Thoracic Epidural Abscesses: A Systematic Review.

Study Design: Systematic review. Objectives: Past research has demonstrated increased speed and severity of progression for spinal epidural abscesses (SEAs) of the thoracic level, specifically, when compared with SEAs of other spinal cord levels. Untreated, this infection can result in permanent neurological sequelae with eventual progression to death if inadequately managed. Despite the seriousness of this disease, no articles have focused on the presentation, diagnosis, and treatment of SEAs of the thoracic level. For this reason, specific focus on SEAs of the thoracic level occurred when researchers designed and implemented the following systematic review. Methods: A query of Ovid-Medline and EMBASE, Cochrane Central, and additional review sources was conducted. Search criteria focused on articles specific to thoracic epidural abscesses. Results: Twenty-five articles met inclusion criteria. The most commonly reported symptoms present on admission included back pain, paraparesis/paraplegia, fever, and loss of bowel/bladder control. Significant risk factors included diabetes, intravenous drug use, and advanced age ( Conclusions: For the first time researchers have focused specifically on SEAs of the thoracic level, as opposed to previously published general analysis of SEAs as a whole. Based on the results, investigators recommend early magnetic resonance imaging of the spine, laboratory workup (sedimentation rate/C-reactive protein, complete blood count), abscess culture followed by empiric antibiotics, and immediate surgical decompression when neurological deficits are present

Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.

Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion

Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.</p

Highly-efficient Cas9-mediated transcriptional programming

The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. We demonstrate its utility in activating endogenous coding and noncoding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).National Human Genome Research Institute (U.S.) (Grant P50 HG005550)United States. Dept. of Energy (Grant DE-FG02-02ER63445)Wyss Institute for Biologically Inspired EngineeringNational Science Foundation (U.S.). Graduate Research FellowshipMassachusetts Institute of Technology. Department of Biological EngineeringHarvard Medical School. Department of Genetic

<title>Cryogen spray cooling of human skin: effects of ambient humidity level, spraying distance, and cryogen boiling point</title>

Recent studies have shown spray cooling of the skin surface with millisecond cryogen spurts to be an effective method for protecting the epidermis from non-specific thermal injury during various laser mediated dermatological procedures. We have investigated the effects of ambient humidity level, spraying distance, and cryogen boiling point on the resulting radiometric surface temperature. Our findings indicate that: 1) decreasing the ambient humidity level results in less ice formation on the skin surface without altering the radiometric surface temperature during a cryogen spurt; 2) increasing the spraying distance to 85 mm lowers the radiometric surface temperature; and 3) boiling point of the cryogen does not directly affect the surface temperature in the geometries studied.</p

Utility of repeat magnetic resonance imaging in surgical patients with lumbar stenosis without disc herniation

© 2018 Elsevier Inc. BACKGROUND CONTEXT: Routine use of magnetic resonance imaging (MRI) as a diagnostic tool in lumbar stenosis is becoming more prevalent due to the aging population. Currently, there is no clinical guideline to clarify the utility of repeat MRI in patients with lumbar stenosis, without instability, neurological deficits, or disc herniation. PURPOSE: To evaluate the utility of routine use of MRI as a diagnostic tool in lumbar stenosis, and to help formulate clinical guidelines on the appropriate use of preoperative imaging for lumbar stenosis. STUDY DESIGN/SETTING: Retrospective radiographic analysis. PATIENT SAMPLE: Retrospective chart review was performed to review patients with lumbar stenosis, who underwent lumbar decompression without fusion from 2011 to 2015 at a single institution. OUTCOME MEASURES: Previously established stenosis grading systems were used to measure and compare the initial and the subsequent repeat lumbar MRIs performed preoperatively. If patients were found to have a moderate or severe grade change, and if the surgical plan was altered due to such exacerbated radiographic findings, then their grade changes were considered clinically meaningful. METHODS: We identified patients with lumbar stenosis without radiographic instability or neurological deficits, who had at least two preoperative lumbar MRIs performed and underwent decompressive surgeries. At each pathologic disc level, the absolute value of the change in grade for central and lateral recess stenosis, right foraminal stenosis, and left foraminal stenosis from the first preoperative MRI to the repeated MRI was calculated. These changed data were then used to calculate the mean and median changes in each of the three types of stenosis for each pathologic disc level. Identical calculations were carried out for the subsample of patients who only underwent discectomy or had a discectomy included as part of their surgery. RESULTS: Among the 103 patients who met the inclusion criteria, 37 of those patients had more than one level surgically addressed, and a total of 161 lumbar levels were reviewed. Among the subset of patients that had any grade change, the majority of the grades only had a mild change of 1 (36 out of 42 patients, 85.7%, 95% confidence interval [CI]: 73.1%–94.1%); there was a moderate grade change of 2 in two patients (4.8%, CI: 0.8%–14.0%), and a severe change of 3 in one patient (2.4%, CI: 0.2%–10.1%). There were three patients with decreased grade change (7.1%, CI: 1.8%–17.5%). All clinically meaningful grade changes were from the subset of patients who had only discectomy or discectomy as part of the procedure. Lastly, both patients that had a clinically meaningful grade change had their MRIs performed at an interval of greater than 360 days. CONCLUSIONS: The radiographic evaluation of the utility of routinely repeated MRIs in lumbar stenosis without instability, neurological deficits, or disc herniations demonstrated that there were no significant changes found in the repeated MRI in the preoperative setting, especially if the MRIs were performed less than one year apart. The results of this present study can help to standardize the diagnostic evaluation of lumbar stenosis and to formulate clinical guidelines on the appropriate use of preoperative imaging for lumbar stenosis patients

Ref # TITB-00244-2006.R2 Automated Retinal Image Analysis over the Internet

Abstract—Retinal clinicians and researchers make extensive use of images, and the current emphasis is on digital imaging of the retinal fundus. The goal of this paper is to introduce a system, known as RIVERS (Retinal Image Vessel Extraction and Registration System), which provides the community of retinal clinicians, researchers, and study directors an integrated suite of advanced digital retinal image analysis tools over the Internet. The capabilities include vasculature tracing and morphometry, joint (simultaneous) montaging of multiple retinal fields, cross-modality registration (color/red-free fundus photographs, and fluorescein angiograms), and generation of flicker animations for visualization of changes from longitudinal image sequences. Each capability has been carefully-validated in our previous research work. The integrated internet-based system can enable significant advances in retina-related clinical diagnosis, visualization of the complete fundus at full resolution from multiple low-angle views, analysis of longitudinal changes, research on the retinal vasculature, and objective, quantitative computer-assisted scoring of clinical trials imagery. It could pave the way for future screening services from optometry facilities. Index Terms—internet-based, registration, alignment, retinal image analysis, vasculature tracing