Innovative Methodology for Antimicrobial Susceptibility Determination in Biofilms.

spp. are facultative pathogens that contribute to the pathogenesis of multiple bovine diseases, including the bovine respiratory disease complex, and have been shown to form biofilms. Biofilm formation is associated with increased antibiotic resistance in many organisms, but accurate determination of antimicrobial susceptibility in biofilms is challenging.

Cost Comparison of Prostatic Artery Embolization Between In-Hospital and Outpatient-Based Lab Settings.

Purpose This study aimed to determine the costs associated with prostatic artery embolization (PAE) performed in hospital and outpatient-based lab (OBL) settings. Methods Procedures were performed in similarly equipped procedure suites located within a tertiary hospital or OBL. Time-driven activity-based costing (TDABC) was utilized to calculate procedural costs incurred by the institution.

Changes in 24(S)-Hydroxycholesterol Are Associated with Cognitive Performance in Early Huntington's Disease: Data from the TRACK and ENROLL HD Cohorts.

Background: There is evidence for dysregulated cholesterol homeostasis in Huntington's disease (HD). The brain-specific cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-OHC) is decreased in manifest HD. 24(S)-OHC is an endogenous positive allosteric modulator (PAM) of the N-methyl-D-aspartate (NMDA) receptor, suggesting lower 24(S)-OHC may contribute to NMDA receptor hypofunction in HD.

Patient-Specific Prediction of Immediate Phase Lung Microwave Ablation Zone Size.

Purpose: To investigate the effect of patient and tumor-specific characteristics on the size of immediate phase lung microwave ablation (MWA) zone and establish a prediction model.

Materials And Methods: This institutional review board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant cohort included 164 lesions from 99 patients who underwent computed tomography (CT)-guided lung MWA, and the 2-dimensional elliptical ground-glass opacity ablation zone was measured. Duration, maximum temperature, tumor depth, presence of emphysema, history of ipsilateral lung ablation, surgery, and radiotherapy were recorded.

Dalzanemdor (SAGE-718), a novel, investigational N-methyl-D-aspartate receptor positive allosteric modulator: Safety, tolerability, and clinical pharmacology in randomized dose-finding studies in healthy participants and an open-label study in participants with Huntington's disease.

N-methyl-D-aspartate receptor (NMDAR)-positive allosteric modulators (PAMs) represent a potential therapeutic strategy for cognitive impairment in disorders associated with NMDAR hypofunction, including Huntington's disease (HD) and Alzheimer's disease. Dalzanemdor (SAGE-718) is a novel, investigational NMDAR PAM being evaluated for the potential treatment of cognitive impairment in these disorders. We report first-in-human, phase I, double-blind, dose-finding studies to assess the safety, tolerability, and clinical pharmacology of dalzanemdor.

Safety and Effectiveness of Track Cauterization for Lung Cryoablation.

Purpose: To evaluate the safety and effectiveness of track cauterization for lung cryoablation through comparison of postprocedural adverse event (AE) rates.

Materials And Methods: Fifty-nine patients who underwent 164 percutaneous lung cryoablation procedures between 2013 and 2018 were included in this retrospective study. The study cohort was subdivided by whether track cauterization was conducted or not at the end of the procedure.

Pharmacological characterization of SAGE-718, a novel positive allosteric modulator of N-methyl-d-aspartate receptors.

Background And Purpose: Select neuroactive steroids tune neural activity by modulating excitatory and inhibitory neurotransmission, including the endogenous cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC), which is an N-methyl-d-aspartate (NMDA) receptor positive allosteric modulator (PAM). NMDA receptor PAMs are potentially an effective pharmacotherapeutic strategy to treat conditions associated with NMDA receptor hypofunction.

Experimental Approach: Using in vitro and in vivo electrophysiological recording experiments and behavioural approaches, we evaluated the effect of SAGE-718, a novel neuroactive steroid NMDA receptor PAM currently in clinical development for the treatment of cognitive impairment, on NMDA receptor function and endpoints that are altered by NMDA receptor hypoactivity and assessed its safety profile.

Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers.

Objective: Complexity and lack of standardization have mostly limited the use of event-related potentials (ERPs) and quantitative EEG (QEEG) biomarkers in drug development to small early phase trials. We present results from a clinical study on healthy volunteers (HV) and patients with schizophrenia (SZ) that assessed test-retest, group differences, variance, and correlation with functional assessments for ERP and QEEG measures collected at clinical and commercial trial sites with standardized instrumentation and methods, and analyzed through an automated data analysis pipeline.

Methods: 81 HV and 80 SZ were tested at one of four study sites.

Novel neuroactive steroids as positive allosteric modulators of NMDA receptors: mechanism, site of action, and rescue pharmacology on GRIN variants associated with neurological conditions.

N-methyl-D-aspartate receptors (NMDARs) play vital roles in normal brain functions (i.e., learning, memory, and neuronal development) and various neuropathological conditions, such as epilepsy, autism, Parkinson's disease, Alzheimer's disease, and traumatic brain injury.

SAGE-718: A First-in-Class -Methyl-d-Aspartate Receptor Positive Allosteric Modulator for the Potential Treatment of Cognitive Impairment.

-Methyl-d-aspartate receptor (NMDAR) positive allosteric modulators (PAMs) have received increased interest as a powerful mechanism of action to provide relief as therapies for CNS disorders. Sage Therapeutics has previously published the discovery of endogenous neuroactive steroid 24()-hydroxycholesterol as an NMDAR PAM. In this article, we detail the discovery of development candidate SAGE-718 (), a potent and high intrinsic activity NMDAR PAM with an optimized pharmacokinetic profile for oral dosing.

Icon arrays reduce concern over COVID-19 vaccine side effects: a randomized control study.

On April 13, 2021, the CDC announced that the administration of Johnson and Johnson's COVID-19 vaccine would be paused due to a rare blood clotting side effect in ~ 0.0001% of people given the vaccine. Most people who are hesitant to get a COVID-19 vaccine list potential side effects as their main concern (PEW, 2021); thus, it is likely that this announcement increased vaccine hesitancy among the American public.

How well do ordinary Americans forecast the growth of COVID-19?

Across three experiments (N = 1565), we investigated how forecasts about the spread of COVID 19 are impacted by data trends, and whether patterns of misestimation predict adherence to social-distancing guidelines. We also investigated how mode of data presentation influences forecasting of future cases by showing participants data on the number of COVID-19 cases from a 5-week period in either graphical, tabular, or text-only form. We consistently found that people shown tables produced more accurate forecasts compared to people shown line-graphs of the same data; yet people shown line-graphs were more confident in their estimates.

Predictors of heart failure symptoms in hereditary hemorrhagic telangiectasia patients with hepatic arteriovenous malformations.

Background: Hepatic arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT) patients are most commonly hepatic artery to hepatic venous shunts which can result in high-output heart failure. This condition can be debilitating and is a leading cause of liver transplantation in HHT patients. However, it is not known what characteristics can discriminate between asymptomatic patients and those who will develop heart failure symptoms.

Allosteric modulation of NMDA receptors prevents the antibody effects of patients with anti-NMDAR encephalitis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disease characterized by a complex neuropsychiatric syndrome in association with an antibody-mediated decrease of NMDAR. About 85% of patients respond to immunotherapy (and removal of an associated tumour if it applies), but it often takes several months or more than 1 year for patients to recover. There are no complementary treatments, beyond immunotherapy, to accelerate this recovery.

Alternatives to Surgery for Early-Stage Non-Small Cell Lung Cancer: Thermal Ablation.

Thermal ablation involves the application of heat or cold energy to the lung under image guidance to eradicate tumors. It is indicated for treatment of early-stage non-small cell lung cancer in nonsurgical patients. Ablation technologies have advanced, such that nearly all small tumors can now be treated safely and effectively.

Measuring media exposure to acute mass violence.

Objective: Researchers have studied the influence of media exposure to acute mass violence (e.g., terror attack, mass shooting, etc.

Neuroactive Steroid -Methyl-d-aspartate Receptor Positive Allosteric Modulators: Synthesis, SAR, and Pharmacological Activity.

Neuroactive steroids (NASs) play a pivotal role in maintaining homeostasis is the CNS. We have discovered that one NAS in particular, 24()-hydroxycholesterol (24()-HC), is a positive allosteric modulator (PAM) of NMDA receptors. Using 24()-HC as a chemical starting point, we have identified other NASs that have good in vitro potency and efficacy.

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile.

The Steglich esterification is a widely-used reaction for the synthesis of esters from carboxylic acids and alcohols. While efficient and mild, the reaction is commonly performed using chlorinated or amide solvent systems, which are hazardous to human health and the environment. Our methodology utilizes acetonitrile as a greener and less hazardous solvent system.