Cutibacterium acnes, a commensal, lipophilic, anaerobic Gram-positive bacterium, is well known for its potential to cause infections, particularly in the field of orthopedics, notably in the shoulder. However, its indolent strain nature presents challenges in the diagnosis of the bacterium using clinical, laboratory, and culture-based methods. There are controversies surrounding its actual threat as an infection-causing agent, leading to an incomplete consensus on treatment strategies after the infection. Furthermore, research is ongoing to explore preventive procedures before the onset of infection. This review aimed to comprehensively explore the diagnosis and treatment of C. acnes and determine whether it is a risk factor for shoulder joint infections.

Cutibacterium acnes, a commensal, lipophilic, anaerobic Gram-positive bacterium, is well known for its potential to cause infections, particularly in the field of orthopedics, notably in the shoulder. However, its indolent strain nature presents challenges in the diagnosis of the bacterium using clinical, laboratory, and culture-based methods. There are controversies surrounding its actual threat as an infection-causing agent, leading to an incomplete consensus on treatment strategies after the infection. Furthermore, research is ongoing to explore preventive procedures before the onset of infection. This review aimed to comprehensively explore the diagnosis and treatment of C. acnes and determine whether it is a risk factor for shoulder joint infections.

Cutibacterium acnes, a commensal, lipophilic, anaerobic Gram-positive bacterium, is well known for its potential to cause infections, particularly in the field of orthopedics, notably in the shoulder. However, its indolent strain nature presents challenges in the diagnosis of the bacterium using clinical, laboratory, and culture-based methods. There are controversies surrounding its actual threat as an infection-causing agent, leading to an incomplete consensus on treatment strategies after the infection. Furthermore, research is ongoing to explore preventive procedures before the onset of infection. This review aimed to comprehensively explore the diagnosis and treatment of C. acnes and determine whether it is a risk factor for shoulder joint infections.

Cutibacterium acnes, a commensal, lipophilic, anaerobic Gram-positive bacterium, is well known for its potential to cause infections, particularly in the field of orthopedics, notably in the shoulder. However, its indolent strain nature presents challenges in the diagnosis of the bacterium using clinical, laboratory, and culture-based methods. There are controversies surrounding its actual threat as an infection-causing agent, leading to an incomplete consensus on treatment strategies after the infection. Furthermore, research is ongoing to explore preventive procedures before the onset of infection. This review aimed to comprehensively explore the diagnosis and treatment of C. acnes and determine whether it is a risk factor for shoulder joint infections.

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.

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

In the brain, a reduction in extracellular osmolality causes water-influx and swelling, which subsequently triggers Cl⁻- and osmolytes-efflux via volume-regulated anion channel (VRAC). Although LRRC8 family has been recently proposed as the pore-forming VRAC which is activated by low cytoplasmic ionic strength but not by swelling, the molecular identity of the pore-forming swelling-dependent VRAC (VRAC(swell)) remains unclear. Here we identify and characterize Tweety-homologs (TTYH1, TTYH2, TTYH3) as the major VRAC(swell) in astrocytes. Gene-silencing of all Ttyh1/2/3 eliminated hypo-osmotic-solution-induced Cl⁻ conductance (I(Cl,swell)) in cultured and hippocampal astrocytes. When heterologously expressed in HEK293T or CHO-K1 cells, each TTYH isoform showed a significant I(Cl,swell) with similar aquaporin-4 dependency, pharmacological properties and glutamate permeability as I(Cl,swell) observed in native astrocytes. Mutagenesis-based structure-activity analysis revealed that positively charged arginine residue at 165 in TTYH1 and 164 in TTYH2 is critical for the formation of the channel-pore. Our results demonstrate that TTYH family confers the bona fide VRAC(swell) in the brain.
Arginine ; Astrocytes ; Brain ; Cytoplasm ; Glutamic Acid ; Humans ; Osmolar Concentration ; Permeability

3-Carene, a bicyclic monoterpene, is one of the major components of the pine tree essential oils. It has been reported that, in addition to its known properties as a phytoncide, 3-carene has anti-inflammatory, antimicrobial, and anxiolytic effects. We have previously demonstrated that α-pinene, the major component of pine tree, has a hypnotic effect through GABA(A)-benzodiazepine (BZD) receptors. However, a hypnotic effect of 3-carene has not been studied yet. Here, we report that oral administration of 3-carene increases the sleep duration and reduces sleep latency in pentobarbital-induced sleep test. 3-Carene potentiates the GABA(A) receptor-mediated synaptic responses by prolonging the decay time constant of inhibitory synaptic responses. These enhancing effects of 3-carene are reproduced by zolpidem, a modulator for GABA(A)-BZD receptor, and fully inhibited by flumazenil, an antagonist for GABA(A)-BZD receptor. The molecular docking of 3-carene to the BZD site of GABA(A) protein structure, suggests that 3-carene binds to the BZD site of α1 and ϒ2 subunits of GABA(A)-BZD receptor. These results indicate that, similar to α-pinene, 3-carene shows a sleep-enhancing effect by acting as a positive modulator for GABA(A)-BZD receptor.
Administration, Oral ; Anti-Anxiety Agents ; Flumazenil ; Hypnotics and Sedatives ; Oils, Volatile ; Pinus

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

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*