Neuropathology of COVID-19 (neuro-COVID): clinicopathological update.

Coronavirus disease 2019 (COVID-19) is emerging as the greatest public health crisis in the early 21century. Its causative agent, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), is an enveloped single stranded positive-sense ribonucleic acid virus that enters cells via the angiotensin converting enzyme 2 receptor or several other receptors. While COVID-19 primarily affects the respiratory system, other organs including the brain can be involved.

Effect of repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD) on cognitive control.

Background: Major Depressive Disorder (MDD) is commonly accompanied by cognitive control dysfunction that may persist after remission of clinical symptoms with antidepressant medication treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment alternative for medication-resistant MDD. In this study, we investigated whether rTMS treatment had a beneficial effect not only on depressive symptoms, but on also cognitive control dysfunction.

Use of Phenobarbital in Delirium Tremens.

The standard of care for alcohol withdrawal centers on the use of escalating doses of benzodiazepines until clinical improvement is achieved. However, there is no established standard in the care of patients with severe alcohol withdrawal and delirium tremens that is refractory to benzodiazepine therapy. One potential therapy that is gaining traction is the use of phenobarbital, which may be mechanistically superior to benzodiazepines in treating delirium tremens because of its effects on GABA and N-methyl-D-aspartate receptors.

Tumor-suppressive miR148a is silenced by CpG island hypermethylation in IDH1-mutant gliomas.

Purpose: IDH1/2-mutant gliomas harbor a distinct glioma-CpG island methylation phenotype (G-CIMP) that may promote the initiation and progression of secondary pathway gliomas by silencing tumor-suppressive genes. The potential role of tumor-suppressive microRNAs (miRNA; miR) in this process is not understood.

Experimental Design: To identify potential tumor-suppressive miRNA hypermethylated in glioma, the methylation profiles of IDH1/2(WT) gliomas (n = 11) and IDH1(MUT) glioma (n = 20) were compared by using massively parallel reduced representation bisulfite sequencing (RRBS).

The procurement, storage, and quality assurance of frozen blood and tissue biospecimens in pathology, biorepository, and biobank settings.

Well preserved frozen biospecimens are ideal for evaluating the genome, transcriptome, and proteome. While papers reviewing individual aspects of frozen biospecimens are available, we present a current overview of experimental data regarding procurement, storage, and quality assurance that can inform the handling of frozen biospecimens. Frozen biospecimen degradation can be influenced by factors independent of the collection methodology including tissue type, premortem agonal changes, and warm ischemia time during surgery.

A review of room temperature storage of biospecimen tissue and nucleic acids for anatomic pathology laboratories and biorepositories.

Unlabelled: Frozen biospecimens are crucial for translational research and contain well-preserved nucleic acids and protein. However, the risks of freezer failure as well as space, cost, and environmental concerns of frozen biospecimens are substantial.

Objective: The purpose of the study was to review the current status of room temperature biospecimen storage.

Lyophilized brain tumor specimens can be used for histologic, nucleic acid, and protein analyses after 1 year of room temperature storage.

Frozen tissue, a gold standard biospecimen, can yield well preserved nucleic acids and proteins after over a decade but is vulnerable to thawing and has substantial fiscal, spatial, and environmental costs. A long-term room temperature biospecimen storage alternative that preserves broad analytical utility can potentially empower tissue-based research. As there is scant data on the analytical utility of lyophilized brain tumor biospecimens, we evaluated lyophilized (freeze-dried) samples stored for 1 year at room temperature.

Combined analysis of O6-methylguanine-DNA methyltransferase protein expression and promoter methylation provides optimized prognostication of glioblastoma outcome.

Background: Promoter methylation of the DNA repair gene, O-6-methylguanine-DNA methyltransferase (MGMT), is associated with improved treatment outcome for newly diagnosed glioblastoma (GBM) treated with standard chemoradiation. To determine the prognostic significance of MGMT protein expression as assessed by immunohistochemistry (IHC) and its relationship with methylation, we analyzed MGMT expression and promoter methylation with survival in a retrospective patient cohort.

Methods: We identified 418 patients with newly diagnosed GBM at University of California Los Angeles Kaiser Permanente Los Angeles, nearly all of whom received chemoradiation, and determined MGMT expression by IHC, and MGMT promoter methylation by methylation-specific PCR (MSP) and bisulfite sequencing (BiSEQ) of 24 neighboring CpG sites.

Overexpression of isocitrate dehydrogenase mutant proteins renders glioma cells more sensitive to radiation.

Mutations in isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) are found in a subset of gliomas. Among the many phenotypic differences between mutant and wild-type IDH1/2 gliomas, the most salient is that IDH1/2 mutant glioma patients demonstrate markedly improved survival compared with IDH1/2 wild-type glioma patients. To address the mechanism underlying the superior clinical outcome of IDH1/2 mutant glioma patients, we investigated whether overexpression of the IDH1(R132H) protein could affect response to therapy in the context of an isogenic glioma cell background.

A review of radio frequency identification technology for the anatomic pathology or biorepository laboratory: Much promise, some progress, and more work needed.

Patient safety initiatives throughout the anatomic laboratory and in biorepository laboratories have mandated increasing emphasis on the need for accurately identifying and tracking biospecimen assets throughout their production lifecycle and for archiving/retrieval purposes. However, increasing production volume along with complex workflow characteristics, reliance on manual production processes, and required asset movement to disparate destinations throughout asset lifecycles continue to challenge laboratory efforts. Radio Frequency Identification (RFID) technology, use of radio waves to communicate data between electronic tags attached to objects and a reader, shows significant potential to facilitate and overcome these hurdles.

Tolerance testing of passive radio frequency identification tags for solvent, temperature, and pressure conditions encountered in an anatomic pathology or biorepository setting.

Background: Radio frequency identification (RFID) tags have potential for use in identifying and tracking biospecimens in anatomic pathology and biorepository laboratories. However, there is little to no data on the tolerance of tags to solutions, solvents, temperatures, and pressures likely to be encountered in the laboratory. The functioning of the Hitachi Mu-chip RFID tag, a candidate for pathology use, was evaluated under such conditions.