Accurate gamma-ray dose measurement up to 10 MeV by glass dosimeter with a sensitivity control filter for BNCT.

Glass dosimeters are very useful and convenient detection elements in radiation dosimetry. In this study, this glass dosimeter was applied to a BNCT treatment field. Boron Neutron Capture Therapy (BNCT) is a next-generation radiation therapy that can selectively kill only cancer cells. In the BNCT treatment field, both neutrons and secondary gamma-rays are generated. In other words, it is a mixed radiation field of neutrons and gamma-rays. We thus proposed a novel method to measure only gamma-ray dose in the mixed field using two RPLGD (Radiophoto-luminescence Glass Dosimeter) and two sensitivity control filters in order to control the dose response of the filtered RPLGD to be proportional to the air kerma coefficients, even if the gamma-ray energy spectrum is unknown. As the filter material iron was selected, and it was finally confirmed that reproduction of the air kerma coefficients was excellent within an error of 5.3% in the entire energy range up to 10 MeV. In order to validate this method, irradiation experiments were carried out using standard gamma-ray sources. As the result, the measured doses were in acceptably good agreement with the theoretical calculation results by PHITS. In the irradiation experiment with a volume source in a nuclear fuel storage room, the measured dose rates showed larger compared with survey meter values. In conclusion, the results of the standard sources showed the feasibility of this method, however for the volume source the dependence of the gamma-ray incident angle on the dosimeter was found to be not neglected. In the next step, it will be necessary to design a thinner filter in order to suppress the effect of the incident angle.

Response control of RPLGD for gamma-ray dose measurement using lead filters for BNCT.

Boron Neutron Capture Therapy (BNCT) is a cell-selective radiotherapy using a neutron capture reaction of 10B. In recent years, Accelerator Based Neutron Sources (ABNS) are under development instead of nuclear reactors for the next-generation neutron irradiation system for BNCT. However, ABNS as well as nuclear reactor usually generates unavoidable secondary gamma-rays by neutron-nuclear reactions such as capture reaction. In this research, we aimed to develop a separate measurement method of only gamma-rays in a mixed field of neutrons and gamma-rays using a fluorescent glass dosimeter (RPLGD), because most dosimeters have sensitivity to both radiation types. For this purpose, we proposed a lead filter method using two RPLGDs and lead filters. However, this method has a problem that the sensitivity to low energy gamma-rays (∼100 keV) is very small. In order to improve the sensitivity to low energy gamma-rays, we devised a method using a specially shaped lead filter. From theoretical calculations, we have shown that it was possible to estimate the air dose rate of the field where the gamma-ray energy spectrum shape was known for energies up to 10 MeV. In addition, we produced the specially shaped lead filter and experimentally confirmed the validity of the lead filter method using several gamma-ray standard sources and by measurements in a nuclear fuel storage room.

Optimal timing of endoscopic sinus surgery for the retention cyst of maxillary sinus.

OBJECTIVE: The optimal timing of functional endoscopic sinus surgery for odontogenic infections precipitated by retention cysts of the maxillary sinus was investigated. METHODS: Five adults who underwent functional endoscopic sinus surgery were examined. RESULTS: The root apexes of all teeth that had odontogenic infection protruded into the maxillary sinus. All teeth with odontogenic infections precipitated by the retention cysts had percussion pain, indicating they had periodontitis and pulpitis around the root apex. They were vital teeth, indicating they did not have pulp necrosis. The small area of cyst wall attached to the floor of the maxillary sinus and root apex were left intact. The teeth that had odontogenic infections precipitated by retention cysts continued to be vital with no symptoms. CONCLUSION: Functional endoscopic sinus surgery should be performed before periodontitis and pulpitis of the root apex progress to ascending pulpitis and pulp necrosis. In other words, functional endoscopic sinus surgery should be performed while the affected tooth is still vital.

Volume and effectiveness assessment of articain 4% versus mepivacaine 2% used in third molar surgery: randomized, double-blind, split-mouth controlled clinical trial.

BACKGROUND: The different indications for extraction of the lower third molars, require resources to manage pain and discomfort, such as, for example, adequate anesthetic techniques, and the type of anesthetic used can influence the management of pain in tooth extractions. Few studies in the literature compare the anesthetics 4% articaine hydrochloride and 2% mepivacaine hydrochloride showing evidence that both allow for successful pain management. This study sought to compare the volume, efficacy and safety of these two anesthetic drugs, both associated with epinephrine at a ratio of 1:100,000, used in the extraction of lower third molars. MATERIAL AND METHODS: A controlled, clinical, split-mouth compared these both local anesthetics in a sample of 20 patients requiring bilateral extraction of teeth. Pain was the main parameter to be assessed by means of the visual analogue scale (VAS) applied during and immediately after the surgery. Hemodynamic parameters, adverse events, presence of paresthesia and satisfaction of patients and surgeon were also analysed. RESULTS: Pain management was more effective with mepivacaine up to two hours after surgery (p=0.014), whereas the surgeon was more satisfied with the use of articaine during divulsion and suture (p<0.05). However no statistically significant differences were found between both anesthetics regarding pain perception. CONCLUSIONS: It was observed that both anesthetics are efficient and safe in the management of pain for extraction of third molars, in which less amount of mepivacaine is needed. The satisfaction of patients and surgeon was the same for both anesthetics, with articaine being highlighted during divulsion and suture.

Neurolymphatic biomarkers of brain endothelial inflammatory activation: Implications for multiple sclerosis diagnosis.

AIMS: Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults, and its diagnosis is often delayed due to the lack of diagnostic markers. Initiation of disease -modifying therapy in the early stages of MS is especially critical because currently available therapy mostly target relapsing-remitting MS, and is less effective as disease progresses into the more chronic form of secondary-progressive MS. Therefore, exploring specific and sensitive biomarkers will facilitate an expedited and more accurate diagnosis to allow currently available therapies to be more effective. MAIN METHODS: Western blotting was conducted to detect the expression of neurolymphatic proteins in human brain endothelial cells in culture. Additionally, using a cohort of 150 patients with relapsing remitting MS, 26 with secondary progressive MS, and 60 healthy control samples, neurolymphatic protein expression was detected in serum samples using dot blot analysis. KEY FINDINGS: Human brain microvascular endothelial cells express neurolymphatic markers. Neurolymphatic protein abundance increases with tumor necrosis factor (TNF)-α stimulation but decreases with interferon (IFN)- γ or combined (TNF + IFN) treatment. Circulating neurolymphatic protein levels is significantly lower in MS patients. Further, one of the markers, FOXC2, is associated with the clinical stages of MS, with significantly lower expression in secondary progressive MS compared to relapsing remitting MS. SIGNIFICANCE: Our findings describe brain endothelial expression of neurolymphatic proteins, which is altered under inflammatory stress, and provide a possibility of using a collective pool of circulating neurolymphatic proteins as a diagnostic and prognostic biomarker of MS.

Is there a correlation between arthroscopic findings and the clinical signs and symptoms of patients with internal derangement of the temporomandibular joint? A prospective study.

The aim of this study was to evaluate the correlation between clinical signs and symptoms of patients with internal derangement of the temporomandibular joint (TMJ) and arthroscopic findings. The study included a sample of 67 patients who underwent TMJ arthroscopy. The variables evaluated were the arthroscopic findings of synovitis, chondromalacia, adhesion, and roofing. The Spearman correlation index was used to correlate these findings with the clinical signs and symptoms of internal derangement of the TMJ, namely maximum mouth opening, pain (visual analogue scale, VAS), and the Wilkes classification. The mean age of the population was 36.16 years, and 85% were female. There was a correlation between pain and synovitis (P=0.0029, r=0.3508), between mouth opening limitation and the amount of adhesion (P=0.0004, r=-0.4084), and between Wilkes classification and the presence of chondromalacia and disc displacement (P=0.001, r=0.374 and P=0.0045, r=-0.3357, respectively). No correlation was found between age and the presence of chondromalacia (P=0.3444, r=0.1147). Patients who had worse pain symptoms had more advanced stages of synovitis, and the increased presence of adhesions was associated with limitations in mouth opening. Furthermore, those with more advanced Wilkes stages had greater disc displacement and more severe stages of chondromalacia.

Transcription factor DEC1 is required for maximal experimentally induced periodontal inflammation.

BACKGROUND AND OBJECTIVES: Disruption of transcriptional regulation is a confounding factor associated with a wide range of human inflammatory diseases. To investigate mechanistic links between transcription factor DEC1 and pathways underlying inflammation, wild-type and DEC1 knockout (KO) C57BL/6 mice were treated with Porphyromonas gingivalis (or carboxymethyl cellulose as a control) to induce periodontal inflammation. It provoked an inflammatory response within the oral environment, which showed robust variation in alveolar bone resorption and expression of inflammatory cytokines. MATERIAL AND METHODS: Male DEC1KO mice and their wild-type littermates were used for the experimental periodontitis model. Measurement of alveolar bone resorption, micro-computed tomography, isolation of gingival mononuclear cells (GMCs), flow cytometry and immunohistochemical analysis were used in this study. Human gingival fibroblast cells (HGF-1) were used for DEC1 over-expression and short interference RNA (siRNA) studies and quantitative real-time polymerase chain reaction and western blot analysis were performed. RESULTS: Micro-computed tomography analysis demonstrated that P. gingivalis caused a decrease in bone area of wild-type mice compared with DEC1KO mice. Expression of inflammatory and immune markers in GMCs was significantly decreased in DEC1KO mice after treatment with P. gingivalis. Conversely, interleukin (IL)-4 and IL-10 mRNAs were significantly increased in GMCs isolated from DEC1KO mice. The results show that treatment of DEC1KO mice with P. gingivalis decreased the numbers of CD11b+ F4/80+ and CD4+ RANKL+ T cells. Moreover, expression of CD4, F4/80, RANKL and cathepsin K in inflammatory cell infiltrates was significantly reduced in DEC1KO mice treated with P. gingivalis compared with controls. Furthermore, over-expression of DEC1 in HGF-1 cells increased the expression of IL-1ß and tumor necrosis factor-α mRNAs and their expression levels reached a maximum in response to treatment with lipopolysaccharide. Inhibition of DEC1 by short interference RNA interference suppressed the P. gingivalis-derived lipopolysaccharide-induced expression of IL-1ß, tumor necrosis factor-α and toll-like receptor4. CONCLUSION: These results suggest that transcription factor DEC1 can modulate P. gingivalis-induced periodontitis in the oral mucosa.

A 10 Minute Self-Care Program May Reduce Breast Cancer-Related Lymphedema: A Six-Month Prospective Longitudinal Comparative Study.

Patients with breast cancer-related lymphedema (BCRL) need a life-long self-care program that they can adhere to enable them to manage their lymphedema. The objective of this study was to assess the effectiveness of a holistic BCRL self-care program that patients could easily adhere to and comply with. A prospective, longitudinal, comparative study between affected arms and unaffected arms in unilateral breast cancer patients was implemented over a six-month period. Both the lymphedematous and unaffected arms of 23 patients with unilateral BCRL were followed and measured. The daily 10-minute holistic BCRL self-care program consisted of modified Japanese rajio taiso (Japanese radio calisthenics), a gentle arm exercise combined with deep breathing, skin moisturizing care using a traditional lymphatic drainage technique, and basic self-care education. Arm and edema volume, relative volume change, resistance of the skin to compression (fibrosis), lymphedema-related symptoms, skin condition, and self-care were assessed. At the end of six-months the volume of all limb segments and resistance of the tissues to compression at all measurement points of the affected arm were significantly reduced. On the unaffected side, only the volume of the forearm and the whole arm was significantly reduced and fibrosis significantly reduced only in the forearm. There was no significant difference in edema volume and relative volume change. Lymphedema-related symptoms significantly improved. Perceived adherence, effectiveness, burden, score and average time for self-care significantly increased. Our results demonstrate that this 10-minute self-care program may improve BCRL and its self-care.

A feasibility design study on a neutron spectrometer for BNCT with liquid moderator.

Neutrons generated by accelerators have various energy spectra. However, only limited methods are available to measure the whole neutron energy spectrum, especially when including the epithermal region that is normally used in BNCT. In the present study, we carried out the design study on a new neutron spectrometer that can measure such a neutron spectrum more accurately, precisely and with higher energy resolution, using an unfolding technique and a liquid moderator.

Blood circulating microparticle species in relapsing-remitting and secondary progressive multiple sclerosis. A case-control, cross sectional study with conventional MRI and advanced iron content imaging outcomes.

BACKGROUND: Although multiple sclerosis (MS) is thought to represent an excessive and inappropriate immune response to several central nervous system (CNS) autoantigens, increasing evidence also suggests that MS may also be a neurovascular inflammatory disease, characterized by endothelial activation and shedding of cell membrane microdomains known as 'microparticles' into the circulation. OBJECTIVE: To investigate the relationships between these endothelial biomarkers and MS. METHODS: We examined the relative abundance of CD31(+)/PECAM-1, CD51(+)CD61(+) (αV-ß3) and CD54(+) (ICAM-1) bearing microparticles in sera of healthy individuals, patients with relapsing-remitting MS, and secondary-progressive MS. We also investigated the correlation among circulating levels of different microparticle species in MS with conventional MRI (T2- and T1-lesion volumes and brain atrophy), as well as novel MR modalities [assessment of iron content on susceptibility-weighted imaging (SWI)-filtered phase]. RESULTS: Differences in circulating microparticle levels were found among MS groups, and several microparticle species (CD31(+)/CD51(+)/CD61(+)/CD54(+)) were found to correlate with conventional MRI and SWI features of MS. CONCLUSION: These results indicate that circulating microparticles' profiles in MS may support mechanistic roles for microvascular stress and injury which is an underlying contributor not only to MS initiation and progression, but also to pro-inflammatory responses.

Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model.

We established a mouse model of microenvironment-dependent human lymphoma, and assessed the therapeutic potential of bevacizumab, an antitumor agent acting on the microenvironment. NOD/Shi-scid, IL-2Rγ(null) (NOG) mice were used as recipients of primary tumor cells from a patient with diffuse large B-cell lymphoma (DLBCL), which engraft and proliferate in a microenvironment-dependent manner. The lymphoma cells could be serially transplanted in NOG mice, but could not be maintained in in vitro cultures. Injection of bevacizumab together with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) significantly increased necrosis and decreased vascularization in the tumor, compared with CHOP alone. Levels of human soluble interleukin-2 receptor (sIL2R) in the serum of bevacizumab+CHOP-treated mice (reflecting the DLBCL tumor burden) were significantly lower than in CHOP recipients. Mice receiving bevacizumab monotherapy also showed significant benefit in terms of tumor necrosis and vascularization, as well as decreased serum sIL2R concentrations. The present DLBCL model reflects the human DLBCL in vivo environment more appropriately than current mouse models using established tumor cell lines. This is the first report to evaluate the efficacy of bevacizumab in such a tumor microenvironment-dependent model. Bevacizumab may be a potential treatment strategy for DLBCL patients.

Comparison of five different fixation techniques of sagittal split ramus osteotomy using three-dimensional finite elements analysis.

The aim of this study was to compare the mechanical stress over hemimandible substrate and hardware after sagittal split ramus osteotomy (SSRO) fixed with five different techniques using three-dimensional (3D) finite element analysis. A 3D finite element model of a hemimandible was created and a 5mm advancement SSRO was simulated on a computer model. The model was fixed with five different techniques: 3 linear 60° screw arrangement; 3 linear 90° screw arrangement; 3 inverted L screw arrangement; 1 conventional miniplate; and 1 locking miniplate with four monocortical screws. Load was applied until 3mm displacement was reached and the results were compared with previous mechanical and photoelastic tests, thus analysing the mechanical stresses developed in the proximity of miniplates and screws and within the fixation system itself. The maximum principal stress values demonstrate a lower mechanical stress rate in bone and in the fixation system with the inverted L arrangement, followed by the linear 90° and linear 60° arrangements. The locking miniplate/screw system presented lower maximum principal stress and better stress distribution compared with the conventional system. Under the conditions tested, the reversed L arrangement provided the most favourable stress dissipation behaviour.

Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma.

BACKGROUND: The association between dietary folate intake, two polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS), and survival in head and neck squamous cell carcinoma (HNSCC) patients is not clarified. PATIENTS AND METHODS: We conducted a retrospective cohort study of 437 HNSCC patients treated at Aichi Cancer Center. We evaluated the survival impact of pretreatment dietary folate intake, which was estimated using a food-frequency questionnaire, and two polymorphisms, MTHFR C677T and a 6-bp insertion/deletion in the 3'-untranslated region of TYMS, using multivariate proportional hazard models. RESULTS: Patients with high folate intake (≥320 µg/day; n=144) had significantly higher survival than patients with low or medium folate intake (<320 µg/day; n=278; 79.1% versus 68.2%, respectively, P=0.020). This association was consistent with multivariate analyses adjusted for established prognostic factors (hazard ratio 0.56; 95% confidence interval 0.37-0.84). MTHFR and TYMS polymorphisms did not show significant association with survival, although the TYMS 6-bp insertion allele showed potential association with a reduced risk of death. Notably, no significant interaction was observed between folate intake and the two examined polymorphisms. CONCLUSIONS: High pretreatment dietary folate intake was identified as an independent prognostic factor associated with improved clinical outcomes in HNSCC patients. Further study is warranted.

Simultaneous treatment of pulmonary AV malformation with rheumatic heart disease.

Only 13 cases of pulmonary arteriovenous malformation (PAVM) combined with rheumatic heart disease have been reported, and only 3 have been treated simultaneously by surgery. Transcatheter embolotherapy, the first-line treatment of PAVM, avoids major surgery, general anesthesia, and the loss of pulmonary parenchyma, but the subsequent PAVM reperfusion can occur through recanalization of the embolized arteries. We report a case of PAVM with rheumatic heart disease, in which both diseases were simultaneously treated by surgery.

Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c.

We investigated expression profiles of microRNA (miRNA) in renal cell carcinoma [clear cell carcinomas (CCC) and chromophobe renal cell carcinomas (ChCC)] and in normal kidneys by using a miRNA microarray platform which covers a total of 470 human miRNAs (Sanger miRBase release 9.1). Unsupervised hierarchical cluster analysis revealed that CCC and ChCC were separable and that no subgroups were identified in CCCs. We found that 43 miRNAs were differentially expressed between CCC and normal kidney, of which 37 were significantly down-regulated in CCC and the other 6 were up-regulated. We also found that 57 miRNAs were differentially expressed between ChCC and normal kidney, of which 51 were significantly down-regulated in ChCC and the other 6 were up-regulated. Together, these observations indicate that expression of miRNAs tends to be down-regulated in both CCC and ChCC compared with normal kidney. We observed that miR-141 and miR-200c were the most significantly down-regulated miRNAs in CCCs. Indeed, in all cases of CCC analysed, both miR-141 and miR-200c were down-regulated in comparison with normal kidney. Microarray data and quantitative RT-PCR showed that these two miRNAs were expressed concordantly. TargetScan algorithm revealed that ZFHX1B mRNA is a hypothetical target of both miR-141 and -200c. We established by quantitative RT-PCR that, in CCCs in which miR-141 and miR-200c were down-regulated, ZFHX1B, a transcriptional repressor for CDH1/E-cadherin, tended to be up-regulated. Furthermore, we found that overexpression of miR-141 and miR-200c caused down-regulation of ZFHX1B and up-regulation of E-cadherin in two renal carcinoma cell lines, ACHN and 786-O. On the basis of these findings, we suggest that down-regulation of miR-141 and miR-200c in CCCs might be involved in suppression of CDH1/E-cadherin transcription via up-regulation of ZFHX1B.

High-resolution analysis of DNA copy number alterations and gene expression in renal clear cell carcinoma.

We analysed chromosomal copy number aberrations (CNAs) in renal cell carcinomas by array-based comparative genomic hybridization, using a genome-wide scanning array with 2304 BAC and PAC clones covering the whole human genome at a resolution of roughly 1.3 Mb. A total of 30 samples of renal cell carcinoma were analysed, including 26 cases of clear cell carcinoma (CCC) and four cases of chromophobe renal cell carcinoma (ChCC). In CCCs, gains of chromosomes 5q33.1-qter (58%), 7q11.22-q35 (35%) and 16p12.3-p13.12 (19%), and losses of chromosomes 3p25.1-p25.3 (77%), 3p21.31-p22.3 (81%), 3p14.1-p14.2 (77%), 8p23.3 (31%), 9q21.13-qter (19%) and 14q32.32-qter (38%) were detected. On the other hand, the patterns of CNAs differed markedly between CCCs and ChCCs. Next, we examined the correlation of CNAs with expression profiles in the same tumour samples in 22/26 cases of CCC, using oligonucleotide microarray. We extracted genes that were differentially expressed between cases with and without CNAs, and found that significantly more up-regulated genes were localized on chromosomes 5 and 7, where recurrent genomic gains have been detected. Conversely, significantly more down-regulated genes were localized on chromosomes 14 and 3, where recurrent genomic losses have been detected. These results revealed that CNAs were correlated with deregulation of gene expression in CCCs. Furthermore, we compared the patterns of genomic imbalance with histopathological features, and found that loss of 14q appeared to be a specific and additional genetic abnormality in high-grade CCC. When we compared the expression profiles of low-grade CCCs with those of high-grade CCCs, differentially down-regulated genes tended to be localized on chromosomes 14 and 9. Thus, it is suggested that copy number loss at 14q in high-grade CCC may be involved in the down-regulation of genes located in this region.

Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma.

The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter hypermethylation was examined by real-time methylation-specific polymerase chain reaction in 259 human esophageal tissues. Hypermethylation of this promoter showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from normal esophagus (NE) (P<0.001). NELL1 normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's (D) and EAC than in NE (P<0.0000001). NELL1 hypermethylation frequency was zero in NE but increased early during neoplastic progression, to 41.7% in BE from patients with Barrett's alone, 52.5% in D and 47.8% in EAC. There was a significant correlation between NELL1 hypermethylation and BE segment length. Three (11.5%) of 26 ESCCs exhibited NELL1 hypermethylation. Survival correlated inversely with NELL1 hypermethylation in patients with stages I-II (P=0.0264) but not in stages III-IV (P=0.68) EAC. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2'-deoxycytidine reduced NELL1 methylation and increased NELL1 mRNA expression. NELL1 mRNA levels in EACs with an unmethylated NELL1 promoter were significantly higher than those in EACs with a methylated promoter (P=0.02). Promoter hypermethylation of NELL1 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker of poor prognosis in early-stage EAC.

Cause of death and neoplasia in mice continuously exposed to very low dose rates of gamma rays.

Four thousand 8-week-old SPF B6C3F1 mice (2000 of each sex) were divided into four groups, one nonirradiated (control) and three irradiated. The irradiated groups were exposed to (137)Cs gamma rays at dose rates of 21, 1.1 and 0.05 mGy day(-1) for approximately 400 days with total doses equivalent to 8000, 400 and 20 mGy, respectively. All mice were kept until natural death, and pathological examination was performed to determine the cause of death. Neoplasms accounted for >86.7% of all deaths. Compared to the nonirradiated controls, the frequency of myeloid leukemia in males, soft tissue neoplasms and malignant granulosa cell tumors in females, and hemangiosarcoma in both sexes exposed to 21 mGy day(-1) were significantly increased. The number of multiple primary neoplasms per mouse was significantly increased in mice irradiated at 21 mGy day(-1). Significant increases in body weights were observed from 32 to 60 weeks of age in males and females exposed to 1.1 mGy day(-1) and 21 mGy day(-1), respectively. Our results suggest that life shortening (Tanaka et al., Radiat. Res. 160, 376-379, 2003) in mice continuously exposed to low-dose-rate gamma rays is due to early death from a variety of neoplasms and not from increased incidence of specific neoplasms.