Microglia Activation in Basal Ganglia Is a Late Event in Huntington Disease Pathophysiology

ObjectiveTo define the role played by microglia in different stages of Huntington disease (HD), we used the TSPO radioligand [11C]-ER176 and PET to evaluate microglial activation in relation to neurodegeneration and in relation to the clinical features seen at premanifest and manifest stages of the disease.MethodsThis is a cross-sectional study in which 18 subjects (6 controls, 6 premanifest, and 6 manifest HD gene carriers) underwent a [11C]-ER176 PET scan and an MRI for anatomic localization. Segmentation of regions of interest (ROIs) was performed, and group differences in [11C]-ER176 binding (used to evaluate the extent of microglial activation) were assessed by the standardized uptake value ratio (SUVR). Microglial activation was correlated with ROIs volumes, disease burden, and the scores obtained in the clinical scales. As an exploratory aim, we evaluated the dynamic functions of microglia in vitro, by using induced microglia-like (iMG) cells from peripheral blood monocytes.ResultsIndividuals with manifest HD present higher [11C]-ER176 SUVR in both globi pallidi and putamina in comparison with controls. No differences were observed when we compared premanifest HD with controls or with manifest HD. We also found a significant correlation between increased microglial activation and cumulative disease burden, and with reduced volumes. iMG from controls, premanifest HD, and manifest HD patients showed similar phagocytic capacity.ConclusionsAltogether, our data demonstrate that microglial activation is involved in HD pathophysiology and is associated with disease progression.

Depressive rumination is correlated with brain responses during self-related processing

BackgroundRumination, a tendency to focus on negative self-related thoughts, is a central symptom of depression. Studying the self-related aspect of such symptoms is challenging due to the need to distinguish self effects per se from the emotional content of task stimuli. This study employs an emotionally neutral self-related paradigm to investigate possible altered self processing in depression and its link to rumination.MethodsPeople with unipolar depression (MDD; n = 25) and controls (n = 25) underwent task-based EEG recording. Late event-related potentials were studied along with low frequency oscillatory power. EEG metrics were compared between groups and correlated with depressive symptoms and reported rumination.ResultsThe MDD group displayed a difference in late potentials across fronto-central electrodes between self-related and non-self-related conditions. No such difference was seen in controls. The magnitude of this difference was positively related with depressive symptoms and reported rumination. MDD also had elevated theta oscillation power at central electrodes in self-related conditions, which was not seen in controls.ConclusionsRumination appears linked to altered self-related processing in depression, independently of stimuli-related emotional confounds. This connection between self-related processing and depression may point to self-disorder being a core component of the condition.

Distinct genomic profiles of gestational choriocarcinoma, a unique cancer of pregnant tissues

Little is known about genomic alterations of gestational choriocarcinoma (GC), unique cancer that originates in pregnant tissues, and the progression mechanisms from the nonmalignant complete hydatidiform mole (CHM) to GC. Whole-exome sequencing (20 GCs) and/or single-nucleotide polymorphism microarray (29 GCs) were performed. We analyzed copy-neutral loss-of-heterozygosity (CN-LOH) in 29 GCs that exhibited androgenetic CN-LOHs (20 monospermic, 8 dispermic) and no CN-LOH (one with NLRP7 mutation). Most GCs (25/29) harboring recurrent copy number alterations (CNAs) and gains on 1q21.1-q44 were significantly associated with poor prognosis. We detected five driver mutations in the GCs, most of which were chromatin remodeling gene (ARID1A, SMARCD1, and EP300) mutations but not in common cancer genes such as TP53 and KRAS. One patient’s serial CHM/invasive mole/GC showed consistent CN-LOHs, but only the GC harbored CNAs, indicating that CN-LOH is an early pivotal event in HM-IM-GC development, and CNAs may be a late event that promotes CHM progression to GC. Our data indicate that GCs have unique profiles of CN-LOHs, mutations and CNAs that together differentiate GCs from non-GCs. Practically, CN-LOH and CNA profiles are useful for the molecular diagnosis of GC and the selection of GC patients with poor prognosis for more intensive treatments, respectively.

Neuroendocrine tumour of the ampulla of Vater: a rare neoplasm at an atypical site

The periampullary neuroendocrine tumour is an infrequently occurring tumour. Its prevalence among gastrointestinal neuroendocrine neoplasms is less than 0.3%, and less than 2% out of periampullary tumours. These neoplasms have relatively poor prognosis. Jaundice and pain in the abdomen are the early and most commonly occurring symptoms with weight loss being a late event. The carcinoid syndrome presents infrequently in periampullary neuroendocrine tumour and happens only if hepatic metastasis occurs. In this scenario, histopathology plays a paramount role in the diagnosis. Specific immunohistochemical staining is used for diagnosis while the treatment options are local excision, endoscopic excision and pancreaticoduodenectomy. Here is a case report of a 42-year-old patient who presented with complaint of obstructive jaundice for one month. Periampullary carcinoid tumour was diagnosed on biopsy, and she underwent Pancreaticoduodenectomy as treatment. Continuou...

In context: emotional intent and temporal immediacy of contextual descriptions modulate affective ERP components to facial expressions

In this study, we explored how contextual information about threat dynamics affected the electrophysiological correlates of face perception. Forty-six healthy native Swedish speakers read verbal descriptions signaling an immediate vs delayed intent to escalate or deescalate an interpersonal conflict. Each verbal description was followed by a face with an angry or neutral expression, for which participants rated valence and arousal. Affective ratings confirmed that the emotional intent expressed in the descriptions modulated emotional reactivity to the facial stimuli in the expected direction. The electrophysiological data showed that compared to neutral faces, angry faces resulted in enhanced early and late event-related potentials (VPP, P300 and LPP). Additionally, emotional intent and temporal immediacy modulated the VPP and P300 similarly across angry and neutral faces, suggesting that they influence early face perception independently of facial affect. By contrast, the LPP amplitude to faces revealed an interaction between facial expression and emotional intent. Deescalating descriptions eliminated the LPP differences between angry and neutral faces. Together, our results suggest that information about a person’s intentions modulates the processing of facial expressions.

The Pathway from Radiation to Fibrosis: LET Dependence

It is well-known that Radiation-induced fibrosis (RIF) is a late event occurring months to years after the initial radiation exposure. Fibrotic lesions have been shown to manifest in many tissues including the skin, heart, lung, liver and kidney. Fibrosis occurs due to abnormal accumulation of extracellular matrix (ECM) proteins that result in loss of normal tissue and organ function. The cell type involved in RIF is myofibroblasts, which do not undergo apoptosis after healing but instead continue to accumulate, producing excessive amounts of ECM proteins, thereby damaging the tissues and organs. Reactive oxygen species, generated in response to radiation, is one signal that helps maintain the myofibroblast phenotype. In this review, we discuss molecular mechanisms leading to this late radiation event, known biomarkers for prediction, preclinical animal models of radiation-induced toxicity and current clinical trials designed for mitigation and treatment of radiation-induced fibrosis. We also discuss other physical properties such as linear energy transfer (LET) than the ones used in the clinics today which may have the potential to change our understanding on this inevitable pathway from radiation treatment to organ fibrosis.