Application of Static Headspace GC-MS Method for Selective 1,4-Dioxane Detection in Food Additives.

Efficient detection methods must be developed for 1,4-dioxane due to its suspected status as a human carcinogen, which is highly mobile in food and environmental resources. In this regard, this experiment has been conducted to develop reliable and selective detection and measurement methods by using static headspace (SH) isolation, followed by gas chromatography-mass spectrometry (GC-MS). A new method was developed for determining the spiked 1,4-dioxane contents in a polyethylene glycol 600 (PEG 600). The optimal condition for SH-GC-MS was discussed. The representative ions of 1,4-dioxane and 1,4-dioxane-d8 in the SIM mode of MS are 88 and 96, respectively, and the peaks of the SIM mode were separated and confirmed. The linear range for the method covers 0.25 to 100 mg/L with a coefficient of determination (R2) ≥ 0.999. The method applicability was demonstrated by spike recovery across a variety of food additives (i.e., chlorine bitartrate, choline chloride, polysorbate 20 and 60, and PEG 1000). All spike recovery from the tested samples was in the range of 89.50-102.68% with a precision of 0.44-11.22%. These findings suggest a new analytical method for food safety inspection, and could be applicable for ensuring the safety of foods and environmental and public health on a broad scale.

Predictive value of the videofluoroscopic swallowing study for long-term mortality in patients with subacute stroke.

ABSTRACT: To investigate the usefulness of the videofluoroscopic swallowing study (VFSS) for subacute stroke in predicting long-term all-cause mortality, including not only simple parameters obtained from VFSS results, but also recommended dietary type as an integrated parameter.This was a retrospective study of patients with subacute (<1 month) stroke at a university hospital between February 2014 and September 2019. The independent risk factors were investigated using stepwise Cox regression analysis, which increased the all-cause mortality of patients with stroke among VFSS parameters.A total of 242 patients with subacute stroke were enrolled. The significant mortality-associated factors were age, history of cancer, recommended dietary type (modified dysphagia diet; adjusted hazard ratio [HR], 6.971; P = .014; tube diet, adjusted HR: 10.169; P = .019), and Modified Barthel Index. In the subgroup survival analysis of the modified dysphagia diet group (n = 173), the parameters for fluid penetration (adjusted HR: 1.911; 95% confidence interval, 1.086-3.363; P = .025) and fluid aspiration (adjusted HR: 2.236; 95% confidence interval, 1.274-3.927; P = .005) were significantly associated with mortality.The recommended dietary type determined after VFSS in subacute stroke was a significant risk factor for all-cause mortality as an integrated parameter for dysphagia. Among the VFSS parameters, fluid penetration and aspiration were important risk factors for all-cause mortality in patients with moderate dysphagia after stroke. Therefore, it is important to classify the degree of dysphagia by performing the VFSS test in the subacute period of stroke and to determine the appropriate diet and rehabilitation intervention for mortality-related prognosis.

An Exploratory Study on the Effects of Forest Therapy on Sleep Quality in Patients with Gastrointestinal Tract Cancers.

The improvement of sleep quality in patients with cancer has a positive therapeutic effect on them. However, there are no specific treatment guidelines for treating sleep disturbance in cancer patients. We investigated the effect of forest therapy on the quality of sleep in patients with cancer. This study was conducted on nine patients (one male, eight female; mean age, 53.6 ± 5.8 years) with gastrointestinal tract cancer. All patients participated in forest therapy for six days. They underwent polysomnography (PSG) and answered questionnaires on sleep apnea (STOP BANG), subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI), sleepiness (Stanford and Epworth Sleepiness Scales), and anxiety and depression (Hospital Anxiety and Depression Scale) to evaluate the quality of sleep before and after forest therapy. Sleep efficiency from the PSG results was shown to have increased from 79.6 ± 6.8% before forest therapy to 88.8 ± 4.9% after forest therapy (p = 0.027) in those patients, and total sleep time was also increased, from 367.2 ± 33.4 min to 398 ± 33.8 min (p = 0.020). There was no significant difference in the STOP BANG score, PSQI scores, daytime sleepiness based on the results of the Stanford and Epworth Sleepiness Scales, and depression and anxiety scores. Based on the results of this study, we suggest that forest therapy may be helpful in improving sleep quality in patients with gastrointestinal cancers.

Cognitive improvement after long-term electrical stimulation of bilateral anterior thalamic nucleus in refractory epilepsy patients.

INTRODUCTION: The cognitive and behavioral effect of deep brain stimulation (DBS) administered to the deep cerebral nuclei for epilepsy treatment is unknown. We investigated the cognitive outcomes at least 12 months after DBS to the bilateral anterior thalamic nucleus (ATN) for controlling intractable epilepsy. METHODS: Nine patients with intractable epilepsy who were not candidates for resective surgery, but who were treated by bilateral ATN DBS underwent cognitive and behavioral assessments before implantation and more than 1 year after DBS surgery. Postoperative cognitive assessments were carried out under a continuous stimulation mode. RESULTS: The mean seizure-reduction rate of these patients after ATN DBS was 57.9% (35.6-90.4%). Cognitive testing showed favorable results for verbal fluency tasks (letter and category, p<0.05), and a significant improvement in delayed verbal memory was observed (p=0.017). However, we did not observe any significant changes in general abilities (IQ, MMSE), information processing (digit forward and backward, Trail A, and Digit Symbol), or executive function (Trail B and WCST). Interestingly, we did not observe any significant cognitive decline approximately 1 year (mean, 15.9 months) after ATN DBS surgery. CONCLUSIONS: We showed that ATN DBS not only resulted in promising clinical effects but was also associated with improvements in both verbal recall and oral information processing, which may be related to the bilateral activation of the fronto-limbic circuit following DBS surgery. Further controlled, long-term studies with larger populations are warranted for elucidating the clinical effects of ATN DBS.

Supra-additive neuroprotection by renexin, a mixed compound of ginkgo biloba extract and cilostazol, against apoptotic white matter changes in rat after chronic cerebral hypoperfusion.

BACKGROUND AND PURPOSE: White-matter (WM) lesions are known to potentiate cognitive impairment in poststroke patients. The present study was designed to assess whether Ginkgo biloba extract (GB) and cilostazol, which were evaluated alone and in a combination formula (Renexin), can attenuate the WM lesions and cognitive decline caused by chronic hypoperfusion in the rat. METHODS: ANIMALS WERE DIVIDED INTO FIVE TREATMENT GROUPS: cilostazol (25 mg/kg/day), GB (20 mg/kg/day), Renexin (25 mg/kg/day cilostazol + 20 mg/kg/day GB), vehicle, and sham. The animals received the treatments orally 1 day after bilateral common carotid artery occlusion [two-vessel occlusion (2VO); except for the sham group, which underwent the surgery but the arteries were not occluded], and then the same dose every day for 21 days thereafter. Prior to sacrificing the rats, repetitive eight-arm radial maze testing was performed to examine their cognitive abilities. After drug administration and cognitive testing, brain tissues were isolated for Klüver-Barrera and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling (TUNEL) staining, immunohistochemical assessment of glial fibrillary acidic protein (GFAP) and CD11b (OX-42), and to assay free-radical scavenging activity. RESULTS: We found that the significant WM lesions induced by 2VO was ameliorated significantly by treatment with cilostazol, GB, and Renexin, in association with increased TUNEL-positive cells. In addition, chronic cerebral hypoperfusion caused a large increase in the degree of GFAP and OX-42 immunoreactivity and free-radical activity in the optic tract. These abnormalities were significantly reversed by the three drugs, but most prominently by Renexin, suggesting a markedly enhanced or supra-additive effect of cilostazol and GB when administered together. CONCLUSIONS: Significant attenuation of cytoarchitectural damage and apoptotic cell death was found with GB and cilostazol, but a markedly enhanced effect was seen for treatment with their combination in the WM of rat brains after bilateral occlusion of the common carotid arteries. We suggest that combination therapy with GB and cilostazol provides enhanced neuroprotective effects and induces subsequent cognitive improvement in patients with chronic ischemic conditions.

Differential expression of activating transcription factor-2 and c-Jun in the immature and adult rat hippocampus following lithium-pilocarpine induced status epilepticus.

PURPOSE: Lithium-pilocarpine induced status epilepticus (LPSE) causes selective and age-dependent neuronal death, although the mechanism of maturation-related injury has not yet been clarified. The activating transcription factor-2 (ATF-2) protein is essential for the normal development of mammalian brain and is activated by c-Jun N-terminal kinase (JNK). It induces the expression of the c-jun gene and modulates the function of the c-Jun protein, a mediator of neuronal death and survival. Therefore, we investigated the expression of c-Jun and ATF-2 protein in the immature and adult rat hippocampus to understand their roles in LPSE-induced neuronal death. MATERIALS AND METHODS: Lithium chloride was administrated to P10 and adult rats followed by pilocarpine. Neuronal injury was assessed by silver and cresyl violet staining, performed 72 hours after status epilepticus. For evaluation of the expression of ATF-2 and c-Jun by immunohistochemical method and Western blot, animals were sacrificed at 0, 4, 24, and 72 hours after the initiation of seizure. RESULTS: Neuronal injury and expression of c-Jun were maturation-dependently increased by LPSE, whereas ATF-2 immunoreactivity decreased in the mature brain. Since both c-Jun and ATF-2 are activated by JNK, and targets and competitors in the same signal transduction cascade, we could speculate that ATF-2 may compete with c-Jun for JNK phosphorylation. CONCLUSION: The results suggested a neuroprotective role of ATF-2 in this maturation-related evolution of neuronal cell death from status epilepticus.

No evidence of perfusion abnormalities in the basal ganglia of a patient with generalized chorea-ballism and polycythaemia vera: analysis using subtraction SPECT co-registered to MRI.

Polycythaemia vera is a well-known cause of symptomatic chorea, however, the pathophysiology of this correlation remains unclear. We report on a patient with generalized chorea-ballism associated with polycythaemia vera, and we present the findings of 99mTc-hexamethylpropylene amine oxime (HMPAO) SPECT done in both the choreic state and the non-choreic state. The SPECT during both the choreic and the non-choreic states did not reveal any definite perfusion changes in specific regions of the brain, as compared with 6 age-matched controls. In addition, the subtraction SPECT co-registered to MRI (SISCOM) analysis did not show any difference in cerebral blood flow during the choreic and non-choreic states. This result suggests that the basic mechanism of chorea associated with polycythaemia vera does not appear to be associated with a reduction in cerebral perfusion to a specific cerebral area, such as the basal ganglia or its thalamocortical connections.

Ramipril protects from free radical induced white matter damage in chronic hypoperfusion in the rat.

We investigated whether the angiotensin converting enzyme inhibitor, ramipril, could attenuate white matter lesions caused by chronic hypoperfusion in the rat, and whether suppression of oxidative stress is involved in the resulting neuroprotection. The ramipril treatment group showed significant protection from development of white matter lesions in the optic tract, the anterior commissure, the corpus callosum, the internal capsule and the caudoputamen. The level of malondialdehyde (MDA) and the oxidized glutathione (GSSG)/total glutathione (GSH t) ratio was also significantly decreased in the ramipril group compared to the vehicle-treated group. These results suggest that ramipril can protect against white matter lesions that result from chronic ischemia due to its effects on free radical scavenging. Further efficacy should be studied in the treatment of cerebrovascular insufficiency states and vascular dementia.

COMP-angiopoietin 1 Gene Transfer Enhances Cutaneous Wound Healing by Promoting Angiogenesis.

BACKGROUND: Angiogenesis is crucial for wound healing and exogenous supplements of the angiogenic growth factors have been known to promote cutaneous wound healing. Angiopoietin (Ang) 1 is a recently discovered angiogenic factor and there have been few studies of its effect on cutaneous wound healing. OBJECTIVE: We examined the effect of Ang 1 on cutaneous wound healing. METHODS: Cartilage oligomeric matrix protein (COMP)-Ang 1 (Ade-COMP-Ang 1)- was intravenously injected to rats two days before surgery creating full-thickness wounds. The clinical wound healing rate and the number of vessels in the skin samples were evaluated on days 3, 7 and 14 post operation. RESULTS: At post-operation day 3, 7 and 14, the clinical wound healing rate was 38.3%, 59.4% and 92.1%, respectively, in the Ade-COMP-Ang 1-treated group, compared with 20.5%, 47.5% and 87.3%, respectively, in the Ade-LacZ-treated group. There were significant differences in the results of day 3 and day 7 between two groups (p<0.05). Histopathologically, the number of the vessels of the Ade-COMP-Ang 1-treated group was 73.7, 94.1 and 62.7 at day 3, 7 and 14, compared with that of the Ade-LacZ-treated group, 53.5, 83.9, and 56.9. The differences in the results of the two groups were statistically significant (p<0.05). CONCLUSION: These results indicate that Ade-COMP-Ang 1 therapy significantly accelerats wound healing by promoting angiogenesis. However, further study using Ade-COMP-Ang 1 gene therapy for chronic wounds in which the formation of new blood vessels is impaired is needed in the near future.

Focal hand dystonia secondary to Basal Ganglia germinoma.

Descriptions of symptomatic focal dystonia caused by focal lesions of the central nervous system (CNS) are rare in the literature. We report a 9-year-old child who experienced sudden-onset left-hand dystonia for 6 months. Brain magnetic resonance imaging showed a mass lesion involving the putamen, globus pallidus, head of caudate, and the anterior limb of the internal capsule. Histopathological and immunocytochemical examinations of the mass revealed features characteristic of malignant germinoma. CNS germinoma in the basal ganglia is very rare. Combining previous reports in the literature with the anatomical and clinical presentation of our case suggests that this phenomenon results from disruption of the pathways within and adjacent to the basal ganglia.

Effect of chronic deep brain stimulation of the subthalamic nucleus for frontal lobe epilepsy: subtraction SPECT analysis.

OBJECTIVES: Experimental data and case reports of patients with intractable epilepsy treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) suggest a considerable anticonvulsant effect. However, no satisfactory mechanisms of action have yet been elucidated. We investigated the putative therapeutic mechanisms of DBS from cerebral perfusion changes as measured by subtracting the SPECT image of the pre-DBS period from that of the chronic post-DBS state. METHODS: Two patients who had previous resective surgery on their right frontal cortices with or without anterior callosotomy were selected for DBS of the STN. Both of them showed frequent bilateral asymmetric tonic seizures (left > right) with rare drop attacks, and 1 patient's seizure frequency was more than 15/month during the pre-DBS period. They had both taken more than four antiepileptic agents for more than 10 years. After video-EEG monitoring, the irritative zones of the brain were delineated. The regional cerebral blood flow (rCBF) changes between the two SPECT images (pre-DBS and post-DBS after at least 6 months) were analyzed by SPECT subtraction with the volumetric MRI coregistration method using Analyze 5.0 software. RESULTS: After chronic STN DBS (18 months, case 1; 6 months, case 2), both patients experienced markedly reduced seizure frequencies (86.7% reduction in patient 1, 88.6% in patient 2). In patient 1, the increased rCBF was observed in the right frontal areas (dorsolateral and inferior frontal area), which corresponded to the irritative zones as confirmed by previous EEG recording. Unexpectedly, there was definite hyperperfusion in the right superior and inferior temporal areas as well as rCBF increase in the right superior frontal area (SMA) in patient 2. CONCLUSIONS: We demonstrated that the cerebral perfusion increase in the irritative zones of epilepsy patients is associated with favorable seizure reduction after STN DBS in 2 cases of frontal lobe epilepsy. Although the exact mechanism remains unknown, our findings suggest that the perfusion changes after STN DBS in frontal lobe epilepsy patients are quite different from those in subjects with Parkinson's disease. Our preliminary data suggest the clinical relevance of subtraction SPECT imaging in assessing the postprocedural outcome as well as the characteristics of SPECT perfusion patterns in other epilepsy syndromes.