Plasma Concentration as a Proxy for Perilymph Drug Levels: Preclinical and Clinical Dexamethasone Measures with a Long-Acting Formulation for Precise Delivery to the Round Window Membrane.

Objective: To use animal pharmacokinetic data and FluidSIM modeling to estimate human dexamethasone perilymph concentrations from plasma concentration measurements over time following a single intratympanic administration of SPT-2101.

Study Design: Perilymph and plasma dexamethasone concentrations were measured in guinea pigs and African green monkeys over 3 to 6 weeks post-intratympanic administration of SPT-2101. Plasma concentrations of dexamethasone were measured in Ménière's disease patients post-intratympanic administration of SPT-2101.

Early Experience with a Novel Treatment for Menière's Disease: A Long Acting Dexamethasone Formulation for Precise Delivery to the Round Window Membrane.

Objective: To investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Menière's disease.

Study Design: Prospective, unblinded, cohort study.

Setting: Tertiary care neurotology clinic.

The inflammasome pathway is activated by dengue virus non-structural protein 1 and is protective during dengue virus infection.

Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play.

Rotator cuff tear patterns: MRI appearance and its surgical relevance.

A new perspective on rotator cuff anatomy has allowed a better understanding of the patterns of the different rotator cuff tears. It is essential for radiologists to be aware of these different patterns of tears and to understand how they might influence treatment and surgical approach. Our objective is to review the arthroscopy correlated magnetic resonance imaging appearance of the different types of rotator cuff tears based on current anatomical concepts.

Presurgical perspective and postsurgical evaluation of acromioclavicular joint instability.

Acromioclavicular joint (ACJ) dislocations are a common cause of pain in patients of any age. Athletes who participate in contact sports, such as hockey, football, rugby, and soccer, are particularly susceptible to such injuries. The ACJ has an important role in the function of the upper limb, and its complexity of movement makes it susceptible to acute injuries and chronic dysfunction with debilitating effects that must be treated appropriately and promptly to preserve function.

Macular vessel density in central retinal artery occlusion with retinal arterial cannulation.

To characterize and compare macular vessel density in central retinal artery occlusion (CRAO) eyes with retinal arterial cannulation and CRAO eyes with standard treatment. This study was Cross-sectional, observational study. Twenty-two eyes with nonarteric CRAO which underwent retinal arterial cannulation and 19 eyes with nonarteric CRAO with standard treatment were included.

Development of handheld induction heaters for magnetic fluid hyperthermia applications andevaluation on ovarian and prostate cancer cell lines.

Magnetic fluid hyperthermia (MFH) is a still experimental technique found to have a potential application in the treatment of cancer. The method aims to reach around 41 °C-47 °C in the tumor site by exciting magnetic nanoparticles with an externally applied alternating magnetic field (AMF), where cell death is expected to occur. Applying AMFs with high spatial resolution is still a challenge.

Distinct signatures of loss of consciousness in focal impaired awareness versus tonic-clonic seizures.

Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies.

Incorporation of Hydrophilic Macrocycles Into Drug-Linker Reagents Produces Antibody-Drug Conjugates With Enhanced Performance.

Antibody-drug conjugates (ADCs) have begun to fulfil their promise as targeted cancer therapeutics with ten clinical approvals to date. As the field matures, much attention has focused upon the key factors required to produce safe and efficacious ADCs. Recently the role that linker-payload reagent design has on the properties of ADCs has been highlighted as an important consideration for developers.

Development of the Port Delivery System with ranibizumab for neovascular age-related macular degeneration.

Purpose Of Review: This review provides background on the remaining unmet needs with antivascular endothelial growth factor (VEGF) therapies for the treatment of neovascular age-related macular degeneration (nAMD). We also discuss the developmental story of the Port Delivery System with ranibizumab (PDS; SUSVIMO, Genentech, Inc., South San Francisco, CA, USA).

Pharmacokinetics of genistein distribution in blood and retinas of diabetic and non-diabetic rats.

Genistein, a natural tyrosine kinase inhibitor, may act as an intraocular antiangiogenic agent. Its therapeutical use, however, is limited by its nonlinear pharmacokinetics. We aimed to determine genistein's kinetics and retinal tissue distributions in normal and diabetic rats.

increases alcohol intake and tonic immobility whilst decreasing food intake in Wistar rats.

The kappa-opioid system (KOP) is the key in drug abuse. Of all the compounds isolated from (), salvinorin-A (Sal-A) is predominant. Further, Sal-A is the only compound within which is reported to have psychoactive properties as a powerful kappa-opioid receptor (KOPr) agonist.

Can collagenase effectiveness in Dupuytren's contracture be improved by using ultrasound-guided Injection? A comparative study.

The objective of this study was to compare the effectiveness of ultrasound-guided injection of collagenase Clostridium histolyticum (CCH) in patients with Dupuytren's contracture (DC), with the standard injection. We hypothesised that the ultrasound-guided Injection of CCH is more effective than the standard injection. A prospective cohorts study in patients with DC was done.

Structural basis for antibody inhibition of flavivirus NS1-triggered endothelial dysfunction.

Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown.

Local Sleep Slow-Wave Activity Colocalizes With the Ictal Symptomatogenic Zone in a Patient With Reflex Epilepsy: A High-Density EEG Study.

: Slow-wave activity (SWA) during non-rapid eye movement (NREM) sleep reflects synaptic potentiation during preceding wakefulness. Epileptic activity may induce increases in state-dependent SWA in human brains, therefore, localization of SWA may prove useful in the presurgical workup of epileptic patients. We analyzed high-density electroencephalography (HDEEG) data across vigilance states from a reflex epilepsy patient with a clearly localizable ictal symptomatogenic zone to provide a proof-of-concept for the testability of this hypothesis.

Endovascular surgery in the field of ophthalmology.

In this article, we provide an overview of the current perspectives on endovascular surgery in ophthalmology, including a description of the various approaches, recent clinical results and future prospects. Experimental studies of endovascular surgery in ophthalmology started in the 1980s; since then, a considerable amount of research has been done to develop the procedure for clinical use. During the past two decades endovascular surgery has been performed on eyes with retinal vascular disorders, including central retinal vein occlusion and central retinal artery occlusion.

Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group.

The analysis of spontaneous EEG activity and evoked potentialsis a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). Thepast few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury,opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of bothconsolidated and investigational electrophysiological techniquesfor the prognostic and diagnostic assessment of DoC.

Gradual Increase in Environmental Light Intensity Induces Oxidative Stress and Inflammation and Accelerates Retinal Neurodegeneration.

Purpose: Retinitis pigmentosa (RP) is a blinding neurodegenerative disease of the retina that can be affected by many factors. The present study aimed to analyze the effect of different environmental light intensities in rd10 mice retina.

Methods: C57BL/6J and rd10 mice were bred and housed under three different environmental light intensities: scotopic (5 lux), mesopic (50 lux), and photopic (300 lux).

Mobile Extracorporeal Membrane Oxygenation Teams for Organ Donation After Circulatory Death.

The shortage of available organ donors is a significant problem worldwide, and various efforts have been carried out to avoid the loss of potential organ donors. Among them, organ donation from cardiocirculatory deceased donors (DCD), in which withdrawal of life-sustaining therapies is ongoing (Maastricht type III donors), is one emerging strategy. Thanks to the latest advances in transplantation and organ preservation, such as normothermic regional perfusion (NRP), ex vivo perfusion techniques, and good organization and communication among prehospital care providers, emergency departments, intensive care units, and transplantation units, DCD is rapidly increasing; it's estimated that it will increase the number of donations of lungs and splanchnic organs by more than 40%.

New Nrf2-Inducer Compound ITH12674 Slows the Progression of Retinitis Pigmentosa in the Mouse Model rd10.

Background/aims: It is well established that oxidative stress and inflammation are common pathogenic features of retinal degenerative diseases. ITH12674 is a novel compound that induces the transcription factor Nrf2; in so doing, the molecule exhibits anti-inflammatory, and antioxidant properties, and affords neuroprotection in rat cortical neurons subjected to oxidative stress. We here tested the hypothesis that ITH12674 could slow the retinal degeneration that causes blindness in rd10 mice, a model of retinitis pigmentosa.

In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer.

Background: Magnetic Fluid Hyperthermia (MFH) is a promising adjuvant for chemotherapy, potentiating the action of anticancer agents. However, drug delivery to cancer cells must be optimized to improve the overall therapeutic effect of drug/MFH combination treatments.

Purpose: The aim of this work was to demonstrate the potentiation of 2-phenylethynesulfonamide (PES) at various combination treatments with MFH, using low-intensity ultrasound as an intracellular delivery enhancer.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

Purpose: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients.

Methods: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing.