An extremely energetic cosmic ray observed by a surface detector array.

Cosmic rays are energetic charged particles from extraterrestrial sources, with the highest-energy events thought to come from extragalactic sources. Their arrival is infrequent, so detection requires instruments with large collecting areas. In this work, we report the detection of an extremely energetic particle recorded by the surface detector array of the Telescope Array experiment. We calculate the particle's energy as [Formula: see text] (~40 joules). Its arrival direction points back to a void in the large-scale structure of the Universe. Possible explanations include a large deflection by the foreground magnetic field, an unidentified source in the local extragalactic neighborhood, or an incomplete knowledge of particle physics.

Hydrocephalus due to marked enlargement of spinal roots in a patient with chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Hydrocephalus or papilledema has rarely been reported in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We report a 65-year-old woman with a 12-year history of CIDP presenting with progressive dementia, hallucination and deterioration of gait. RESULTS: Neurological examination revealed cognitive impairment, symmetric proximal and distal weakness with areflexia and muscle atrophy in the distal four limbs. The cerebrospinal fluid examination showed marked elevation of protein concentration. Magnetic resonance imaging revealed hydrocephalus and marked enlarged cervical and lumbar roots and plexus. The cervical cord and cauda equina were compressed by the swollen roots. A ventriculoperitoneal shunt resulted in reduction of the ventricles size along with improvement of her cognitive impairment. CONCLUSION: In our patient with CIDP, hydrocephalus was likely caused by hypertrophic nerve roots. Our findings suggest that CIDP patients with pronounced hypertrophic nerve roots require careful observation.

A comparative effectiveness pilot study of teriparatide for medication-related osteonecrosis of the jaw: daily versus weekly administration.

We studied the effectiveness of teriparatide (TPTD) for treating medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis and examined differences in the clinical outcomes following daily versus weekly TPTD. The outcomes were significantly improved in the entire patient series and the daily group. PURPOSE: Teriparatide (TPTD) treatment for Stage II-III medication-related osteonecrosis of the jaw (MRONJ) in osteoporotic patients has yielded promising results in uncontrolled studies. The daily administration and the weekly administration of TPTD have been reported to improve outcomes in MRONJ. Herein, we sought to identify differences in the clinical outcomes of MRONJ patients treated with daily TPTD versus weekly TPTD. METHODS: We enrolled 13 patients and randomly assigned them to receive either of two treatments: 1×/week 56.5-µg TPTD injection for 6 months (weekly group; n = 6 patients after 1 dropout), or 20-µg TPTD injection daily for 6 months (daily group; n = 6 patients). Patients in both groups received conventional therapy plus intensive antibiotic therapy as necessary. We compared the changes in the patients' clinical stage of MRONJ, bone metabolism, percentage of bone formation, and bone turnover markers between the weekly and daily groups. RESULTS: TPTD treatment with MRONJ led to partial remission or complete remission in 5 daily-group patients and 3 weekly-group patients. The MRONJ stage was significantly improved from baseline to 6 months of treatment in the entire series of 12 patients (p = 0.008); the weekly group did not show significant improvement, but the daily group did (p = 0.01). CONCLUSIONS: This study provides the first comparison of clinical outcomes between MRONJ patients who received daily or weekly TPTD injections. Six months of treatment with TPTD realized a significant improvement of MRONJ stage in both the entire patient series and the daily group.

Estimating transboundary transported anthropogenic sulfate deposition in Japan using the sulfur isotopic ratio.

High emissions of air pollutants from Northeast Asia are strongly influenced by air quality as well as by ecosystems. This study investigated the spatiotemporal variations in the sulfur isotopic ratio (δ34S) in atmospheric deposition at eleven monitoring stations in Japan from 2011 to 2016 and estimated the amount of transboundary transported anthropogenic sulfate (TRB) deposition using mass balance calculations. The δ34S of sulfate in precipitation ranged from -0.42 to +22.7‰. Sea salt (SS), TRB, and domestic anthropogenic sources (DOM) were the dominant sources of sulfate deposition in Japan. TRB sulfate deposition was largest on the Sea of Japan side, with an annual average value of 1.5 ±â€¯0.3-6.9 ±â€¯0.5 mg m-2 d-1 (36-44%), followed by Mt. Happo (4.5 ±â€¯0.1 mg m-2 d-1; 88%), the Pacific Ocean side (1.5 ±â€¯0.8, 4.3 ±â€¯0.9 mg m-2 d-1; 24-50%), and the remote islands in the North Pacific Ocean (1.1 ±â€¯0.2, 2.0 ±â€¯0.8 mg m-2 d-1; 19-32%). TRB sulfate deposition on the Sea of Japan side was 2-12 times higher in winter and 1-2 times higher in summer than that of DOM. In contrast, TRB sulfate deposition on the Pacific Ocean side was 1.5-3 times higher in summer than in winter due to high precipitation levels. In Tokyo, the annual contribution from DOM sulfate deposition is approximately three times higher than that from TRB. Annual TRB sulfate deposition is lowest at Ogasawara at 1.1 ±â€¯0.2 mg m-2 d-1, and the annual oceanic DMS contribution to sulfate deposition is high, accounting for 1.3 mg m-2 d-1 (20 ±â€¯6%). The contribution of Asian dust was estimated to be 1-5.2 mg m-2 d-1(3-6%), which occurred in a single Asian dust event on the Sea of Japan side.

Effect of surface charge, particle size, and modification by polyethylene glycol of liposomes on their association with Caco-2 cells across an unstirred water layer.

For the development of orally available liposomes, understanding the interaction of liposomes with the intestinal mucosa is important. An unstirred water layer (UWL) on the intestinal epithelium surface is a considerable permeability barrier for lipophilic drugs. Therefore, the effects of an UWL on liposome transport across intestinal epithelial cells must be elucidated. We evaluated the effects of the surface charge, particle size, and polyethylene glycol (PEG) modification of liposomes on their association with Caco-2 cells across an UWL. When the association of cationic liposomes with Caco-2 cells was evaluated under a reduction in UWL thickness by shaking, the uptake and/or amount of surface-bound cationic liposomes in cells was increased significantly in a shaking rate-dependent manner. The uptake and/or amount of surface-bound neutral liposomes were increased only at the highest shaking rate. No significant differences in the cellular association of anionic liposomes and PEG-modified liposomes were observed with or without shaking. The association of large liposomes with Caco-2 cells was affected considerably by an UWL compared with that of small liposomes. These results suggest that an UWL affects the surface binding and subsequent uptake of liposomes in Caco-2 cells according to their particle size, surface charge, and PEG modification.

Development of high-order harmonic focusing system based on ellipsoidal mirror.

We have developed a focusing system for extreme ultraviolet light produced by high-order harmonic generation. An ellipsoidal mirror with a precise surface shape was fabricated and installed into the focusing system. A rigid mirror manipulator and a beam profiler were employed to perform precise and stable mirror alignment. As a demonstration of the focusing performance, high-order harmonics in the wavelength range of 13.5-19.5 nm were successfully focused into a 2.4 × 2.3 µm(2) spot.

PP075. Endothelial dysfunction may be impaired by increased oxidative stress in preeclamptic women.

INTRODUCTION: The essential pathogenesis in preeclampsia is vasospasm induced by endothelial cell injury. The vascular endothelium regulates vascular smooth muscle tone by producing vasoconstrictors and vasodilators, such as nitric oxide (NO). Recently, it has been reported that the levels of oxidative stress are increased and they may impair endothelial NO production and induce endothelial dysfunction in preeclampsia. OBJECTIVES: To determine whether maternal release of oxygen free radical and antioxidants are associated with maternal vascular endothelial cell injury, we measured serum parameters of oxidative stress and endothelial function during pregnancy in women with or without preeclampsia. METHODS: We evaluated 20 participants with uncomplicated pregnancies, 15 with mild preeclampsia, and 18 with severe preeclampsia. Plasma concentrations were measured for derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) as markers of oxygen free radicals and antioxidants, respectively. Flow-mediated vasodilation (FMD) was also assessed as a marker of endothelial function. RESULTS: D-ROMs were increased in the maternal blood of the severe preeclamptic group compared with the control group (681.0±239.0 vs 478.6±101.4 CARR U, P<0.001), but not in the mild preeclamptic group (562.0±106.5 CARR U). Plasma BAP levels did not change significant in all three groups. The proportion of d-ROMs to BAP was higher in the severe preeclamptic group than in controls (0.28±0.11 vs 0.21±0.05, P<0.01), but not in the mild preeclamptic group (0.24±0.08). FMD was significantly decreased in both preeclamptic groups (severe, 4.3±3.3%, P<0.001; mild, 6.5±3.6%, P<0.001) compared with controls (10.5±2.3%), but FMD in the severe preeclamptic group was significantly greater than in the mild preeclamptic group. A negative correlation between FMD and d-ROM concentrations was observed in all participants (r=-0.376, P<0.05), and the ratio of serum d-ROMsto BAP correlated negatively with FMD (r=-0.413, P<0.05) in all participants. CONCLUSION: We found that the production of oxygen free radicals increased, but not the production of antioxidants which decreased, as a result, an imbalance between reactive oxygen species formation and antioxidant defence mechanisms may have impaired endothelial function in preeclamptic women.

Video-assisted thoracic surgery for lung cancer in hemodialysis patients.

INTRODUCTION: In recent years, the number of hemodialysis patients has been continuously increasing. At the same time, the use of video-assisted thoracic surgery (VATS) for lung cancer has also increased. However, reports of the outcome of VATS in hemodialysis patients are still quite rare. METHODS: From 1995 to 2011, 14 patients with non-small cell lung cancer who were also receiving hemodialysis underwent lung resection by open thoracotomy or VATS at our institution. These patients were divided into two groups as follows: open (five men and four women, mean age: 68.7 years) and (2) VATS (three men and two women, mean age: 64.0 years). We compared the clinical outcomes of these two groups. RESULTS: Lobectomy was performed in eight patients in the open group, including one patient who also underwent a pneumonectomy, and in four patients in the VATS group, including one who also underwent a wedge resection. There were no significant difference between the groups' operation times, intraoperative blood loss, length of postoperative chest drainage, and length of postoperative hospitalization. There were no hospital deaths in either group. The 5-year survival rate was 42.9% in the open group and 37.5% in the VATS group. This difference was not significant (P=0.73). CONCLUSION: VATS lung resection for lung cancer patients on hemodialysis is considered an acceptable treatment modality, though the long-term survival rate of such patients is relatively low, which can be attributed to the diseases underlying the need for hemodialysis.

Prognosis of patients after pulmonary artery plasty for non-small cell lung cancer.

OBJECTIVE: We evaluated the clinical outcomes of patients after lung resection with pulmonary artery (PA) plasty for non-small cell lung cancer (NSCLC). METHODS: From 1995 to 2006, 36 patients (26 males and 10 females) with NSCLC underwent lobectomy or segmentectomy with PA plasty at our institution. The mean age of the patients was 65.9 years old (range 45-87 years old). There were 17 left upper lobectomies, 10 right upper lobectomies, five left lower lobectomies, two right upper-and-middle bilobectomies, one right lower lobectomy, and one left upper division segmentectomy. Both bronchoplasty and PA plasty were performed in 15 patients. Six patients received preoperative chemotherapy, and one had preoperative radiotherapy. RESULTS: The postoperative morbidity rate was 27.8 % (10/36), and the mortality rate (30 days) was 2.8 % (1/36). One patient underwent completion pneumonectomy on postoperative day 13. Macroscopic residual cancer was identified in two patients at the thoracic wall and aorta, respectively; microscopic residual cancers were identified in two patients at the stumps of the pulmonary artery and in one patient at the bronchial stump. Postoperative radiation therapy was additionally given to those four patients, except one. The 5-year survival rate for all patients was 51.8 %. There was no significant difference in the 5-year survival rate between clinical N (cN) 0-1 patients and cN2 patients. However, in pathological N (pN) 0-1 patients, the 5-year survival rate was significantly better than that of pN2 patients (71.9 % versus 0.0 %; P < 0.001). CONCLUSIONS: PA plasty for NSCLC is acceptable and highly recommended for pN0-1 patients. Strict patient selection should be considered so as to avoid surgical operations in patients with pN2 staging.

Cross-sectional study on respiratory effect of toner-exposed work in manufacturing plants, Japan: pulmonary function, blood cells, and biochemical markers.

The aim of the study is to examine the relationship between toner-exposed work and health indices related to respiratory disorders and to confirm the baseline of a cohort study to clarify the effect of toner exposure in manufacturing plants. Subjects were 1614 male workers (809 toner-exposed workers and 805 referents) who were engaged in toner manufacturing plants in Japan (Fuji Xerox Co., Ltd). The age of subjects was from 19 to 59 years, and the average age was 40.2 years(median 40 years, SD 7.67). We conducted a pulmonary function test (PEFR, VC, FVC, FEV(1.0)%, V25/Ht) and a blood cell test (RBC, Hb, Hct, Plt, WBC, cell contents of WBC) and measured biochemical indices in blood (ALT, AST, gamma-GTP, CRP, IgE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine. Student t-test and logistic regression analysis were applied to compare between the toner-exposed workers and the referents and to analyze the relationship among indices of effects and independent factors. There was no significant difference between the two groups in blood cell count and biochemical indices. Inflammation- and allergy-related markers such as 8OHdG and IgE also showed no significant difference between toner-exposed workers and the referents. The influence of smoking on pulmonary function indices was observed, but there was no relationship between the pulmonary function and toner-exposed work. In this article, we report a preliminary cross-sectional analysis in the subjects of a cohort study. No difference in pulmonary function indices was observed between the toner-exposed workers and the referents, and there was no consistent relationship between the exposure status and examined indices; however, the prevalence of subjective respiratory symptoms was higher in the exposed workers as presented in another report. Further analysis is important in the ongoing cohort study to clarify the effect of toner exposure on respiratory systems.

[Thoracic drainage].

The thoracic drainage system is a sophisticated and useful technology, especially in thoracic surgery. therefore, lung resections are able to be performed safely in spite of air leaks which are a common problem after pulmonary resection. The thoracic drainage system is called the 3 bottles system, which are consisted of a drainage-bottle, an underwater-seal-bottle, and a continuous low-pressure-suction devise. Based on this basic structure, a lot of convenient thoracic drainage products such as a small thoracic drainage kit for pneumothorax have been developed. Some chest tubes which changed tubal form for efficient drainage are developed as well. However, each product has both advantages and disadvantages, then, we should understand characteristics of those new products and know the physiology of respiratory, when we use them.

Dendritic cells and macrophages in the genitourinary tract.

Dendritic cells (DCs) and macrophages are antigen-presenting cells (APCs) that are important in innate immune defense as well as in the generation and regulation of adaptive immunity against a wide array of pathogens. The genitourinary (GU) tract, which serves an important reproductive function, is constantly exposed to numerous agents of sexually transmitted infections (STIs). To combat these STIs, several subsets of DCs and macrophages are strategically localized within the GU tract. In the female genital mucosa, recruitment and function of these APCs are uniquely governed by sex hormones. This review summarizes the latest advances in our understanding of DCs and macrophages in the GU tract with respect to their subsets, lineage, and function. In addition, we discuss the divergent roles of these cells in immune defense against STIs as well as in maternal tolerance to the fetus.

[Sleeve lobectomy for primary lung cancer].

We reviewed Fukuoka University Hospital thoracic surgery data base of 60 sleeve lobectomy (SL) and 40 pneumonectomy (PN) [for T1-3 disease] for primary lung cancer during 1993-2006. Morbidity rates were 20.0% and 37.5% in SL and PN group, respectively (p = 0.054). Three and 1 patient from PN and SL group, respectively, presented with bronchial anastomotic complications. Multivariate analysis showed that adjuvant chemotherapy and preoperative concomitant respiratory disease, but not the surgical procedures SL or PN, were risk factors for surgical morbidity. SL requires special consideration on its surgical technique either bronchial anastomosis or associated angioplastic procedure, however, it is safe and valuable less invasive surgical option especially for elderly patients.

Ezrin is a key element in the human vagina.

OBJECTIVE: The vagina is a complex tubular structure that has reproductive, support and barrier functions. These depend on the cytoarchitecture of the vaginal cells, which is controlled by key proteins. Cytoskeletal proteins determine cell polarity and membrane specializations by integrating the actin cytoskeleton with cell membranes. This integration is the domain of cytoskeletal proteins including the MERM protein family (moesin-ezrin-radixin-Merlin). Nothing is known about the cyto-localization of the MERM's in the vaginal epithelium or how it influences the cytoarchitecture of the vaginal epithelium and stroma. DESIGN: Full-thickness human vaginal fornix samples were obtained from 20 normal human specimens obtained at surgery for pelvic relaxation. Light- and electron microscopical immunohistochemistry (IHC) were used to identify and study activation and cellular localization of immuno-reactive-ezrin (ir-ezrin), a prototypical MERM. RESULTS: Ir-ezrin was identified in the stratified squamous vaginal epithelium and connective tissue (fibroblasts, blood vessels and leucocytes). "H" scoring indicated that ir-ezrin staining is denser in the vaginal epithelium than in other layers, that the ir-ezrin staining was associated with increased keratinization and with the size of the tight junctions (p<0.01). Both the amounts and localization of ir-ezrin were associated with high levels of estrogen, identified by the menstrual history and keratinization of the superficial vaginal epithelium. The density of stromal ir-ezrin was increased in the presence of dense epithelial keratinization. Immuno-reactive-ezrin staining was most pronounced near the cell membranes of both keratinized and non-keratinized epithelium, indicating that ezrin activation (unfolding and movement to the membrane) had occurred. Ultra-structural examination of the epithelium showed intra-cellular ir-ezrin to be localized to junctional complexes that have been associated with decreased mucosal penetration by microorganisms. Ir-ezrin was widely distributed throughout stromal fibro-muscular cell, vessels and immunocytes. CONCLUSIONS: MERM's, represented by ezrin, are widely present in the vaginal wall. This has implications for the strength and resilience of this tubular structure and may be the case in other internal genital tissues. Ezrin's localization and association with cell specializations indicate that in the vagina, as in other tissues, ezrin likely modulates vaginal cell-cell interactions including the changing vaginal cellular interface with the external environment, the regulation of the elasticity of the vagina, and the regulation of microbial and chemical traffic that determine the pH and microbial environment of the vagina. In other work we have shown that ezrin expression is induced by estradiol. The increase of ir-ezrin staining during the appearance of keratinization and maturation of the vaginal cytology indicates that estrogen may regulate vaginal ezrin and thereby the properties of the vaginal wall and epithelium.

Thoracoscopic lobectomy with systemic lymph node dissection for lymph node positive non-small cell lung cancer--is thoracoscopic lymph node dissection feasible?

INTRODUCTION: The impact of thoracoscopic systemic lymph node dissection (LND) on loco-regional control of non-small cell lung cancer (NSCLC) with positive lymph node metastasis was investigated. PATIENTS AND METHODS: Thoracoscopic lobectomy with systemic LND was performed for clinical stage I NSCLC. 340 patients were admitted for either a thoracoscopic (n = 98) or a standard open (n = 242) lobectomy with systemic LND. Of those 340 cases, 75 cases (20 thoracoscopic and 55 open) were pathologically diagnosed with node-positive disease. A retrospective chart review of these 75 cases was performed. RESULTS: No significant difference in the overall or loco-regional recurrence-free survival was observed between the groups. The results of a multivariate analysis of the overall and the loco-regional recurrence-free survival demonstrated that the significant factors were tumor size for overall recurrence-free survival, and sex and surgical procedure (use of thoracoscopic surgery) for loco-regional recurrence-free survival, respectively. CONCLUSION: In general, thoracoscopic lobectomy for c-stage I disease may have no survival disadvantage over open procedures. It might, however, increase the risk of local recurrence when used to treat pathologically node-positive disease. Caution should be used when treating those cases with thoracoscopic surgery.

New trainer for video-assisted thoracic surgery lobectomy.

BACKGROUND: Only a few simulators are available which offer training in video-assisted thoracic surgery (VATS). We have developed a VATS training model for surgeons. METHODS: The simulator consists of a training module housing three disposable components: the lung (made of polyurethane), the bronchus, and the artificial circulatory pulmonary vessels (made of polyvinyl chloride), connected to a pump. VATS procedures were videotaped and evaluated using a checklist assessment method. RESULTS: This unique module has been tested at several VATS seminars in Japan. In the questionnaire, training participants strongly agreed that the trainer was helpful and prepared them well for VATS lobectomy prior to performing actual surgery. Evaluation of the dexterity score for thoracoscopic surgery with our simulator correlated with the surgeons' experience with actual surgery. Technical factors were well taught using this model. CONCLUSIONS: Our unique trainer may enhance the skill of VATS surgeons at a national level.

Is systemic node dissection for accuracy staging in clinical stage I non-small cell lung cancer worthwhile in the elderly?

OBJECTIVE: The therapeutic role of systematic node dissection (SND) for early lung cancer remains controversial. Elderly patients have a background of insufficient physiological function and comorbidity, and a shorter life expectancy than that of younger patients. Therefore, we have evaluated the impact on survival, local recurrence, and complications of not performing systematic lymph node dissection in the elderly. METHODS: A retrospective analysis of 126 patients, including the elderly (75 - 89 years), who underwent a lobectomy for clinical stage I was performed. The patients were grouped according to node dissection numbers after surgery, and finally separated into two groups (SG: sufficient group, dissections of more than 10 nodes and 3 or more mediastinal stations; IG: insufficient group, less than 10 nodes and one or two mediastinal stations). Postoperative morbidity and sites of recurrence were evaluated between the two groups, and the survival rates were analyzed at 5 years. RESULTS: Upstage was identified in 12.6% of patients: 7.3% in IG (n = 45), 15.2% in SG (n = 86). Postoperative mortality occurred in 2 cases (1.58%). The incidence of postoperative respiratory or cardiac complications was more frequent in the SG, while there were fewer complications in the IG. There was no significant difference in recurrence rates between the two groups. Both local and distant recurrence was observed in the two groups. The 5-year survival rates were 61.5% for the SG and 59.4% for the IG. There was no significant difference in the survival rate between the IG and SG patients. CONCLUSIONS: Proper staging and the avoidance of nontherapeutic lymph node dissection seems acceptable for clinical stage I lung cancer in the group of elderly patients.

Comparison between a case-matched analysis of left upper lobe trisegmentectomy and left upper lobectomy for small size lung cancer located in the upper division.

BACKGROUND: Although an increasing number of approaches for pulmonary segmentectomy to treat early lung cancer are being used, there have been few reports on left upper lobe trisegmentectomy, which is midway between single segmentectomy and lobectomy, for lung cancer. METHODS: We retrospectively reviewed the medical charts of 86 clinical stage I case-matched patients with a tumor size of less than 2.0 cm in diameter located in the left upper division who underwent resection between June 1998 and December 2005. The patients were divided into two groups as follows: LTS (31), left upper lobe trisegmentectomy; LUL (55), left upper lobectomy. We evaluated these groups with respect to several factors. RESULTS: The characteristics of the two groups (LTS vs. LUL) demonstrated no significant differences with respect to gender, histological type, tumor size, or upstaging of pathological node, or the mode of video-assisted thoracic surgery (VATS). Patients with LTS had a significantly lower pulmonary function compared to the LUL group. There were no significant differences between the two groups with respect to factors such as blood loss and duration of chest tube drainage. Morbidity and recurrence rates did not differ between the two groups, and there was no mortality in our series. The overall survival rate at 5 years was 69.7 % in the LTS and 72.5 % in the LUL group. There was no significant difference in survival rates between the LTS and the LUL group after resection. CONCLUSION: LTS may be suitable as a standard treatment if the tumor is small and the suspected margins are well away from the lingula.