Intranasal Calcitriol Accelerates Improvement of Sinonasal Inflammation and Olfactory Impairment in Mice After Cessation of Chronic Cigarette-Smoke Exposure.

Rationale: Smoking has been shown to be associated with circulating deficiencies in 25(OH)D3 and reduced sinonasal tissue levels of the active form of vitamin D, 1,25(OH)2D3. Given vitamin D's ability to reduce inflammation, we sought to examine if intranasal (IN) delivery of calcitriol [clinical analog of 1,25(OH)2D3] could reduce inflammation and improve disease severity in a murine model of chronic cigarette smoke-induced sinonasal inflammation (CS-SI).

Methods: Mice were exposed to CS 5 h/day, 5 days/week for 9 months, and then began IN calcitriol three times per week for 4 weeks.

Sustained fentanyl exposure inhibits neuronal activity in dissociated striatal neuronal-glial cocultures through actions independent of opioid receptors.

Besides having high potency and efficacy at the µ-opioid (MOR) and other opioid receptor types, fentanyl has some affinity for some adrenergic receptor types, which may underlie its unique pathophysiological differences from typical opioids. To better understand the unique actions of fentanyl, we assessed the extent to which fentanyl alters striatal medium spiny neuron (MSN) activity via opioid receptors or α-adrenoceptors in dopamine type 1 or type 2 receptor (D1 or D2)-expressing MSNs. In neuronal and mixed-glial cocultures from the striatum, acute fentanyl (100 nM) exposure decreased the frequency of spontaneous action potentials.

Generation of induced pluripotent stem cells from rat fibroblasts and optimization of its differentiation into mature functional neurons.

Background: Induced pluripotent stem cells (iPSCs) derived neural stem cells (NSCs) provide a potential for autologous neural transplantation therapy following neurological insults. Thus far, in preclinical studies the donor iPSCs-NSCs are mostly of human or mouse origin with concerns centering around graft rejection when applied to rat brain injury models. For better survival and integration of transplanted cells in the injured brain in rat models, use of rat-iPSC-NSCs and in combination with biomaterials is of advantageous.

Yin Yang 1 controls cerebellar astrocyte maturation.

Diverse subpopulations of astrocytes tile different brain regions to accommodate local requirements of neurons and associated neuronal circuits. Nevertheless, molecular mechanisms governing astrocyte diversity remain mostly unknown. We explored the role of a zinc finger transcription factor Yin Yang 1 (YY1) that is expressed in astrocytes.

Adult-onset depletion of sulfatide leads to axonal degeneration with relative myelin sparing.

3-O-sulfogalactosylceramide (sulfatide) constitutes a class of sphingolipids that comprise about 4% of myelin lipids in the central nervous system. Previously, our group characterized a mouse with sulfatide's synthesizing enzyme, cerebroside sulfotransferase (CST), constitutively disrupted. Using these mice, we demonstrated that sulfatide is required for establishment and maintenance of myelin, axoglial junctions, and axonal domains and that sulfatide depletion results in structural pathologies commonly observed in Multiple Sclerosis (MS).

Resolution of post-lung transplant ischemia-reperfusion injury is modulated via Resolvin D1-FPR2 and Maresin 1-LGR6 signaling.

Background: Dysregulation of inflammation-resolution pathways leads to postlung transplant (LTx) ischemia-reperfusion (IR) injury and allograft dysfunction. Our hypothesis is that combined treatment with specialized pro-resolving lipid mediators, that is, Resolvin D1 (RvD1) and Maresin-1 (MaR1), enhances inflammation-resolution of lung IR injury.

Methods: Expression of RvD1 and MaR1 was analyzed in bronchoalveolar lavage (BAL) fluid of patients on days 0, 1, and 7 post-LTx.

Pre-operative imaging for surgical decision-making and the frequency of wrist arthrodesis and carpectomy procedures: a scoping review.

Objectives: Our objectives were to (1) analyze the imaging modalities utilized pre-operatively that influence surgical decision-making for wrist arthrodesis and carpectomy procedures and (2) determine the type and frequency of these procedures for the treatment of wrist arthritis.

Materials And Methods: This review was performed according to the guidelines of PRISMA Extension for Scoping Reviews. Using PubMed, Embase, and Scopus, peer-reviewed literature from 2011 to 2022 was searched for use of imaging in pre-operative decision-making for wrist arthrodesis and carpectomy surgical procedures.

Hypoxia and Hypoxia-Inducible Factors in Lymphedema.

Lymphedema is a chronic inflammatory disorder characterized by edema, fat deposition, and fibrotic tissue remodeling. Despite significant advances in lymphatic biology research, our knowledge of lymphedema pathology is incomplete. Currently, there is no approved pharmacological therapy for this debilitating disease.

Chronic Morphine Induces IL-18 in Ileum Myenteric Plexus Neurons Through Mu-opioid Receptor Activation in Cholinergic and VIPergic Neurons.

The gastrointestinal epithelium is critical for maintaining a symbiotic relationship with commensal microbiota. Chronic morphine exposure can compromise the gut epithelial barrier in mice and lead to dysbiosis. Recently, studies have implicated morphine-induced dysbiosis in the mechanism of antinociceptive tolerance and reward, suggesting the presence of a gut-brain axis in the pharmacological effects of morphine.

Chloride channels with ClC-1-like properties differentially regulate the excitability of dopamine receptor D1- and D2-expressing striatal medium spiny neurons.

Dynamic chloride (Cl) regulation is critical for synaptic inhibition. In mature neurons, Cl influx and extrusion are primarily controlled by ligand-gated anion channels (GABA and glycine receptors) and the potassium chloride cotransporter K-Cl cotransporter 2 (KCC2), respectively. Here, we report for the first time, to our knowledge, a presence of a new source of Cl influx in striatal neurons with properties similar to chloride voltage-gated channel 1 (ClC-1).

Effects of subanesthetic ketamine and (2R,6R) hydroxynorketamine on working memory and synaptic transmission in the nucleus reuniens in mice.

Rationale: Acute cognitive impairment and abuse potential of ketamine incentivizes the search for alternatives to ketamine for clinical management of treatment-resistant depression. Recently, (2R,6R) hydroxynorketamine ((2R,6R)-HNK), a metabolite of ketamine, has shown promise due to its reported lack of ketamine-like reinforcing properties. Nonetheless, the effect of (2R,6R)-HNK on cognition has not been reported.

Pro-inflammatory IgG1 N-glycan signature correlates with primary graft dysfunction onset in COPD patients.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. The pathogenesis of COPD is complex; however, recent studies suggest autoimmune changes, characterized by the presence of autoantibodies to elastin and collagen, may contribute to disease status. COPD patients make up approximately 30% of all lung transplants (LTx) annually, however, little is known regarding the relationship between COPD-related autoantibodies and LTx outcomes.

Nucleus Reuniens Afferents in Hippocampus Modulate CA1 Network Function Monosynaptic Excitation and Polysynaptic Inhibition.

The thalamic midline nucleus reuniens modulates hippocampal CA1 and subiculum function dense projections to the stratum lacunosum-moleculare (SLM). Previously, anatomical data has shown that reuniens inputs in the SLM form synapses with dendrites of both CA1 principal cells and inhibitory interneurons. However, the ability of thalamic inputs to excite the CA1 principal cells remains controversial.

Set Up for Failure: Pre-Existing Autoantibodies in Lung Transplant.

Lung transplant patients have the lowest long-term survival rates compared to other solid organ transplants. The complications after lung transplantation such as primary graft dysfunction (PGD) and ultimately chronic lung allograft dysfunction (CLAD) are the main reasons for this limited survival. In recent years, lung-specific autoantibodies that recognize non-HLA antigens have been hypothesized to contribute to graft injury and have been correlated with PGD, CLAD, and survival.

HIV-1 Tat and Morphine Differentially Disrupt Pyramidal Cell Structure and Function and Spatial Learning in Hippocampal Area CA1: Continuous versus Interrupted Morphine Exposure.

About half the people infected with human immunodeficiency virus (HIV) have neurocognitive deficits that often include memory impairment and hippocampal deficits, which can be exacerbated by opioid abuse. To explore the effects of opioids and HIV on hippocampal CA1 pyramidal neuron structure and function, we induced HIV-1 transactivator of transcription (Tat) expression in transgenic mice for 14 d and co-administered time-release morphine or vehicle subcutaneous implants during the final 5 d (days 9-14) to establish steady-state morphine levels. Morphine was withheld from some slices during recordings to begin to assess the initial pharmacokinetic consequences of opioid withdrawal.

Chronic adolescent stress causes sustained impairment of cognitive flexibility and hippocampal synaptic strength in female rats.

Females that experience chronic stress during development, particularly adolescence, are the most vulnerable group to stress-induced disease. While considerable attention has been devoted to stress-induced manifestation of anxiety, depression, and PTSD, evidence indicates that a history of chronic stress is also a risk factor for cognitive decline and dementia - with females again in a higher risk group. This interplay between sex and stress history indicates specific mechanisms drive neural dysfunction across the lifespan.

The Entorhinal Cortical Alvear Pathway Differentially Excites Pyramidal Cells and Interneuron Subtypes in Hippocampal CA1.

The entorhinal cortex alvear pathway is a major excitatory input to hippocampal CA1, yet nothing is known about its physiological impact. We investigated the alvear pathway projection and innervation of neurons in CA1 using optogenetics and whole cell patch clamp methods in transgenic mouse brain slices. Using this approach, we show that the medial entorhinal cortical alvear inputs onto CA1 pyramidal cells (PCs) and interneurons with cell bodies located in stratum oriens were monosynaptic, had low release probability, and were mediated by glutamate receptors.

HIV and opiates dysregulate K- Cl cotransporter 2 (KCC2) to cause GABAergic dysfunction in primary human neurons and Tat-transgenic mice.

Approximately half of people infected with HIV (PWH) exhibit HIV-associated neuropathology (neuroHIV), even when receiving combined antiretroviral therapy. Opiate use is widespread in PWH and exacerbates neuroHIV. While neurons themselves are not infected, they incur sublethal damage and GABAergic disruption is selectively vulnerable to viral and inflammatory factors released by infected/affected glia.

Photodynamic Modification of Native HCN Channels Expressed in Thalamocortical Neurons.

The photodynamic process requires three elements: light, oxygen, and photosensitizer, and involves the formation of singlet oxygen, the molecular oxygen in excited electronic states. Previously, we reported that heterologously expressed hyperpolarization-activated cAMP-gated (HCN) channels in excised membrane patches are sensitive to photodynamic modification (PDM). Here we extend this study to native HCN channels expressed in thalamocortical (TC) neurons in the ventrobasal (VB) complex of the thalamus and dopaminergic neurons (DA) of the ventral tegmental area (VTA).

Acetylcholine Release Inhibits Distinct Excitatory Inputs Onto Hippocampal CA1 Pyramidal Neurons via Different Cellular and Network Mechanisms.

In hippocampal CA1, muscarinic acetylcholine (ACh) receptor (mAChR) activation via exogenous application of cholinergic agonists has been shown to presynaptically inhibit Schaffer collateral (SC) glutamatergic inputs in stratum radiatum (SR), and temporoammonic (TA) and thalamic nucleus reuniens (RE) glutamatergic inputs in stratum lacunosum-moleculare (SLM). However, steady-state uniform mAChR activation may not mimic the effect of ACh release in an intact hippocampal network. To more accurately examine the effect of ACh release on glutamatergic synaptic efficacy, we measured electrically evoked synaptic responses in CA1 pyramidal cells (PCs) following the optogenetic release of ACh in genetically modified mouse brain slices.

Cardiac Computed Tomography for Atrial Fibrillation Patients Undergoing Ablation: Implications for the Prediction of Early Recurrence.

Objective: The objective of this study was to correlate early recurrence of atrial fibrillation (AF) after ablation with noninvasive imaging using cardiac computed tomography (CT).

Methods: CT image data of 260 patients who had undergone wide area circumferential ablation (WACA) between October 2005 and August 2010 as well as from 30 subjects in sinus rhythm without a history of AF (control group) were retrospectively analyzed. To evaluate early outcome of AF ablation, all AF patients underwent follow-up with a 30-day event monitor 3 to 4 months after ablation.

Recent insights into PERK-dependent signaling from the stressed endoplasmic reticulum.

The unfolded protein response (UPR) is an evolutionarily conserved stress response to intra- and extracellular conditions that disrupt endoplasmic reticulum (ER) protein-folding capacity. The UPR is engaged by a variety of disease conditions, including most cancers as well as both metabolic and neurodegenerative disorders. Three transmembrane transducers-PERK, IRE1, and ATF6-are responsible for activating downstream signaling pathways that mediate the UPR and subsequent stress response pathways.

Corrigendum: A Novel Retinal Oscillation Mechanism in an Autosomal Dominant Photoreceptor Degeneration Mouse Model.

[This corrects the article on p. 513 in vol. 9, PMID: 26793064.

Segmentations of the cartilaginous skeletons of chondrichthyan fishes by the use of state-of-the-art computed tomography.

Aim: To apply dual-source multidetector computed tomography (DSCT) scanning technology in conjunction with computationally assisted segmentation in order to explore and document skeletal variation that has occurred over the course of evolution.

Methods: We examined 4 divergent species of elasmobranchs with high-resolution 3 generation DSCT. The formalin prepared species examined were: , , and .

Selective Vulnerability of Striatal D2 versus D1 Dopamine Receptor-Expressing Medium Spiny Neurons in HIV-1 Tat Transgenic Male Mice.

Despite marked regional differences in HIV susceptibility within the CNS, there has been surprisingly little exploration into the differential vulnerability among neuron types and the circuits they underlie. The dorsal striatum is especially susceptible, harboring high viral loads and displaying marked neuropathology, with motor impairment a frequent manifestation of chronic infection. However, little is known about the response of individual striatal neuron types to HIV or how this disrupts function.