Spatial Fluctuation of Central Nervous System Lesions in X-linked Charcot-Marie-Tooth Disease with a Novel GJB1 Mutation.

X-linked Charcot-Marie-Tooth disease type 1 (CMTX1), the most common form of CMTX, is caused by gap-junction beta 1 (GJB1) mutations. We herein report a 25-year-old Japanese man with disorientation, right hemiparesis, and dysarthria. Brain magnetic resonance imaging (MRI) showed high signal intensities in the bilateral cerebral white matter on diffusion-weighted imaging. He had experienced 2 episodes of transient central nervous system symptoms (at 7 and 13 years old). A genetic analysis identified a novel GJB1 mutation, c.169C>T, p.Gln57*. MRI abnormalities shifted from the cerebral white matter to the corpus callosum and had disappeared at the five-month follow-up. Transient changes between these lesions may indicate CMTX1.

Neuroendocrine carcinoma of the small intestine diagnosed as a result of paraneoplastic neurological syndrome.

Paraneoplastic neurological syndromes, a diverse group of neurological syndromes, are associated with small cell lung, testicular, ovarian, and breast cancers; however, their association with neuroendocrine carcinoma of the small intestine remains unreported. In this report, we present the case of a 78-year-old man diagnosed with neuroendocrine carcinoma of the small intestine and experienced symptoms such as subacute progressive numbness of the extremities and impaired gait. These symptoms were diagnosed as tumor-associated neurological syndrome. The patient had also undergone pyloric gastrectomy for early-stage gastric cancer several years prior to the appearance of the neurological symptoms. Therefore, we could not determine whether the tumor-related neurologic syndrome was owing to gastric cancer or neuroendocrine carcinoma of the small intestine; however, one of these conditions was the cause of the neuropathy. The gait disturbance and numbness relatively improved after surgery for the neuroendocrine carcinoma of the small intestine, suggesting that the neuroendocrine carcinoma of the small intestine likely caused the paraneoplastic neurological syndrome. Collectively, we present a unique report highlighting the putative relationship between small bowel neuroendocrine carcinoma and tumor-associated neurologic syndromes.

Influence of mandibular incisor agenesis and growth pattern on symphysis characteristics: A retrospective cephalometric study.

OBJECTIVE: This study was performed to investigate the effects of mandibular incisor (MnI) agenesis and divergent malocclusion type on mandibular symphysis inclination and morphology. METHODS: A total of 162 selected patients were divided into two groups: one group consisted of patients with one or two congenitally missing MnIs, and another group comprised patients without tooth agenesis. Patients in each group were categorized into three divergent malocclusion groups (hypodivergent, normodivergent and hyperdivergent) according to the Frankfort mandibular plane angle, with 27 patients per group. Lateral cephalograms were used to evaluate mandibular symphysis inclination and morphology. Two-way analysis of variance, simple main effect analysis and Tukey's test were used for statistical comparisons. RESULTS: The agenesis group demonstrated a significantly greater retroclination of the mandibular symphysis than the non-agenesis group in the normodivergent group. In the hypodivergent and normodivergent groups, the agenesis group showed a significantly smaller area of the alveolar bone with thinner width and shorter height than the non-agenesis group. CONCLUSION: For the Japanese orthodontic patients, MnI agenesis caused a significantly great retroclination of the mandibular symphysis in patients with normodivergent malocclusion and significantly small area of the alveolar bone with thin width and short height in patients with hypo- and normodivergent malocclusions.

Association between Serum Biomarkers and Peripheral Neuropathy in Microscopic Polyangiitis.

This study aimed to elucidate the pathomechanism of peripheral neuropathy (PN) in microscopic polyangiitis (MPA) and to identify biomarkers useful for diagnosis and severity assessment. Patients with MPA (n = 37) and other non-inflammatory neurological diseases (ONDs; n = 12) were enrolled, and the peripheral nerves of all patients were evaluated using nerve conduction studies. We compared the clinical characteristics and 14 serum biomarker profiles among patients with MPA and PN, MPA without PN, and ONDs. Patients with MPA had a higher prevalence of motor neuropathy than patients with ONDs. Among the patients with MPA, those with motor neuropathy had significantly higher total Birmingham Vasculitis Activity Scores and serum levels of C-reactive protein (CRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and interleukin-6 than patients without motor neuropathy. Multivariable analyses adjusted for age, serum CRP level, and diabetes mellitus showed that high serum levels of TIMP-1 were independently related to a diagnosis of motor neuropathy in MPA. Additionally, there were significant negative correlations between the serum levels of TIMP-1 and compound muscle action potential amplitudes. Serum levels of TIMP-1 may be associated with the pathomechanism of motor neuropathy in MPA and could be a useful biomarker for diagnosing and evaluating the severity of motor neuropathy in MPA.

Examination of facial measurement on the image using a noncontact three-dimensional measurement device.

Background: Producing dentures for edentulous patients is important to improve quality of life of elderly. The determination of the occlusal vertical dimension on producing dentures is one of the key factors for using the dentures comfortably. The purpose of this study is to consider the usefulness of the determination of the occlusal vertical dimension of a facial measurement method applied on scanned facial image using a noncontact three-dimensional measurement device. Materials and Methods: Twenty-four dentulous individuals (mean age 26.6 ± 2.4 years old) were examined in this study. A noncontact three-dimensional measurement device was used for the scanning of the face both in the holding by hand and the fixing to the camera stands situations. The distances between subnasal and gnathion, pupil and oral slit, middle of glabella and subnasal, and right and left corners of the mouth were measured on the scanned face image and compared with the actual values. Results: The significant differences were not recognized on the four measurement items between the distance of actual values and obtained on scanned data (fixing conditions). The coefficients of variation of the distances between subnasal and gnathion, and pupil and oral slit on scanned data (fixing condition) were significantly lower than those at actual conditions (P < 0.05). Conclusion: The results of this study suggested that a stable facial measurement can be successfully implemented by using a noncontact three-dimensional measurement device. This method yields outcomes which match the actual values.

Initial serum GM-CSF levels are associated with the severity of cerebral small vessel disease in microscopic polyangiitis patients.

Serum cytokine levels were comprehensively measured, and the association with cerebrovascular lesions on brain magnetic resonance imaging (MRI) in microscopic polyangiitis (MPA) patients was investigated. The initial serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were significantly higher in the high-grade white matter hyperintensities (WMH) group than those in the low-grade WMH group. In multivariate analyses, high serum levels of GM-CSF were independently associated with high-grade WMH. The initial serum GM-CSF levels correlated positively with the Birmingham Vasculitis Activity Score and semi-quantitative scales of WMH. The initial serum GM-CSF levels were associated with the severity of WMH in MPA patients.

Shear bond strength of orthodontic brackets bonded with resin coating material.

The purpose of this study was to determine whether a system using a resin coating material (PRG Barrier Coat) with anticariogenic ability can effectively bond orthodontic brackets to human teeth. Resin-modified glass-ionomer cement system (Fuji Ortho LC, group 1) and resin composite cement systems (BeautyOrtho Bond) combined with a self-etching primer (group 2), with the resin coating material (group 3), and with the resin coating material after an organic acid etching agent (group 4) were used for bracket bonding. The mean shear bond strength (SBS) was significantly higher in group 1 than in groups 2, 3 and 4. Groups 2 and 4 exhibited a significantly higher mean SBS than group 3. The resin composite cement system combined with the resin coating material after the organic acid etching agent can serve as an alternative for orthodontic bracket bonding.

[A CASE OF ANAPHYLAXIS DUE TO STINGING OF A Brachyponera chinensis].

The case involved a man in his forties. While working at the restaurant that the patient runs, the patient experienced a stab-like pain on the left shoulder and developed systemic pruritic eruptions. He was diagnosed with anaphylaxis upon visiting our emergency department. Conjunctival hyperemia, lip swelling, cold sweats, and nausea presented later. A cap fluorescence enzyme immunoassay using the serum of the patient showed specific immunoglobulin E (IgE) positivity for wasps; therefore, we hypothesized that he had anaphylaxis caused by the insect's sting. Insects of the same species as that by which the patient had been stung were collected and finally identified as the Asian needle ant (Brachyponera chinensis). The freeze-dried insects' bodies were sonicated into powders and stored for following examinations. Next, a basophil activation test was performed using the patient's whole blood treated with the reagent above, which showed positivity. Furthermore, a skin prick test using the same reagent showed a positive result, and the reaction increased in a concentrationdependent manner. Based on these results, the patient was diagnosed with anaphylaxis after a sting by the ant. Based on the results of the allergen component specific IgE test, we speculated that the pathogens in this case was group5 allergen of the Asian needle ant. Anaphylaxis following insect stings by this ant has been reported frequently in South Korea. However, it is quite rare in Japan, although the ant is native to Japan. Clinicians should consider that this allergy can occur indoors, unlike allergies to other types of venom.

Prevalence and patterns of tooth agenesis among malocclusion classes in a Japanese orthodontic population.

The purpose of the present study was to assess, in detail, the association between tooth agenesis (TA) and various sagittal skeletal malocclusion groups in a Japanese orthodontic population. One thousand and twenty patients were divided into skeletal Class I, II, or III malocclusion groups using the A point, nasion, and B point angle. TA was identified in each group using panoramic radiographs. Patients with class III malocclusion exhibited a significantly higher prevalence of third molar (M3) agenesis, bilateral and overall agenesis of the maxillary M3s than those patients with a class II malocclusion. Those with a Class II malocclusion demonstrated a significantly lower prevalence of overall agenesis of the mandibular M3s than those with class I or III malocclusions. There were no significant differences in the prevalence of agenesis of teeth other than the M3s between the skeletal malocclusion groups. In each group, there was significantly more M3 agenesis present in the maxilla than in the mandible, and agenesis of the incisors and second premolars was found more often in the mandible than in the maxilla. Sagittal jaw relationships were significantly associated with M3 agenesis but were not associated with agenesis of the maxillary and mandibular incisors and second premolars.

Clinical characteristics of long-term survival with noninvasive ventilation and factors affecting the transition to invasive ventilation in amyotrophic lateral sclerosis.

INTRODUCTION: We evaluated post-noninvasive ventilation survival and factors for the transition to tracheostomy in amyotrophic lateral sclerosis (ALS). METHODS: We analyzed 197 patients using a prospectively collected database with 114 patients since 2000. RESULTS: Among 114 patients, 59 patients underwent noninvasive ventilation (NIV), which prolonged the total median survival time to 43 months compared with 32 months without treatment. The best post-NIV survival was associated with a lack of bulbar symptoms, higher measured pulmonary function, and a slower rate of progression at diagnosis. The transition rate from NIV to tracheostomy gradually decreased over the years. Patients using NIV for more than 6 months were more likely to refuse tracheostomy and to be women. DISCUSSION: This study confirmed a positive survival effect with NIV, which was less effective in patients with bulbar dysfunction. Additional studies are required to determine the best timing for using NIV with ALS in patients with bulbar dysfunction. Muscle Nerve 58:770-776 2018.

AN ADULT CASE OF ANAPHYLAXIS CAUSED BY ALLERGY TO JELLYFISH.

A 35-year-old female, professional diver, reported nausea, vomiting, and systemic hives 20 to 30 minutes after ingestion of antipasto made with jellyfish. Patient reported prior episodes of swelling after stings from several different creatures, including jelly fish. She also developed a systemic allergic reaction after sting from an unknown creature while diving. On the initial visit to our hospital, serum total IgE level was 545IU/ml. We extracted crude allergen from jellyfish and evaluated allergen specific IgE antibody levels using ELISA. Patient samples showed higher levels of jellyfish-derived allergen specific IgE than healthy control samples. Basophils were isolated from the peripheral blood of patient. Stimulation with jellyfish-derived allergen showed expression of surface antigens on basophils increased in a concentration-dependent manner. Methods using sodium dodecyl sulfate poly acrylamide gel electrophoresis and immunoblotting showed acid-soluble collagen fraction from jellyfish contained above 250kDa weighed protein that may have caused this current event. A provocation test using jellyfish samples was not performed due to risk of anaphylactic shock. The patient was diagnosed with a jellyfish allergy due to IgE mediated anaphylaxis after ingestion. She was asked to refrain from consuming any food containing jellyfish. IgE-mediated food allergy caused by jellyfish is rare worldwide. Collagen was speculated to be an allergen in this study. Additional study to detect specific allergens related to jellyfish allergy would be particularly useful to specify disease phenotypes and individual care in future.

Definitive radiotherapy plus regional hyperthermia for high-risk and very high-risk prostate carcinoma: Thermal parameters correlated with biochemical relapse-free survival.

PURPOSE: The aim of this study was to assess the efficacy of definitive radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential contribution of HT to clinical outcomes in patients with prostate carcinoma. MATERIALS AND METHODS: Following our institution's treatment protocol, HT was combined with RT to improve clinical outcomes in selected patients with high-risk or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT and 64 patients treated with RT alone were retrospectively analysed. RESULTS: Median follow-up duration was 61 months. The 5-year biochemical disease-free survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas bDFS for the 64 patients treated with RT alone was 72%; this difference was not significant. Among the 75 patients treated with RT plus HT who underwent intra-rectal temperature measurements, higher thermal parameters were significant prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 °CT90 thermal parameter and a T stage of T1-2 were significant prognostic factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients with a higher CEM43 °CT90 and the 64 patients treated with RT alone were significantly different, whereas 5-year bDFS for the 35 patients with a lower CEM43 °CT90 and the 64 patients treated with RT alone were not. CONCLUSIONS: The addition of HT with higher thermal parameters to RT may improve bDFS for patients with high-risk or very high-risk prostate cancer. These findings also demonstrate the importance of careful selection of treatable patients with higher thermal parameters.

Definitive radiotherapy plus regional hyperthermia for high-risk and very high-risk prostate carcinoma: Thermal parameters correlated with biochemical relapse-free survival.

PURPOSE: The aim of this study was to assess the efficacy of definitive radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential contribution of HT to clinical outcomes in patients with prostate carcinoma. MATERIALS AND METHODS: Following our institution's treatment protocol, HT was combined with RT to improve clinical outcomes in selected patients with high-risk or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT and 64 patients treated with RT alone were retrospectively analysed. RESULTS: Median follow-up duration was 61 months. The 5-year biochemical disease-free survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas bDFS for the 64 patients treated with RT alone was 72%; this difference was not significant. Among the 75 patients treated with RT plus HT who underwent intra-rectal temperature measurements, higher thermal parameters were significant prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 °CT90 thermal parameter and a T stage of T1-2 were significant prognostic factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients with a higher CEM43 °CT90 and the 64 patients treated with RT alone were significantly different, whereas 5-year bDFS for the 35 patients with a lower CEM43 °CT90 and the 64 patients treated with RT alone were not. CONCLUSIONS: The addition of HT with higher thermal parameters to RT may improve bDFS for patients with high-risk or very high-risk prostate cancer. These findings also demonstrate the importance of careful selection of treatable patients with higher thermal parameters.

Tracheostomy and invasive ventilation in Japanese ALS patients: decision-making and survival analysis: 1990-2010.

OBJECTIVE: To evaluate the factors related to the choice of a tracheostomy and invasive ventilation in amyotrophic lateral sclerosis patients and to determine survival time after a tracheostomy at a single institute in Japan between 1990 and 2010. METHODS: Data for survival time until death or tracheostomy were obtained from 160 patients. Fifty-two patients (33%) underwent tracheostomy/mechanical ventilation. RESULTS: Tracheostomy and invasive ventilation prolonged median survival time (74 months), as did non-invasive ventilation (48 months) when compared to a non-ventilation-supported control group (32 months; p<0.001 each). The ratio of tracheostomy/mechanical ventilation in patients >65 years old significantly increased after 1999 (27%) compared to earlier years (10%, p=0.002). Cox proportional modeling confirmed an age of ≤65 years as advantageous for long-term survival after a tracheostomy. In univariate logistic regression analysis, factors related to the decision to perform a tracheostomy included an age of ≤65 years, greater use of non-invasive ventilation, the presence of a spouse, interval and speed from disease onset to diagnosis/tracheostomy and preservation of motor function. In multivariate logistic regression analysis, age, shorter duration from disease onset until tracheostomy and the presence of a spouse were independently associated with the decision to perform a tracheostomy. Kaplan-Meier plots revealed longer survival times in patients who resided at home after a tracheostomy compared to patients who stayed at a hospital (p=0.007). CONCLUSIONS: Tracheostomy and invasive ventilation are frequently used in Japan. Various factors impact patients' decisions to have these procedures. This study identified factors related to the decision-making process and post-tracheostomy survival.

Copper-catalyzed nucleophilic trifluoromethylation of benzylic chlorides.

Reactions of primary and secondary benzylic chlorides with trifluoromethyltrimethylsilane in the presence of a catalytic amount of copper(i) thiophene-2-carboxylate (CuTC) have been found to give the corresponding benzylic trifluoromethylated products in good to high yields.

Copper-catalyzed nucleophilic trifluoromethylation of propargylic halides.

Reactions of propargylic halides with trifluoromethyltrimethylsilane in the presence of a catalytic amount of copper(I) thiophene-2-carboxylate (CuTC) have been found to give the corresponding trifluoromethylated products in good to high yields with a high selectivity.

Efficient derivation of multipotent neural stem/progenitor cells from non-human primate embryonic stem cells.

The common marmoset (Callithrix jacchus) is a small New World primate that has been used as a non-human primate model for various biomedical studies. We previously demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) derived from mouse and human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) promote functional locomotor recovery of mouse spinal cord injury models. However, for the clinical application of such a therapeutic approach, we need to evaluate the efficacy and safety of pluripotent stem cell-derived NS/PCs not only by xenotransplantation, but also allotransplantation using non-human primate models to assess immunological rejection and tumorigenicity. In the present study, we established a culture method to efficiently derive NS/PCs as neurospheres from common marmoset ESCs. Marmoset ESC-derived neurospheres could be passaged repeatedly and showed sequential generation of neurons and astrocytes, similar to that of mouse ESC-derived NS/PCs, and gave rise to functional neurons as indicated by calcium imaging. Although marmoset ESC-derived NS/PCs could not differentiate into oligodendrocytes under default culture conditions, these cells could abundantly generate oligodendrocytes by incorporating additional signals that recapitulate in vivo neural development. Moreover, principal component analysis of microarray data demonstrated that marmoset ESC-derived NS/PCs acquired similar gene expression profiles to those of fetal brain-derived NS/PCs by repeated passaging. Therefore, marmoset ESC-derived NS/PCs may be useful not only for accurate evaluation by allotransplantation of NS/PCs into non-human primate models, but are also applicable to analysis of iPSCs established from transgenic disease model marmosets.

Synthetic utilization of 2-chloro-1,1,1,2-tetrafluoroethane.

ß-Substituted α-fluoro-α,ß-unsaturated carboxylic acids have been successfully synthesized, usually in a (Z)-stereospecific manner by way of a stepwise or a one-pot three-step procedure starting from 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124), one of the major byproducts of the industrial process for tetrafluoroethene formation from chlorofluoromethane (HCFC-22).