Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment ...and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such mechanism. Recent clinical studies have suggested that epigenetic modification, particularly methylation of gene regulatory regions, also acts to shape human brain function associated with risk for mental illness. However, it is not yet clear whether differential gene methylation as a function of adversity contributes to the emergence of individual risk for mental illness. Using prospective longitudinal epigenetic, neuroimaging and behavioral data from 132 adolescents, we demonstrate that changes in gene methylation associated with lower socioeconomic status (SES) predict changes in risk-related brain function. Specifically, we find that lower SES during adolescence is associated with an increase in methylation of the proximal promoter of the serotonin transporter gene, which predicts greater increases in threat-related amygdala reactivity. We subsequently demonstrate that greater increases in amygdala reactivity moderate the association between a positive family history for depression and the later manifestation of depressive symptoms. These initial results suggest a specific biological mechanism through which adversity contributes to altered brain function, which in turn moderates the emergence of general liability as individual risk for mental illness. If replicated, this prospective pathway may represent a novel target biomarker for intervention and prevention among high-risk individuals.
Abstract Recent literature contains numerous articles on osteonecrosis of the jaws (ONJ) associated with bisphosphonate treatment (BPT), with most advocating a conservative approach to management. A ...prospective study was designed to review the surgical management of cases of ONJ that did not respond to conservative management. Forty patients, referred with ONJ that did not respond to conservative management, were treated surgically and followed up for 6 months to 4 years. Four patients were taking i.v. BPT as part of their bone cancer management and 16 were taking oral BPT for osteoporosis. The surgical management of ONJ involved antibiotic therapy, surgical debridement of all necrotic bone and tension-free primary closure. All 40 cases healed uneventfully with no wound breakdown during follow-up. Most of the literature supports the conservative management of ONJ, but the condition leaves the patient debilitated. Many cases do not respond to conservative management and the infection and bone destruction is progressive. The conservative management of ONJ is to be supported, but this prospective study has shown that those cases that do not respond may be managed surgically. It should be recognized that while the results of this paper are encouraging, some cases will be resistant to all treatments.
Objective: The goal of this study was to investigate the relationship between default mode network connectivity and the severity of post‐traumatic stress disorder (PTSD) symptoms in a sample of ...eleven acutely traumatized subjects.
Method: Participants underwent a 5.5 min resting functional magnetic resonance imaging scan. Brain areas whose activity positively correlated with that of the posterior cingulate/precuneus (PCC) were assessed. To assess the relationship between severity of PTSD symptoms and PCC connectivity, the contrast image representing areas positively correlated with the PCC was correlated with the subjects’ Clinician Administered PTSD Scale scores.
Results: Results suggest that resting state connectivity of the PCC with the perigenual anterior cingulate and the right amygdala is associated with current PTSD symptoms and that correlation with the right amygdala predicts future PTSD symptoms.
Conclusion: These results may contribute to the development of prognostic tools to distinguish between those who will and those who will not develop PTSD.
FKBP5 SNPs showing significant interaction effects with emotional neglect on right dorsal amygdala reactivity.
Individual variation in physiological responsiveness to stress mediates risk for mental ...illness and is influenced by both experiential and genetic factors. Common polymorphisms in the human gene for FK506 binding protein 5 (FKBP5), which is involved in transcriptional regulation of the hypothalamic–pituitary–adrenal (HPA) axis, have been shown to interact with childhood abuse and trauma to predict stress‐related psychopathology. In the current study, we examined if such gene–environment interaction effects may be related to variability in the threat‐related reactivity of the amygdala, which plays a critical role in mediating physiological and behavioral adaptations to stress including modulation of the HPA axis. To this end, 139 healthy Caucasian youth completed a blood oxygen level‐dependent functional magnetic resonance imaging probe of amygdala reactivity and self‐report assessments of emotional neglect (EN) and other forms of maltreatment. These individuals were genotyped for 6 FKBP5 polymorphisms (rs7748266, rs1360780, rs9296158, rs3800373, rs9470080 and rs9394309) previously associated with psychopathology and/or HPA axis function. Interactions between each SNP and EN emerged such that risk alleles predicted relatively increased dorsal amygdala reactivity in the context of higher EN, even after correcting for multiple testing. Two different haplotype analyses confirmed this relationship as haplotypes with risk alleles also exhibited increased amygdala reactivity in the context of higher EN. Our results suggest that increased threat‐related amygdala reactivity may represent a mechanism linking psychopathology to interactions between common genetic variants affecting HPA axis function and childhood trauma.
Abstract Proliferative diabetic retinopathy (PDR) is a condition that carries a high risk of severe visual impairment. The hallmark of PDR is neovascularisation, the growth of abnormal new vessels. ...This paper describes an automated method for the detection of new vessels in retinal images. Two vessel segmentation approaches are applied, using the standard line operator and a novel modified line operator. The latter is designed to reduce false responses to non-vessel edges. Both generated binary vessel maps hold vital information which must be processed separately. This is achieved with a dual classification system. Local morphology features are measured from each binary vessel map to produce two separate feature sets. Independent classification is performed for each feature set using a support vector machine (SVM) classifier. The system then combines these individual classification outcomes to produce a final decision. Sensitivity and specificity results using a dataset of 60 images are 0.862 and 0.944 respectively on a per patch basis and 1.00 and 0.90 respectively on a per image basis.
To investigate the presence of autoantibody deposition against type 2 tissue transglutaminase (TG2; a reliable marker of the whole spectrum of gluten sensitivity) in the jejunal tissue and brain of ...patients with gluten ataxia and in control subjects.
The authors evaluated jejunal biopsy samples from nine patients with gluten ataxia and seven patients with other causes of ataxia for the presence of TG2-related immunoglobulin deposits using double-color immunofluorescence. Autopsy brain tissue from one patient with gluten ataxia and one neurologically intact brain were also studied.
IgA deposition on jejunal TG2 was found in the jejunal tissue of all patients with gluten ataxia and in none of the controls. The intestinal IgA deposition pattern was similar to that seen in patients with overt and latent celiac disease and in those with dermatitis herpetiformis. Widespread IgA deposition around vessels was found in the brain of the patient with gluten ataxia but not the control brain. The deposition was most pronounced in the cerebellum, pons, and medulla.
Anti-tissue transglutaminase IgA antibodies are present in the gut and brain of patients with gluten ataxia with or without an enteropathy in a similar fashion to patients with celiac disease, latent celiac disease, and dermatitis herpetiformis but not in ataxia control subjects. This finding strengthens the contention that gluten ataxia is immune mediated and belongs to the same spectrum of gluten sensitivity as celiac disease and dermatitis herpetiformis.
This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive ...assessment (Photochemical and Photobiological Sciences, 2019, 18, 595–828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.
In response to LIGO’s observation of GW170104, we performed a series of full numerical simulations of binary black holes, each designed to replicate likely realizations of its dynamics and radiation. ...These simulations have been performed at multiple resolutions and with two independent techniques to solve Einstein’s equations. For the nonprecessing and precessing simulations, we demonstrate the two techniques agree mode by mode, at a precision substantially in excess of statistical uncertainties in current LIGO’s observations. Conversely, we demonstrate our full numerical solutions contain information which is not accurately captured with the approximate phenomenological models commonly used to infer compact binary parameters. To quantify the impact of these differences on parameter inference for GW170104 specifically, we compare the predictions of our simulations and these approximate models to LIGO’s observations of GW170104.
The brown planthopper, Nilaparvata lugens, is an economically significant pest of rice throughout Asia and has evolved resistance to many insecticides including the neonicotinoid imidacloprid. The ...resistance of field populations of N. lugens to imidacloprid has been attributed to enhanced detoxification by cytochrome P450 monooxygenases (P450s), although, to date, the causative P450(s) has (have) not been identified. In the present study, biochemical assays using the model substrate 7‐ethoxycoumarin showed enhanced P450 activity in several resistant N. lugens field strains when compared with a susceptible reference strain. Thirty three cDNA sequences encoding tentative unique P450s were identified from two recent sequencing projects and by degenerate PCR. The mRNA expression level of 32 of these was examined in susceptible, moderately resistant and highly resistant N. lugens strains using quantitative real‐time PCR. A single P450 gene (CYP6ER1) was highly overexpressed in all resistant strains (up to 40‐fold) and the level of expression observed in the different N. lugens strains was significantly correlated with the resistance phenotype. These results provide strong evidence for a role of CYP6ER1 in the resistance of N. lugens to imidacloprid.
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