes with histological analyses to evaluate the recruitment of peripheral immune cells. Results and discussion: We uncovered an early involvement of microglia that precedes invasion of the CNS by the parasite. We accomplished a detailed characterization of the progressive sequence of events that correlates with microglial morphological changes and microgliosis. Our findings unveiled a heterogeneous microglial response in places of initial homeostatic disruption near brain barriers and pointed out an exceptional capability of microglia to hamper parasite proliferation inside the brain. We also found early signs of inflammation in the meninges, which synchronize with the microglial response. Moreover, we observed a massive infiltration of peripheral immune cells into the parenchyma as a signature in the final disease stage. Overall, our study provides new insights into the host-pathogen immune interactions in the meningeal and parenchymal compartments of the neocortex.


Subject(s)
Trypanosoma brucei brucei , Trypanosomiasis, African , Mice , Animals , Microglia/pathology , Brain , Central Nervous System/pathology
7.
Chest ; 164(6): 1466-1475, 2023 12.
Article in English | MEDLINE | ID: mdl-37541339

ABSTRACT

BACKGROUND: Clinical practice guidelines separately describe radiologic patterns of usual interstitial pneumonia (UIP) and fibrotic hypersensitivity pneumonitis (fHP), without direction on whether or how to apply these approaches concurrently within a single patient. RESEARCH QUESTION: How can we integrate guideline-defined radiologic patterns to diagnose interstitial lung disease (ILD) and what are the pitfalls associated with described patterns that require reassessment in future guidelines? STUDY DESIGN AND METHODS: Patients from the Canadian Registry for Pulmonary Fibrosis underwent detailed reevaluation in standardized multidisciplinary discussion. CT scan features were quantified by chest radiologists masked to clinical data, and guideline-defined patterns were assigned. Clinical data then were provided to the radiologist and an ILD clinician, who jointly determined the leading diagnosis. RESULTS: Clinical-radiologic diagnosis in 1,593 patients was idiopathic pulmonary fibrosis (IPF) in 26%, fHP in 12%, connective tissue disease-associated ILD (CTD-ILD) in 34%, idiopathic pneumonia with autoimmune features in 12%, and unclassifiable ILD in 10%. Typical and probable UIP patterns corresponded to a diagnosis of IPF in 66% and 57% of patients, respectively. Typical fHP pattern corresponded to an fHP clinical diagnosis in 65% of patients, whereas compatible fHP was nonspecific and associated with CTD-ILD or IPAF in 48% of patients. No pattern ruled out CTD-ILD. Gas trapping affecting > 5% of lung parenchyma on expiratory imaging was an important feature broadly separating compatible and typical fHP from other patterns (sensitivity, 0.77; specificity, 0.91). INTERPRETATION: An integrated approach to guideline-defined UIP and fHP patterns is feasible and supports > 5% gas trapping as an important branch point. Typical or probable UIP and typical fHP patterns have moderate predictive values for a corresponding diagnosis of IPF and fHP, although occasionally confounded by CTD-ILD; compatible fHP is nonspecific.


Subject(s)
Alveolitis, Extrinsic Allergic , Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Humans , Canada , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Lung/diagnostic imaging , Alveolitis, Extrinsic Allergic/diagnostic imaging
8.
Psychol Med ; 53(8): 3652-3660, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35172913

ABSTRACT

BACKGROUND: Adolescent antisocial behavior (AB) is a public health concern due to the high financial and social costs of AB on victims and perpetrators. Neural systems involved in reward and loss processing are thought to contribute to AB. However, investigations into these processes are limited: few have considered anticipatory and consummatory components of reward, response to loss, nor whether associations with AB may vary by level of callous-unemotional (CU) traits. METHODS: A population-based community sample of 128 predominantly low-income youth (mean age = 15.9 years; 42% male) completed a monetary incentive delay task during fMRI. A multi-informant, multi-method latent variable approach was used to test associations between AB and neural response to reward and loss anticipation and outcome and whether CU traits moderated these associations. RESULTS: AB was not associated with neural response to reward but was associated with reduced frontoparietal activity during loss outcomes. This association was moderated by CU traits such that individuals with higher levels of AB and CU traits had the largest reductions in frontoparietal activity. Co-occurring AB and CU traits were also associated with increased precuneus response during loss anticipation. CONCLUSIONS: Findings indicate that AB is associated with reduced activity in brain regions involved in cognitive control, attention, and behavior modification during negative outcomes. Moreover, these reductions are most pronounced in youth with co-occurring CU traits. These findings have implications for understanding why adolescents involved in AB continue these behaviors despite severe negative consequences (e.g. incarceration).


Subject(s)
Antisocial Personality Disorder , Conduct Disorder , Humans , Male , Adolescent , Female , Antisocial Personality Disorder/diagnostic imaging , Antisocial Personality Disorder/epidemiology , Antisocial Personality Disorder/psychology , Conduct Disorder/diagnostic imaging , Conduct Disorder/epidemiology , Conduct Disorder/psychology , Brain , Magnetic Resonance Imaging , Emotions/physiology
9.
J Child Psychol Psychiatry ; 64(6): 918-929, 2023 06.
Article in English | MEDLINE | ID: mdl-36579796

ABSTRACT

BACKGROUND: Stressful events, such as the COVID-19 pandemic, are major contributors to anxiety and depression, but only a subset of individuals develop psychopathology. In a population-based sample (N = 174) with a high representation of marginalized individuals, this study examined adolescent functional network connectivity as a marker of susceptibility to anxiety and depression in the context of adverse experiences. METHODS: Data-driven network-based subgroups were identified using an unsupervised community detection algorithm within functional neural connectivity. Neuroimaging data collected during emotion processing (age 15) were extracted from a priori regions of interest linked to anxiety and depression. Symptoms were self-reported at ages 15, 17, and 21 (during COVID-19). During COVID-19, participants reported on pandemic-related economic adversity. Differences across subgroup networks were first examined, then subgroup membership and subgroup-adversity interaction were tested to predict change in symptoms over time. RESULTS: Two subgroups were identified: Subgroup A, characterized by relatively greater neural network variation (i.e., heterogeneity) and density with more connections involving the amygdala, subgenual cingulate, and ventral striatum; and the more homogenous Subgroup B, with more connections involving the insula and dorsal anterior cingulate. Accounting for initial symptoms, subgroup A individuals had greater increases in symptoms across time (ß = .138, p = .042), and this result remained after adjusting for additional covariates (ß = .194, p = .023). Furthermore, there was a subgroup-adversity interaction: compared with Subgroup B, Subgroup A reported greater anxiety during the pandemic in response to reported economic adversity (ß = .307, p = .006), and this remained after accounting for initial symptoms and many covariates (ß = .237, p = .021). CONCLUSIONS: A subgrouping algorithm identified young adults who were susceptible to adversity using their personalized functional network profiles derived from a priori brain regions. These results highlight potential prospective neural signatures involving heterogeneous emotion networks that predict individuals at the greatest risk for anxiety when experiencing adverse events.


Subject(s)
COVID-19 , Pandemics , Young Adult , Humans , Adolescent , Prospective Studies , Brain Mapping/methods , Magnetic Resonance Imaging/methods , Anxiety/epidemiology , Brain
10.
Psychoneuroendocrinology ; 144: 105855, 2022 10.
Article in English | MEDLINE | ID: mdl-35835021

ABSTRACT

Threat-related amygdala reactivity and the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis have been linked to negative psychiatric outcomes. The amygdala and HPA axis have bidirectional connections, suggesting that functional variation in one system may influence the other. However, research on the functional associations between these systems has demonstrated mixed findings, potentially due to small sample sizes and cortisol sampling and data analytic procedures that investigate only pre-post differences in cortisol rather than the specific phases of the cortisol stress response. Further, previous research has primarily utilized samples of adults of mostly European descent, limiting generalizability to those of other ethnoracial identities and ages. Therefore, studies addressing these limitations are needed in order to investigate the functional relations between amygdala reactivity to threat and HPA axis stress responsivity. Using a sample of 159 adolescents from a diverse cohort (75% African American, ages 15-17 years), the present study evaluated associations between amygdala reactivity during socioemotional processing using fMRI and HPA axis reactivity to a socially-evaluative cold pressor task. Greater amygdala activation to fearful and neutral faces was associated with greater cortisol peak values and steeper activation slope. As cortisol peak values and cortisol activation slope capture the intensity of the cortisol stress response, these data suggest that greater activation of the amygdala in response to social distress and ambiguity among adolescents may be related to hyper-reactivity of the HPA axis.


Subject(s)
Hydrocortisone , Pituitary-Adrenal System , Adolescent , Adult , Amygdala , Humans , Hypothalamo-Hypophyseal System , Saliva , Stress, Psychological
11.
Chest ; 162(3): 614-629, 2022 09.
Article in English | MEDLINE | ID: mdl-35738345

ABSTRACT

Recent clinical practice guidelines have addressed the diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). These disease-specific guidelines were developed independently, without clear direction on how to apply their respective recommendations concurrently within a single patient, where discrimination between these two fibrotic interstitial lung diseases represents a frequent diagnostic challenge. The objective of this review, created by an international group of experts, was to suggest a pragmatic approach on how to apply existing guidelines to distinguish IPF and fHP. Key clinical, radiologic, and pathologic features described in previous guidelines are integrated in a set of diagnostic algorithms, which then are placed in the broader context of multidisciplinary discussion to guide the generation of a consensus diagnosis. Although these algorithms necessarily reflect some uncertainty wherever strong evidence is lacking, they provide insight into the current approach favored by experts in the field based on currently available knowledge. The authors further identify priorities for future research to clarify ongoing uncertainties in the diagnosis of fibrotic interstitial lung diseases.


Subject(s)
Alveolitis, Extrinsic Allergic , Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Alveolitis, Extrinsic Allergic/diagnosis , Alveolitis, Extrinsic Allergic/pathology , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/pathology , Lung/diagnostic imaging , Lung/pathology , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/pathology , Tomography, X-Ray Computed
12.
Chest ; 162(1): 156-178, 2022 07.
Article in English | MEDLINE | ID: mdl-35038455

ABSTRACT

Organizing pneumonia (OP), characterized histopathologically by patchy filling of alveoli and bronchioles by loose plugs of connective tissue, may be seen in a variety of conditions. These include but are not limited to after an infection, drug reactions, radiation therapy, and collagen vascular diseases. When a specific cause is responsible for this entity, it is referred to as "secondary OP." When an extensive search fails to reveal a cause, it is referred to as "cryptogenic OP" (previously called "bronchiolitis obliterans with OP"), which is a clinical, radiologic, and pathologic entity classified as an interstitial lung disease. The clinical presentation of OP often mimics that of other disorders, such as infection and cancer, which can result in a delay in diagnosis and inappropriate management of the underlying disease. The radiographic presentation of OP is polymorphous but often has subpleural consolidations with air bronchograms or solitary or multiple nodules, which can wax and wane. Diagnosis of OP sometimes requires histopathologic confirmation and exclusion of other possible causes. Treatment usually requires a prolonged steroid course, and disease relapse is common. The aim of this article is to summarize the clinical, radiographic, and histologic presentations of this disease and to provide a practical diagnostic algorithmic approach incorporating clinical history and characteristic imaging patterns.


Subject(s)
Bronchiolitis Obliterans , Cryptogenic Organizing Pneumonia , Lung Diseases, Interstitial , Pneumonia , Bronchiolitis Obliterans/complications , Cryptogenic Organizing Pneumonia/diagnostic imaging , Cryptogenic Organizing Pneumonia/etiology , Humans , Lung/pathology , Lung Diseases, Interstitial/complications , Pneumonia/complications
13.
Dev Psychopathol ; 34(1): 129-146, 2022 02.
Article in English | MEDLINE | ID: mdl-33070808

ABSTRACT

Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1-15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1-15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.


Subject(s)
Hydrocortisone , Mental Health , Parenting , Adolescent , Adolescent Health , Anxiety , Caregivers , Child , Child, Preschool , Depression , Humans , Hydrocortisone/analysis , Infant , Parents/psychology , Stress, Psychological
14.
Am J Surg Pathol ; 46(4): e71-e93, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34753865

ABSTRACT

Assessment of lung biopsies for the diagnosis of hypersensitivity pneumonitis (HP) is one of the most difficult diagnostic problems for surgical pathologists. It is a form of interstitial lung disease resulting from an immune reaction provoked by an inhaled antigen in susceptible individuals. Although this definition sounds simple, in practice, the diagnosis of HP can be challenging. To address these issues, the American College of Chest Physicians (CHEST) has recently published a guideline for the diagnosis of HP. In this review, we will explore the multidisciplinary diagnostic evaluation of HP with a focus on the pathologic features as outlined in the CHEST guidelines. The histologic criteria are divided into 4 diagnostic categories: (1) Typical nonfibrotic HP or fibrotic HP; (2) Compatible with nonfibrotic HP or fibrotic HP; (3) Indeterminate for nonfibrotic or fibrotic HP; and (4) Alternative Diagnosis. It is important to emphasize that patterns 1 to 3 do not represent discrete histologic entities or pathologic diagnoses. Rather, these categories are meant to serve as a practical guide for organizing a complex set of overlapping histologic patterns into an integrated diagnostic framework for facilitating multidisciplinary discussion. High-resolution computed tomography features are also summarized, emphasizing how the correlation of lung biopsies with computed tomography findings can help to favor the diagnosis, particularly in cases where biopsies are not typical for HP. This review highlights details of the histologic spectrum of HP as well as the utility of different types of biopsies and bronchoalveolar lavage. We also emphasize the importance of multidisciplinary discussion and the complex differential diagnosis.


Subject(s)
Alveolitis, Extrinsic Allergic , Lung Diseases, Interstitial , Physicians , Alveolitis, Extrinsic Allergic/diagnosis , Alveolitis, Extrinsic Allergic/pathology , Biopsy , Diagnosis, Differential , Fibrosis , Humans , Lung/pathology , Lung Diseases, Interstitial/pathology
15.
J Cogn Neurosci ; 34(10): 1866-1891, 2022 09 01.
Article in English | MEDLINE | ID: mdl-34942644

ABSTRACT

Accumulating literature has linked poverty to brain structure and function, particularly in affective neural regions; however, few studies have examined associations with structural connections or the importance of developmental timing of exposure. Moreover, prior neuroimaging studies have not used a proximal measure of poverty (i.e., material hardship, which assesses food, housing, and medical insecurity) to capture the lived experience of growing up in harsh economic conditions. The present investigation addressed these gaps collectively by examining the associations between material hardship (ages 1, 3, 5, 9, and 15 years) and white matter connectivity of frontolimbic structures (age 15 years) in a low-income sample. We applied probabilistic tractography to diffusion imaging data collected from 194 adolescents. Results showed that material hardship related to amygdala-prefrontal, but not hippocampus-prefrontal or hippocampus-amygdala, white matter connectivity. Specifically, hardship during middle childhood (ages 5 and 9 years) was associated with greater connectivity between the amygdala and dorsomedial pFC, whereas hardship during adolescence (age 15 years) was related to reduced amygdala-orbitofrontal (OFC) and greater amygdala-subgenual ACC connectivity. Growth curve analyses showed that greater increases of hardship across time were associated with both greater (amygdala-subgenual ACC) and reduced (amygdala-OFC) white matter connectivity. Furthermore, these effects remained above and beyond other types of adversity, and greater hardship and decreased amygdala-OFC connectivity were related to increased anxiety and depressive symptoms. Results demonstrate that the associations between material hardship and white matter connections differ across key prefrontal regions and developmental periods, providing support for potential windows of plasticity for structural circuits that support emotion processing.


Subject(s)
White Matter , Adolescent , Amygdala/diagnostic imaging , Child , Child, Preschool , Humans , Magnetic Resonance Imaging/methods , Neural Pathways/diagnostic imaging , Prefrontal Cortex/diagnostic imaging , White Matter/diagnostic imaging
16.
Life (Basel) ; 11(10)2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34685408

ABSTRACT

Chagas disease, caused by the kinetoplastid parasite Trypanosoma cruzi, is a human tropical illness mainly present in Latin America. The therapies available against this disease are far from ideal. Proteases from pathogenic protozoan have been considered as good drug target candidates. T. cruzi acidic M17 leucyl-aminopeptidase (TcLAP) mediates the major parasite's leucyl-aminopeptidase activity and is expressed in all parasite stages. Here, we report the inhibition of TcLAP (IC50 = 66.0 ± 13.5 µM) by the bestatin-like peptidomimetic KBE009. This molecule also inhibited the proliferation of T. cruzi epimastigotes in vitro (EC50 = 28.1 ± 1.9 µM) and showed selectivity for the parasite over human dermal fibroblasts (selectivity index: 4.9). Further insight into the specific effect of KBE009 on T. cruzi was provided by docking simulation using the crystal structure of TcLAP and a modeled human orthologous, hLAP3. The TcLAP-KBE009 complex is more stable than its hLAP3 counterpart. KBE009 adopted a better geometrical shape to fit into the active site of TcLAP than that of hLAP3. The drug-likeness and lead-likeness in silico parameters of KBE009 are satisfactory. Altogether, our results provide an initial insight into KBE009 as a promising starting point compound for the rational design of drugs through further optimization.

17.
Radiol Cardiothorac Imaging ; 3(1): e200314, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33778654

ABSTRACT

Chronic lung allograft dysfunction (CLAD) is the most common cause of mortality in lung transplant recipients after the 1st year of transplantation. CLAD has traditionally been classified into two distinct obstructive and restrictive forms: bronchiolitis obliterans syndrome and restrictive allograft syndrome. However, CLAD may manifest with a spectrum of imaging and pathologic findings and a combination of obstructive and restrictive physiologic abnormalities. Although the initial CT manifestations of CLAD may be nonspecific, the progression of findings at follow-up should signal the possibility of CLAD and may be present on imaging studies prior to the development of functional abnormalities of the lung allograft. This review encompasses the evolution of CT findings in CLAD, with emphasis on the underlying pathogenesis and pathologic condition, to enhance understanding of imaging findings. The purpose of this article is to familiarize the radiologist with the initial and follow-up CT findings of the obstructive, restrictive, and mixed forms of CLAD, for which early diagnosis and treatment may result in improved survival. Supplemental material is available for this article. © RSNA, 2021.

18.
Dev Psychobiol ; 63(5): 1597-1605, 2021 07.
Article in English | MEDLINE | ID: mdl-33559157

ABSTRACT

Early life stress (ELS) is a well-established risk factor for psychopathology across the lifespan. Cognitive vulnerability to stress-induced cortisol may explain risk and resilience. The current study aimed to elucidate a psychobiological pathway linking stress to altered memory for affective words among youth with and without exposure to ELS. One hundred and fifteen youth (ages 9-16, 47% female) were randomized either to a psychosocial stressor or a control condition. Immediately following the stress or control condition, participants completed a memory task for affective words. Change in salivary cortisol from immediately before to 25 min after stress onset were used to predict memory for affective words. Exposure to the acute laboratory stressor led to activation of the HPA axis. Greater cortisol reactivity was associated with less accurate recognition of negative valence words. Among youth exposed to ELS, greater cortisol reactivity to acute stress was associated with poorer recognition of dysphoric and neutral words. Acute increases in cortisol may interfere with negatively-valenced information processing that has implications for memory. Youth exposed to high ELS may be particularly vulnerable to the effects of cortisol, which may explain one pathway through which stress leads to psychopathology among at-risk youth.


Subject(s)
Adverse Childhood Experiences , Hydrocortisone , Adolescent , Child , Female , Humans , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Male , Pituitary-Adrenal System/metabolism , Saliva/metabolism , Stress, Psychological/metabolism
19.
Can Assoc Radiol J ; 72(4): 806-813, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33138634

ABSTRACT

PURPOSE: The RSNA expert consensus statement and CO-RADS reporting system assist radiologists in describing lung imaging findings in a standardized manner in patients under investigation for COVID-19 pneumonia and provide clarity in communication with other healthcare providers. We aim to compare diagnostic performance and inter-/intra-observer among chest radiologists in the interpretation of RSNA and CO-RADS reporting systems and assess clinician preference. METHODS: Chest CT scans of 279 patients with suspected COVID-19 who underwent RT-PCR testing were retrospectively and independently examined by 3 chest radiologists who assigned interpretation according to the RSNA and CO-RADS reporting systems. Inter-/intra-observer analysis was performed. Diagnostic accuracy of both reporting systems was calculated. 60 clinicians participated in a survey to assess end-user preference of the reporting systems. RESULTS: Both systems demonstrated almost perfect inter-observer agreement (Fleiss kappa 0.871, P < 0.0001 for RSNA; 0.876, P < 0.0001 for CO-RADS impressions). Intra-observer agreement between the 2 scoring systems using the equivalent categories was almost perfect (Fleiss kappa 0.90-0.92, P < 0.001). Positive predictive values were high, 0.798-0.818 for RSNA and 0.891-0.903 CO-RADS. Negative predictive value were similar, 0.573-0.585 for RSNA and 0.573-0.58 for CO-RADS. Specificity differed between the 2 systems, 68-73% for CO-RADS and 52-58% for RSNA with superior specificity of CO-RADS. Of 60 survey participants, the majority preferred the RSNA reporting system rather than CO-RADS for all options provided (66.7-76.7%; P < 0.05). CONCLUSIONS: RSNA and CO-RADS reporting systems are consistent and reproducible with near perfect inter-/intra-observer agreement and excellent positive predictive value. End-users preferred the reporting language in the RSNA system.


Subject(s)
COVID-19/diagnostic imaging , Radiologists , Radiology Information Systems/statistics & numerical data , Tomography, X-Ray Computed/methods , Consensus , Humans , Lung/diagnostic imaging , North America , Observer Variation , Radiology , Reproducibility of Results , Retrospective Studies , SARS-CoV-2 , Sensitivity and Specificity , Societies, Medical
20.
Can Assoc Radiol J ; 72(1): 159-166, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32615802

ABSTRACT

PURPOSE: To assess the interobserver variability between chest radiologists in the interpretation of the Radiological Society of North America (RSNA) expert consensus statement reporting guidelines in patients with suspected coronavirus disease 2019 (COVID-19) pneumonia in a setting with limited reverse transcription polymerase chain reaction testing availability. METHODS: Chest computed tomography (CT) studies in 303 consecutive patients with suspected COVID-19 were reviewed by 3 fellowship-trained chest radiologists. Cases were assigned an impression of typical, indeterminate, atypical, or negative for COVID-19 pneumonia according to the RSNA expert consensus statement reporting guidelines, and interobserver analysis was performed. Objective CT features associated with COVID-19 pneumonia and distribution of findings were recorded. RESULTS: The Fleiss kappa for all observers was almost perfect for typical (0.815), atypical (0.806), and negative (0.962) COVID-19 appearances (P < .0001) and substantial (0.636) for indeterminate COVID-19 appearance (P < .0001). Using Cramer V analysis, there were very strong correlations between all radiologists' interpretations, statistically significant for all (typical, indeterminate, atypical, and negative) COVID-19 appearances (P < .001). Objective CT imaging findings were recorded in similar percentages of typical cases by all observers. CONCLUSION: The RSNA expert consensus statement on reporting chest CT findings related to COVID-19 demonstrates substantial to almost perfect interobserver agreement among chest radiologists in a relatively large cohort of patients with clinically suspected COVID-19. It therefore serves as a reliable reference framework for radiologists to accurately communicate their level of suspicion based on the presence of evidence-based objective findings.


Subject(s)
COVID-19/diagnostic imaging , Practice Guidelines as Topic , Radiologists/statistics & numerical data , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Observer Variation , SARS-CoV-2 , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...