Drainage of anorectal abscesses in the operating room is associated with a decreased risk of abscess recurrence and fistula formation.

Background: Timely incision and drainage (I&D) is first line management for anorectal abscesses. We aimed to define current practices in anorectal abscess management and identify factors associated with abscess recurrence and fistula formation.

Methods: Index episodes of anorectal abscesses treated with I&D in 2014-2018 at a multi-hospital healthcare system were included.

Increased Serotonin Transporter Expression in Huntington's Disease Patients Is Not Consistently Replicated in Murine Models.

Background: Selective serotonin reuptake inhibitors (SSRIs) target the serotonin transporter (SERT) and are commonly prescribed for depression in Huntington's disease (HD) patients. However, SERT expression in HD has not been carefully evaluated in patients or mouse models.

Objective: In this study, we investigated SERT levels in HD patients and HD mouse models.

Mutant huntingtin disrupts mitochondrial proteostasis by interacting with TIM23.

Mutant huntingtin (mHTT), the causative protein in Huntington's disease (HD), associates with the translocase of mitochondrial inner membrane 23 (TIM23) complex, resulting in inhibition of synaptic mitochondrial protein import first detected in presymptomatic HD mice. The early timing of this event suggests that it is a relevant and direct pathophysiologic consequence of mHTT expression. We show that, of the 4 TIM23 complex proteins, mHTT specifically binds to the TIM23 subunit and that full-length wild-type huntingtin (wtHTT) and mHTT reside in the mitochondrial intermembrane space.

Improved Outcomes Associated with the use of Shock Protocols: Updates from the National Cardiogenic Shock Initiative.

Background: The National Cardiogenic Shock Initiative is a single-arm, prospective, multicenter study to assess outcomes associated with early mechanical circulatory support (MCS) in patients presenting with acute myocardial infarction and cardiogenic shock (AMICS) treated with percutaneous coronary intervention (PCI).

Methods: Between July 2016 and February 2019, 35 sites participated and enrolled into the study. All centers agreed to treat patients with AMICS using a standard protocol emphasizing invasive hemodynamic monitoring and rapid initiation of MCS.

Mitochondria modulate programmed neuritic retraction.

Neuritic retraction in the absence of overt neuronal death is a shared feature of normal aging and neurodegenerative disorders, but the intracellular mechanisms modulating this process are not understood. We propose that cumulative distal mitochondrial protein damage results in impaired protein import, leading to mitochondrial dysfunction and focal activation of the canonical apoptosis pathway in neurites. This is a controlled process that may not lead to neuronal death and, thus, we term this phenomenon "neuritosis.

Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release.

G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT), its associated G protein, and β-arrestins are on and within neuronal mitochondria. We discovered that the ligand melatonin is exclusively synthesized in the mitochondrial matrix and released by the organelle activating the mitochondrial MT signal-transduction pathway inhibiting stress-mediated cytochrome release and caspase activation.

Tissue plasminogen activator mediates deleterious complement cascade activation in stroke.

The use of intravenous tissue plasminogen activator (tPA) in the treatment of ischemic stroke is limited by its propensity to exacerbate brain edema and hemorrhage. The mechanisms underlying these deleterious effects of tPA remain incompletely understood. The purpose of this study was to delineate a pathway of tPA-mediated complement cascade activation in stroke and to determine whether complement inhibition ameliorates the adverse effects of post-ischemic tPA administration.

Analysis of heterogeneity in T2-weighted MR images can differentiate pseudoprogression from progression in glioblastoma.

Purpose: To develop an image analysis technique that distinguishes pseudoprogression from true progression by analyzing tumour heterogeneity in T2-weighted images using topological descriptors of image heterogeneity called Minkowski functionals (MFs).

Methods: Using a retrospective patient cohort (n = 50), and blinded to treatment response outcome, unsupervised feature estimation was performed to investigate MFs for the presence of outliers, potential confounders, and sensitivity to treatment response. The progression and pseudoprogression groups were then unblinded and supervised feature selection was performed using MFs, size and signal intensity features.

Multiparametric MR Imaging of Diffusion and Perfusion in Contrast-enhancing and Nonenhancing Components in Patients with Glioblastoma.

Purpose To determine whether regions of low apparent diffusion coefficient (ADC) with high relative cerebral blood volume (rCBV) represented elevated choline (Cho)-to-N-acetylaspartate (NAA) ratio (hereafter, Cho/NAA ratio) and whether their volumes correlated with progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma (GBM). Materials and Methods This retrospective analysis was approved by the local research ethics committee. Volumetric analysis of imaging data from 43 patients with histologically confirmed GBM was performed.

Assessing Oxidative Stress in Tumors by Measuring the Rate of Hyperpolarized [1-13C]Dehydroascorbic Acid Reduction Using 13C Magnetic Resonance Spectroscopy.

Rapid cancer cell proliferation promotes the production of reducing equivalents, which counteract the effects of relatively high levels of reactive oxygen species. Reactive oxygen species levels increase in response to chemotherapy and cell death, whereas an increase in antioxidant capacity can confer resistance to chemotherapy and is associated with an aggressive tumor phenotype. The pentose phosphate pathway is a major site of NADPH production in the cell, which is used to maintain the main intracellular antioxidant, glutathione, in its reduced state.

Less Invasive Phenotype Found in Isocitrate Dehydrogenase-mutated Glioblastomas than in Isocitrate Dehydrogenase Wild-Type Glioblastomas: A Diffusion-Tensor Imaging Study.

Purpose To explore the diffusion-tensor (DT) imaging-defined invasive phenotypes of both isocitrate dehydrogenase (IDH-1)-mutated and IDH-1 wild-type glioblastomas. Materials and Methods Seventy patients with glioblastoma were prospectively recruited and imaged preoperatively. All patients provided signed consent, and the local research ethics committee approved the study.

Posttreatment Apparent Diffusion Coefficient Changes in the Periresectional Area in Patients with Glioblastoma.

Background: Although targeted by radiotherapy, recurrence in glioblastoma occurs mainly periresectionally owing to tumor infiltration. An increase in the apparent diffusion coefficient (ADC) has been shown in the large high-T2 area on magnetic resonance imaging posttreatment; however, until now ADC has not been investigated directly in the more relevant periresectional area.

Methods: Histogram analysis was used to assess periresectional ADC values in patients with glioblastoma postradiotherapy versus preradiotherapy.

Validation of a semi-automatic co-registration of MRI scans in patients with brain tumors during treatment follow-up.

There is an expanding research interest in high-grade gliomas because of their significant population burden and poor survival despite the extensive standard multimodal treatment. One of the obstacles is the lack of individualized monitoring of tumor characteristics and treatment response before, during and after treatment. We have developed a two-stage semi-automatic method to co-register MRI scans at different time points before and after surgical and adjuvant treatment of high-grade gliomas.

Extent of resection of peritumoral diffusion tensor imaging-detected abnormality as a predictor of survival in adult glioblastoma patients.

OBJECTIVE Diffusion tensor imaging (DTI) has been shown to detect tumor invasion in glioblastoma patients and has been applied in surgical planning. However, the clinical value of the extent of resection based on DTI is unclear. Therefore, the correlation between the extent of resection of DTI abnormalities and patients' outcome was retrospectively reviewed.

Na and solute diffusion in aqueous channels of Myverol bicontinuous cubic phase: PGSE NMR and computer modelling.

The apparent diffusion coefficients of Na ions and the solute 2-fluoroethylamine present in the aqueous domain of a Myverol/water bulk bicontinuous cubic phase (BCP) were measured using pulsed field-gradient spin echo (PGSE) NMR spectroscopy. The measured values were dependent on the diffusion time interval, which is a characteristic of restricted diffusion. The translational motion of Na and water in the aqueous channels of a cubic phase were simulated using a Monte-Carlo random walk algorithm, and the simulation results were compared with those from real PGSE NMR experiments.

Total Hip Arthroplasty Complicated by a Gluteal Hematoma Resulting in Acute Foot Drop.

Total hip arthroplasty is a prevalent orthopedic intervention in the United States. Massive postoperative hematomas are a rare albeit serious complication of the procedure. Sequelae of these hematomas can include lower extremity paralysis from compression of the sciatic nerve.

Isolation of functionally active and highly purified neuronal mitochondria from human cortex.

Background: Functional and structural properties of mitochondria are highly tissue and cell dependent, but isolation of highly purified human neuronal mitochondria is not currently available.

New Method: We developed and validated a procedure to isolate purified neuronal mitochondria from brain tissue. The method combines Percoll gradient centrifugation to obtain synaptosomal fraction with nitrogen cavitation mediated synaptosome disruption and extraction of mitochondria using anti mitochondrial outer membrane protein antibodies conjugated to magnetic beads.

(13) C magnetic resonance spectroscopy measurements with hyperpolarized [1-(13) C] pyruvate can be used to detect the expression of transgenic pyruvate decarboxylase activity in vivo.

Purpose: Dissolution dynamic nuclear polarization can increase the sensitivity of the (13) C magnetic resonance spectroscopy experiment by at least four orders of magnitude and offers a novel approach to the development of MRI gene reporters based on enzymes that metabolize (13) C-labeled tracers. We describe here a gene reporter based on the enzyme pyruvate decarboxylase (EC 4.1.

Multimodal MRI can identify perfusion and metabolic changes in the invasive margin of glioblastomas.

Purpose: To use perfusion and magnetic resonance (MR) spectroscopy to compare the diffusion tensor imaging (DTI)-defined invasive and noninvasive regions. Invasion of normal brain is a cardinal feature of glioblastomas (GBM) and a major cause of treatment failure. DTI can identify invasive regions.

(13) C magnetic resonance spectroscopic imaging of hyperpolarized [1-(13) C, U-(2) H5 ] ethanol oxidation can be used to assess aldehyde dehydrogenase activity in vivo.

Purpose: Aldehyde dehydrogenase (ALDH2) is an emerging drug target for the treatment of heart disease, cocaine and alcohol dependence, and conditions caused by genetic polymorphisms in ALDH2. Noninvasive measurement of ALDH2 activity in vivo could inform the development of these drugs and accelerate their translation to the clinic.

Methods: [1-(13) C, U-(2) H5 ] ethanol was hyperpolarized using dynamic nuclear polarization, injected into mice and its oxidation in the liver monitored using (13) C MR spectroscopy and spectroscopic imaging.

Late Imaging with [1-(11)C]Acetate Improves Detection of Tumor Fatty Acid Synthesis with PET.

Unlabelled: Tumors are often characterized by high levels of de novo fatty acid synthesis. The kinetics of acetate incorporation into tricarboxylic acid cycle intermediates and into lipids suggest that detection of tumors with [1-(11)C]acetate PET could be improved by imaging at later time points.

Methods: The uptake and metabolism of [1-(11)C], [1-(13)C], and [1-(14)C]acetate were measured in mouse prostate and lung cancer models to investigate the time course of (11)C label incorporation into tumor metabolites.

Quantitation of a spin polarization-induced nuclear Overhauser effect (SPINOE) between a hyperpolarized (13) C-labeled cell metabolite and water protons.

The spin polarization-induced nuclear Overhauser effect (SPINOE) describes the enhancement of spin polarization of solvent nuclei by the hyperpolarized spins of a solute. In this communication we demonstrate that SPINOEs can be observed between [1,4-(13) C2 ]fumarate, hyperpolarized using the dissolution dynamic nuclear polarization technique, and solvent water protons. We derive a theoretical expression for the expected enhancement and demonstrate that this fits well with experimental measurements.