Unaltered Tonic Inhibition in the Arcuate Nucleus of Diet-induced Obese Mice

The principal inhibitory transmitter, γ-aminobutyric acid (GABA), is critical for maintaining hypothalamic homeostasis and released from neurons phasically, as well as from astrocytes tonically. Although astrocytes in the arcuate nucleus (ARC) of the hypothalamus are shown to transform into reactive astrocytes, the tonic inhibition by astrocytic GABA has not been adequately investigated in diet-induced obesity (DIO). Here, we investigated the expression of monoamine oxidase- B (MAOB), a GABA-synthesizing enzyme, in reactive astrocytes in obese mice. We observed that a chronic high-fat diet (HFD) significantly increased astrocytic MAOB and cellular GABA content, along with enhanced hypertrophy of astrocytes in the ARC. Unexpectedly, we found that the level of tonic GABA was unaltered in chronic HFD mice using whole-cell patch-clamp recordings in the ARC. Furthermore, the GABA-induced current was increased with elevated GABA A receptor α5 (GABRA5) expression. Surprisingly, we found that a nonselective GABA transporter (GAT) inhibitor, nipecotic acid (NPA)-induced current was significantly increased in chronic HFD mice. We observed that GAT1 inhibitor, NO711-induced current was significantly increased, whereas GAT3 inhibitor, SNAP5114-induced current was not altered. The unexpected unaltered tonic inhibition was due to an increase of GABA clearance in the ARC by neuronal GAT1 rather than astrocytic GAT3. These results imply that increased astrocytic GABA synthesis and neuronal GABA A receptor were compensated by GABA clearance, resulting in unaltered tonic GABA inhibition in the ARC of the hypothalamus in obese mice. Taken together, GABA-related molecular pathways in the ARC dynamically regulate the tonic inhibition to maintain hypothalamic homeostasis against the HFD challenge.

Generation of Astrocyte-Specific MAOB Conditional Knockout Mouse with Minimal Tonic GABA Inhibition

Monoamine oxidase B (MAOB) is a key enzyme for GABA production in astrocytes in several brain regions. To date, the role of astrocytic MAOB has been studied in MAOB null knockout (KO) mice, although MAOB is expressed throughout the body. Therefore, there has been a need for genetically engineered mice in which only astrocytic MAOB is targeted. Here, we generated an astrocyte-specific MAOB conditional KO (cKO) mouse line and characterized it in the cerebellar and striatal regions of the brain. Using the CRISPR-Cas9 gene-editing technique, we generated Maob floxed mice (B6-Maob em1Cjl /Ibs) which have floxed exons 2 and 3 of Maob with two loxP sites. By crossing these mice with hGFAP-CreER T2 , we obtained Maob floxed::hGFAP-CreER T2 mice which have a property of tamoxifen-inducible ablation of Maob under the human GFAP (hGFAP) promoter. When we treated Maob floxed::hGFAP-CreER T2 mice with tamoxifen for 5 consecutive days, MAOB and GABA immunoreactivity were significantly reduced in striatal astrocytes as well as in Bergmann glia and lamellar astrocytes in the cerebellum, compared to sunflower oil-injected control mice. Moreover, astrocyte-specific MAOB cKO led to a 74.6% reduction in tonic GABA currents from granule cells and a 76.8% reduction from medium spiny neurons. Our results validate that astrocytic MAOB is a critical enzyme for the synthesis of GABA in astrocytes. We propose that this new mouse line could be widely used in studies of various brain diseases to elucidate the pathological role of astrocytic MAOB in the future.

Prediction of the Expected Extent of Surgical Difficulty When Removing an Idiopathic Epiretinal Membrane

Purpose@#We sought to predict how difficult surgical removal of an epiretinal membrane (ERM) might be by analyzing the preoperative characteristics of the ERM. @*Methods@#From 2016 to 2020, 75 patients diagnosed with idiopathic ERMs who underwent ERM removal were evaluated in terms of surgical time (via video analysis); associations between that time and preoperative color fundus photographs and optical coherence tomography findings were sought. @*Results@#The surgical time was associated with the vascular tortuosity grade, the ERM stage, and fibrillary changes (p = 0.024, p = 0.020, and p = 0.018). Dummy regression analysis showed that EMR stage 4, and vascular tortuosity grades of 2 or 3, increased the surgical time (p = 0.036, p = 0.049). @*Conclusions@#Surgery may be difficult if the ERM is of stage 4 or the vascular tortuosity grade 2 or more. A retinal surgery novice should consider these factors when contemplating surgery.

Prediction of the Expected Extent of Surgical Difficulty When Removing an Idiopathic Epiretinal Membrane

Purpose@#We sought to predict how difficult surgical removal of an epiretinal membrane (ERM) might be by analyzing the preoperative characteristics of the ERM. @*Methods@#From 2016 to 2020, 75 patients diagnosed with idiopathic ERMs who underwent ERM removal were evaluated in terms of surgical time (via video analysis); associations between that time and preoperative color fundus photographs and optical coherence tomography findings were sought. @*Results@#The surgical time was associated with the vascular tortuosity grade, the ERM stage, and fibrillary changes (p = 0.024, p = 0.020, and p = 0.018). Dummy regression analysis showed that EMR stage 4, and vascular tortuosity grades of 2 or 3, increased the surgical time (p = 0.036, p = 0.049). @*Conclusions@#Surgery may be difficult if the ERM is of stage 4 or the vascular tortuosity grade 2 or more. A retinal surgery novice should consider these factors when contemplating surgery.

Factors Affecting Persistent Diplopia after Surgical Repair of Isolated Inferior Orbital Wall Fracture

PURPOSE: To investigate factors affecting persistent diplopia after surgical repair of isolated inferior orbital wall fractures. METHODS: Thirty-three patients who underwent surgical repair of isolated inferior orbital wall fractures in Inha University Hospital Ophthalmology Department from 2014 to 2017 were enrolled in this study. The authors examined facial computed tomography, diplopia, extraocular muscle movement, and Hertel's exophthalmometer before and 6 months after surgery. The diplopia which was not recovered even at 6 months postoperatively was defined as persistent diplopia. Multivariable logistic regression analyses were performed on parameters that were found to be related to persistent diplopia using univariable logistic regression analyses. RESULTS: Univariable regression analysis showed that preoperative ocular motility limitation, preoperative diplopia, the type of fracture, the number of contacts with the fracture site and extraocular muscle (EOM), and EOM tenting were associated with persistent postoperative diplopia. Multivariable regression analysis using the previously mentioned five parameters showed 28.3-fold and 17.4-fold greater probabilities of diplopia after surgery in preoperative diplopia and EOM tenting, respectively (p = 0.023). CONCLUSIONS: Preoperative diplopia and EOM tenting were associated with persistent postoperative diplopia. These parameters were predictors of persistent diplopia in eyes with isolated inferior orbital wall fractures.

Atypical Fundus Manifestation of Ocular Toxocariasis

No abstract available.

End-stage Renal Disease and Risk of Active Tuberculosis: a Nationwide Population-Based Cohort Study

BACKGROUND: The converging epidemics of tuberculosis (TB) and end-stage renal disease (ESRD) have generated a significant public health burden, however, previous studies have been limited to a small number of patients. This nationwide cohort study aimed to assess the rate of developing active TB among patients receiving dialysis for ESRD. METHODS: The Korean national health insurance database was used to identify patients receiving dialysis for new-onset ESRD during 2004–2013, who were propensity score matched to an equivalent number of non-dialysis subjects from the general population. The incidences of active TB in the ESRD and control cohorts were calculated for 2004–2013, and multivariable Cox proportional hazards model was used to evaluate the ESRD-related risk of active TB. RESULTS: During 2004–2013, 59,584 patients received dialysis for newly diagnosed ESRD. In the dialysis and control cohorts, 457 (0.8%) and 125 (0.2%) cases of active TB were detected, respectively. Patients with ESRD were associated with a significantly higher risk of active TB compared to the controls (incidence rate ratio, 4.80). The ESRD cohort had an independently elevated risk of active TB (adjusted hazard ratio, 4.39; 95% confidence interval, 3.60–5.37). CONCLUSION: We found that patients receiving dialysis for ESRD had an elevated risk of active TB. These results highlight the need for detailed and well-organised guidelines for active TB screening among patients with ESRD.

Multiregion Comprehensive Genomic Profiling of a Gastric Mixed Neuroendocrine-Nonneuroendocrine Neoplasm with Trilineage Differentiation

Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) are a group of rare tumors previously known as mixed adenoneuroendocrine carcinomas (MANECs). The neuroendocrine component is high-grade and may consist of small-cell carcinoma or large-cell neuroendocrine carcinoma. The nonneuroendocrine component may consist of adenocarcinoma or squamous cell carcinoma. We report a unique case of a MiNEN with trilineage differentiation: large-cell neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma. The reported patient presented with symptoms of an upper gastrointestinal bleed and was ultimately diagnosed with a MiNEN with trilineage differentiation. This is the first report of this exceedingly rare tumor type to include next-generation sequencing of the 3 separate tumor entities. In addition, we review the current literature and discuss the role of next-generation sequencing in classifying and treating MiNEN tumors.

Primary Systemic Amyloidosis Involving the Lacrimal Sac

No abstract available.