Nrf2 Regulates Basal Glutathione Production in Astrocytes.

Astrocytes produce and export glutathione (GSH), an important thiol antioxidant essential for protecting neural cells from oxidative stress and maintaining optimal brain health. While it has been established that oxidative stress increases GSH production in astrocytes, with Nrf2 acting as a critical transcription factor regulating key components of the GSH synthetic pathway, the role of Nrf2 in controlling constitutive GSH synthetic and release mechanisms remains incompletely investigated. Our data show that naïve primary mouse astrocytes cultured from the cerebral cortices of Nrf2 knockout (Nrf2) pups have significantly less intracellular and extracellular GSH levels when compared to astrocytes cultured from Nrf2 wild-type (Nrf2) pups.

Sex- and age-dependent contribution of System x to cognitive, sensory, and social behaviors revealed by comprehensive behavioral analyses of System x null mice.

Background: System x (Sx) is an important heteromeric amino acid cystine/glutamate exchanger that plays a pivotal role in the CNS by importing cystine into cells while exporting glutamate. Although certain behaviors have been identified as altered in Sx null mutant mice, our understanding of the comprehensive impact of Sx on behavior remains incomplete.

Methods: To address this gap, we compared motor, sensory and social behaviors of male and female mice in mice null for Sx (SLC7A11) with wildtype littermates (SLC7A11) in a comprehensive and systematic manner to determine effects of genotype, sex, age, and their potential interactions.

Both Manuka and Non-Manuka Honey Types Inhibit Antibiotic Resistant Wound-Infecting Bacteria.

Postoperative infections are a major concern in United States hospitals, accounting for roughly 20% of all hospital-acquired infections yearly. Wound-infecting bacteria, in particular, have a high rate of drug resistance (up to 65%), creating life-threatening complications. Manuka honey, native to New Zealand, has been FDA-approved for wound treatment in the United States after studies demonstrated its ability to inhibit a variety of bacterial species and facilitate wound healing.

The Cystine/Glutamate Antiporter, System x , Contributes to Cortical Infarction After Moderate but Not Severe Focal Cerebral Ischemia in Mice.

Understanding the mechanisms underlying ischemic brain injury is of importance to the goal of devising novel therapeutics for protection and/or recovery. Previous work in our laboratory and in others has shown that activation of cystine/glutamate antiporter, system x (Sx ), facilitates neuronal injury in several models of energy deprivation. However, studies on the contribution of this antiporter to ischemic brain damage are more limited.

P2X7-dependent constitutive Interleukin-1β release from pyramidal neurons of the normal mouse hippocampus: Evidence for a role in maintenance of the innate seizure threshold.

Disruption of Interleukin-1β (IL-1β) signaling sensitized mice to convulsant stimuli, suggesting that this quintessential cytokine of the innate immune system contributes to maintenance of the innate seizure threshold (ST). However, much remains unknown about where and how IL-1β secretion occurs in the normal brain. This study examined the possibility that neurons of the hippocampus are key sources of constitutive IL-1β secretion and that the release from these cells is dependent on the purinoceptor, P2X7.

Hyperexcitability and brain morphological differences in mice lacking the cystine/glutamate antiporter, system x.

System x (Sx ) is a heteromeric antiporter (L-cystine/L-glutamate exchanger) expressed predominately on astrocytes in the central nervous system. Its activity contributes importantly to the maintenance of the ambient extracellular glutamate levels, as well as, to cellular redox homeostasis. Since alterations in glutamate levels and redox modifications could cause structural changes, we analyzed gross regional morphology of thionin-stained brain sections and cellular and subcellular morphology of Golgi-Cox stained layer V pyramidal neurons in the primary motor cortex (PM1) of mice naturally null for SLC7A11 (SLC7A11 )-the gene that encodes the substrate specific light chain (xCT) for Sx .

A comparison of two teaching procedures to establish generalized intraverbal-tacting in children with autism.

Previous research has investigated generalized intraverbal-tacting by teaching children with autism to respond using autoclitic frames. The present study compared the effectiveness and efficiency of a Frame and a No Frame procedure across counterbalanced stimulus sets with 4 children with autism. In the Frame condition, children were taught to respond using autoclitic frames (e.

Influence of glutamate and GABA transport on brain excitatory/inhibitory balance.

An optimally functional brain requires both excitatory and inhibitory inputs that are regulated and balanced. A perturbation in the excitatory/inhibitory balance-as is the case in some neurological disorders/diseases (e.g.

The brain in flux: Genetic, physiologic, and therapeutic perspectives on transporters in the CNS.

Active and passive transporters constitute a gene family of approximately 2000 members. These proteins are required for import and export across the blood brain barrier, clearance of neurotransmitters, inter-cellular solute transfer, and transport across the membranes of subcellular organelles. Neurologic, neurodevelopmental, and psychiatric diseases have been linked to alterations in function and/or mutations in every one of these types of transporters, and many of the transporters are targeted by therapeutics.

Sexually dimorphic and brain region-specific transporter adaptations in system x null mice.

System x is a heterodimeric amino acid antiporter that, in the central nervous system, is best known for linking the import of L-cystine (CySS) with the export of L-glutamate for the production and maintenance of cellular glutathione (GSH) and extracellular glutamate levels, respectively. Yet, mice that are null for system x are healthy, fertile, and, morphologically, their brains are grossly normal. This suggests other glutamate and/or cyst(e)ine transport mechanisms may be upregulated in compensation.

Facelift With Power-Assisted Dissection: A Preliminary Report.

Background: Subcutaneous elevation of the skin has remained a key component in all facelift techniques.

Objectives: The aim of this preliminary report was to introduce the ABC facelift as a 3-step method addressing photodamage, soft tissue laxity, and areas of bone and volume loss.

Methods: The procedure consists of: (A) anatomic and regenerative adipose grafting prior to skin elevation; (B) the use of a Baraf elevator for takedown of perpendicular subcutaneous fibers following hydrodissection of the skin flaps with tumescent solution; and (C) cautery dissection of the superficial muscular aponeurotic system (SMAS) and platysma in the neck.

In-Vitro Comparative Examination of the Effect of Stromal Vascular Fraction Isolated by Mechanical and Enzymatic Methods on Wound Healing.

Background: Enzymatic digestion has been the gold standard for stromal vascular fraction (SVF) isolation but remains expensive and raises practical and legal concerns. Mechanical SVF isolation methods have been known to produce lower cell yields, but may potentially produce a more robust product by preserving the extracellular matrix niche.

Objectives: The aim of this study was to compare mechanically dissociated SVF (M-SVF) and enzymatically digested SVF (E-SVF) in terms of wound-healing efficacy.

A Pilot Randomized Clinical Trial of a Multidisciplinary Intervention for Encopresis in Children with Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) are often delayed in achieving bowel continence, resulting in negative outcomes. In this pilot trial, 20 children with ASD and encopresis were randomly assigned to multidisciplinary intervention for encopresis (MIE; n = 10) or a waitlist control group (n = 10). The MIE group was treated for constipation and received a 10-day behavioral intervention that utilized suppositories to produce predictable bowel movements that were reinforced.

Decreased epileptogenesis in mice lacking the System x transporter occurs in association with a reduction in AMPA receptor subunit GluA1.

Objective: Although the cystine/glutamate antiporter System x (Sx ) plays a permissive role in glioma-associated seizures, its contribution to other acquired epilepsies has not been determined. As such, the present study investigates whether and how Sx contributes to the pentylenetetrazole (PTZ) chemical kindling model of epileptogenesis.

Methods: Male Sx null () mice and their wild-type littermates were administered PTZ (i.

Evaluation and accurate diagnoses of pediatric diseases using artificial intelligence.

Artificial intelligence (AI)-based methods have emerged as powerful tools to transform medical care. Although machine learning classifiers (MLCs) have already demonstrated strong performance in image-based diagnoses, analysis of diverse and massive electronic health record (EHR) data remains challenging. Here, we show that MLCs can query EHRs in a manner similar to the hypothetico-deductive reasoning used by physicians and unearth associations that previous statistical methods have not found.

Progressive Improvement in Midfacial Volume 18 to 24 Months After Simultaneous Fat Grafting and Facelift: An Insight to Fat Graft Remodeling.

Background: Although many facelift techniques incorporate fat grafting with tissue repositioning and removal, the intermediate and long-term changes in facial volume after these techniques is unknown. Whereas fillers for facial volume have predictable life spans, we know little about the facial volume changes following fat grafting with facelift surgery.

Objectives: The authors sought to track the short-term and long-term effects on midfacial volume change.

Interleukin-1β Protects Neurons against Oxidant-Induced Injury via the Promotion of Astrocyte Glutathione Production.

Interleukin-1β (IL-1β), a key cytokine that drives neuroinflammation in the Central Nervous System (CNS), is enhanced in many neurological diseases/disorders. Although IL-1β contributes to and/or sustains pathophysiological processes in the CNS, we recently demonstrated that IL-1β can protect cortical astrocytes from oxidant injury in a glutathione (GSH)-dependent manner. To test whether IL-1β could similarly protect neurons against oxidant stress, near pure neuronal cultures or mixed cortical cell cultures containing neurons and astrocytes were exposed to the organic peroxide, tert-butyl hydroperoxide (t-BOOH), following treatment with IL-1β or its vehicle.

Mice lacking L-12/15-lipoxygenase show increased mortality during kindling despite demonstrating resistance to epileptogenesis.

Objective: Studies have addressed the potential involvement of L-12/15-lipoxygenases (LOs), a polyunsaturated fatty acid metabolizing enzyme, in experimental models of acute stroke and chronic neurodegeneration; however, none to our knowledge has explored its role in epilepsy development. Thus, this study characterizes the cell-specific expression of L-12/15 -LO in the brain and examines its contribution to epileptogenesis.

Methods: L-12/15-LO messenger RNA (mRNA) and protein expression and activity were characterized via polymerase chain reaction (PCR), immunocytochemistry and enzyme-linked immunosorbent assay (ELISA), respectively.

A consecutive case series analysis of a behavioral intervention for enuresis in children with developmental disabilities.

Children with developmental disabilities (DD) are more likely than typically developing peers to have issues with enuresis. Past research has shown the success of behavioral treatments consisting of scheduled sits and reinforcement for continent voids. However, this research has included small sample sizes, while studies with larger numbers have lacked key information (i.

Identifying Medical Diagnoses and Treatable Diseases by Image-Based Deep Learning.

The implementation of clinical-decision support algorithms for medical imaging faces challenges with reliability and interpretability. Here, we establish a diagnostic tool based on a deep-learning framework for the screening of patients with common treatable blinding retinal diseases. Our framework utilizes transfer learning, which trains a neural network with a fraction of the data of conventional approaches.

Ethnic Rhinoplasty in Female Patients: The Neoclassical Canons Revisited.

Background: Despite the substantial amount of research devoted to objectively defining facial attractiveness, the canons have remained a paradigm of aesthetic facial analysis, yet their omnipresence in clinical assessments revealed their limitations outside of a subset of North American Caucasians, leading to criticism about their validity as a standard of facial beauty. In an effort to introduce more objective treatment planning into ethnic rhinoplasty, we compared neoclassical canons and other current standards pertaining to nasal proportions to anatomic proportions of attractive individuals from seven different ethnic backgrounds.

Methods: Beauty pageant winners (Miss Universe and Miss World nominees) between 2005 and 2015 were selected and assigned to one of seven regionally defined ethnic groups.

Regenerative Cells For Facial Surgery: Biofilling and Biocontouring.

Zuk et al in 2001 identified stem and regenerative cells within the stromal vascular fraction of fat. In preclinical studies, these cells appeared to stimulate angiogenesis and reduce inflammation, and soon thereafter, clinical use of stromal vascular fraction (SVF) evolved as researchers such as Rigotti, Coleman, Mojallal, our group, and others demonstrated that fat can be used for both therapeutic and aesthetic indications. The regenerative effects of fat and its contents on facial aesthetics have been shown at the histologic and cellular level.

Analysis of acute naproxen administration on memory in young adults: A randomized, double-blind, placebo-controlled study.

Nonsteroidal anti-inflammatory drugs work by non-selectively inhibiting cyclooxygenase enzymes. Evidence indicates that metabolites of the cyclooxygenase pathway play a critical role in the process of learning and memory. We evaluated whether acute naproxen treatment impairs short-term working memory, episodic memory, or semantic memory in a young, healthy adult population.