PURPOSE: To identify the risk factors associated with fluoroquinolone resistance in patients undergoing cataract surgery. METHODS: A total of 1,125 patients (1,125 eyes) who underwent cataract surgery at Veterans Health Service Medical Center from May 2011 to July 2012 were enrolled in this study. Conjunctival cultures were obtained from the patients on the day of surgery before instillation of any ophthalmic solutions. The medical records of patients with positive coagulase negative staphylococcus (CNS) and Staphylococcus aureus (S. aureus) cultures were reviewed to determine factors associated with fluoroquinolone resistance. RESULTS: Of 734 CNS and S. aureus cultures, 175 (23.8%) were resistant to ciprofloxacin, levofloxacin, gatifloxacin, or moxifloxacin. Use of fluoroquinolone within 3 months and within 1 year before surgery, topical antibiotic use other than fluoroquinolone, systemic antibiotic use, recent hospitalization, ocular surgery, intravitreal injection and use of eyedrops containing benzalkonium chloride were significantly more frequent in resistant isolates than in susceptible isolates. In multivariable logistic regression analysis, ocular surgery (odds ratio [OR], 8.457), recent hospitalization (OR, 6.646) and use of fluoroquinolone within 3 months before surgery (OR, 4.918) were significant predictors of fluoroquinolone resistance, along with intravitreal injection (OR, 2.976), systemic antibiotic use (OR, 2.665), use of eyedrops containing benzalkonium chloride (OR, 2.323), use of fluoroquinolone within 1 year before surgery (OR, 1.943) and topical antibiotic use other than fluoroquinolone (OR, 1.673). CONCLUSIONS: Recent topical fluoroquinolone use, hospitalization and ocular surgery were significantly associated with fluoroquinolone resistance in CNS and S. aureus isolates from ocular culture.
Aged ; Anti-Bacterial Agents/*administration & dosage ; *Drug Resistance, Bacterial ; Eye Infections, Bacterial/drug therapy/*microbiology ; Female ; Fluoroquinolones/*administration & dosage ; Humans ; Male ; Ophthalmic Solutions ; Retrospective Studies ; Risk Factors ; Staphylococcal Infections/drug therapy/*microbiology ; Staphylococcus aureus/drug effects/*isolation & purification

OBJECTIVE: Hypotension after emergent endotracheal intubation is a serious complication related to in-hospital mortality. We investigated factors including modified shock index to predict the development of hypotension after emergent intubation. METHODS: This retrospective observational study was conducted between January 2011 and December 2016. The study population included intubated patients among all medical patients admitted to the emergency department (ED) except for patients whose systolic blood pressure was below 90 mmHg at any time before intubation. The postintubation hypotension (PIH) groups were compared with the non-PIH group. The secondary outcome was in-hospital mortality. RESULTS: A total of 285 patients were included in this study, of which 92 patients (32.3%) PIH. The age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01–1.06; P=0.001), serum albumin level (OR, 0.62; 95% CI, 0.41–0.92; P=0.019), shock index (OR, 3.25; 95% CI, 1.26–8.38; P=0.015), and modified shock index (MSI) (OR, 2.18; 95% CI, 1.06–4.47; P=0.034) were more closely associated with PIH than any other factors. The average survival of the PIH group was significantly shorter than that of the non-PIH group (13.6±3.5 vs. 35.6±12.0, log-rank test P=0.019). CONCLUSION: Overall, 32.3% of hemodynamically stable medical patients developed PIH in ED. MSI was associated with PIH.
Blood Pressure ; Emergencies* ; Emergency Medical Services ; Emergency Service, Hospital* ; Hospital Mortality ; Humans ; Hypotension* ; Intubation ; Intubation, Intratracheal ; Mortality ; Observational Study ; Retrospective Studies ; Risk Factors ; Serum Albumin ; Shock*

Sleep is indispensable for living animals to live and maintain a normal life. Due to the growing number of people suffering from sleep disorders such as insomnia, there have been increasing interests in environmentally friendly therapeutic approaches for sleep disorders to avoid any side effects of pharmacological treatment using synthetic hypnotics. It has been widely accepted that the various beneficial effects of forest, such as relieving stress and anxiety and enhancing immune system function, are caused by plant-derived products, also known as phytoncide. Recently, it has been reported that the sleep-enhancing effects of phytoncide are derived from pine trees such as (-)-α-pinene and 3-carene. These are the major constituents of pine tree that potentiate the inhibitory synaptic responses by acting as a positive modulator for GABAA-BZD receptor. In this review, we discuss the effects of phytoncide on sleep and review the latest approaches of sleep-related behavioral assay, electrophysiological recording, and molecular modeling technique.

Isoliquiritigenin (ILTG) is a chalcone compound and shows various pharmacological properties, including antioxidant and anti-inflammatory activities. In recent study, we have reported a novel role of ILTG in sleep through a positive allosteric modulation of gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptors. However, the effect of ILTG in GABA(A)R-mediated synaptic response in brain has not been tested yet. Here we report that ILTG significantly prolonged the decay of spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by GABA(A)R in mouse hippocampal CA1 pyramidal neurons without affecting amplitude and frequency of sIPSCs. This enhancement was fully inhibited by flumazenil (FLU), a specific GABA(A)-BZD receptor antagonist. These results suggest a potential role of ILTG as a modulator of GABAergic synaptic transmission.
Animals ; Brain ; Chalcone* ; Flumazenil ; gamma-Aminobutyric Acid ; Inhibitory Postsynaptic Potentials ; Mice ; Neurons ; Synaptic Transmission

About 5~12% of school-aged children suffer from the Attention-Deficit/Hyperactivity Disorder (ADHD). However, the core mechanism of ADHD remains unclear. G protein-coupled receptor kinase-interacting protein-1 (GIT1) has recently been reported to be associated with ADHD in human and the genetic deletion of GIT1 result in ADHD-like behaviors in mice. Mice lacking GIT1 shows a shift in neuronal excitation/inhibition (E/I) balance. However, the pricise mechanism for E/I imbalance and the role of neuron-glia interaction in GIT1 knockout (KO) mice have not been studied. Especially, a possible contribution of glial GABA and tonic inhibition mediated by astrocytic GABA release in the mouse model for ADHD remains unexplored. Therefore, we investigated the changes in the amount of GABA and degree of tonic inhibition in GIT1 KO mice. We observed a decreased glial GABA intensity in GIT1 KO mice compared to wild type (WT) mice and an attenuation of tonic current from cerebellar granule cells in GIT1 KO mice. Our study identifies the previously unknown mechanism of reduced astrocytic GABA and tonic inhibition in GIT1 lacking mice as a potential cause of hyperactivity disorder.
Animals ; Astrocytes ; Cerebellum* ; Child ; gamma-Aminobutyric Acid* ; Humans ; Mice* ; Neuroglia ; Neurons

PURPOSE: To improve the treatment efficiency of optic nerve diseases by delivering therapeutic materials to the optic nerve directly. METHODS: We tried to optimize liposomal composition to deliver a payload to the optic nerve efficiently when it is injected intravitreally. After loading dexamethasone into this liposome, we tested the therapeutic effect of liposomes in this treatment using a murine model of ischemic optic neuropathy. RESULTS: Our optimized liposome can deliver its payload to the optic nerve more efficiently than other tested compositions. Moreover, dexamethasone-loaded liposomes had a significant therapeutic effect in a murine model of ischemic optic neuropathy. CONCLUSIONS: Here, we demonstrate the optimal composition of liposomes that could efficiently deliver intravitreally injected exogenous compounds to the optic nerve. We expect that the intravitreal injection of liposomes with the suggested composition would improve the delivery efficacy of therapeutic compounds to the optic nerve.
Dexamethasone ; Intravitreal Injections* ; Liposomes* ; Optic Nerve Diseases ; Optic Nerve* ; Optic Neuropathy, Ischemic

Astrocytes are the most abundant cell type in the brain and they make close contacts with neurons and blood vessels. They respond dynamically to various environmental stimuli and change their morphological and functional properties. Both physiological and pathological stimuli can induce versatile changes in astrocytes, as this phenomenon is referred to as ‘astrocytic plasticity’. However, the molecular and cellular mechanisms of astrocytic plasticity in response to various stimuli remain elusive, except for the presence of hypertrophy, a conspicuous structural change which is frequently observed in activated or reactive astrocytes. Here, we investigated differential characteristics of astrocytic plasticity in a stimulus-dependent manner. Strikingly, a stab wound brain injury lead to hypertrophy of astrocytes accompanied by increased GABA expression and tonic GABA release in mouse CA1 hippocampus. In contrast, the mice experiencing enriched environment exhibited astrocytic hypertrophy with enhanced proBDNF immunoreactivity but without GABA signal. Based on the results, we define proBDNF-positive/GABA-negative hypertrophic astrocytes as ‘active’ astrocytes and GABA-positive hypertrophic astrocytes as ‘reactive’ astrocytes, respectively. We propose for the first time that astrocytic proBDNF can be a bona fide molecular marker of the active astrocytes, which are distinct from the reactive astrocytes which show hypertrophy but with aberrant GABA.
Animals ; Astrocytes* ; Blood Vessels ; Brain ; Brain Injuries ; Cell Plasticity ; gamma-Aminobutyric Acid* ; Hippocampus* ; Hypertrophy ; Mice ; Neurons ; Plastics ; Wounds and Injuries ; Wounds, Stab

PURPOSE: Children with asthma frequently have allergic rhinitis (AR) as a comorbidity. Asthmatic children with AR have a higher exhaled nitric oxide (eNO) level and bronchial hyperresponsiveness (BHR) than those without. The purpose of this study is to investigate the difference in lung function, eNO, and BHR between atopic asthma with and without AR, and the association of eNO and BHR with atopic intensity in total asthmatics. METHODS: We recruited 69 atopic asthmatic children with AR, 19 atopic asthmatic children without AR, 38 children with AR, and 43 nonatopic controls. We measured forced expiratory volume in one second (FEV1) and forced expiratory flow at 25% to 75% of forced vital capacity (FEF(25%-75%)), dose response slope (DRS) of bronchial challenge with methacholine and adenosine 5'-monophosphate (AMP), the levels of eNO, and the ratio of sum of allergen wheal diameter to histamine using skin prick tests. RESULTS: Atopic asthmatic children with AR had a higher eNO level compared to those without AR (P<0.05). However, there was no difference in FEV1 %predicted, FEF(25%-75%) %predicted, methacholine DRS, and AMP DRS between asthmatic children with and without AR. In total asthmatics, methacholine DRS and AMP DRS significantly correlated with eNO levels (r=0.338, P<0.001; r=0.365, P<0.001), but not with total IgE levels. However, eNO significantly correlated with total IgE levels (r=0.479, P<0.001). CONCLUSION: These results suggest that AR may enhance airway inflammation but may not lead to enhanced BHR in children with asthma.
Adenosine ; Asthma ; Bronchial Hyperreactivity ; Child* ; Comorbidity ; Forced Expiratory Volume ; Histamine ; Humans ; Immunoglobulin E ; Inflammation ; Lung ; Methacholine Chloride ; Nitric Oxide* ; Rhinitis* ; Skin ; Vital Capacity

Brain is a rich environment where neurons and glia interact with neighboring cells as well as extracellular matrix in three-dimensional (3D) space. Astrocytes, which are the most abundant cells in the mammalian brain, reside in 3D space and extend highly branched processes that form microdomains and contact synapses. It has been suggested that astrocytes cultured in 3D might be maintained in a less reactive state as compared to those growing in a traditional, two-dimensional (2D) monolayer culture. However, the functional characterization of the astrocytes in 3D culture has been lacking. Here we cocultured neurons and astrocytes in 3D and examined the morphological, molecular biological, and electrophysiological properties of the 3D-cultured hippocampal astrocytes. In our 3D neuron-astrocyte coculture, astrocytes showed a typical morphology of a small soma with many branches and exhibited a unique membrane property of passive conductance, more closely resembling their native in vivo counterparts. Moreover, we also induced reactive astrocytosis in culture by infecting with high-titer adenovirus to mimic pathophysiological conditions in vivo. Adenoviral infection induced morphological changes in astrocytes, increased passive conductance, and increased GABA content as well as tonic GABA release, which are characteristics of reactive gliosis. Together, our study presents a powerful in vitro model resembling both physiological and pathophysiological conditions in vivo, and thereby provides a versatile experimental tool for studying various neurological diseases that accompany reactive astrocytes.
Adenoviridae ; Astrocytes* ; Brain ; Carisoprodol ; Coculture Techniques ; Extracellular Matrix ; gamma-Aminobutyric Acid ; Gliosis ; In Vitro Techniques ; Membranes ; Neuroglia ; Neurons ; Synapses

The neuronal activity-dependent change in the manner in which light is absorbed or scattered in brain tissue is called the intrinsic optical signal (IOS), and provides label-free, minimally invasive, and high spatial (~100 µm) resolution imaging for visualizing neuronal activity patterns. IOS imaging in isolated brain slices measured at an infrared wavelength (>700 nm) has recently been attributed to the changes in light scattering and transmittance due to aquaporin-4 (AQP4)-dependent astrocytic swelling. The complexity of functional interactions between neurons and astrocytes, however, has prevented the elucidation of the series of molecular mechanisms leading to the generation of IOS. Here, we pharmacologically dissected the IOS in the acutely prepared brain slices of the stratum radiatum of the hippocampus, induced by 1 s/20 Hz electrical stimulation of Schaffer-collateral pathway with simultaneous measurement of the activity of the neuronal population by field potential recordings. We found that 55% of IOSs peak upon stimulation and originate from postsynaptic AMPA and NMDA receptors. The remaining originated from presynaptic action potentials and vesicle fusion. Mechanistically, the elevated extracellular glutamate and K⁺ during synaptic transmission were taken up by astrocytes via a glutamate transporter and quinine-sensitive K2P channel, followed by an influx of water via AQP-4. We also found that the decay of IOS is mediated by the DCPIB- and NPPB-sensitive anion channels in astrocytes. Altogether, our results demonstrate that the functional coupling between synaptic activity and astrocytic transient volume change during excitatory synaptic transmission is the major source of IOS.
Action Potentials ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; Amino Acid Transport System X-AG ; Astrocytes ; Brain ; Electric Stimulation ; Glutamic Acid ; Hippocampus ; Jupiter ; Neurons ; Receptors, N-Methyl-D-Aspartate ; Synaptic Transmission ; Water