Sarcoidosis is a systemic disease characterized by granulomatous inflammation. Cardiac involvement is associated with increased morbidity. However, differences in clinical characteristics and ...outcomes based on initial sarcoidosis organ manifestation in patients with cardiac sarcoidosis (CS) have not been described.
A retrospective cohort of 252 patients with CS at an urban, quaternary medical center was studied. Presentation, treatment and outcomes of de novo CS and prior ECS groups were compared. Survival free of primary composite outcome (left ventricular assist device implantation, orthotopic heart transplantation (OHT), or death) was assessed.
There were 124 de novo CS patients and 128 with prior ECS at time of CS diagnosis. De novo CS patients were younger at CS diagnosis (p = 0.020). De novo CS patients had a more advanced cardiac presentation: lower left ventricular ejection fraction (LVEF) (p < 0.001), more frequent sustained ventricular arrhythmias (VA) (p = 0.001), and complete heart block (p = 0.001). During follow-up, new VA (p < 0.001), ventricular tachycardia ablation (p < 0.001), and OHT (p = 0.003) were more common in the de novo CS group. Outcome free survival was significantly shorter for de novo CS patients (p = 0.005), with increased hazard of primary composite outcome (p = 0.034) and development of new VA (p = 0.027) when compared to ECS patients. Overall mortality was similar between groups.
Patients presenting with CS as their first recognized organ manifestation of sarcoidosis have an increased risk of adverse cardiac outcomes as compared to those with a prior history of ECS. Improved awareness and diagnosis of CS is warranted for earlier recognition.
Display omitted
•De novo cardiac sarcoidosis (CS) presents with more advanced cardiomyopathy, ventricular arrhythmia and heart block.•De novo CS patients have increased adverse cardiac outcomes compared to those with a prior extracardiac sarcoidosis (ECS).•In those with CS, de novo and prior ECS patients have similar mortality.•Improved awareness and diagnosis of CS is warranted for earlier recognition.
The causes of cognitive impairment among older HIV+ individuals may overlap with causes among elderly HIV seronegative (HIV-) individuals. The objective of this study was to determine if beta-amyloid ...(Aβ) deposition measured by
18
F AV-45 (florbetapir) positron emission tomography (PET) is increased in older HIV+ individuals compared to HIV- individuals. Forty-eight HIV+ and 25 HIV- individuals underwent
18
F AV-45 PET imaging.
18
F AV-45 binding to Aβ was measured by standardized uptake value ratios (SUVR) relative to the cerebellum in 16 cortical and subcortical regions of interest. Global and regional cortical SUVRs were compared by (1) serostatus, (2) HAND stage, and (3) age decade, comparing individuals in their 50s and
>
60s. There were no differences in median global cortical SUVR stratified by HIV serostatus or HAND stage. The proportion of HIV+ participants in their 50s with elevated global amyloid uptake (SUVR > 1.40) was significantly higher than the proportion in HIV- participants (67% versus 25%,
p
= 0.04), and selected regional SUVR values were also higher (
p
< 0.05) in HIV+ compared to HIV- participants in their 50s. However, these group differences were not seen in participants in their 60s. In conclusion, PET imaging found no differences in overall global Aβ deposition stratified by HIV serostatus or HAND stage. Although there was some evidence of increased Aβ deposition in HIV+ individuals in their 50s compared to HIV- individuals which might indicate premature aging, the most parsimonious explanation for this is the relatively small sample size in this cross-sectional cohort study.
The optimization of resources for research in developing countries forces us to consider strategies in the wet lab that allow the reuse of molecular biology reagents to reduce costs. In this study, ...we used linear regression as a method for predictive modeling of coverage depth given the number of MinION reads sequenced to define the optimum number of reads necessary to obtain >200X coverage depth with a good lineage-clade assignment of SARS-CoV-2 genomes. The research aimed to create and implement a model based on machine learning algorithms to predict different variables (
, coverage depth) given the number of MinION reads produced by Nanopore sequencing to maximize the yield of high-quality SARS-CoV-2 genomes, determine the best sequencing runtime, and to be able to reuse the flow cell with the remaining nanopores available for sequencing in a new run. The best accuracy was -0.98 according to the R squared performance metric of the models. A demo version is available at https://genomicdashboard.herokuapp.com/.
(R,S)-methadone ((R,S)-MTD) is a µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers. (S)-MTD is being developed as an antidepressant and is considered an ...N-methyl-D-aspartate receptor (NMDAR) antagonist. We compared the pharmacology of (R)-MTD and (S)-MTD and found they bind to MORs, but not NMDARs, and induce full analgesia. Unlike (R)-MTD, (S)-MTD was a weak reinforcer that failed to affect extracellular dopamine or induce locomotor stimulation. Furthermore, (S)-MTD antagonized motor and dopamine releasing effects of (R)-MTD. (S)-MTD acted as a partial agonist at MOR, with complete loss of efficacy at the MOR-galanin Gal
receptor (Gal
R) heteromer, a key mediator of the dopaminergic effects of opioids. In sum, we report novel and unique pharmacodynamic properties of (S)-MTD that are relevant to its potential mechanism of action and therapeutic use. One-sentence summary: (S)-MTD, like (R)-MTD, binds to and activates MORs in vitro, but (S)-MTD antagonizes the MOR-Gal
R heteromer, decreasing its abuse liability.
Purpose: Rasmussen syndrome (RS) is a rare form of epilepsy characterized by progressive destruction of a single hemisphere. To characterize the profile of cortical involvement in RS, we studied the ...pathological changes in the cerebral cortex of 45 hemispherectomies performed at Johns Hopkins Hospital between 1985 and 2002.
Methods: The patterns of pathologic changes and stages of cortical abnormalities were studied by histology and immunocy to chemistry methods. The burden of pathology (BP) was quantified in all brain regions of each of the 45 hemispheres.
Results: Our study demonstrated significant heterogeneity in the stages of cortical pathology and the multifocal nature of the disease. These stages varied from early inflammation defined by infiltration of T lymphocytes and neuroglial reactions, to more severe stages with extensive neuronal cell death and cavitation of the cerebral cortex. A greater BP was significantly associated with an early age at onset (p = 0.01) and longer duration of disease (p ≤ 0.001). The BP was similar in all brain regions except the occipital lobe, where the BP was significantly lower (p = 0.032).
Conclusions: The multifocal distribution of pathologic changes, as well as the heterogeneity in the stages of cortical damage in each patient, is consistent with an ongoing and progressive immune‐mediated process of neuronal damage that involves neuroglial and lymphocytic responses, resembling other autoimmune CNS disorders such as multiple sclerosis.
ABSTRACTInterfacing magnetic resonance imaging (MRI) with pathology is critically important for understanding the pathologic basis of MRI signal changes in vivo and for clinicopathologic ...correlations. Postmortem MRI is an intermediate step in this process; unfortunately, however, relating the data to standard pathologic sections, which are relatively thick and often nonparallel, is both time-consuming and insufficiently accurate. The aim of this project was to develop technology to integrate postmortem, high-resolution, whole-brain MRI into the planning and execution of pathologic analysis through precise localization of the target and coordinates of cut. Compared with standard pathologic sectioning, the use of an individualized, 3-dimensionally printed cutting box—designed based on postmortem MRI of formalin-fixed whole brains—improved the speed, quality, and accuracy of radiologic-pathologic correlations and, specifically, the histopathologic localization of imaging findings. The technology described herein is easily implemented, applicable to any brain disorder, and potentially extendable to other organs. From the point of view of the pathologist, this technique can improve localization of small or subtle abnormalities, whereas from the point of view of the radiologist, it has the potential to improve understanding of MRI signal changes observed in diseases.
Immunity, neuroglia and neuroinflammation in autism Pardo, Carlos A.; Vargas, Diana L.; Zimmerman, Andrew W.
International review of psychiatry (Abingdon, England),
12/2005, Letnik:
17, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Autism is a complex neurodevelopmental disorder of early onset that is highly variable in its clinical presentation. Although the causes of autism in most patients remain unknown, several lines of ...research support the view that both genetic and environmental factors influence the development of abnormal cortical circuitry that underlies autistic cognitive processes and behaviors. The role of the immune system in the development of autism is controversial. Several studies showing peripheral immune abnormalities support immune hypotheses, however until recently there have been no immune findings in the CNS. We recently demonstrated the presence of neuroglial and innate neuroimmune system activation in brain tissue and cerebrospinal fluid of patients with autism, findings that support the view that neuroimmune abnormalities occur in the brain of autistic patients and may contribute to the diversity of the autistic phenotypes. The role of neuroglial activation and neuroinflammation are still uncertain but could be critical in maintaining, if not also in initiating, some of the CNS abnormalities present in autism. A better understanding of the role of neuroinflammation in the pathogenesis of autism may have important clinical and therapeutic implications.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To determine the underlying etiology in a patient with progressive dementia with extrapyramidal signs and chronic inflammation referred to the National Institutes of Health Undiagnosed ...Diseases Program.
Methods
Extensive investigations included metabolic profile, autoantibody panel, infectious etiologies, genetic screening, whole exome sequencing, and the phage‐display assay, VirScan, for viral immune responses. An etiological diagnosis was established postmortem.
Results
Using VirScan, enrichment of dengue viral antibodies was detected in cerebrospinal fluid as compared to serum. No virus was detected in serum or cerebrospinal fluid, but postmortem analysis confirmed dengue virus in the brain by immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, and sequencing. Dengue virus was also detectable by polymerase chain reaction and sequencing from brain biopsy tissue collected 33 months antemortem, confirming a chronic infection despite a robust immune response directed against the virus. Immunoprofiling and whole exome sequencing of the patient did not reveal any immunodeficiency, and sequencing of the virus demonstrated wild‐type dengue virus in the central nervous system.
Interpretation
Dengue virus is the most common arbovirus worldwide and represents a significant public health concern. Infections with dengue virus are usually self‐limiting, and chronic dengue infections have not been previously reported. Our findings suggest that dengue virus infections may persist in the central nervous system causing a panencephalitis and should be considered in patients with progressive dementia with extrapyramidal features in endemic regions or with relevant travel history. Furthermore, this work highlights the utility of comprehensive antibody profiling assays to aid in the diagnosis of encephalitis of unknown etiology. ANN NEUROL 2019;86:695–703
Purpose
Low-flow spinal arteriovenous fistulas (SAVFs) with intradural venous drainage typically manifest with a progressive venous hypertensive myelopathy (VHM) in older patients. VHM is difficult ...to identify. MRI is often nonspecific, and many cases are initially misdiagnosed, most often as transverse myelitis. The workup of myelopathic patients frequently includes thoracic and/or abdominal contrast-enhanced CT (CECT) that are generally not reviewed by neuroradiologists. The purpose of this work was to investigate how often abnormal enhancing intracanalar structures corresponding to the draining veins of a low-flow SAVF were documented by CECT.
Materials and methods
We evaluated 92 consecutive patients with low-flow SAVFs and VHM treated at our institution between 2009 and 2018. The study group included 22 of these patients with at least one thoracoabdominal CECT available for review. The control group consisted of 20 consecutive myelopathy patients with negative angiography and at least one thoracoabdominal CECT. Intracanalar enhancing structures were classified either as (i) conspicuous or (ii) equivocal or absent.
Results
One CECT in the study group was technically inadequate. Conspicuous intracanalar enhancing structures were observed in 20 of the remaining 21 patients with SAVFs (95.2%) and in 2 of 20 control patients (10%). None of the enhancing intracanalar structures was mentioned in official study reports.
Conclusions
The presence of enhancing vascular structures within the spinal canal on thoracoabdominal CECT obtained during the workup of myelopathies appears to represent a powerful but currently underappreciated tool for the detection of low-flow SAVFs.
PDF
