PURPOSE: In this study, porous type I collagen scaffolds were cross-linked using dehydrothermal(DHT) treatment and/or 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide(EDC), in the presence and absence of chondroitin-6-sulfate(CS) and cultured autologous chondrocytes(Chondro) for cartilage regeneration. METHODS: Cartilage defects were created in the proximal part of the ear of New Zealand rabbits. Four prepared types of scaffolds(n=4) were inserted. The groups included Chondro-Collagen-DHT(Group 1), Chondro- Collagen-DHT-EDC(Group 2), Chondro-CS-Collagen- DHT(Group 3), and Chondro-CS-Collagen-DHT-EDC (Group 4). Histomorphometric analysis and cartilage- specific gene expression of the reconstructed tissues were evaluated 4, 8, and 12 weeks after implantation . RESULTS: EDC cross-linked groups 2 and 4 regenerated more cartilage than other groups. However, calcification was observed in the 4th week after implantation. CS did not increase chondrogenesis in all groups. Cartilage-specific type II collagen mRNA expression increased in the course of time in all groups. CONCLUSION: EDC cross-linking methods maintain the scaffold and promote extracellular matrix production of chondrocytes.
Cartilage* ; Chondrocytes ; Chondrogenesis ; Chondroitin Sulfates ; Collagen Type I* ; Collagen Type II ; Ear ; Extracellular Matrix ; Gene Expression ; Rabbits ; Regeneration* ; RNA, Messenger

Dementia pugilistica (DP) or chronic traumatic encephalopathy (CTE) is a neurodegenerative disease or dementia that may affect amateur or professional boxers as well as athletes in other sports who suffer concussions. The condition is thought to affect around 15% to 20% of professional boxers and caused by repeated concussive or subconcussive blows. CTE was in the past referred to as dementia pugilistica, which reflected the prevailing notion that this condition was restricted to boxers. Recent research, however, has demonstrated neuropathological evidence of CTE in retired American football players, a professional wrestler, a professional hockey player and a soccer player, as well as in nonathletes. It is probable that many individuals are susceptible to CTE, including those who experience falls, motor vehicle accidents, assaults, epileptic seizures, or military combat, and that repeated mild closed head trauma of diverse origin is capable of instigating the neurodegenerative cascade leading to CTE. We report a 62-year old man suspicious of dementia pugilistica with clinical features of frontotemporal dementia and parkinsonism.
Athletes ; Brain Injury, Chronic ; Dementia ; Epilepsy ; Football ; Frontotemporal Dementia ; Head Injuries, Closed ; Hockey ; Humans ; Military Personnel ; Motor Vehicles ; Neurodegenerative Diseases ; Parkinsonian Disorders ; Soccer ; Sports

Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway.
Animals ; Apoptosis* ; Calcium ; Calcium Channel Blockers ; Caspase 3 ; Diltiazem ; Dizocilpine Maleate ; In Situ Nick-End Labeling ; MAP Kinase Signaling System* ; N-Methylaspartate ; Neurodegenerative Diseases ; Neurons* ; Neuroprotection ; Nifedipine ; Plants, Edible ; Rats

Objectives: Our study aimed to present the distinctive correlates of formal thought disorder in patients with schizophrenia, using the Clinical Language Disorder Rating Scale (CLANG). Methods: We compared clinical characteristics between schizophrenia patients with (n = 84) and without (n = 82) formal thought disorder. Psychometric scales including the CLANG, the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS), the Calgery Depression Scale for Schizophrenia (CDSS) and the Word Fluency Test (WFT) were used. Results: After adjusting the effects of age, sex and total scores on the BPRS, YMRS and WFT, the subjects with disorganized speech presented significantly higher score on the abnormal syntax (p = 0.009), lack of semantic association (p = 0.005), discourse failure (p < 0.0001), pragmatics disorder (p = 0.001), dysarthria (p < 0.0001), and paraphasic error (p = 0.005) items than those without formal thought disorder. With defining the mentioned item scores as covariates, binary logistic regression model predicted that discourse failure (adjusted odds ratio [aOR] = 5.88, p < 0.0001) and pragmatics disorder (aOR = 2.17, p = 0.04) were distinctive correlates of formal thought disorder in patients with schizophrenia. Conclusions This study conducted Clinician Rated Dimensions of Psychosis Symptom Severity (CRDPSS) and CLANG scales on 166 hospitalized schizophrenia patients to explore the sub-items of the CLANG scale independently related to formal thought disorders in schizophrenia patients. Discourse failure and pragmatics disorder might be used as the distinctive indexes for formal thought disorder in patients with schizophrenia.

PURPOSE: For a single time-point hyperpolarized 13C magnetic resonance spectroscopy imaging (MRSI) of animal models, scan-time window after injecting substrates is critical in terms of signal-to-noise ratio (SNR) of downstream metabolites. Prescans of time-resolved magnetic resonance spectroscopy (MRS) can be performed to determine the scan-time window. In this study, based on two-site exchange model, protocol-specific simulation approaches were developed for 13C MRSI and the optimal scan-time window was determined to maximize the SNR of downstream metabolites. MATERIALS AND METHODS: The arterial input function and conversion rate constant from injected substrates (pyruvate) to downstream metabolite (lactate) were precalibrated, based on pre-scans of time-resolved MRS. MRSI was simulated using twosite exchange model with considerations of scan parameters of MRSI. Optimal scantime window for mapping lactate was chosen from simulated lactate intensity maps. The performance was validated by multiple in vivo experiments of BALB/C nude mice with MDA-MB-231 breast tumor cells. As a comparison, MRSI were performed with other scan-time windows simply chosen from the lactate signal intensities of prescan time-resolved MRS. RESULTS: The optimal scan timing for our animal models was determined by simulation, and was found to be 15 s after injection of the pyruvate. Compared to the simple approach, we observed that the lactate peak signal to noise ratio (PSNR) was increased by 230%. CONCLUSIONS: Optimal scan timing to measure downstream metabolites using hyperpolarized 13C MRSI can be determined by the proposed protocol-specific simulation approaches.
Animals ; Breast Neoplasms ; Lactic Acid ; Magnetic Resonance Spectroscopy ; Mice ; Mice, Nude ; Models, Animal ; Pyruvic Acid ; Signal-To-Noise Ratio

PURPOSE: Clostridium difficile (C. difficile) is an important cause of nosocomial diarrhea. Diagnostic methods for detection of C. difficile infection (CDI) are shifting to molecular techniques, which are faster and more sensitive than conventional methods. Although recent advances in these methods have been made in terms of their cost-benefit, ease of use, and turnaround time, anaerobic culture remains an important method for detection of CDI. MATERIALS AND METHODS: In efforts to evaluate a novel chromogenic medium for the detection of C. difficile (chromID CD agar), 289 fecal specimens were analyzed using two other culture media of blood agar and cycloserine-cefoxitin-fructose-egg yolk agar while enzyme immunosorbent assay and polymerase chain reaction-based assay were used for toxin detection. RESULTS: ChromID showed the highest detection rate among the three culture media. Both positive rate and sensitivity were higher from chromID than other culture media. ChromID was better at detecting toxin producing C. difficile at 24 h and showed the highest detection rate at both 24 h and 48 h. CONCLUSION: Simultaneous use of toxin assay and anaerobic culture has been considered as the most accurate and sensitive diagnostic approach of CDI. Utilization of a more rapid and sensitive chromogenic medium will aid in the dianogsis of CDI.
Chromogenic Compounds/chemistry ; Clostridium difficile/chemistry/*isolation & purification ; Culture Media/*chemistry

BACKGROUND/AIMS: It remains unclear whether atrophic gastritis can affect dyspeptic symptoms. We aimed to investigate whether the extent of atrophic gastritis is associated with specific dyspeptic symptoms. METHODS: Consecutive adults in a routine health-checkup program were enrolled in the study. The extent of atrophic gastritis was classified into 3 groups based on the Kimura-Takemoto criteria; the gastritis with no or little atrophy (group A: C0), the gastritis with atrophy mainly in the antrum (group B: C1 and C2), and the gastritis with atrophy in the large area of the corpus (group C: C3 and O). Upper gastrointestinal symptoms were categorized into "typical reflux symptoms," "epigastric pain syndrome (EPS)-related symptoms," and "postprandial distress syndrome (PDS)-related symptoms." RESULTS: A total of 1827 patients (1009 males, mean age 45.1 years) were included in the analysis. The subgroups of atrophic gastritis were as follows: group A (n = 1218, 66.7%), group B (n = 392, 21.4%), and group C (n = 217, 11.9%). Typical reflux, EPS-related, and PDS-related symptoms were present in 10.5%, 19.8%, and 16.2% of the subjects, respectively. PDS-related and EPS-related symptoms were significantly more prevalent in the group C of male patients and the group B of female patients, respectively, compared with other groups. PDS-related and EPS-related symptoms were independently associated with the group C in males (OR, 2.123; 95% CI, 1.090-4.136) and the group B in females (OR, 2.571; 95% CI, 1.319-5.025), respectively. CONCLUSIONS: The extent of atrophic gastritis appears to affect the generation of specific dyspeptic symptoms in a gender-dependent manner.
Adult ; Atrophy ; Dyspepsia ; Female ; Gastritis ; Gastritis, Atrophic* ; Humans ; Male

PURPOSE: To investigate the exchange and redistribution of hyperpolarized ¹³C metabolites between different pools by temporally analyzing the relative fraction of dual T₂* components of hyperpolarized ¹³C metabolites. MATERIALS AND METHODS: A dual exponential decay analysis of T₂* is performed for [1-¹³C] pyruvate and [1-¹³C] lactate using nonspatially resolved dynamic ¹³C MR spectroscopy from mice brains with tumors (n = 3) and without (n = 4) tumors. The values of shorter and longer T₂* components are explored when fitted from averaged spectrum and temporal variations of their fractions. RESULTS: The T₂* values were not significantly different between the tumor and control groups, but the fraction of longer T₂* [1-¹³C] lactate components was more than 10% in the tumor group over that of the controls (P < 0.1). The fraction of shorter T₂* components of [1-¹³C] pyruvate showed an increasing tendency while that of the [1-¹³C] lactate was decreasing over time. The slopes of the changing fraction were steeper for the tumor group than the controls, especially for lactate (P < 0.01). In both pyruvate and lactate, the fraction of the shorter T₂* component was always greater than the longer T₂* component over time. CONCLUSIONS: The exchange and redistribution of pyruvate and lactate between different pools was investigated by dual component analysis of the free induction decay signal from hyperpolarized ¹³C experiments. Tumor and control groups showed differences in their fractions rather than the values of longer and shorter T₂* components. Fraction changing dynamics may provide an aspect for extravasation and membrane transport of pyruvate and lactate, and will be useful to determine the appropriate time window for acquisition of hyperpolarized ¹³C images.
Animals ; Brain ; Lactic Acid ; Magnetic Resonance Spectroscopy ; Membranes ; Mice ; Pyruvic Acid

Objective: This study aimed to investigate the blood-brain barrier (BBB) disruption in mild traumatic brain injury (mTBI) patients with post-concussion syndrome (PCS) using dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and automatic whole brain segmentation. Materials and Methods: Forty-two consecutive mTBI patients with PCS who had undergone post-traumatic MR imaging, including DCE MR imaging, between October 2016 and April 2018, and 29 controls with DCE MR imaging were included in this retrospective study. After performing three-dimensional T1-based brain segmentation with FreeSurfer software (Laboratory for Computational Neuroimaging), the mean Ktrans and vp from DCE MR imaging (derived using the Patlak model and extended Tofts and Kermode model) were analyzed in the bilateral cerebral/cerebellar cortex, bilateral cerebral/cerebellar white matter (WM), and brainstem. Ktrans values of the mTBI patients and controls were calculated using both models to identify the model that better reflected the increased permeability owing to mTBI (tendency toward higher Ktrans values in mTBI patients than in controls). The Mann-Whitney U test and Spearman rank correlation test were performed to compare the mean Ktrans and vp between the two groups and correlate Ktrans and vp with neuropsychological tests for mTBI patients. Results: Increased permeability owing to mTBI was observed in the Patlak model but not in the extended Tofts and Kermode model. In the Patlak model, the mean Ktrans in the bilateral cerebral cortex was significantly higher in mTBI patients than in controls (p = 0.042). The mean vp values in the bilateral cerebellar WM and brainstem were significantly lower in mTBI patients than in controls (p = 0.009 and p = 0.011, respectively). The mean Ktrans of the bilateral cerebral cortex was significantly higher in patients with atypical performance in the auditory continuous performance test (commission errors) than in average or good performers (p = 0.041). Conclusion BBB disruption, as reflected by the increased Ktrans and decreased vp values from the Patlak model, was observed throughout the bilateral cerebral cortex, bilateral cerebellar WM, and brainstem in mTBI patients with PCS.