A Preliminary Study on the Potential Protective Role of the Antioxidative Stress Markers of Cognitive Impairment: Glutathione and Glutathione Reductase.

Objective: : To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer's dementia and cognitive decline. Methods: : In all, 20 participants with Alzheimer's dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: : The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer's dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion: : The higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer's dementia and cognitive decline.

Changes in inflammatory and immune drivers in response to immunomodulatory therapies in COVID-19

As the global community strives to discover effective therapies for COVID-19, immunomodulatory strategies have emerged as a leading contender to combat the cytokine storm and improve clinical outcomes in patients with severe disease. Systemic corticosteroids and selective cytokine inhibitory agents have been utilized both as empiric therapies and in clinical trials. While multiple randomized, placebo controlled trials have now demonstrated that corticosteroids improve survival in patients with COVID-19,1, 2 IL-6 inhibition, which gained significant early interest based on observational studies, has not demonstrated reliable efficacy in randomized, placebo controlled trials.3, 4 To better understand the mechanistic basis of immunomodulatory therapies being implemented for treatment of COVID-19, we assessed longitudinal biochemical changes in response to such approaches in hospitalized patients with COVID-19. We demonstrate broad suppression of multiple immunomodulatory factors associated with adverse clinical outcomes in COVID-19 in patients who received corticosteroids, but no such response was seen in patients who either received tocilizumab or no immunomodulatory therapy. Our findings provide early insights into molecular signatures that correlate with immunomodulatory therapies in COVID-19 which may be useful in understanding clinical outcomes in future studies of larger patient cohorts.

A neutrophil activation signature predicts critical illness and mortality in COVID-19

Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of over 3,300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, HGF, IL-8, and G-CSF, as the strongest predictors of critical illness. Neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, we define an essential role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular neutrophil markers that distinguish patients at risk of future clinical decompensation.

Protectin DX suppresses hepatic gluconeogenesis through AMPK-HO-1-mediated inhibition of ER stress.

Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6. We found that PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation, thereby inducing heme oxygenase 1 (HO-1) expression. This induction blocked hepatic gluconeogenesis by suppressing endoplasmic reticulum (ER) stress in hepatocytes under hyperlipidemic conditions. These effects were significantly dampened by silencing AMPK or HO-1 expression with small interfering RNA (siRNA). We also demonstrated that administration of PDX to high fat diet (HFD)-fed mice resulted in increased hepatic AMPK phosphorylation and HO-1 expression, whereas hepatic ER stress was substantially attenuated. Furthermore, PDX treatment suppressed the expression of gluconeogenic genes, thereby decreasing blood glucose levels in HFD-fed mice. In conclusion, our findings suggest that PDX inhibits hepatic gluconeogenesis via AMPK-HO-1-dependent suppression of ER stress. Thus, PDX may be an effective therapeutic target for the treatment of insulin resistance and type 2 diabetes through the regulation of hepatic gluconeogenesis.

Brain Activation Evoked by Sensory Stimulation in Patients with Spinal Cord Injury : Functional Magnetic Resonance Imaging Correlations with Clinical Features.

OBJECTIVE: The purpose of this study is to determine whether the changes of contralateral sensorimotor cortical activation on functional magnetic resonance imaging (fMRI) can predict the neurological outcome among spinal cord injury (SCI) patients when the great toes are stimulated without notice. METHODS: This study enrolled a total of 49 patients with SCI and investigated each patient's preoperative fMRI, postoperative fMRI, American Spinal Injury Association (ASIA) score, and neuropathic pain occurrence. Patients were classified into 3 groups according to the change of blood oxygenation level dependent (BOLD) response on perioperative fMRI during proprioceptive stimulation with repetitive passive toe movements : 1) patients with a response of contralateral sensorimotor cortical activation in fMRI were categorized; 2) patients with a response in other regions; and 3) patients with no response. Correlation between the result of fMRI and each parameter was analyzed. RESULTS: In fMRI data, ASIA score was likely to show greater improvement in patients in group A compared to those belonging to group B or C (p<0.001). No statistical significance was observed between the result of fMRI and neuropathic pain (p=0.709). However, increase in neuropathic pain in response to the signal change of the ipsilateral frontal lobe on fMRI was statistically significant (p=0.030). CONCLUSION: When there was change of BOLD response at the contralateral sensorimotor cortex on perioperative fMRI after surgery, relief of neurological symptoms was highly likely for traumatic SCI patients. In addition, development of neuropathic pain was likely to occur when there was change of BOLD response at ipsilateral frontal lobe.

Grisel's Syndrome Induced by Mycobacterium tuberculosis.

Grisel's syndrome is a non-traumatic subluxation of the atlantoaxial joints, which is caused by an inflammatory process in the upper neck. It is rare to find literary reports of Grisel's syndrome with an evident pathogen in a lesion. For the first time in Korea, we report a 36-year-old female with Grisel's syndrome having an atlantoaxial subluxation, which was caused by a retropharyngeal abscess secondary to pulmonary Mycobacterium tuberculosis. The patient was treated with an anti-tuberculosis regimen and was prescribed a Philadelphia collar for the control of torticollis. The result of magnetic resonance imaging (MRI) showed an improved atlantoaxial alignment, after drug treatment and immobilization. This patient was neurologically intact and free from symptomatic complaints at follow-up visit. Dynamic cervical radiograph confirmed that the atlantoaxial joints had been stable. The pathophysiology of Grisel's syndrome, along with anatomical attributes, was explained on the basis of the patient's clinical course.

Gintonin stimulates gliotransmitter release in cortical primary astrocytes.

Lysophosphatidic acid (LPA) is a simple and minor phospholipid, but serves as a lipid-derived neurotransmitter via activation of G protein-coupled LPA receptors. Astrocytes abundantly express LPA receptors and contain gliotransmitters that modulate astrocyte-neuron interactions. Gintonin is a novel ginseng-derived G protein-coupled LPA receptor ligand. Gintonin induces [Ca(2+)]i transients in neuronal and non-neuronal cells via activation of LPA receptors, which regulate calcium-dependent ion channels and receptors. A line of evidence shows that neurotransmitter-mediated [Ca(2+)]i elevations in astrocytes are coupled with gliotransmitter release. However, little is known about whether gintonin-mediated [Ca(2+)]i transients are coupled to gliotransmitter release in astrocytes. In the present study, we examined the effects of gintonin on adenosine triphosphate (ATP) and glutamate release in mouse cortical primary astrocytes. Application of gintonin to astrocytes induced [Ca(2+)]i transients in a concentration-dependent and reversible manner. However, ginsenosides, other active ingredients in ginseng, had no effect on [Ca(2+)]i transients. The induction of gintonin-mediated [Ca(2+)]i transients was attenuated/blocked by the LPA1/3 receptor antagonist Ki16425, a phospholipase C inhibitor, an inositol 1,4,5-triphosphate receptor antagonist, and an intracellular Ca(2+) chelator. Gintonin treatment on astrocytes increased ATP and glutamate release in a concentration- and time-dependent manner. BAPTA and Ki16425 attenuated gintonin-mediated ATP and glutamate release in astrocytes. The present study shows that gintonin-mediated [Ca(2+)]i transients are coupled to gliotransmitter release via LPA receptor activation. Finally, gintonin-mediated [Ca(2+)]i transients and gliotransmitter release from astrocytes via LPA receptor activation might explain one mechanism of gintonin-mediated neuromodulation in the central nervous system.

Internal Fixation Using Clavicle Hook Plates for Distal Clavicle Fractures

BACKGROUND: To report the radiological and clinical outcomes of internal fixation using distal clavicle hook plates for distal clavicle fractures. METHODS: From April 2008 to December 2012, 32 patients with distal clavicle fractures underwent surgery using an AO hook plate. The reduction was qualified and evaluated according to the radiological findings. The evaluation of the clinical outcomes was performed with the University of California at Los Angeles (UCLA) score, the Korean Shoulder score, and the visual analogue scale (VAS) pain score. RESULTS: By radiological evaluation, we found that 31 of 32 patients showed anatomical reduction and solid bone union. Although we obtained satisfactory UCLA scores, Korean Shoulder Scale scores, and VAS pain scores, 12 cases of complications were present. We found 4 cases of osteolysis of the acromion, 1 case of nonunion, 3 cases of periprosthetic fractures, 3 cases of subacromial pain, and 1 case of skin irritation. We performed re-operations in 2 patients. CONCLUSIONS: To avoid complications associated with clavicle hook plates, choosing the appropriate hook size and bending of the hook according to the slope of the acromion undersurface is critical. Also, we believe that early removal of clavicle plates may help reduce complications.

Internal Fixation Using Clavicle Hook Plates for Distal Clavicle Fractures

BACKGROUND: To report the radiological and clinical outcomes of internal fixation using distal clavicle hook plates for distal clavicle fractures. METHODS: From April 2008 to December 2012, 32 patients with distal clavicle fractures underwent surgery using an AO hook plate. The reduction was qualified and evaluated according to the radiological findings. The evaluation of the clinical outcomes was performed with the University of California at Los Angeles (UCLA) score, the Korean Shoulder score, and the visual analogue scale (VAS) pain score. RESULTS: By radiological evaluation, we found that 31 of 32 patients showed anatomical reduction and solid bone union. Although we obtained satisfactory UCLA scores, Korean Shoulder Scale scores, and VAS pain scores, 12 cases of complications were present. We found 4 cases of osteolysis of the acromion, 1 case of nonunion, 3 cases of periprosthetic fractures, 3 cases of subacromial pain, and 1 case of skin irritation. We performed re-operations in 2 patients. CONCLUSIONS: To avoid complications associated with clavicle hook plates, choosing the appropriate hook size and bending of the hook according to the slope of the acromion undersurface is critical. Also, we believe that early removal of clavicle plates may help reduce complications.

Grisel's Syndrome Induced by Mycobacterium tuberculosis

Grisel's syndrome is a non-traumatic subluxation of the atlantoaxial joints, which is caused by an inflammatory process in the upper neck. It is rare to find literary reports of Grisel's syndrome with an evident pathogen in a lesion. For the first time in Korea, we report a 36-year-old female with Grisel's syndrome having an atlantoaxial subluxation, which was caused by a retropharyngeal abscess secondary to pulmonary Mycobacterium tuberculosis. The patient was treated with an anti-tuberculosis regimen and was prescribed a Philadelphia collar for the control of torticollis. The result of magnetic resonance imaging (MRI) showed an improved atlantoaxial alignment, after drug treatment and immobilization. This patient was neurologically intact and free from symptomatic complaints at follow-up visit. Dynamic cervical radiograph confirmed that the atlantoaxial joints had been stable. The pathophysiology of Grisel's syndrome, along with anatomical attributes, was explained on the basis of the patient's clinical course.

Brain Activation Evoked by Sensory Stimulation in Patients with Spinal Cord Injury : Functional Magnetic Resonance Imaging Correlations with Clinical Features

OBJECTIVE: The purpose of this study is to determine whether the changes of contralateral sensorimotor cortical activation on functional magnetic resonance imaging (fMRI) can predict the neurological outcome among spinal cord injury (SCI) patients when the great toes are stimulated without notice. METHODS: This study enrolled a total of 49 patients with SCI and investigated each patient's preoperative fMRI, postoperative fMRI, American Spinal Injury Association (ASIA) score, and neuropathic pain occurrence. Patients were classified into 3 groups according to the change of blood oxygenation level dependent (BOLD) response on perioperative fMRI during proprioceptive stimulation with repetitive passive toe movements : 1) patients with a response of contralateral sensorimotor cortical activation in fMRI were categorized; 2) patients with a response in other regions; and 3) patients with no response. Correlation between the result of fMRI and each parameter was analyzed. RESULTS: In fMRI data, ASIA score was likely to show greater improvement in patients in group A compared to those belonging to group B or C (p<0.001). No statistical significance was observed between the result of fMRI and neuropathic pain (p=0.709). However, increase in neuropathic pain in response to the signal change of the ipsilateral frontal lobe on fMRI was statistically significant (p=0.030). CONCLUSION: When there was change of BOLD response at the contralateral sensorimotor cortex on perioperative fMRI after surgery, relief of neurological symptoms was highly likely for traumatic SCI patients. In addition, development of neuropathic pain was likely to occur when there was change of BOLD response at ipsilateral frontal lobe.

Resveratrol inhibits glycine receptor-mediated ion currents.

Resveratrol is found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-nociceptive, and life-prolonging effects. However, the single cellular mechanisms by which resveratrol acts are relatively unknown, especially in terms of possible regulation of receptors involved in synaptic transmission. The glycine receptor is an inhibitory ligand-gated ion channel involved in fast synaptic transmission in spinal cord. In the present study, we investigated the effect of resveratrol on human glycine receptor channel activity. Glycine α1 receptors were expressed in Xenopus oocytes and glycine receptor channel activity was measured using a two-electrode voltage clamp technique. Treatment with resveratrol alone had no effect on oocytes injected with H2O or on oocytes injected with glycine α1 receptor cRNA. In the oocytes injected with glycine α1 receptor cRNA, co- or pre-treatment of resveratrol with glycine inhibited the glycine-induced inward peak current (IGly) in a reversible manner. The inhibitory effect of resveratrol on IGly was also concentration dependent, voltage independent, and non-competitive. These results indicate that resveratrol regulates glycine receptor channel activity and that resveratrol-mediated regulation of glycine receptor channel activity is one of several cellular action mechanisms of resveratrol for pain regulation.

Comparison of the Effects on Dynamic Balance Ability of Warming up in Water Versus on the Ground.

[Purpose] This research was designed to find out how the so-called "dynamic balance" is affected by doing different types of warm up exercises. In particular, the research is focused on the difference in the effect on dynamic Balance of warming up in water versus on the ground. [Subjects and Methods] Twenty healthy adults were the subjects of this study, with 10 people assigned each to two groups, one warming up in water and another warming up on the ground. The dynamic balance was measured for all subjects before the warming up. The group warming up on the ground conducted active stretching on the ground, and the group warming up in water conducted stretching in water by using water as resistance. [Results] The results indicate that warming up in water has a more powerful effect on a subject's dynamic balance than warming up on the ground. [Conclusion] The group warming up in water, who made use of the viscosity and flow of the water, showed better balance than the group warming up on the ground. Warming up in water, which entails an element of resistance, should be implemented in warm-up routines in the future.

Effects on hamstring muscle extensibility, muscle activity, and balance of different stretching techniques.

[Purpose] The purpose of this study was to investigate the effects of two different stretching techniques on range of motion (ROM), muscle activation, and balance. [Subjects] For the present study, 48 adults with hamstring muscle tightness were recruited and randomly divided into three groups: a static stretching group (n=16), a PNF stretching group (n=16), a control group (n=16). [Methods] Both of the stretching techniques were applied to the hamstring once. Active knee extension angle, muscle activation during maximum voluntary isometric contraction (MVC), and static balance were measured before and after the application of each stretching technique. [Results] Both the static stretching and the PNF stretching groups showed significant increases in knee extension angle compared to the control group. However, there were no significant differences in muscle activation or balance between the groups. [Conclusion] Static stretching and PNF stretching techniques improved ROM without decrease in muscle activation, but neither of them exerted statistically significant effects on balance.

Peroneus Tendon Dislocation Associated with Fracture of Lateral Process of Talus: A Case Report

Traumatic peroneal tendon dislocation in association with fracture of the lateral process of the talus is a rare injury, which is difficult to diagnose. As a result, early detection is often delayed, which in turn leads to ankle pain and dysfunction. We treated a patient by open reduction and screw fixation in fracture of the lateral process of talus and primary repair of the superior peroneal retinaculum. We report this case with a brief review of the literature.

Improvement in sensory function via granulocyte-macrophage colony-stimulating factor in rat spinal cord injury models.

OBJECT: The aim in this study was to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) leads to sensory improvement in rat spinal cord injury (SCI) models. METHODS: Thirty male Sprague-Dawley rats were included in this study: 10 in the sham group (laminectomy alone without SCI), 10 in the SCI group (SCI treated with phosphate-buffered saline), and 10 in the GM-CSF treatment group (SCI treated with GM-CSF). A locomotor function test and pain sensitivity test were conducted weekly for 9 weeks after SCI or sham injury. Spinal tissue samples from all rats were immunohistochemically examined for the expression of calcitonin gene-related peptide (CGRP) and abnormal sprouting at Week 9 post-SCI. RESULTS: Granulocyte-macrophage colony-stimulating factor treatment improves functional recovery after SCI. In the tactile withdrawal threshold and frequency of the hindlimb paw, the GM-CSF group always responded with a statistically significant lower threshold than the SCI group 9 weeks after SCI (p < 0.05). The response of the forelimb and hindlimb paws to cold in the GM-CSF group always reflected a statistically significant lower threshold than in the SCI group 9 weeks after injury (p < 0.05). Decreased CGRP expression, observed by density and distribution area, was noted in the GM-CSF group (optical density 113.5 ± 20.4) compared with the SCI group (optical density 143.1 ± 18.7; p < 0.05). CONCLUSIONS: Treatment with GM-CSF results in functional recovery, improving tactile and cold sense recovery in a rat SCI model. Granulocyte-macrophage colony-stimulating factor also minimizes abnormal sprouting of sensory nerves after SCI.

Polarus Intramedullary Nail for Proximal Humeral and Humeral Shaft Fractures in Elderly Patients with Osteoporosis

PURPOSE: To assess the effectiveness of optimal treatment of proximal humeral fractures and humeral shaft fractures in elderly patients with osteoporosis using the Polarus nail. MATERIALS AND METHODS: Twenty-three patients with proximal humeral and humeral shaft fractures in elderly osteoporosis patients were treated using the Polarus intramedullary nail. Nine patients had proximal humeral fracture, 10 had humeral shaft fracture and 4 had the proximal humeral frac-ture extended diaphyseally. Radiological outcomes included the bone-union and the degree of re-sidual deformity. The residual deformities of the proximal humerus were assessed by the neck-shaft angle and the shaft angulation. Clinical outcome was assessed with the American Shoulder and Elbow Surgeons (ASES) score. RESULTS: All cases had bony union and the mean union period was 16.5 weeks. The average neck/shaft alignment at the time of bone union was 135degrees and varus deformities of neck-shaft angle was not seen in all patients. Varus shaft angulation was seen in 5 patients. The mean ASES score after surgery was 86.7 points. CONCLUSION: The Polarus intramedullary nail is effective for the treatment of proximal humeral and humeral shaft fractures in elderly patients with osteoporosis because it not only enables early postoperative mobilization, but also obtains bone-union without avascular necrosis and nonunion.

The prophylactic effects of gabapentin on postoperative sore throat after thyroid surgery / 대한마취과학회지

BACKGROUND: Postoperative sore throat (POST) is considered a usual complication after tracheal intubation, especially, thyroid surgery. Gabapentin is a widely studied multimodal perioperative drug, which can be used to treat acute postoperative pain. The primary endpoints of this study was a reduction of the incidence of POST at rest and during the swallowing movements after thyroid surgery. And the second endpoints was a reduction of the intensity of the POST after thyroid surgery. METHODS: Seventy-one patients that underwent elective thyroid surgery received either gabapentin (Neurontin(TM) 600 mg) or placebo, orally, one hour before anesthesia. The VAS scores and incidences of POST and adverse effects were determined at 1 hr, 6 hr, 12 hr, and 24 hr after surgery at rest and during swallowing movement. RESULTS: The gabapentin group (N = 36) showed a lower incidence of POST than the placebo group (N = 35) (47% vs. 78%, P = 0.038), and had significant lower VAS score at 6 and 24 hours after surgery in the resting state. However, during the movement, no intergroup differences were found in terms of the incidence of POST (83% vs. 91%, P = 0.305) or VAS score. Furthermore, no significant difference was observed between the two groups, in adverse effects. CONCLUSIONS: Gabapentin (Neurontin(TM) 600 mg) administered 1 hr before anesthesia reduced the intensity and incidence of POST during the resting state without a significant adverse event, during the 24 hr after thyroid surgery. However, gabapentin did not reduce the intensity and incidence of POST during the swallowing movement.

Superficial Siderosis in Central Nervous System: A Case Report and Literature Review / 대한신경손상학회지

Superficial siderosis (SS) in central nervous system is a rare, slowly progressive disease and usually misdiagnosed or diagnosed too late when the patient is chronically devastated. A 55-year-old man with deafness and gait disturbance for ten years was referred from otorhinologist for evaluation of brain. Magnetic resonance image (MRI) showed symmetric hypointense rim partially delineated the bilateral hemisphere on gradient-recalled-echo T2-weighted image, and it was diagnosed as hemosiderin deposition in subarachnoid and subpial meningeal layer. The correct diagnosis of cerebral superficial siderosis can be achieved by careful neurological examination and MRI because computed tomography findings and symptoms are ambiguous. Serial follow-up of imaging study and education for patient are necessary to prevent progression of SS.

Superficial Siderosis in Central Nervous System: A Case Report and Literature Review / 대한신경손상학회지

Superficial siderosis (SS) in central nervous system is a rare, slowly progressive disease and usually misdiagnosed or diagnosed too late when the patient is chronically devastated. A 55-year-old man with deafness and gait disturbance for ten years was referred from otorhinologist for evaluation of brain. Magnetic resonance image (MRI) showed symmetric hypointense rim partially delineated the bilateral hemisphere on gradient-recalled-echo T2-weighted image, and it was diagnosed as hemosiderin deposition in subarachnoid and subpial meningeal layer. The correct diagnosis of cerebral superficial siderosis can be achieved by careful neurological examination and MRI because computed tomography findings and symptoms are ambiguous. Serial follow-up of imaging study and education for patient are necessary to prevent progression of SS.