Methamphetamine Increases the Proportion of SIV-Infected Microglia/Macrophages,Alters Metabolic Pathways,and Elevates Cell Death Pathways: A Single-Cell Analysis

Both substance use disorder and HIV infection continue to affect many individuals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse, such as the psychostimulant methamphetamine. To determine the interaction of HIV and methamphetamine, we isolated microglia and brain macrophages from SIV-infected rhesus monkeys that were treated with or without methamphetamine. Cells were subjected to single-cell RNA sequencing and results were analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of the microglia and/or macrophages were infected by SIV. In addition, gene encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of microglia and/or macrophages from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain.     

Vogt-Koyanagi-Harada syndrome: a rare but important differential diagnosis of viral meningitis

Vogt-Koyanagi-Harada syndrome (VKHS) is an inflammatory syndrome affecting melanocyte-containing organs. The clinical onset is often acute with neurological and ophthalmological symptoms and there is considerable risk of sequelae if the condition is not promptly diagnosed and treated. We present a case illustrating that VKHS is a rare but important differential diagnosis of viral meningitis.     

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome

Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene, Sparcl1, a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence.     

Within-hospital and 30-day outcomes in 107,994 patients undergoing invasive coronary angiography with different low-osmolar iodinated contrast media

Comparative clinical outcomes after exposure to alternate low osmolar contrast media (LOCM) during invasive coronary angiography (ICA) and/or percutaneous coronary intervention (PCI) have been incompletely examined. From a retrospective multicenter observational study, we identified 107,994 adults without previous hemodialysis undergoing ICA and/or PCI with iohexol, iopamidol, or ioversol. We created a propensity score for contrast media type using age, gender, coverage status, route of hospitalization, illness severity, physician specialty, co-morbidities, and procedure type. Propensity matching was performed in a 1:1 fashion for iohexol (n = 10,204) and iopamidol (n = 10,204) and in a 1:1 fashion for iohexol (n = 19,482) and ioversol (n = 19,482). Groups were examined for differences in in-hospital mortality or subsequent hemodialysis, length of stay, and 30-day readmission for contrast-induced nephropathy (CIN). Compared to patients exposed to iohexol, no differences were observed for patients exposed to iopamidol or ioversol for in-hospital hemodialysis (0.5% vs 0.4%, p = 0.45; 0.3% vs 0.5%, p = 0.05), in-hospital mortality (0.7% vs 0.6%, p = 0.60; 0.5% vs 0.6%, p = 0.42), or composite hemodialysis or mortality (1.1% vs 1.0%, p = 0.58; 0.8% vs 1.0%, p = 0.06); for hospital length of stay (2.9 ± 2.7 vs 2.9 ± 2.7 days, p = 0.05; 2.8 ± 2.6 vs 2.9 ± 3.1 days, p = 0.35); or for 30-day readmission for CIN (0.1% vs 0.1%, p = 0.82; 0.1% vs 0.1%, p = 0.52). In conclusion, for patients undergoing ICA and/or PCI exposed to alternate LOCM, in-hospital death, need for hemodialysis, or readmission for CIN are uncommon, with no apparent clinical advantage among LOCM agents.     

Acute-Onset Cerebellar Symptoms in Lhermitte–Duclos Disease: Case Report

Adult-onset Lhermitte–Duclos disease (LD), or dysplastic cerebellar gangliocytoma, is a hamartoma considered pathognomonic for Cowden disease. Classically, LD has a progressive and insidious onset of symptoms. In this case report, we present a patient having rapid neurological deterioration from acute-onset LD. There are only three reported cases of acute LD presentation. A 22-year-old female presented to the emergency department with diplopia, dysarthria, dysphagia, and gait instability which developed within 6 h. A non-contrast CT scan revealed diffuse attenuation in the left cerebellum and mild ventricular dilatation. LP revealed no organisms. Magnetic resonance imaging revealed salient “tiger stripe” appearance of the left cerebellar cortex and effacement of the fourth ventricle. The patient subsequently underwent suboccipital craniotomy and gross total resection of the lesion. The tumor histology showed distortion of normal cerebellar architecture with dysplastic ganglion cells, loss of Purkinje cells, atrophy of the white matter, and expansion of cerebellar folia. Findings were consistent with adult-onset Lhermitte–Duclos disease.