The Nasoseptal Flap for Reconstruction of Lateral Oropharyngectomy Defects: A Clinical Series.

Objectives/hypothesis: To study use of the nasoseptal flap (NSF) to reconstruct lateral transoral robotic surgery (TORS) oropharyngectomy defects.

Study Design: Retrospective case series.

Methods: A clinical series of six patients undergoing NSF reconstruction of lateral TORS oropharyngectomy defects was retrospectively studied.

Modulation of proteasome activity by curcumin and didemethylcurcumin.

Modulation of proteasome function by pharmacological interventions and molecular biology tools is an active area of research in cancer biology and neurodegenerative diseases. Curcumin (diferuloylmethane) is a naturally occurring polyphenol that affects multiple signaling pathways. Curcumin shows anti-inflammatory, antioxidant, anti-angiogenic, or anti-apoptotic properties.

A Novel PDE4D Inhibitor BPN14770 Reverses Scopolamine-Induced Cognitive Deficits via cAMP/SIRT1/Akt/Bcl-2 Pathway.

A global, quantitative proteomics/systems-biology analysis of the selective pharmacological inhibition of phosphodiesterase-4D (PDE4D) revealed the differential regulation of pathways associated with neuroplasticity in memory-associated brain regions. Subtype selective inhibitors of PDE4D bind in an allosteric site that differs between mice and humans in a single amino acid (tyrosine vs. phenylalanine, respectively).

Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics.

The first 17 amino acid residues of Huntingtin protein (Nt17 of htt) are thought to play an important role in the protein's function; Nt17 is one of two membrane binding domains in htt. In this study the binding ability of Nt17 peptide with vesicles comprised of two subclasses of phospholipids is studied using electrospray ionization - mass spectrometry (ESI-MS) and molecular dynamics (MD) simulations. Overall, the peptide is shown to have a greater propensity to interact with vesicles of phosphatidylcholine (PC) rather than phosphatidylethanolamine (PE) lipids.

Adjuvant therapy with Astragalus membranaceus for post-stroke fatigue: a systematic review.

Post-stroke fatigue (PSF) is a common symptom after stroke and interferes with the rehabilitation. There are limited pharmacological therapies for managing PSF. Astragalus membranaceus (Huangqi) is a frequently used Chinese herbal medicine (CHM) in the treatment of fatigue in China.

Executive functioning: perspectives on neurotrophic activity and pharmacology.

Executive functioning is a high-level cognitive ability, regulating other abilities and behaviors to achieve desired goals. A typical executive task can be defined as the capacity to maintain one's attention on the current task, that is, responding only to the correct but not to distractive stimuli. Impairments of executive functions, or executive dysfunctions, have a growing impact on everyday life and academic achievement and are usually an early feature, and one of the core features, in brain injury and memory and behavioral disorders.

Fasudil in Combination With Bone Marrow Stromal Cells (BMSCs) Attenuates Alzheimer's Disease-Related Changes Through the Regulation of the Peripheral Immune System.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation.

An Algorithm for Preclinical Diagnosis of Alzheimer's Disease.

Almost all Alzheimer's disease (AD) therapeutic trials have failed in recent years. One of the main reasons for failure is due to designing the disease-modifying clinical trials at the advanced stage of the disease when irreversible brain damage has already occurred. Diagnosis of the preclinical stage of AD and therapeutic intervention at this phase, with a perfect target, are key points to slowing the progression of the disease.

Sex differences in a rabbit eyeblink conditioning model of PTSD.

We have developed a rabbit model of posttraumatic stress disorder (PTSD) which recapitulates several core features of PTSD, particularly hyperarousal and conditioned responding to trauma-associated cues. The work conducted with this model has all been done in male rabbits and, given sex differences in PTSD prevalence, it is important to expand our animal model of PTSD to include female rabbits to determine if they develop core features of PTSD, and if those core features can be treated. This is particularly important because, contrary to human studies, nearly all animal studies have found that males are consistently more vulnerable to various forms of acute and chronic stress than females.

Protein kinase C activator bryostatin-1 modulates proteasome function.

Proteasome activity in ubiquitin-proteasome pathway plays a pivotal role in degradation and clearance of aggregated, oxidized, damaged, and misfolded unwanted proteins to control protein homeostasis or proteostasis. Proteasome activity decreases with cellular senescence, aging, and age-related diseases. Therefore, enhancement of impaired proteasome function by molecular biological and/or pharmacological intervention is an active area of research.

Propranolol produces short-term facilitation of extinction in a rabbit model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a learning-based anxiety disorder with significant public health challenges due to difficulties in treating the complex, multiple symptomology. We have developed an animal model of PTSD, based on Pavlovian eyeblink conditioning in rabbits, that addresses two key features: conditioned responses (CRs) to cues associated with an aversive event and a form of conditioned hyperarousal referred to as conditioning-specific reflex modification (CRM). We have found previously that unpaired extinction is ideal for reducing both CRs and CRM simultaneously and shows sensitivity to systemic serotonergic and glutamatergic manipulations.

Hippocampal microvasculature changes in association with oxidative stress in Alzheimer's disease.

Vascular endothelial dysfunction is a primary phenotype of aging, and microvascular (MV) lesion is mainly associated with Alzheimer's disease (AD). Here we have studied the correlation of MV wall thickness and CA1 pyramidal neuronal pathology in autopsy-confirmed AD brains. Both hyaline (h-MV) and increased cell number (c-MV) associated MV wall thickening was found in age-matched control (AC) hippocampus without significant change in Aβ level (Braak stages 0-III).

Task-specific sensory coding strategies are matched to detection and discrimination performance.

The acquisition of sensory information is limited by the neural encoding method used, constraining perceptual abilities. The most relevant aspects of stimuli may change as behavioral context changes, making efficient encoding of information more challenging. Sensory systems must balance rapid detection of a stimulus with perception of fine details that enable discrimination between similar stimuli.

Delayed unpaired extinction as a treatment for hyperarousal of the rabbit nictitating membrane response and its implications for treating PTSD.

Treatment for PTSD (Post-traumatic stress disorder) is rarely available immediately after trauma and often delayed for weeks or months after an event. In a rabbit eyeblink conditioning model of PTSD, we have previously shown that presentations of a tone conditioned stimulus (CS) and shock unconditioned stimulus (US) in an explicitly unpaired manner known as unpaired extinction is effective in reducing CS responding and US hyperarousal even if shock intensity is reduced eight-fold and elicits only minimal responding. Here we determined if delayed delivery of unpaired extinction would still be effective in extinguishing hyperarousal.

The antioxidant xanthorrhizol prevents amyloid-β-induced oxidative modification and inactivation of neprilysin.

Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer's disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess antioxidant and anti-inflammatory properties.

Face size biases emotion judgment through eye movement.

Faces are the most commonly used stimuli to study emotions. Researchers often manipulate the emotion contents and facial features to study emotion judgment, but rarely manipulate low-level stimulus features such as face sizes. Here, I investigated whether a mere difference in face size would cause differences in emotion judgment.

A Neural Signature Encoding Decisions under Perceptual Ambiguity.

People often make perceptual decisions with ambiguous information, but it remains unclear whether the brain has a common neural substrate that encodes various forms of perceptual ambiguity. Here, we used three types of perceptually ambiguous stimuli as well as task instructions to examine the neural basis for both stimulus-driven and task-driven perceptual ambiguity. We identified a neural signature, the late positive potential (LPP), that encoded a general form of stimulus-driven perceptual ambiguity.

Cytokine Signaling in Multiple Sclerosis and Its Therapeutic Applications.

Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known but it is widely accepted that it is autoimmune in nature. Disease onset is believed to be initiated by the activation of CD4+ T cells that target autoantigens of the central nervous system (CNS) and their infiltration into the CNS, followed by the expansion of local and infiltrated peripheral effector myeloid cells that create an inflammatory milieu within the CNS, which ultimately lead to tissue damage and demyelination.

Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

Background: As the human lifespan increases, the number of people affected by agerelated dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypo-perfusion/vascular risk factors enhance amyloid toxicity and other memory- damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome.

Grouping subjects based on conditioning criteria reveals differences in acquisition rates and in strength of conditioning-specific reflex modification.

Averaging behavioral data such as the nictitating membrane response (NMR) across subjects can conceal important individual and group differences. Analyses were conducted of NMR data from rabbits that were grouped based on the point during NMR conditioning when subjects produced 8 conditioned responses (CR) in a set of 10 trials. This resulted in five groups (Early Day 1, Late Day 1, Early Day 2, Late Day 2, Early Day 3) in which group differences in CR acquisition rates were found.

Periplasmic flagella in Borrelia burgdoferi function to maintain cellular integrity upon external stress.

Tapping mode atomic force microscopy (AFM) in solution was used to analyze the role of the internally located periplasmic flagella (PFs) of the Lyme disease spirochete Borrelia burgdorferi in withstanding externally applied cellular stresses. By systematically imaging immobilized spirochetes with increasing tapping forces, we found that mutants that lack PFs are more readily compressed and damaged by the imaging process compared to wild-type cells. This finding suggest that the PFs, aside from being essential for motility and involved in cell shape, play a cytoskeletal role in dissipating energy and maintaining cellular integrity in the presence of external stress.

Attenuation of ethanol abstinence-induced anxiety- and depressive-like behavior by the phosphodiesterase-4 inhibitor rolipram in rodents.

Rationale: Withdrawal symptoms stand as a core feature of alcohol dependence. Our previous results have shown that inhibition of phosphodiesterase-4 (PDE4) decreased ethanol seeking and drinking in alcohol-preferring rodents. However, little is known about whether PDE4 is involved in ethanol abstinence-related behavior.

Decision ambiguity is mediated by a late positive potential originating from cingulate cortex.

People often make decisions in the face of ambiguous information, but it remains unclear how ambiguity is represented in the brain. We used three types of ambiguous stimuli and combined EEG and fMRI to examine the neural representation of perceptual decisions under ambiguity. We identified a late positive potential, the LPP, which differentiated levels of ambiguity, and which was specifically associated with behavioral judgments about choices that were ambiguous, rather than passive perception of ambiguous stimuli.