Pharmacokinetics, Pharmacodynamics and Bioavailability of ACM-001.1 (S-Pindolol Benzoate) in Healthy Volunteers.

Background: S-pindolol has metabolic effects of potential benefit in cancer cachexia: reduced catabolism through nonselective β-blockade; increased anabolism through partial β2 receptor agonism; and increased appetite and reduced fatigue through central 5-hydroxytryptamine/serotonin receptor activity. A Phase 2a clinical trial demonstrated that S-pindolol can reverse weight loss and improve fat-free mass in patients with cancer-related weight loss. A comparative phase I bioavailability study of S-pindolol and racemic pindolol was performed to support the development of S-pindolol in cancer cachexia.

A randomized, placebo-controlled first-in-human study of oral TQS-168 in healthy volunteers: Assessment of safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect.

TQS-168, a first-in-class small-molecule inducer of peroxisome proliferator-activated receptor gamma coactivator 1-alpha gene expression, is in development for the treatment of amyotrophic lateral sclerosis. A single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study of TQS-168 was carried out in healthy male subjects to investigate safety, tolerability, pharmacokinetics (PK), food effect, and preliminary pharmacodynamic effects (PD). Since solubility enhancement could be beneficial, assessment of three formulations was incorporated into the study using an integrated rapid manufacturing and clinical testing approach.

Elevating understanding: Linking high-altitude hypoxia to brain aging through EEG functional connectivity and spectral analyses.

High-altitude hypoxia triggers brain function changes reminiscent of those in healthy aging and Alzheimer's disease, compromising cognition and executive functions. Our study sought to validate high-altitude hypoxia as a model for assessing brain activity disruptions akin to aging. We collected EEG data from 16 healthy volunteers during acute high-altitude hypoxia (at 4,000 masl) and at sea level, focusing on relative changes in power and aperiodic slope of the EEG spectrum due to hypoxia.

The novel rapid formulation of intravenous dantrolene (NPJ5008) versus standard dantrolene (Dantrium®): A clinical part-randomised phase 1 study in healthy volunteers.

Background: Delays in treating anaesthesia-induced malignant hyperthermia increase risks of complications and death. NPJ5008 is a novel formulation of the indicated treatment, dantrolene sodium, developed to shorten preparation and administration times compared with the reference formulation Dantrium®. The two formulations have been compared preclinically.

DIVA Meets EEG: Model Validation Using Formant-Shift Reflex.

The neurocomputational model 'Directions into Velocities of Articulators' (DIVA) was developed to account for various aspects of normal and disordered speech production and acquisition. The neural substrates of DIVA were established through functional magnetic resonance imaging (fMRI), providing physiological validation of the model. This study introduces DIVA_EEG an extension of DIVA that utilizes electroencephalography (EEG) to leverage the high temporal resolution and broad availability of EEG over fMRI.

Odor cueing of declarative memories during sleep enhances coordinated spindles and slow oscillations.

Long-term memories are formed by repeated reactivation of newly encoded information during sleep. This process can be enhanced by using memory-associated reminder cues like sounds and odors. While auditory cueing has been researched extensively, few electrophysiological studies have exploited the various benefits of olfactory cueing.

Influence of acute fasting on pain tolerance in healthy subjects: a randomised crossover study.

Background: Although chronic pain and obesity are global health crises with substantial healthcare costs, little is known about the relationship between pain perception and eating behaviours. Food consumption has been reported to provide an analgesic effect by the release of neurotransmitters modulating the pain network. However, whether short-term (acute) fasting affects pain perception remains unclear.

Multi-disciplinary community-based group intervention for fibromyalgia: a pilot randomized controlled trial.

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances, mood disturbances, and cognitive impairment. Most individuals with fibromyalgia experience poorly managed symptoms and increased healthcare service use. Multicomponent therapies, with a focus on nonpharmacological modalities, are increasingly supported in the literature.

Periodic aggregation patterns of oxide particles on corroding metals: chemical waves due to solution feedback processes.

Chemical waves that produce periodic patterns are common occurrences in nature. The underlying processes involved have been studied in many disciplines of science, but rarely reported in the chemistry of corrosion. In this study of carbon steel corrosion, iron oxide crystals are observed to deposit in concentric wave patterns or in discrete bands, known as Liesegang patterns.

Effects of the Configuration of Hearing Loss on Consonant Perception between Simulated Bimodal and Electric Acoustic Stimulation Hearing.

Background: Cochlear implant technology allows for acoustic and electric stimulations to be combined across ears (bimodal) and within the same ear (electric acoustic stimulation [EAS]). Mechanisms used to integrate speech acoustics may be different between the bimodal and EAS hearing, and the configurations of hearing loss might be an important factor for the integration. Thus, differentiating the effects of different configurations of hearing loss on bimodal or EAS benefit in speech perception (differences in performance with combined acoustic and electric stimulations from a better stimulation alone) is important.

Absence of MMF1 disrupts heme biosynthesis by targeting Hem1pin Saccharomyces cerevisiae.

The RidA subfamily of the Rid (YjgF/YER057c/UK114) superfamily of proteins is broadly distributed and found in all domains of life. RidA proteins are enamine/imine deaminases. In the organisms that have been investigated, lack of RidA results in accumulation of the reactive enamine species 2-aminoacrylate (2AA) and/or its derivative imine 2-iminopropanoate (2IP).

Comparisons in Frequency Difference Limens Between Sequential and Simultaneous Listening Conditions in Normal-Hearing Listeners.

Purpose We compared frequency difference limens (FDLs) in normal-hearing listeners under two listening conditions: sequential and simultaneous. Method Eighteen adult listeners participated in three experiments. FDL was measured using a method of limits for comparison frequency.

Visualizing a Team's Goal Chances in Soccer from Attacking Events: A Bayesian Inference Approach.

We consider the task of determining the number of chances a soccer team creates, along with the composite nature of each chance-the players involved and the locations on the pitch of the assist and the chance. We infer this information using data consisting solely of attacking events, which the authors believe to be the first approach of its kind. We propose an interpretable Bayesian inference approach and implement a Poisson model to capture chance occurrences, from which we infer team abilities.

Development and Evaluation of a Computer-Based ROPS Design Program.

Tractor overturn is the leading cause of agricultural fatalities in the U.S. Most of these fatalities can be eliminated using a rollover protective structure (ROPS) and a seatbelt.

Effect of ferrous ion concentration on the kinetics of radiation-induced iron-oxide nanoparticle formation and growth.

Magnetite nanoparticles were formed by γ-radiolysis of solutions containing different initial concentrations of FeSO without any other chemical additives. The particles formed in a given [Fe] had a narrow size distribution and the average size increased with [Fe]. Five hour irradiation at 0.

Strength and Power Correlates of Throwing Velocity on Subelite Male Cricket Players.

Throwing velocity is an important aspect of fielding in cricket to affect run-outs and reduce the opponent's run-scoring opportunities. Although a relationship between strength and/or power and throwing velocity has been well established in baseball, water polo, and European handball, it has not been adequately explored in cricket. Consequently, this study aimed to determine the relationship between measures of strength and/or power and throwing velocity in cricket players.

An unsuccessful attempt to demonstrate attentional orienting within the purely emotional domain.

Inhibition of return (IOR) is an attentional effect that has been much researched in the spatial domain, whereby people are slower to respond to stimuli presented in a previously attended location. Recently, Chao (2010) reported that participants were slower to respond to a negative schematic facial target compared with a positive facial target if they had previously viewed a cue with a negative expression, which he interpreted as IOR in the purely emotional domain. That is, once their attention is drawn away, people are slower to reattend to negative emotions.

Locally destructive skull base lesion: IgG4-related sclerosing disease.

A unique case of IgG4(+) sclerosing disease was diagnosed in the sphenoid sinus, a previously unreported location, and was treated in a novel manner. This study describes the clinical presentation and management of IgG4 sclerosing disease in the paranasal sinuses. A retrospective case review and review of the medical literature were performed.

Regulation of GIP and GLP1 receptor cell surface expression by N-glycosylation and receptor heteromerization.

In response to a meal, Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-like Peptide-1 (GLP-1) are released from gut endocrine cells into the circulation and interact with their cognate G-protein coupled receptors (GPCRs). Receptor activation results in tissue-selective pleiotropic responses that include augmentation of glucose-induced insulin secretion from pancreatic beta cells. N-glycosylation and receptor oligomerization are co-translational processes that are thought to regulate the exit of functional GPCRs from the ER and their maintenance at the plasma membrane.

Failure of fluorescence to reveal middle ear penetration of quinolone drops.

Objective: To evaluate the utility of fluorescence to assess penetration of quinolone ear drops (EDs) through tympanostomy tubes (TTs), the middle ear, eustachian tube, and into the oropharynx.

Design: Before-and-after trial.

Setting: Academic, tertiary care hospital.

Investigation of microdialysis sampling calibration approaches for lipophilic analytes: doxorubicin.

Microdialysis is an important sampling technique in many pharmacokinetics and pharmacological studies. Applying microdialysis to lipophilic analytes can be difficult as low extraction efficiencies are generally obtained with these types of analytes. In this investigation, the effects of applying microdialysis to the lipophilic compound, doxorubicin are discussed.

Using Bioluminescence Resonance Energy Transfer to measure ion channel assembly.

Bioluminescence Resonance Energy Transfer (BRET) measures protein interactions within 10 nm of each other. Aside from its ability to probe for interactions at high resolution, this technique operates in live, intact cells, and offers a high throughput method of detection. Thus far, BRET has been widely used in measuring G protein receptor dimerization.

Regulation of cell surface expression of functional pacemaker channels by a motif in the B-helix of the cyclic nucleotide-binding domain.

Previous studies have suggested that a portion of the cyclic nucleotide-binding domain (CNBD) of the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) "pacemaker" channel, composed of the A- and B-helices and the interceding beta-barrel, confers two functions: inhibition of channel opening in response to hyperpolarization and promotion of cell surface expression. The sequence determinants required for each of these functions are unknown. In addition, the mechanism underlying plasma membrane targeting by this subdomain has been limitedly explored.

CE-LIF method for the separation of anthracyclines: application to protein binding analysis in plasma using ultrafiltration.

Anthracyclines are chemotherapeutic drugs that are widely used in the treatment of cancers such as lung and ovarian cancers. The simultaneous determination of the anthracyclines, daunorubicin, doxorubicin and epirubicin, was achieved using CE coupled to LIF, with an excitation and emission wavelength of 488 and 560 nm, respectively. Using a borate buffer (105 mM, pH 9.