Restoring and sustaining human postmortem retinal light responses with scalable methods for testing degenerative disease therapies.

Neuro- and retinal degenerative diseases rob millions of aging individuals of their independence. Researching these diseases in human tissue has been hindered by the immediate loss of electric activity in neurons after the circulation ceases. Recent studies indicate that limited neuronal activity can be revived postmortem, even in the retina.

All-trans retinoic acid induces durable tumor immunity in IDH-mutant gliomas by rescuing transcriptional repression of the CRBP1-retinoic acid axis.

Diffuse gliomas are epigenetically dysregulated, immunologically cold, and fatal tumors characterized by mutations in isocitrate dehydrogenase (IDH). Although IDH mutations yield a uniquely immunosuppressive tumor microenvironment, the regulatory mechanisms that drive the immune landscape of IDH mutant (IDHm) gliomas remain unknown. Here, we reveal that transcriptional repression of retinoic acid (RA) pathway signaling impairs both innate and adaptive immune surveillance in IDHm glioma through epigenetic silencing of retinol binding protein 1 (RBP1) and induces a profound anti-inflammatory landscape marked by loss of inflammatory cell states and infiltration of suppressive myeloid phenotypes.

Bilateral Carotid Artery Dissections and Ischemic Stroke in a Patient With COVID-19: A Case Report.

An unresponsive patient with COVID-19 infection should prompt immediate evaluation with consideration of a vast differential diagnosis entailing a multitude of diagnostic and therapeutic interventions in the emergency department. We report a case of an unresponsive 41-year-old female with COVID-19 infection and a history of rheumatoid arthritis who presented to the emergency department with bilateral carotid artery dissections and left internal carotid artery thrombus that extended into the middle cerebral artery. This case calls into question if COVID-19 is coincidentally or causally associated with acute vascular and thromboembolic disease.

Percutaneous fixation for the treatment of metastatic spinal disease provides effective symptom palliation with low rates of hardware failure.

Background: The incidence of survival from metastatic spinal disease (MSD) continues to rise. However, open surgery for MSD is associated with significant perioperative morbidity, while minimally invasive percutaneous pedicle screw fixation (MIPPSF) offers reduced tissue trauma, less blood loss, and a reduction in complications. Lytic bone disease plus perioperative radiation further increase risk for instrument failure, especially in long construct MIPPSF.

In vivo efficacy of decitabine as a natural killer cell-mediated immunotherapy against isocitrate dehydrogenase mutant gliomas.

Objective: Isocitrate dehydrogenase (IDH) mutations are found in more than 80% of low-grade gliomas and in the majority of secondary glioblastomas. IDH mutation (IDHmut) leads to aberrant production of an oncogenic metabolite that promotes epigenetic dysregulation by inducing hypermethylation to suppress transcription of various tumor suppressor genes. Hypermethylation in IDHmut gliomas leads to transcriptional repression of NKG2D ligands, especially UL16-binding protein (ULBP)-1 and ULBP-3, and subsequent evasion of natural killer (NK) cell-mediated lysis.

History of atopy confers improved outcomes in IDH mutant and wildtype lower grade gliomas.

Purpose: A history of atopy or allergy has been shown to be protective against the development of glioma, however the effect of atopy on patient outcomes, especially in conjunction with the survival benefit associated with IDH mutation, has not yet been investigated, and is the focus of the study we present here.

Methods: Low grade glioma (LGG) data from the TCGA was downloaded, along with IDH, TERT, 1p/19q and ATRX mutational status and genetic alterations. History of asthma, eczema, hay fever, animal, or food allergies, as documented in TCGA, was used to determine patient atopy status.

Characterization of systemic immunosuppression by IDH mutant glioma small extracellular vesicles.

Background: Gliomas are the most common primary brain tumors and are universally fatal. Mutations in the isocitrate dehydrogenase genes (IDH1 and IDH2) define a distinct glioma subtype associated with an immunosuppressive tumor microenvironment. Mechanisms underlying systemic immunosuppression in IDH mutant (mutIDH) gliomas are largely unknown.

TIGIT and PD-1 Immune Checkpoint Pathways Are Associated With Patient Outcome and Anti-Tumor Immunity in Glioblastoma.

Glioblastoma (GBM) remains an aggressive brain tumor with a high rate of mortality. Immune checkpoint (IC) molecules are expressed on tumor infiltrating lymphocytes (TILs) and promote T cell exhaustion upon binding to IC ligands expressed by the tumor cells. Interfering with IC pathways with immunotherapy has promoted reactivation of anti-tumor immunity and led to success in several malignancies.

How I Do It: Modification of technique to safely position patients with super obesity in dorsal lithotomy for ureteroscopic management of kidney stones.

Obesity is a known risk factor for recurrent nephrolithiasis and it can be challenging to provide safe surgical intervention in the super obese population. Despite high weight limits on surgical beds, these often do not take into account positioning the patient on the end of the bed for dorsal lithotomy, which can risk an unsteady bed. In addition, depending on patient habitus the leg stirrups may not accommodate.

Histologic Heterogeneity of Extirpated Renal Cell Carcinoma Specimens: Implications for Renal Mass Biopsy.

Pathologic characteristics of extirpated renal cell carcinoma (RCC) specimens <7 cm were reviewed to get better information on technical nuances of renal mass biopsy (RMB). Specimens were stratified according to tumor stage, nuclear grade, size, histology, presence of lymphovascular invasion (LVI), necrosis, and sarcomatoid features. When considering pT1 (0-7 cm) tumors, pT1b (4-7 cm) RCC masses were more likely to have necrosis (43% vs 16%, P < 0.

The use of nephrostomy tubes in optimizing surgical conditions for a patient with xanthogranulomatous pyelonephritis.

Xanthogranulomatous pyelonephritis is a rare variant of pyelonephritis that often requires radical surgery. We report a case of a 51-year-old female patient who was managed with prolonged placement of nephrostomy tubes prior to surgery. This case illustrates the importance of surgical optimization of a poor operative candidate and the use of nephrostomy tubes as a temporizing management strategy.

Recent divergences in stratospheric water vapor measurements by frost point hygrometers and the Aura Microwave Limb Sounder.

Balloon-borne frost point hygrometers (FPs) and the Aura Microwave Limb Sounder (MLS) provide high-quality vertical profile measurements of water vapor in the upper troposphere and lower stratosphere (UTLS). A previous comparison of stratospheric water vapor measurements by FPs and MLS over three sites - Boulder, Colorado (40.0° N); Hilo, Hawaii (19.

Procedural povidone iodine rectal preparation reduces bacteriuria and bacteremia following prostate needle biopsy.

Introduction: To determine if a povidone iodine rectal preparation (PIRP) reduces rates of bacteriuria and bacteremia following transrectal ultrasound guided prostate needle biopsy (TRUS PNB).

Materials And Methods: Men undergoing TRUS PNB were prospectively enrolled in a study comparing the impact of PIRP versus standard of care (two pills of ciprofloxacin 500 mg). Urine, blood, and rectal cultures were obtained 30 minutes post-procedure with colony forming units (CFUs) determined after 48 hours.

Controlled weather balloon ascents and descents for atmospheric research and climate monitoring.

In situ upper-air measurements are often made with instruments attached to weather balloons launched at the surface and lifted into the stratosphere. Present-day balloon-borne sensors allow near-continuous measurements from the Earth's surface to about 35 km (3-5 hPa), where the balloons burst and their instrument payloads descend with parachutes. It has been demonstrated that ascending weather balloons can perturb the air measured by very sensitive humidity and temperature sensors trailing behind them, particularly in the upper troposphere and lower stratosphere (UTLS).

Advancements, measurement uncertainties, and recent comparisons of the NOAA frost point hygrometer.

The NOAA frost point hygrometer (FPH) is a balloon-borne instrument flown monthly at three sites to measure water vapor profiles up to 28 km. The FPH record from Boulder, Colorado, is the longest continuous stratospheric water vapor record. The instrument has an uncertainty in the stratosphere that is < 6 % and up to 12 % in the troposphere.

Validation of Aura Microwave Limb Sounder stratospheric water vapor measurements by the NOAA frost point hygrometer.

Differences between stratospheric water vapor measurements by NOAA frost point hygrometers (FPHs) and the Aura Microwave Limb Sounder (MLS) are evaluated for the period August 2004 through December 2012 at Boulder, Colorado, Hilo, Hawaii, and Lauder, New Zealand. Two groups of MLS profiles coincident with the FPH soundings at each site are identified using unique sets of spatiotemporal criteria. Before evaluating the differences between coincident FPH and MLS profiles, each FPH profile is convolved with the MLS averaging kernels for eight pressure levels from 100 to 26 hPa (~16 to 25 km) to reduce its vertical resolution to that of the MLS water vapor retrievals.

Molecular basis of renal adaptation in a murine model of congenital obstructive nephropathy.

Congenital obstructive nephropathy is a common cause of chronic kidney disease and a leading indication for renal transplant in children. The cellular and molecular responses of the kidney to congenital obstruction are incompletely characterized. In this study, we evaluated global transcription in kidneys with graded hydronephrosis in the megabladder (mgb (-/-)) mouse to better understand the pathophysiology of congenital obstructive nephropathy.