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The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation^{1,2}. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole^3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of 8.4_{-1.1}^{+0.5} Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow., 50 pages, 18 figures, 3 tables, author's version of the paper published in Nature

We previously synthesized two retinoid X receptor (RXR) agonists, 4'-hydroxy-3'-propyl-[1,1'-biphenyl]-3-propanoic acid ethyl ester (4'OHE) and 6-hydroxy-3'-propyl-[1,1'-biphenyl]-3-propanoic acid ethyl ester (6OHE), based on the structure of magnaldehyde B, a natural product obtained from Magnolia obovata. 4'OHE and 6OHE exhibited different selectivities for peroxisome proliferator-activated receptor (PPAR)/RXR heterodimers. To examine the regulatory effects of these compounds in adipogenesis, 3T3-L1 mouse preadipocytes were treated with a differentiation cocktail with or without test compounds to induce differentiation, and subsequently treated with test compounds in insulin-containing medium every alternate day. Lipid droplets were stained with Oil Red O to examine lipid accumulation. In addition, adipogenesis-related gene expression was measured using RT-qPCR and immunoblotting. The results showed that a PPARγ agonist, 4'OHE, which exerts agonistic effects on PPARγ and RXRα, enhanced adipogenesis similar to rosiglitazone. However, unlike GW501516, a PPARδ agonist, 6OHE and its hydrolysis product (6OHA), which exert agonistic effects on PPARδ and RXRα, suppressed adipogenesis. In a manner similar to 6OHE and 6OHA, bexarotene, an RXR agonist, suppressed adipocyte differentiation, and its anti-adipogenic effect was reversed by an RXR antagonist. Furthermore, 6OHA and bexarotene inhibited the increase in Pparγ2 and Cebpa mRNA levels 2 days after the induction of differentiation. We demonstrated the adipogenic effect of 4'OHE and anti-adipogenic effects of 6OHE and 6OHA in 3T3-L1 cells. Previously, RXR agonists have been reported to positively regulate the differentiation of mesenchymal stem cells into adipocytes, but our current data showed that they inhibited the differentiation of preadipocytes, at least 3T3-L1 cells, into adipocytes.

Background Image-sharpening algorithms with color adjustments enable real-time processing of the surgical field with a delay of 4 msec for heads-up surgery using digital three-dimensional displays. The aim of this study was to investigate the usefulness of the algorithms with the Artevo 800® digital microscope. Methods Seven vitreoretinal surgeons evaluated the effects of image-sharpening processing on the clarity of the surgical field with the Artevo 800® system that is used for cataract and vitreous surgeries. The scorings were made on a 10-point scale for anterior capsulotomy, phacoemulsification, cortex aspiration, core vitrectomy, and peeling of an epiretinal membrane or an internal limiting membrane. In addition, the images during the internal limiting membrane peeling were processed with or without color adjustments. We also evaluated the skewness (asymmetry in the distribution of the pixels) and kurtosis (sharpness in the distribution of the pixel) of the images to evaluate the contrast with each intensity of image-sharpening. Results Our results showed that the mean visibility score increased significantly from 4.9 ± 0.5 at 0% (original image) to 6.6 ± 0.5 at 25% intensity of the image-sharpening algorithm (P P = 0.012). The mean skewness decreased significantly from 0.83 ± 2.02 at 0% (original source) to 0.55 ± 1.36 at 25% intensity of the image-sharpening algorithm (P = 0.01). The mean kurtosis decreased significantly from 0.93 ± 2.14 at 0% (original image) to 0.60 ± 1.44 at 25% intensity of the image-sharpening algorithm (P = 0.02). Conclusions We conclude that the image-sharpening algorithms can improve the clarity of the surgical field during 3D heads-up surgery by decreasing the skewness and kurtosis. Trial registration This was a prospective clinical study performed at a single academic institution, and the procedures used were approved by the Institutional Review Committee of the Kyorin University School of Medicine (reference number, 1904). The procedures also conformed to the tenets of the Declaration of Helsinki.

Background To determine the incidence and characteristics of the multiple subretinal particles (SRPs) present after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Methods The medical records of 224 eyes of 224 patients that underwent PPV for RRD were reviewed. The presence of SRPs in the subretinal fluid blebs and the presence of subretinal deposits were determined by optical coherence tomography (OCT) and fundus autofluorescence (FAF). The characteristics of the FAF and infrared reflectance (IR) images of a scanning laser ophthalmoscope in eyes with SRPs (SRPs group) were compared to that of eyes without SRPs (control group). Results SRPs were observed in 27 eyes (12%), and they were completely resolved in 20 eyes (74%) after 6 months. The incidence of macula-off RRD (85%) and preoperative precipitates (41%) were significantly higher in the SRPs group than that in the control group (64%, P = 0.046; 12%, P = 0.002). The axial length was significantly shorter in the SRPs group than that in the control group (25.04 ± 1.54 mm, 26.00 ± 1.78 mm, P = 0.012). The preoperative and postoperative best-corrected visual acuity were not significantly different between the two groups (P = 0.702, P = 0.337). The subretinal fluid bleb determined by OCT were hyperfluorescent in the FAF images in 24 eyes (89%), and the subretinal deposits were hypofluorescent with solid appearance by OCT other than fluid in 3 eyes (11%). The hypofluorescent subretinal deposits in the FAF images were bright in the IR images in 2 eyes. Conclusions The SRPs consist of lipofuscin-related hyperfluorescent subretinal fluid and the subretinal deposits containing bright IR melanin particles of proliferating retinal pigment epithelial cells.

We conducted clinical and experimental studies to investigate the effects of image-sharpening algorithms and color adjustments, which enabled real-time processing of live surgical images with a delay of 0.004 s. The images were processed with image-sharpening intensities of 0%, 12.5%, 25%, and 50% during cataract surgery, vitrectomy, peeling of epiretinal membrane, and peeling of internal limiting membrane (ILM) with the Ngenuity 3D visualization system. In addition, the images obtained with a yellow filter during the ILM peeling were processed with color adjustments. Five vitreoretinal surgeons scored the clarity of the images on a 10-point scale. The images of a 1951 United States Air Force grating target placed in no fluid (control), saline, and 0.1% and 1% milk solution were evaluated. The results showed that the mean visibility score increased significantly from 5.0 ± 0.6 at 0% to 6.4 ± 0.6 at 12.5%, 7.3 ± 0.7 at 25%, and 7.5 ± 0.9 at 50% (P P = 0.005). In the experimental study, the contrast of the grating targets blurred by the 0.1% and 1% milk solution increased significantly by the image-sharpening procedure. We conclude that the image-sharpening algorithms and color adjustments improved the intraoperative visibility of 3D heads-up surgery.

The factors affecting the survival of patients with aspiration pneumonia (AP) remain unclear. This study aimed to determine whether factors, including oral status, swallowing function, and oral intake level, were related to survival outcomes in older patients hospitalized for AP. The study enrolled patients with AP who were admitted to our hospital between February 2017 and November 2019. Patients were divided into two groups based on the 90-day mortality after the first swallowing function evaluation: survivors and deceased. The data were compared between the two groups. A total of 29 patients were diagnosed with AP. Of these patients, 13 died within 90 days. The numbers of patients who could not use removable dentures and required sputum suctioning and had cough reflex at rest were significantly higher in the deceased than in the survivors. The salivary pooling and pharyngeal clearance scores evaluated by videoendoscopy, International Dysphagia Diet Standardisation Initiative Functional Diet Scale score determined after swallowing function evaluation, and consciousness level were significantly worse in the deceased than in the survivors. There were significant differences in patients’ oral status, swallowing function, oral intake level, and consciousness level between the survivors and deceased.

To compare the quality of images viewed through an extended depth of focus (EDF) intraocular lens (IOL) to that through multifocal or monofocal IOL. Experimental study EDF IOL (Symfony®, ZXR00V, Johnson & Johnson Vision), diffractive multifocal (ZLB00, + 3.25D or ZMB00, + 4.0D), or monofocal (ZCB00V) IOL with a spherical power of + 20.0 diopter (D) was placed in a fluid-filled model eye with corneal aberrations similar to those of human eyes. A United States Air Force Resolution Grating Target was glued to the posterior surface of the model eye and viewed through a flat contact lens, a 60D or 128D wide-angle non-contact lens (Resight®) or wide-angle contact lens (MiniQuad®). The contrast of the grating images recorded with the EDF and multifocal IOLs were compared to those through the monofocal IOL. The grating images viewed through the flat contact lens were slightly blurred when viewed through the EDF IOL but clearer than those through the multifocal IOLs with very blurred images in the periphery. The contrast of the images viewed through the EDF and multifocal IOLs through the flat contact lens was significantly lower than through the monofocal IOL (P

Anti-vascular endothelial growth factor treatment for macular edema secondary to branch retinal vein occlusion generally provides good visual acuity (VA) improvement but may require repeated injections for years. To reduce the number of patients who suffer from avoidable VA loss caused by treatment drop-out, providing prospects of the correlation between expected vision improvement and required number of injections at the early stages of treatment may be helpful. In this post hoc analysis of the phase IV, randomized, open-label ZIPANGU study, we investigated the correlation between the data from Month 2 and Month 12 in terms of VA and required ranibizumab injection numbers. Fifty-nine patients were evaluated (ranibizumab monotherapy, 29; combination therapy, 30). In the monotherapy group, patients who received 1 and 3 injections by Month 2 received a mean total of 2.8 and 8.3 injections during the year, respectively. Data from the combination group were similar. The correlation coefficients for VA scores at Months 2 and 12 were 0.60 and 0.51 for the monotherapy and combination groups, respectively (both p

Coffee-agroforestry includes biodiversity conservation in tropical regions. The least economically valuable yet widely cultivated “robusta” coffee was studied in Panama, considering management practices and tree diversity. Fifty households were interviewed and a detailed tree census was conducted in 29 coffee plots owned by 13 households. Besides C. canephora there were 638 stems of 90 species in 41 plant families. Coffee plantings ≤ 10 years of age had higher tree diversity. With different degrees of management and original forest conditions, the coffee-agroforestry landscape was not uniform. Local vegetation was partly conserved. Farmers did not focus directly on productivity but instead emphasized flexible use and management, with moderate labor input, under changing socio-economic circumstances. Such rustic management, with attitudes and actions not governed by immediate monetary benefit, influenced biodiversity and rural life.

Background Perimenopausal women experience a wide variety of systemic symptoms: hot flashes, sweating, mental health concerns and various oral sensory complaints (OSC). OSC in perimenopausal women include xerostomia, taste disturbance and burning mouth. However, the factors associated with these OSC have not been identified. The purpose of this investigation was to elucidate the factors associated with OSC in perimenopausal women. Methods The study cohort comprised 43 perimenopausal women aged 45–55 years. Data on medical history, medications, menstrual status, menopausal symptoms, quality of life, xerostomia, taste disturbance and burning mouth were collected. Volumes of unstimulated and stimulated saliva were measured. Tongue coating was evaluated according to a tongue coating index. Univariate analysis was performed to identify factors significantly associated with having xerostomia, taste disturbance, burning mouth and more than two OSC (2OSC). Next, the factors strongly associated with these symptoms were examined by logistic regression analysis. Results The number of menopausal symptoms was significantly higher, and volume of unstimulated saliva was significantly lower in participants with xerostomia, taste disturbance, burning mouth or 2OSC than in those without these characteristics. Agents targeting the central nervous system were more frequently taken by participants with burning mouth and 2OSC than by those without these characteristics. According to logistic regression analysis, the number of menopausal symptoms was an explanatory variable for xerostomia, taste disturbance, burning mouth and 2OSC. Conclusions Our findings suggested that OSC associated with the number of menopausal symptoms. Management of menopausal symptoms may decrease OSC, leading to improved quality of life of perimenopausal women.

Three new sesquiterpenes, phlebidiol, phlebioic acid, and phlebiolide, as well as the known compound tremetriol, were isolated from cultures of the basidiomycete Phlebia tremellosa. The structures of all isolated compounds were established by extensive spectroscopic analyses, including those involving extensive two-dimensional nuclear magnetic resonance. The absolute configurations of phlebidiol, phlebioic acid, and phlebiolide were determined by comparisons of experimental and calculated electronic circular dichroism spectra. Phlebidiol and phlebioic acid have previously unreported carbon skeletons, for which we propose the skeletal names “seco-sterpurane” and “phlebiane,” respectively. Phlebiolide is also the second published example of a merulane sesquiterpene. Electronic supplementary material The online version of this article (10.1007/s11418-019-01286-8) contains supplementary material, which is available to authorized users.

Pathological aggregates of tau proteins accumulate in the brains of neurodegenerative tauopathies including Alzheimer’s disease and frontotemporal lobar degeneration (FTLD-tau). Although immunotherapies of these disorders against tau are emerging, it is unknown whether nasal delivery, which offers many benefits over traditional approaches to vaccine administration, is effective or not for tauopathy. Here, we developed vaccination against a secreted form of pathological tau linked to FTLD-tau using a Sendai virus (SeV) vector infectious to host nasal mucosa, a key part of the immune system. Tau vaccines given as nasal drops induced tissue tau-immunoreactive antibody production and ameliorated cognitive impairment in FTLD-tau model mice. In vivo imaging and postmortem neuropathological assays demonstrated the suppression of phosphorylated tau accumulation, neurotoxic gliosis, and neuronal loss in the hippocampus of immunized mice. These findings suggest that nasal vaccine delivery may provide a therapeutic opportunity for a broad range of populations with human tauopathy., 認知症に対する点鼻ワクチンの開発 --遺伝子治療による免疫療法と分子イメージング--. 京都大学プレスリリース. 2020-03-26.

Neuronal cell death induced by amyloid-β (Aβ) oligomers is implicated in neuronal degeneration and is a leading cause of Alzheimer's disease (AD). Therefore, to identify effective therapeutic agents for AD, we investigated the neuroprotective effects of two naturally occurring retinoid X receptor (RXR) agonists (SPF1 and SPF2), isolated from the root of Sophora tonkinensis Gagnep., on the Aβ

Joint bleeding and resultant arthropathy are major determinants of quality of life in haemophilia patients. We previously developed a mesenchymal stromal cell (MSC)-based treatment approach for haemophilic arthropathy in a mouse model of haemophilia A. Here, we evaluated the long-term safety of intra-articular injection of lentivirally transduced autologous MSCs in non-human primates. Autologous bone-marrow-derived MSCs transduced with a lentiviral vector expressing coagulation factor VIII (FVIII) were injected into the left knee joint of cynomolgus monkeys. We first conducted codon optimization to increase FVIII production in the cells. Lentiviral transduction of autologous MSCs resulted in a significant increase of FVIII in the culture supernatant before transplantation. We did not find any tumour generation around the knee structure at 11-16 months after injection by magnetic resonance imaging. The proviral sequence of the simian immunodeficiency virus lentiviral vector was not detected in the heart, lungs, spleen, liver, testis, or bone marrow by real-time quantitative PCR. We confirmed the long-term safety of intra-articular injection of transduced MSCs in a non-human primate. The procedure may be an attractive therapeutic approach for joint diseases in haemophilia patients.

Community-based forest management is unlikely to be sustainable without a process of social learning between the internal and external actors. This situation is evident in West Lampung District in Lampung Province, Indonesia. This research assessed the processes and outcomes of social learning within three villages (i.e. Villages A, B and C) in West Lampung District that were engaged in a community forestry (CF) program. The data was gathered through questionnaire and interview which then analyzed with Likert Scale. The CF program outcomes were different in each village. Village A had the highest scores for facilitation, egalitarian atmosphere, repeated meetings, and diverse participation. This has resulted in a high level of community involvement in the CF program. In particular, the high level of facilitation by external actors such as training programs, and marketing information and funding has resulted in the community having a good knowledge of CF and the associated socioeconomic development programs available to them. Village B has highest score for multiple sources of knowledge variable. Due to the existing egalitarian atmosphere, each stakeholder in Village A can openly express their opinion without any hesitation, particularly between men and women. Meanwhile, the other sub variables of existing egalitarian atmosphere were scored the same for Village A, B, and C, such as the balances between old and young people as well as rich and poor people. In general, the implemented social learning has a greater positive effect on the livelihoods of CF group members in Village A compared to Villages B and C.

A new stepped septum-type waveguide circular polarizer (SST-CP) was developed to operate in the 230 GHz band for radio astronomy, especially submillimeter-band VLBI observations. For previously reported SST-CP models, the 230 GHz band is too high to achieve the design characteristics in manufactured devices because of unexpected machining errors. To realize a functional SST-CP that can operate in the submillimeter band, a new method was developed, in which the division surface is shifted from the top step of the septum to the second step from the top, and we simulated the expected machining error. The SST-CP using this method can compensate for specified machining errors and suppress serious deterioration. To verify the proposed method, several test pieces were manufactured, and their characteristics were measured using a VNA. These results indicated that the insertion losses were approximately 0.75 dB, and the input return losses and the crosstalk of the left- and right-hand circular polarization were greater than 20 dB at 220–245 GHz on 300 K. Moreover, a 230 GHz SST-CP was developed by the proposed method and installed in a 1.85-m radio telescope receiver systems, and then had used for scientific observations during one observation season without any problems. These achievements demonstrate the successful development of a 230 GHz SST-CP for radio astronomical observations. Furthermore, the proposed method can be applicable for observations in higher frequency bands, such as 345 GHz.

Background To compare the efficacy of 12-month denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTMs) between treatment-naïve osteoporosis patients with rheumatoid arthritis (RA) and those with previous bisphosphonate (BP) therapy. Methods A total of 36 RA patients with osteoporosis completed 12-month follow-up. Twenty-five patients were osteoporotic treatment-naïve (naïve group), and 11 patients were previously treated with BPs (switch group) (average 7.9 years). BMD and BTMs were measured before and 6 and 12 months after treatment. Results BTM levels were higher in the naïve group at baseline. However, the same level of suppression was achieved at 6 months in both groups. Spine BMD increased significantly in both groups. There was no significant difference in the mean percent changes of BMD of the spine (naïve group: 6.8 ± 0.8, switch group: 5.1 ± 1.5), femoral neck (2.9 ± 1.4, 2.9 ± 1.3), and total hip (1.7 ± 0.9, 1.4 ± 1.1) between these two groups at 12 months. Conclusions The effects of denosumab on BMD and BTMs of the switch group after long-term BP treatment are comparable to those of the naïve group in RA patients. Thus, switching BPs to denosumab is one of the useful options to treat osteoporosis with RA.

We examined how attention alters chewing and swallowing behaviors. Twenty-one healthy volunteers were asked to freely eat 8 g of steamed rice in three separate trials, and we obtained the average number of chewing cycles (N) and chewing duration (T) prior to the first swallow in each trial. We also conducted an N-limited test, in which participants chewed the food while independently counting the number of chewing cycles and swallowed the food when they reached N, and a T-limited test, in which they chewed the food for T sec and then swallowed. We recorded electromyograms (EMGs) from masseter and suprahyoid muscles and collected videoendoscopic images. In the N-limited test, chewing speed decreased, masseter muscle activity (area under the curve of the rectified EMG burst) per cycle increased, and suprahyoid muscle activity per cycle decreased. In the T-limited test, the chewing speed increased, muscle activities per cycle decreased, and the number of cycles increased. The occurrence frequency of bolus propulsion into the pharynx before swallowing was smaller in the N- and T-limited tests than in the free chewing test. Further, the whiteout time was longer in the T-limited test than in the free chewing test. Attentional chewing changes not only chewing but also swallowing behavior.

Inflammation induced by innate immunity influences the development of T cell-mediated autoimmunity in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). We found that strong activation of innate immunity induced Nod-like receptor protein 3 (NLRP3) inflammasome-independent and interferon-β (IFNβ)-resistant EAE (termed type B EAE), whereas EAE induced by weak activation of innate immunity requires the NLRP3 inflammasome and is sensitive to IFNβ treatment. Instead, an alternative inflammatory mechanism, including membrane-bound lymphotoxin-β receptor (LTβR) and CXC chemokine receptor 2 (CXCR2), is involved in type B EAE development, and type B EAE is ameliorated by antagonizing these receptors. Relative expression of Ltbr and Cxcr2 genes was indeed enhanced in patients with IFNβ-resistant multiple sclerosis. Remission was minimal in type B EAE due to neuronal damages induced by semaphorin 6B upregulation on CD4+ T cells. Our data reveal a new inflammatory mechanism by which an IFNβ-resistant EAE subtype develops.

Climate change spurs havoc on social-ecological system. People and places vulnerable to climate change have been the focus of many discussions. However, in the forestry sector, limited studies have been conducted that link human vulnerability to recent initiatives, such as reducing emissions from deforestation and forest degradation or REDD+, especially in highly vulnerable countries. Using case studies from the Philippines, this paper focuses on the vulnerability of two community-based forest management (CBFM) organizations, with and without REDD+ readiness intervention, to show the impacts of climate variability and extremes. Two balance-weighted approaches, the livelihood vulnerability index and the IPCC-framework, were used in the vulnerability assessments. Results revealed high vulnerability of both CBFM organizations, although Malitbog Upland Developers for Sustainable Association (MUDSA) livelihood vulnerability is largely aggravated by its exposure to disaster, climate variability and extremes, accessibility to health facilities and water supply. The long history of CBFM implementation in both organizations have minimal contribution in enhancing the adaptive capacity of members to cope with and adapt to climate change impacts. REDD+ (readiness), does not insure reduced vulnerability to climate change, unless sustainable livelihood is achieved. As the State controls forest resources, the rights of CBFM-organizations to commercially benefit from these resources are limited, a disincentive to the development of new and viable development programs in CBFM areas, such as REDD+. This also constrains the achievement of climate resiliency.

This study demonstrates the potential of transformation strategy (an approach that emphasizes strengthening interdependence among social and ecological systems) to rehabilitate degraded land by examining two cases in Bangladesh and one in the Philippines. The study considers the benefits obtained from forests and forest-related activities in the form of income and energy sources as key parameters to link the social system (local people) with the ecological system (forest). Qualitative and quantitative analysis of data on land use and socio-economic changes indicates that the transformation strategy improved both the wellbeing of local people and forest cover. In the case of the Philippines, social and ecological linkages were found to be strong, with local people rehabilitating the degraded land while also obtaining a high proportion of their total income from the activity. For the two Bangladesh cases, however, the level of dependency on the forest for livelihood declined as local people used their income from the forest and forest-related activities for diversification to non-forest activities.

The article Sesquiterpenes with new carbon skeletons from the basidiomycete Phlebia tremellosa, written by Ken ichi Nakashima, Junko Tomida, Takao Hirai, Yoshiaki Kawamura and Makoto Inoue was originally published Online First without Open Access.

Neuronal cell death induced by amyloid-β (Aβ) oligomers is implicated in neuronal degeneration and is a leading cause of Alzheimer's disease (AD). Therefore, to identify effective therapeutic agents for AD, we investigated the neuroprotective effects of two naturally occurring retinoid X receptor (RXR) agonists (SPF1 and SPF2), isolated from the root of Sophora tonkinensis Gagnep., on the Aβ25-35-induced cytotoxicity against nerve growth factor-differentiated rat pheochromocytoma (PC12) cells. Pretreatment with SPFs significantly prevented Aβ25-35-induced apoptosis in PC12 cells, similarly to the synthetic RXR agonist bexarotene. These effects were blocked by the RXR antagonist PA452. When the effects of SPFs were studied in the presence of the liver X receptor (LXR) agonist T0901317, the protective effects of SPFs were enhanced, suggesting that RXR/LXR heterodimers may play a key role in the neuroprotective effects of SPFs. SPFs and T0901317 induced ATP-binding cassette transporter 1 (ABCA1) protein expression in PC12 cells when administered alone or in combination. Intriguingly, a functional inhibitor of ABCA1 cyclosporine A negated the neuroprotective effects of SPFs or T0901317. Taken together, these results demonstrate that the RXR agonists SPF1 and SPF2 protect PC12 cells from Aβ25-35-induced neurotoxicity in an RXR-dependent manner and that their effects are markedly enhanced by the LXR agonist T0901317, in part related to ABCA1 function. These results suggest a novel approach to the treatment or prevention of AD.

This study aimed to elucidate the relationship between the piezoelectric waveform latency, hyoid bone movement, surface electromyogram (sEMG), and the pharyngeal transit time (PTT) during swallowing. Forty-one healthy subjects were divided into three age groups: younger (20-39 years, n = 8), middle-aged (40-59 years, n = 9), and older (60-79 years, n = 24). Motion analysis of the hyoid bone using videofluorography (VF), waveform analysis of the front neck using piezoelectric films, and sEMG of the suprahyoid muscle group were performed simultaneously. Latencies of the three movement phases were defined as upward (VFS1), forward (VFS2), and returning to starting position (VFS3). The three phases of the piezoelectric waveform-from wave initiation of the negative wave to the start of the second deep negative wave; from the start of the second deep negative wave to the start of the last positive wave (SLPW); and from the SLPW to the end of the last positive wave-were defined as PS1, PS2, and PS3, respectively. VFS1-3 and PS1-3 were significantly correlated. VFS1 and PS1 latencies were significantly longer with thick liquid than with thin liquid. VFS2, PS1, and PS2 latencies were longer in the older group than in the other two groups. The start of PS1 was nearly equal to those of sEMG and VFS1. Bolus arrival time in the valleculae was statistically equal to the end of the PS1 with both thin and thick liquids. To establish the swallowing screening using Piezoelectric film, further investigation is necessary in the dysphagia patients.

Unsustainable land use systems in the Chittagong Hill Tracts (CHT) have damaged the environmentandenhancedvulnerabilityofindigenous people. Promoting improved land use in degraded and abandoned shifting cultivation areas has been widely suggested for better livelihoods and environmental conservation. This article analysed four major land uses, agroforestry, fruit orchards, shifting cultivation and village common forest (VCF), in the CHT by correlating them with local perceptions. Traditionally, the indigenous people of the CHT are dependent on shifting cultivation and VCF for their livelihood. Agroforestry and orchards are newly introduced land uses in the CHT area. This analysis is performed by using the Strength, Weakness, Opportunity and Threat (SWOT) approach in combination with the Analytic Hierarchy Process (AHP). The introduction of agro- forestry and fruit orchards influenced marginalised indigenous people to reduce the shifting cultivation area. However, potential weaknesses and threats were associated with shifting cultivation, agroforestry and fruit orchards. Except for shifting cultivation, the positive factors of other land uses outweighed the negative ones. The AHP results indicate that while adopting a land use, the respondents prioritised economic benefits (75 % preference) over social (17 %) and environmental aspects (8 %). Considering these three factors, people ranked four land uses in the order of orchards(agroforestry(VCF(shifting cultivation. This suggests that future land use planning in the CHT cannot secure sustainability by mere trade- offs among the three sustainability factors (social, economic, environmental). Instead, if the activities for achieving social and environmental benefits of a project can be employed to create benefits in terms of income or savings (money/effort/time), they will be well accepted by the marginalised rural communities.

Background To evaluate the quality of the images obtained by an ultra-widefield device in gas-filled eyes after vitrectomy for a retinal detachment. Methods Retrospective case series. The ultra-widefield scanning laser ophthalmoscopic images (Optos 200Tx imaging system) of 40 eyes that were gas-filled with 40 to 90% of the vitreous cavity after vitrectomy for a rhegmatogenous retinal detachment were studied. The rates of detecting the rates of reattachments and the causative retinal tears that were treated and were in the superior or inferior areas in eyes with intravitreal gas of ≥60% were compared to that to eyes with intravitreal gas of

To evaluate the surgical outcomes of small-gauge vitrectomy with subretinal injection of recombinant tissue plasminogen activator (rt-PA) for a submacular hemorrhage caused by a ruptured retinal arterial macroaneurysm (RAM). Non-comparative, consecutive case-series performed at two ophthalmological institutions. We examined 22 eyes of 22 patients with a submacular hemorrhage associated with a RAM but without a preretinal or sub-internal limiting membrane hemorrhage at the fovea. During 25-gauge vitrectomy, approximately 4000–8000 IU of rt-PA was injected subretinally, followed by the injection of air or 10 % sulfur hexafluoride as a tamponade. The patients maintained an upright position for 1 hour, then turned to a facedown position for 1 to 3 days. The best-corrected visual acuity (BCVA) and postoperative complications were evaluated. The average interval from the onset of symptoms to surgery was 8.4 ± 7.6 days, and the average size of the subretinal hemorrhage was 3.4 ± 1.0 disc diameters. The submacular hemorrhage was displaced from the foveal area in all eyes after 1 week. The mean baseline BCVA was 1.41 ± 0.41 logMAR units, and it improved to 0.91 ± 0.43 at 1 month and to 0.64 ± 0.45 at the final visit (P = 0.0001, P

The purpose of this study was to evaluate the clinical features, optical coherence tomography (OCT) findings, and surgical outcomes of eyes with macular retinoschisis associated with glaucomatous optic neuropathy and normal intraocular pressure (IOP). In this retrospective interventional observational study, 11 eyes of 11 patients who underwent pars plana vitrectomy for macular retinoschisis and glaucomatous optic neuropathy were studied. All eyes had a vertical cup-to-disc ratio of ≥0.7 and retinal nerve fiber layer (RNFL) defects. Intraocular pressure (IOP) was

Homestead forests in the Teknaf Peninsula ecologically critical area of Cox’s Bazar in Bangladesh have not been widely studied. This paper explores floristic diversity of homestead forests together with their contribution to the household economy and climate change mitigation. Data were collected from a survey of 140 households and a vegetation survey of 70 homesteads in three sites. Villagers allocated 70 % of their homestead area for homestead forestry and altogether 73 plant species were recorded from the study sites. The average density was 4,000 plants/ha. The above-ground biomass was estimated 235.45 Mg/ha, equivalent to 117.73 Mg C/ha. Villagers maintain sustainability of homestead forests by planting seedlings every year and thus ensure several diameter and height classes. Homestead forests contribute substantially to household income, provide fuelwood and timber for own consumption and sale, and protect villagers during cyclones. Homestead forests thus meet the conditions to be a clean development mechanism forestry project which would provide a win–win strategy for involving small-scale farmers in climate change mitigation and adaptation initiatives, and biodiversity conservation.

Even though many forest villagers have been living on forest department land and serving the department in the northeastern hill forests region of Bangladesh since the early 1950s, their livelihood has not yet been fully explored. This paper examines the livelihoods of forest villagers (Khasia ethnic people) and their contribution to forest conservation, using data from the Sylhet forest division. The forest villagers are well-endowed with all the elements of a sustainable livelihoods framework, though human capital in terms of education is not satisfactory. Strong social capital, stable natural capital and a productive market-oriented agroforestry system facilitate the generation of financial and physical capital that make the livelihoods of Khasia people sustainable. At the same time, their reciprocal contributions in terms of forest protection and plantation development support forest conservation. However, some institutional issues such as insecure land tenure with regular agreement renewal problems need to be resolved for the sake of their livelihoods and forest conservation. Lessons learned from the study can be utilized in formulating future participatory forest management schemes in the country.

Decentralized forest policy has been moderately successful in delivering resource-use rights to local people. At the same time, it is possible that decentralization leads to recentralization because governments never give their authority over forest resources. Recentralization studies have paid little attention to the potential of local dynamics to lead to institutional arrangements that affect forest outcomes. This paper uses a case study of Community-based Forest Management (CBFM) in the Philippines to explore how local realities lead to the development of effective institutions for forest management. In this case study, local informal regulations of forest resource use were created through the process of settling local conflicts among competing CBFM interests, including members and non-members of people’s organizations, and frontline foresters who are working at local level. Frontline foresters played a role as coordinator of institutional arrangements that regulate local forest exploitation within the CBFM implementation process. The behavior of frontline foresters affected by their own personalities and existing social relations among residents, can deter recentralization in some ways. More attention is needed on the role of frontline foresters and non-members of people’s organization as influential negotiators in state-society relations concerning forests.

When chewing solid food, part of the bolus is propelled into the oropharynx before swallowing; this is named stage II transport (St2Tr). However, the tongue movement patterns that comprise St2Tr remain unclear. We investigated coronal jaw and tongue movements using videofluorography. Fourteen healthy young adults ate 6 g each of banana, cookie, and meat (four trials per foodstuff). Small lead markers were glued to the teeth and tongue surface to track movements by videofluorography in the anteroposterior projection. Recordings were divided into jaw motion cycles of four types: stage I transport (St1Tr), chewing, St2Tr, and swallowing. The range of horizontal tongue motion was significantly larger during St1Tr and chewing than during St2Tr and swallowing, whereas vertical tongue movements were significantly larger during chewing and St2Tr than during swallowing. Tongue movements varied significantly with food consistency. We conclude that the small horizontal tongue marker movements during St2Tr and swallowing were consistent with a "squeeze-back" mechanism of bolus propulsion. The vertical dimension was large in chewing and St2Tr, perhaps because of food particle reduction and transport in chewing and St2Tr.

Decentralizing property rights from state control to user communities has encouraged people’s participation in forest management. Relatively few studies, however, examine the forest regulations required for exercising such property rights. To address this issue, Schlager and Ostrom’s ‘bundle of rights’ framework was used to examine various forms of property rights and regulations in three systems of community-based forest management. The field research was undertaken in the northern Philippines, using eight cases of community-based forest management at sites in the provinces of Nueva Vizcaya and Ifugao. Local communities were found to informally retain the authority to create locally crafted property rights and regulations in a central government-initiated program. While forest regulations and practices prescribed at the national level have improved forest conditions, the flow of forest benefits to communities has been limited because of decentralization without devolution of authority. A case study of a site initiated by a local government indicated that the transfer of responsibility from the central government to local government units can create more favourable conditions for the flow of forest benefits to communities. But due to a lack of clarity about devolution of cutting permits and about the locations of afforested critical watershed areas, authorized local users lose their authorization. When forest is managed traditionally, communities can have more assured rights than in government-initiated programs, particularly in relation to tree ownership. This is because individuals have the authority to devise collective-choice rights as well as operational rights.

Purpose The purpose of the current study was to assess the feasibility of diffusion tensor imaging (DTI) parameters for determining the prognosis of Alzheimer’s disease (AD). We also analyzed the correlation among DTI, voxel-based morphometry (VBM), and results of the mini-mental state examination (MMSE). Methods The subjects of this prospective study were patients with AD and mild cognitive impairment. We performed annual follow-ups with DTI, VBM, and MMSE for 2 or 3 years. On DTI, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the uncinate fascicles were measured. VBM was performed to provide a z-score for the parahippocampal gyrus. The correlations among these factors were evaluated in the same period and the next period of the follow-up study. Results For evaluation of the same period, both DTI parameters and z-scores showed statistically significant correlations with the MMSE score. Also for evaluation of the next period, both DTI parameters and z-scores showed statistically significant correlations with the MMSE score of the next period. We observed a statistically significant correlation between the ADC value of the uncinate fascicles and the z-score of the next period. Conclusions Diffusion tensor parameters (ADC and FA) of the uncinate fascicles correlated well with cognitive function in the next year and seemed to be feasible for use as biomarkers for predicting the progression of AD. In addition, the white matter changes observed in the ADC seemed to precede changes in the gray matter volume of the parahippocampal gyrus that were represented by z-scores of VBM.

Decentralized forest management is a pivotal approach in Ethiopia for balancing biodiversity conservation with demand for economic development, and for improving forest-dependent local peoples’ livelihoods. With the aim of filling the literature gap on Ethiopia, this paper explores the dynamics of decentralization in the forestry sector using the actor-power-accountability framework. Generally, three forms of decentralization are practiced: deconcentration to government administrative branches, devolution of selected decision-making power to local people, and delegation to enterprises. Although transfer of meaningful discretionary power to local people or to downwardly accountable lower-tier governments is a precondition for achieving positive outcomes from decentralization, this prerequisite has been realized in none of the three forms decentralization. Overall, three important trends emerged from the latest decentralization reform, which was a switch from the conservation-oriented deconcentration form of decentralization to the income generation-oriented delegation form of decentralization. Those trends are as follows: monetary income generation for local people through enterprise, albeit with possible risk of being deprived of income and subsistence opportunities on which local people depend for their livelihoods; moving decision-making power away from the grassroots; and lack of incentive to manage natural forests, a major source of biodiversity.

We have proposed minimum requirements for commissioning and long-term quality assurance (QA) of an Elekta multi-leaf collimator (MLC) for volumetric modulated arc therapy (VMAT). The MLC leaf position accuracy during VMAT delivery was evaluated with the use of three different QA test plans: (1) a leaf gap-width test between opposing leaves by measurement of the isocenter dose during constant-gap sliding-window delivery with varied dose rates, MLC leaf speeds, and gantry angles; (2) a leaf position test by picket-fence delivery with and without gantry rotation; and (3) a leaf-bank symmetry test by measurement of the field geometry with different collimator angles at a fixed gantry position. All the QA test plans were created using an ERGO++ treatment-planning system. The leaf gap-width deviation was within 0.2 mm, the leaf position deviation was within 0.5 mm, and the leaf-bank symmetry error was within 0.5 mm under all the test conditions. MLC leaf position accuracy and long-term stability were confirmed by the proposed procedures.

To evaluate the relationship between compliance with ophthalmic examinations before vitrectomy for proliferative diabetic retinopathy (PDR) and postoperative vision. The clinical findings and visual acuity in 128 eyes of 94 patients who had undergone vitrectomy for PDR were reviewed. The patients were divided into the never-examined group with no previous ophthalmic examination until the first visit when vitrectomy was prescribed, the noncompliant group with a history of missing ophthalmic examinations over a 1-year period, and the compliant group with ophthalmic examinations at least once a year before the vitrectomy. Compliance with general medical examinations in the never-examined group (19 %) and in the noncompliant group (26 %) was significantly lower than that in the compliant group (100 %; P

Social forestry as a development strategy has evolved since the 1970s, especially in the tropics, to address forest degradation and promote local community development amidst the burgeoning population in these areas. As a practice, however, social forestry has been in place since ancient times in many parts of the world, including Japanese forest communities. Forest-people relationships in Japan drastically changed through massive afforestation programs after the energy source change and with the industrialization of the forest sector in 1950s. The majority of the planted forests are underutilized today and forest communities are marginalized due to the decline of forestry operations, depopulation, and changes in people’s values. Some communities address this concern by inviting potential urban migrants who may be interested in settling in rural areas. Using the case of the Nishiawakura Village in Okayama Prefecture, this paper explores the recent challenges confronting social forestry in Japan. It is found that underutilization of forest resources can be a cause of serious environmental degradation and marginalization of forest communities, and that Nishiawakura’s journey to renew forest management in partnership with migrants is a process of revisiting and creating the forest-people relationship. This study advances two related arguments, namely (1) the interaction of the local people and the migrants brings new perspectives to forest management, and (2) in a community facing depopulation and underutilization of forest resources, social forestry can be an effective approach to rediscover traditional forest management in a new form and revitalize forests and local communities.

2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) is known to accumulate in benign conditions such as infection and inflammation as well as in malignancy. Vaccination may cause transient inflammation of lymph nodes, which may induce false-positive findings on FDG-positron emission tomography (PET) imaging. This study investigated the influence of influenza vaccination on FDG-PET/CT imaging in normal subjects.Between November 2008 and March 2009, a total of 172 examinees underwent FDG-PET/CT during an annual cancer-screening program at our hospital, 83 of whom had a history of recent non-adjuvanted seasonal influenza vaccination. They were asked the date and injection site of the vaccination. Examinees were divided into 2 groups based on the interval after vaccination using a cutoff value of 7 days (1 week). Two double board-certified nuclear medicine physicians and radiologists visually interpreted the FDG-PET/CT images with reference to PET/CT fusion and CT images and checked the location and the number of abnormal accumulations by consensus reading.Intervals between vaccination and FDG-PET were less than 7 days in 5 examinees, and 7 days or more in 78 examinees. Unexpected accumulations were visualized in 4 examinees in the axilla and medial upper arm, and all of them belonged to the group who underwent vaccination less than 7 days previously. In the second group there was no abnormal FDG accumulation.Recent influenza vaccination before FDG-PET/CT examination may cause ipsilateral axillary lymph node accumulations, especially within several days after vaccination. Questionnaires about vaccination can help to avoid false interpretation of FDG avid axillary lymph nodes.

A 62-year-old man on continuous ambulatory peritoneal dialysis was transferred to our hospital with recurrent abdominal pain and a cloudy peritoneal effluent. Three weeks before the transfer, his symptoms were successfully treated with broad-spectrum antibiotics. However, their effectiveness was lost for his recurrent symptoms. Fungal peritonitis was diagnosed because of an increased white blood cell count in the peritoneal fluid on admission and isolation of Candida albicans from a peritoneal fluid culture. Intravenous fos-fluconazole was immediately started, although it was ineffective for his deteriorating symptoms. The concomitant isolation of Candida albicans in a stool culture suggested that fungal peritonitis had an enteric origin. An emergency laparotomy revealed multiple diverticulosis and sigmoid colon diverticulitis. A surgical drainage was performed in addition to peritoneal catheter removal. Postoperatively, the patient's symptoms improved rapidly and there were no signs of recurrence with continuous administration of fos-fluconazole. Surgical drainage accelerated the recovery from fungal peritonitis. This patient is the first case showing the usefulness of stool culture in the diagnosis of fungal peritonitis secondary to prior bacterial peritonitis. This case also demonstrated the importance of laparotomy to confirm the enteric origin of the fungus, and the efficacy of early surgical drainage for the treatment.

This report presents a case of nephrotic syndrome and renal failure that developed in a 53-year-old female with metastatic breast carcinoma. She was diagnosed to have osteolytic bone metastases 5 years prior to admission, and had been administered pamidronate with a total dose of approximately 6800 mg. A renal biopsy revealed tubulointerstitial damage and marked wrinkling and retraction of the glomerular basement membrane with hypertrophy and hyperplasia of the epithelial cells, compatible with the collapsing form of focal segmental glomerulosclerosis (FSGS). Despite the discontinuation of pamidronate after admission, her renal function gradually decreased. She was finally managed with continuous palliative care for advanced malignancy through a shared effort, and died 96 days after undergoing the renal biopsy. Although the clinical impact of the pamidronate-associated kidney injury on the longitudinal changes in renal function remains to be delineated, it is therefore reasonable to consider that the collapsing FSGS associated with tubulointerstitial damage may have resulted in the irreversible renal injuries that were observed in the current case. Further studies and accumulated experience with renal biopsy are required to better determine the relationship between pathological alterations and prognostic characteristics among patients with pamidronate-associated renal impairments.

Although the clinical benefits of antiviral treatment in the management of membranous nephropathy (MN) in patients with chronic hepatitis B virus (HBV) infection have been suggested, it should be evaluated more carefully. In this report, we present two cases with quiescent HBV who were administered lamivudine for either the initial treatment of MN or to control the reactivation of HBV during treatment with corticosteroids. No clinical benefit of lamivudine as an initial treatment was observed in one patient, which obliged us to commence administration of prednisolone (PSL). On the other hand, lamivudine seemed to play a pivotal role in the remission of an acute exacerbation of hepatitis B during treatment with PSL and mizoribine in the other patient. These two patients seemed to tolerate administration of PSL with or without an immunosuppressive agent well, since gradual and prompt improvements of nephrotic status were confirmed within a few months, thus suggesting the potential benefit of steroid treatment. There is little consensus regarding the optimal choice of steroids and immunosuppressants for the treatment of MN with chronic HBV infection, due to the potential for stimulation of viral replication and precipitation of hepatic flares. Our observations, however, suggest that treatment with PSL still should be reserved for quiescent HBV carriers with MN. Further studies will be required to determine the optimal timing and appropriate duration of antiviral treatment in such patients requiring long-term immunosuppression.

Sendai viral vector (SeV) is emerging as a promising vector for gene therapy. However, little information is available regarding the combination of SeV-mediated gene and mesenchymal stem cell (MSC) therapy in dealing with ischemic diseases. In this study, we infected SeV to the MSCs in vitro; and injected MSCs modified with SeV harboring human angiopoietin-1 gene (SeVhAng-1) into the ischemic limb of rats in vivo. We found SeV had high transductive efficiency to the MSCs. Both MSCs and SeVhAng-1-modified MSCs improved the blood flow recovery and increased the capillary density of the ischemic limb, compared with the control. However, in contrast to MSCs, SeVhAng-1-modified MSCs had a better improvement of blood flow recovery in the ischemic limb. We further found the ischemic limb injected with SeVhAng-1-modified MSCs had strong expression of p-Akt, which improved survival of MSCs injected into the ischemic limb. This indicated SeVhAng-1 modification enhanced angiogenetic effect of MSCs by both angiogenesis and cell protection. We conclude that SeVhAng-1-modified MSCs may serve as a more effective tool in dealing with ischemic limb disease.

To report the results of immunohistochemical analyses of a retinal angioma obtained from a patient with von Hippel-Lindau (VHL) disease.A 13-year-old girl with VHL disease presented with bilateral retinal angiomas and decreased vision in the right eye. Although transpupillary thermotherapy was performed to treat the angiomas, the tractional and exudative retinal detachment progressed OD, requiring vitreous surgery. Intraoperatively, a large retinal angioma was excised together with the surrounding retina to aid in reattaching the retina. The excised tissue was prepared for standard histopathology and immunohistochemistry.Histological examination showed that the excised tissue was made up of highly vascularized cells, and the retina was gliotic. The stromal cells had intracytoplasmic vacuoles and were located between the numerous vessels. These findings are identical to those of a hemangioblastoma. The stromal cells stained positively for vascular endothelial growth factor and neuron specific enolase, and weakly for glial fibrillary acidic protein. Some of the stromal cells stained positively for inhibin alpha. Isolated erythropoietin-positive cells, indicative of developmentally arrested angioblasts, were observed among the endothelial cells.The results indicate that stromal cells in retinal angiomas are neuroectodermal in origin with immunohistochemical features, for example, inhibin alpha, similar to cerebellar hemangioblastomas and renal cell carcinomas associated with VHL disease.

The Khasia ethnic community of Bangladesh has been a population of forest villagers in the north-eastern hill forests of Bangladesh since the early 1950s, practicing a betel leaf-based agroforestry system on land granted by the Forest Department. Taking a sample forest village of the Sylhet forest division as a case study, this article examines the sustainability attributes of betel leaf production in the agroforestry system. The presence of several positive attributes of sustainability including the composition of agroforestry, disease control, soil fertility management, profitability, socio-cultural acceptability and institutional support indicate that betel leaf production within the agroforestry system is stable under the prevailing traditional management system. Income from the sale of betel leaf is the principal livelihood means and villager’s reciprocal contributions help to conserve forest resources. However, problems with land ownership and regular agreement renewal need to be resolved for the sake of their livelihoods and forest conservation.

To determine the factors associated with high molecular weight adiponectin (HMW-ad) levels during the first year of life, the longitudinal changes in serum HMW-ad were investigated from birth to 12 mo of age. The total adiponectin levels, HMW-ad, and leptin were measured longitudinally from birth to 12 mo of age in 56 healthy infants (or=35 wk of gestation). Serum HMW-ad levels were positively correlated with total adiponectin levels (R2 = 0.93, p0.0001). Serum HMW-ad levels at birth, six, and 12 mo were 13.7 +/- 0.9 (mean +/- SE), 13.3 +/- 0.8, and 7.7 +/- 0.5 microg/mL, respectively. The levels at 12 mo were significantly lower than those at birth and 6 mo, respectively. In a multiple regression analysis, the HMW-ad levels at 12 mo were found to be related only to cord blood HMW-ad levels (beta = 0.680, p0.001) and not to any other factors. These results imply that postnatal production of HMW-ad at least during infancy may be regulated before birth. Further study is necessary to determine whether cord blood HMW-ad has an effect and whether it is involved in the development of metabolic syndrome.

We previously reported the development of a prototype 'oncolytic Sendai virus (SeV) vector' formed by introducing two major genomic modifications to the original SeV, namely deletion of the matrix (M) gene to avoid budding of secondary viral particles and manipulation of the trypsin-dependent cleavage site of the fusion (F) gene to generate protease-specific sequences. As a result, the 'oncolytic SeV' that was susceptible to matrix metalloproteinases (MMPs) was shown to selectively kill MMP-expressing tumors through syncytium formation in vitro and in vivo. However, its efficacy has been relatively limited because of the requirement of higher expression of MMPs and smaller populations of MMP-expressing tumors. To overcome these limitations, we have designed an optimized and dramatically powerful oncolytic SeV vector. Truncation of 14-amino acid residues of the cytoplasmic domain of F protein resulted in dramatic enhancement of cell-killing activities of oncolytic SeV, and the combination with replacement of the trypsin cleavage site with the new urokinase type plasminogen activator (uPA)-sensitive sequence (SGRS) led a variety of human tumors, including prostate (PC-3), renal (CAKI-I), pancreatic (BxPC3) and lung (PC14) cancers, to extensive death through massive cell-to-cell spreading without significant dissemination to the surrounding noncancerous tissue in vivo. These results indicate a dramatic improvement of antitumor activity; therefore, extensive utility of the newly designed uPA-targeted oncolytic SeV has significant potential for treating patients bearing urokinase-expressing cancers in clinical settings.