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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Objetivos: Depois de confirmada a doença de Pompe, avaliar as características morfológicas dos achados histológicos nas biópsias desses pacientes e examinar a possibilidade de diagnosticar ou excluir o diagnóstico da doença de Pompe através das características vacuolares apresentadas. Métodos: Estudo observacional, retrospectivo e analítico, que tem como material primário consta de fichas de atendimento do ambulatório de Investigação de Doenças Neuromusculares da Universidade Federal de São Paulo, seguido pela análise das biópsias musculares dos pacientes selecionados através de técnicas de coloração e histoquímica para a visualização das características histológicas. Resultados: Com base no diagnóstico clínico, foram selecionadas 2167 biópsias que pudessem apresentar vacúolos, e as dividimos como doenças metabólicas e não metabólicas. Dentro do grupo das glicogenose tipo II, foi observado que 23 receberam o diagnóstico com idade igual ou acima de 18 anos, com média de idade igual a 43,1 anos e 10 receberam o diagnóstico com idade inferior a 18 anos, com média de idade igual a 8,2 anos. Treze casos pertencem ao sexo feminino e 20 casos do sexo masculino. Nas glicogenoses e nas Miopatias Mitocondriais podemos observar que os vacúolos possuem membrana delimitante e localização subsarcolemal, características encontradas em 86,6% dos casos estudados. Em nossa população, encontramos 62,5% dos casos com integração entre as membranas dos vacúolos, sendo desses 81,8% diagnosticados com a forma tardia. Porém o tipo de vacúolo mais comumente observado é do tipo Rimmed Vacuole, sendo esse uma característica importante como fator classificatório para outras doenças. Conclusão: A biópsia muscular continua sendo uma ferramenta poderosa para o diagnóstico de doenças neuromusculares, particularmente para casos com sintomatologia semelhantes fornecendo informações sobre as condições específicas de cada caso. O vacúolo na doença de Pompe apresenta uma série de peculiaridades: eles são múltiplos, delimitados por membrana, em região subsarcolemal, vazios, corados por PAS, e com tendência à fusão. Desta maneira, a análise histológica da biópsia muscular demonstra ser certeira, permitindo chegar a uma rápida conclusão e identificar fatores determinantes para a condução clínica e da manutenção da qualidade de vida do paciente com Doença de Pompe. Objectives: After Pompe's disease is confirmed, evaluate the morphological characteristics of the histological findings in patient biopsies and examine the possibility of diagnosing or excluding the diagnosis of Pompe's disease through the vacuolar characteristics. Methods: Observational, retrospective and analytical study, whose primary material consists of attendance sheets from the Neuromuscular Diseases Investigation Clinic at the Federal University of São Paulo, followed by the analysis of the muscle biopsies of the selected patients using staining and histochemical techniques for visualization of histological characteristics. Results: Based on the clinical diagnosis, were selected 2167 biopsies that could present vacuoles, and them divided as metabolic and non-metabolic diseases. Within the group of glycogenosis type II, it was observed that 23 received the diagnosis aged 18 years or over, with the average age of 43.1 years and 10 received the diagnosis under 18 years, with the average age of 8.2 years. Thirteen cases related to females and 20 cases related to males. In glycogenoses and Mitochondrial Myopathies, we can observe that vacuoles have a delimiting membrane and subsarcolemal location, characteristics found in 86.6% of the studied cases. In our population, we found 62.5% of the cases with integration between the vacuole membranes, 81.8% of which were diagnosed with the late form. However, the type of vacuole most observed is the Rimmed Vacuole type, which is an important characteristic as a classifying factor for other diseases. Conclusion: Muscle biopsy remains a powerful tool for the diagnosis of neuromuscular diseases, particularly for cases with symptomatology, providing information on the specific conditions of each case. The vacuole in Pompe's disease presents a series of peculiarities: they are multiple, bounded by a membrane, in the subsarcolemal region, empty, stained by PAS and with a tendency to fusion. In this way, the histological analysis of the muscle biopsy proves to be accurate, allowing to reach a quick conclusion and to identify determining factors for the clinical management and maintenance of the quality of life of the patient with Pompe's disease. 001

The apparent digestibility coefficients for crude protein (ADCCP), dry matter (ADCDM), and gross energy (ADCGE) of ingredients were determined for piapara (Megaleporinus obtusidens). Test diets were formulated to contain 69.5% of reference diet, 0.5% of chromium oxide, and 30% of test ingredients. The protein ingredients evaluated were tilapia processing residue meal (TPRM), feather and poultry blood meal (FPBM), poultry by-product meal (PBM), meat and bone meal (MBM), cottonseed meal (CM), corn gluten meal (CGM), and soybean meal (SM); the energy ingredients tested were corn (C), corn germ meal (CGRM), rice meal (RM), wheat bran (WB), and sorghum (S). Groups of 30 piaparas were fed twice daily during five days with test diets. Intestinal morphometry of fish were also evaluated. Digestibility coefficients of protein and energy ingredients were highest for soybean meal (ADCDM = 85.8%; ADCCP = 95.2%; and ADCGE = 87.2%) and corn (ADCDM = 94.5%; ADCCP = 76.2%; and ADCGE = 89.3%), respectively. Of the energy test ingredients analyzed, corn had the highest digestibility coefficients and induced beneficial changes on intestinal morphology compared to sorghum and corn germ meal. All protein ingredients showed potential for use in piapara diets, except meat and bone meal .

Made available in DSpace on 2022-04-29T08:32:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-06-22 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The apparent digestibility coefficients for crude protein (ADCCP), dry matter (ADCDM), and gross energy (ADCGE) of ingredients were determined for piapara (Megaleporinus obtusidens). Test diets were formulated to contain 69.5% of reference diet, 0.5% of chromium oxide, and 30% of test ingredients. The protein ingredients evaluated were tilapia processing residue meal (TPRM), feather and poultry blood meal (FPBM), poultry by-product meal (PBM), meat and bone meal (MBM), cottonseed meal (CM), corn gluten meal (CGM), and soybean meal (SM); the energy ingredients tested were corn (C), corn germ meal (CGRM), rice meal (RM), wheat bran (WB), and sorghum (S). Groups of 30 piaparas were fed twice daily during five days with test diets. Intestinal morphometry of fish were also evaluated. Digestibility coefficients of protein and energy ingredients were highest for soybean meal (ADCDM = 85.8%; ADCCP = 95.2%; and ADCGE = 87.2%) and corn (ADCDM = 94.5%; ADCCP = 76.2%; and ADCGE = 89.3%), respectively. Of the energy test ingredients analyzed, corn had the highest digestibility coefficients and induced beneficial changes on intestinal morphology compared to sorghum and corn germ meal. All protein ingredients showed potential for use in piapara diets, except meat and bone meal and feather and blood meal. Universidade Estadual Paulista-UNESP Centro de Aquicultura da Unesp-CAUNESP, Jaboticabal. Via de Acesso Prof. Paulo Donato Castellane, s/n Universidade Estadual Paulista-UNESP Faculdade de Ciências Agrárias e Tecnológicas-FCAT-UNESP, Rod. Comte. João Ribeiro de Barros, km 651 Universidade Brasil, Campus Fernandópolis. Estrada Projetada F-1, s/n Universidade Estadual Paulista-UNESP Centro de Aquicultura da Unesp-CAUNESP, Jaboticabal. Via de Acesso Prof. Paulo Donato Castellane, s/n Universidade Estadual Paulista-UNESP Faculdade de Ciências Agrárias e Tecnológicas-FCAT-UNESP, Rod. Comte. João Ribeiro de Barros, km 651 FAPESP: 2018/06405-6 FAPESP: 2018/21871-3 CNPq: 312051/2018-2

Background: Systemic lupus erythematosus(SLE) is a systemic disease that may affect the inner ear. Objectives: To study hearing function in SLE and its possible association with clinical and serological profile as well as with antimalarial use. Methods: Cross sectional study of 84 individuals(43 SLE patients and 41 controls) with audiometry and impedanciometry tests. Epidemiological, clinical, serological and treatment profile of SLE patients were extracted from the charts. Results: SLE patients had more sensorineural hearing loss than controls(23.2% vs 0; p=0.001). The hearing loss was seen at 250 Hz, 500 Hz, 1000 Hz and 4000 Hz. No bone conduction impairment was observed. Serological and clinical profile in patients with and without hearing loss was the same (all p=ns). Patients on antimalarial had the same prevalence of hearing loss than those not using it but at 8.000 Hz, antimalarial non-users performed worse than users(p=0.03). Conclusion: There is a high prevalence of hearing loss in SLE that is not affected by disease characteristics neither by antimalarial use. References [1] - Di Stadio A, Ralli M. Systemic Lupus Erythematosus and hearing disorders: Literature review and meta-analysis of clinical and temporal bone findings. J Int Med Res. 2017; 45:1470-80. [2] - Ralli M, D’Aguanno V, Di Stadio A, De Virgilio A, Croce A, Longo L, et al. Audiovestibular symptoms in systemic autoimmune diseases. J Immunol Res. 2018; 2018: 5798103. eCollection 2018. [3] - Jourde-Chiche N, Mancini J, Dagher N, Taugourdeau S, Thomas G, Brunet C, et al. Antimalarial ototoxicity: an underdiagnosed complication? A study of spontaneous reports to the French Pharmacovigilance Network. Ann Rheum Dis. 2012; 71: 1586. Disclosure of Interests: None declared

We assessed whether the impacts of various increases in global mean temperature from preindustrial levels (∆GMT) on terrestrial ecosystems and water resources could be approximated by linear scaling of the impacts of ∆GMT = 2 °C at global and large regional scales. Impacts on net primary production, CO2 emissions from biomass burning, soil erosion, and surface runoff calculated by impact model simulations driven by multiple climate scenarios were assessed for a ∆GMT range of 1.5–4 °C. The results showed that the linear scaling was tolerable for net primary production, biomass burning, and surface runoff for a global average. However, for regional averages, the linear scaling was unacceptable for net primary production and biomass burning as well as for soil erosion at around 3 °C in numerous regions around the world. The linear scaling was judged to be tolerable for surface runoff in most regions where the impacts of 2 °C were statistically significant, but there were large uncertainties in future changes in surface runoff in many regions. Exploring the applicability of linear scaling could help simplify and streamline climate-change impact assessments at various ∆GMTs. Our approach leaves room for refinement, and further investigation will be worthwhile.

Isolates of an unidentified Rhizoctonia sp. (NP isolates), obtained from creeping bentgrass (Agrostis stolonifera var. palustris) in Japan that exhibited symptoms of a new disease, were compared with isolates of three varieties of Waitea circinata var. oryzae, var. zeae, and var. circinata. NP isolates also were compared with isolates of R. oryzae obtained from creeping bent-grass exhibiting white patch-like symptoms (RW isolates). The color and size of sclerotia, color of mycelia, and pigment deposition of NP isolates was similar to that of RW isolates and W. circinata var. circinata, but distinctly different from W. circinata var. oryzae and W. circinata var. zeae. The optimal temperature for hyphal growth of NP isolates, RW isolates, and W. circinata var. circinata was 28°C, and for W. circinata var. oryzae and W. circinata var. zeae was 30°C. Pathogenicity tests on creeping bentgrass showed that the severity of disease caused by NP isolates, RW isolates, and W. circinata var. circinata was greater than with W. circinata var. oryzae, but lower than with W. circinata var. zeae. No significant differences in symptom expression were apparent among NP isolates, RW isolates, and W. circinata var. circinata. A phylogenic tree, obtained using the results of random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR), showed that isolates of W. circinata var. oryzae and W. circinata var. zeae separated into individual clusters, while NP isolates, RW isolates, and W. circinata var. circinata clustered together. The lengths of the rDNA internal transcribed spacer (ITS) region of NP isolates, RW isolates, and W. circinata var. circinata were identical but smaller than those of W. circinata var. oryzae and W. circinata var. zeae. Restriction fragment length polymorphism (RFLP) analysis of the rDNA-ITS region, using three enzymes (HapII, HinfI, and MboI), also showed that NP isolates were the same as RW isolates and W. circinata var. circinata, but different from W. circinata var. oryzae and W. circinata var. zeae. Based on these results, the NP isolates causing a new disease on bentgrass are W. circinata var. circinata, and that RW isolates are also W. circinata var. circinata but not R. oryzae. We propose that the name of the disease on creeping bentgrass caused by W. circinata var. circinata is brown ring patch.

Responses to future changes in climatic and socio-economic conditions can be expected to vary between sectors and regions, reflecting differential sensitivity to these highly uncertain factors. A sensitivity analysis was conducted using a suite of impact models (for health, agriculture, biodiversity, land use, floods and forestry) across Europe with respect to changes in key climate and socio-economic variables. Depending on the indicators, aggregated grid or indicative site results are reported for eight rectangular sub-regions that together span Europe from northern Finland to southern Spain and from western Ireland to the Baltic States and eastern Mediterranean, each plotted as scenario-neutral impact response surfaces (IRSs). These depict the modelled behaviour of an impact variable in response to changes in two key explanatory variables. To our knowledge, this is the first time the IRS approach has been applied to changes in socio-economic drivers and over such large regions. The British Isles region showed the smallest sensitivity to both temperature and precipitation, whereas Central Europe showed the strongest responses to temperature and Eastern Europe to precipitation. Across the regions, sensitivity to temperature was lowest for the two indicators of river discharge and highest for Norway spruce productivity. Sensitivity to precipitation was lowest for intensive agricultural land use, maize and potato yields and Scots pine productivity, and highest for Norway spruce productivity. Under future climate projections, North-eastern Europe showed increases in yields of all crops and productivity of all tree species, whereas Central and East Europe showed declines. River discharge indicators and forest productivity (except Holm oak) were projected to decline over southern European regions. Responses were more sensitive to socio-economic than to climate drivers for some impact indicators, as demonstrated for heat-related mortality, coastal flooding and land use. ISSN:1436-3798 ISSN:1436-378X

Morquio A syndrome features systemic skeletal dysplasia. To date, there has been no curative therapy for this skeletal dysplasia. No systemic report on a long-term effect of hematopoietic stem cell transplantation (HSCT) for Morquio A has been described. We conducted HSCT for 4 cases with Morquio A (age at HSCT: 4-15years, mean 10.5years) and followed them at least 10years (range 11-28years; mean 19years). Current age ranged between 25 and 36years of age (mean 29.5years). All cases had a successful full engraftment of allogeneic bone marrow transplantation without serious GVHD. Transplanted bone marrow derived from HLA-identical siblings (three cases) or HLA-identical unrelated donor. The levels of the enzyme activity in the recipient's lymphocytes reached the levels of donors' enzyme activities within two years after HSCT. For the successive over 10years post-BMT, GALNS activity in lymphocytes was maintained at the same level as the donors. Except one case who had osteotomy in both legs one year later post BMT, other three cases had no orthopedic surgical intervention. All cases remained ambulatory, and three of them could walk over 400m. Activity of daily living (ADL) in patients with HSCT was better than untreated patients. The patient who underwent HSCT at four years of age showed the best ADL score. In conclusion, the long-term study of HSCT has demonstrated therapeutic effect in amelioration of progression of the disease in respiratory function, ADL, and biochemical findings, suggesting that HSCT is a therapeutic option for patients with Morquio A.

Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is caused by deficient activity of the enzyme, N-acetylgalactosamine-4-sulfatase, resulting in impaired degradation of the glycosaminoglycan dermatan sulfate. Patients experience a range of manifestations including joint contractures, short stature, dysostosis multiplex, coarse facial features, decreased pulmonary function, cardiac abnormalities, corneal clouding and shortened life span. Recently, clinicians from institutions in the Asia-Pacific region met to discuss the occurrence and implications of delayed diagnosis and misdiagnosis of MPS VI in the patients they have managed. Eighteen patients (44% female) were diagnosed. The most common sign presented by the patients was bone deformities in 11 patients (65%). Delays to diagnosis occurred due to the lack of or distance to diagnostic facilities for four patients (31%), alternative diagnoses for two patients (15%), and misleading symptoms experienced by two patients (15%). Several patients experienced manifestations that were subtler than would be expected and were subsequently overlooked. Several cases highlighted the unique challenges associated with diagnosing MPS VI from the perspective of different specialties and provide insights into how these patients initially present, which may help to elucidate strategies to improve the diagnosis of MPS VI.

The aim of this study was to assess the activities of daily living (ADL) in patients with Hunter syndrome (mucopolysaccharidosis II; MPS II) using a newly designed ADL questionnaire. We applied the questionnaire to evaluate clinical phenotypes and therapeutic efficacies of enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). We also explored early signs and symptoms to make early diagnosis feasible. We devised a new ADL questionnaire with three domains: "movement," "movement with cognition," and "cognition." Each domain has four subcategories rated on a 5-point scale based on level of assistance. We also scored signs and symptoms unique to MPS by 12 subcategories (five points per category), providing 60 points in total. The questionnaire was first administered to 138 healthy Japanese controls (0.33-50 years), and successively, to 74 Japanese patients with Hunter syndrome (4-49 years). The patient cohort consisted of 51 severe and 23 attenuated phenotypes; 20 patients treated with HSCT, 23 patients treated early with ERT (≤8 years), 25 patients treated late with ERT (>8 years), and 4 untreated patients. Among 18 severe phenotypic patients treated by HSCT, 10 were designated as early HSCT (≤5years), while 8 were designated as late HSCT (>5years). Scores from patients with severe phenotypes were lower than controls and attenuated phenotypes in all categories. Among patients with severe phenotypes, there was a trend that HSCT provides a higher ADL score than early ERT, and there was a significant difference in ADL scores between late ERT and HSCT groups. Early ERT and early HSCT provided a higher score than late ERT and late HSCT, respectively. In conclusion, we have evaluated the feasibility of a new questionnaire in control population and patients with Hunter syndrome, leading to a novel evaluation method for clinical phenotypes and therapeutic efficacy. Early treatment with HSCT provides a better consequence in ADL of patients.

The Enhanced Recovery after Surgery (ERAS) program has been proposed as a postoperative recovery-enhancing strategy. We frequently apply the Modified-ERAS program following oesophagectomy. This study aims to elucidate the impact of goal-directed fluid therapy (GDT) for the perioperative management of oesophageal cancer on the postoperative recovery of patients undergoing oesophagectomy.This is an interventional before-after comparative observational study conducted at Kanagawa Cancer Centre, Japan. Patients who underwent elective oesophagectomy for oesophageal cancer were recruited. Group H (retrospectively collected) received intraoperative and postoperative management consisting of fluid administration without haemodynamic monitoring and the M-ERAS program, while Group S prospectively received management consisting of GDT and the M-ERAS program. The primary endpoint was the speed of gastrointestinal functional recovery, while secondary endpoints were the level of postoperative mobilisation, incidence of complications, postoperative length of hospital stay (LOS), and nutritional status after discharge.The proportion of patients who completely egested Gastrografin by postoperative day 4, the level of postoperative mobilisation, and achievement ratio for a 100-m walk on the first postoperative attempt were significantly higher in Group S than in Group H (P = 0.034, P = 0.0197, and P 0.0001, respectively). No significant differences were observed in the postoperative LOS and incidence of complications within 30 days between the groups. The serum albumin levels at 6 months after discharge was higher in Group S than in Group H (P = 0.0002).The GDT-ERAS program enhanced postoperative gastrointestinal recovery and mobilisation, as well as postoperative nutritional status and protein synthesis. The program did not affect either postoperative LOS or the incidence of complications.UMIN registration number: UMIN000013705, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000015999.

Patients with Hunter syndrome (mucopolysaccharidosis II) present with skeletal dysplasia including short stature as well as CNS and visceral organ involvement. A previous study on Hunter syndrome indicated an impact on brain and heart involvement after hematopoietic stem cell therapy (HSCT) at an early stage but little impact after enzyme replacement therapy (ERT) (Tanaka et al. 2012). Meanwhile, impact on growth in patients with Hunter syndrome treated with ERT and HSCT has not been compared until now. We recently developed baseline growth charts for untreated patients with Hunter syndrome to evaluate the natural history of growth of these patients compared to unaffected controls (Patel et al., 2014). To assess impact of ERT and HSCT on growth, clinical data were obtained from 44 Japanese male patients with MPS II; 26 patients had been treated with ERT, 12 patients had been treated with HSCT, and 6 had been treated with both ERT and HSCT. Height and weight were compared to untreated patients and unaffected controls from the previous study. We demonstrated 1) that MPS II patients, who had been treated with either ERT or HSCT, had increased height and weight when compared to untreated patients, and 2) that HSCT and ERT were equally effective in restoring growth of MPS II patients. In conclusion, HSCT should be considered as one of the primary therapeutic options for early stage treatment of MPS II, as HSCT has also been reported to have a positive effect on brain and heart valve development (Tanaka et al. 2012)., Highlights • Effect on growth of patients with MPS II was evaluated. • Both ERT and HSCT provided a significant impact on growth. • No clear difference in growth was observed between therapies. • Patients showed improved weight gain. • The reader will understand therapeutic efficacy on growth in patients with MPS II.

We assessed the impacts of climate change and agricultural autonomous adaptation measures (changes in crop variety and planting dates) on food consumption and risk of hunger considering uncertainties in socioeconomic and climate conditions by using a new scenario framework. We combined a global computable general equilibrium model and a crop model (M-GAEZ), and estimated the impacts through 2050 based on future assumptions of socioeconomic and climate conditions. We used three Shared Socioeconomic Pathways as future population and gross domestic products, four Representative Concentration Pathways as a greenhouse gas emissions constraint, and eight General Circulation Models to estimate climate conditions. We found that (i) the adaptation measures are expected to significantly lower the risk of hunger resulting from climate change under various socioeconomic and climate conditions. (ii) population and economic development had a greater impact than climate conditions for risk of hunger at least throughout 2050, but climate change was projected to have notable impacts, even in the strong emission mitigation scenarios. (iii) The impact on hunger risk varied across regions because levels of calorie intake, climate change impacts and land scarcity varied by region.

Percutaneous transtracheal ventilation (PTV) can be life-saving in a cannot ventilate, cannot intubate situation. The aim of this study was to investigate the efficacy of PTV by measuring tidal volumes (VTs) and airway pressure (Paw) in high-flow oxygen ventilation and manual ventilation using a model lung.We examined 14G, 16G, 18G, and 20G intravenous catheters and minitracheotomy catheters. In high-flow oxygen ventilation, the flow was set to 10 L/min, while the inspiratory:expiratory phases (I:E) were 1 s:4 s in the complete upper airway obstruction model and 1 s:1 s in the incomplete obstruction model. In manual ventilation, I:E were 2 s:4 s in the complete obstruction model and 2 s:3 s in the incomplete obstruction model. We ventilated through each catheter for 2 min and measured VT and Paw.In high-flow ventilation, the average VTs were approximately 150 ml and100 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. The VTs obtained were reduced when the bore size was decreased. In manual ventilation, the average VTs were over 300 ml and approximately 260 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. In high-flow ventilation, the airway pressure tended to be higher. The minitracheotomy catheters produced over 800 ml of VT and created almost no positive end-expiratory pressure.High-flow ventilation tends to result in higher airway pressure despite a smaller VT, which is probably due to a PEEP effect caused by high flow.

The alcoholic fermentation process with agitation/static, followed by the acetic fermentation submerged in banana was evaluated. Kinetics parameters of alcoholic fermentation for the maximum ethanol/glycerol metabolites in agitated process was 29 and 27 h, and in static 47 and 45 h, respectively. For acetic fermentation, the kinetics parameters were medium time of 39.9 h, acetic acid yield of 53.1% and acetic acid productivity of 0.216 g/Lh. Wines from agitated/static process presented 5.73 and 6.81% (v/v) of alcohol content, respectively. Wine obtained by the static process presented higher concentrations of volatile compounds. The vinegar showed 49.2 g/L of acetic acid and the esters concentrations were higher than in wine. The wine and vinegar minerals were consistent with amount observed in the pulp, with an increase in sulphur concentration after alcoholic fermentation and decrease after acetic fermentation. Products showed chemical and composition of sensory and nutritional interest.

The aim of this study was to evaluate the activity of daily living (ADL) and surgical interventions in patients with mucopolysaccharidosis IVA (MPS IVA). The factor(s) that affect ADL are age, clinical phenotypes, surgical interventions, therapeutic effect, and body mass index. The ADL questionnaire comprises three domains: "Movement," "Movement with cognition," and "Cognition." Each domain has four subcategories rated on a 5-point scale based on the level of assistance. The questionnaire was collected from 145 healthy controls and 82 patients with MPS IVA. The patient cohort consisted of 63 severe and 17 attenuated phenotypes (2 were undefined); 4 patients treated with hematopoietic stem cell transplantation (HSCT), 33 patients treated with enzyme replacement therapy (ERT) for more than a year, and 45 untreated patients. MPS IVA patients show a decline in ADL scores after 10years of age. Patients with a severe phenotype have a lower ADL score than healthy control subjects, and lower scores than patients with an attenuated phenotype in domains of "Movement" and "Movement with cognition." Patients, who underwent HSCT and were followed up for over 10years, had higher ADL scores and fewer surgical interventions than untreated patients. ADL scores for ERT patients (2.5years follow-up on average) were similar with the-age-matched controls below 10years of age, but declined in older patients. Surgical frequency was higher for severe phenotypic patients than attenuated ones. Surgical frequency for patients treated with ERT was not decreased compared to untreated patients. In conclusion, we have shown the utility of the proposed ADL questionnaire and frequency of surgical interventions in patients with MPS IVA to evaluate the clinical severity and therapeutic efficacy compared with age-matched controls.

Introduction Mucopolysaccharidosis (MPS) type VI (Maroteaux–Lamy syndrome) is a clinically heterogeneous lysosomal storage disorder. It presents significant diagnostic and treatment challenges due to the rarity of the disease and complexity of the phenotype. As information about MPS VI in Asia-Pacific countries is limited, a survey was conducted to assess current practices for diagnosis and management of MPS VI in this region. The participants were selected based on their experience in diagnosing and managing MPS patients. Methods The survey comprised 29 structured quantitative or qualitative questions. Follow-up consultations were undertaken to discuss the data further. Results Thirteen physicians from eight countries or regions (Australia, China, Hong Kong, Japan, Malaysia, Philippines, Taiwan and Thailand) were surveyed. At the time of the survey twenty-two patients with MPS VI were directly treated by the respondents and most (~ 80%) had rapidly progressing disease. A wide range of medical specialists are involved in managing patients with MPS VI, the most common being orthopedic surgeons, pediatricians and geneticists. The availability/accessibility of diagnostic tools, therapies and national insurance coverage vary greatly across the countries/regions and, in some cases, between different regions within the same country. Currently, there are national MPS management groups in Australia and Japan. Australia, Taiwan and Hong Kong have local guidelines for managing MPS and local MPS registries are available in Australia, Taiwan, and Japan. Conclusions This survey highlights differences in the diagnosis and management of MPS VI between Asia-Pacific countries/regions. Important barriers to advancing the identification, understanding and treatment of MPS VI include the paucity of epidemiological information, limited access to laboratory diagnostics and therapies, low disease awareness, and a lack of monitoring and treatment guidelines. There is a clear need to facilitate communications between physicians and establish regional or national disease registries, a multidisciplinary referral network, and a centralized diagnostic and management framework.

Very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare and life-threatening disease characterized by an enzymatic defect in the fatty acid β-oxidation pathway. A nulliparous woman with VLCADD showed improvements in serum levels of the long-chain acylcarnitine moiety (C14:1) during pregnancy and successfully delivered a healthy infant vaginally. Pregnancy and vaginal delivery can be successfully completed in patients with VLCADD with careful management.

Malnutrition and metabolic disorder of patients undergoing living donor liver transplantation (LDLT) can affect post-transplant prognosis. The aim of this study was to establish whether perioperative usage of branched-chain amino-acid (BCAA)-enriched nutrients improve metabolic abnormalities of patients undergoing LDLT.We designed a randomized pilot study (UMIN registration number; 000004323). Twenty-five consecutive adult elective LDLT recipients were enroled and divided into two groups: the BCAA group (BCAA-enriched nutrients, n = 12) and the control group (standard diet, n = 13). Metabolic and nutritional parameters, including BCAA-to-tyrosine ratio (BTR), retinol binding protein (RBP), and prealbumin were regularly measured from 1 week before to 4 weeks after LDLT. Non-protein respiratory quotient (npRQ) was measured before and 4 weeks after LDLT.BTR and RBP improved considerably in the BCAA group compared with the controls. npRQ significantly increased from 1 week before LDLT to 4 weeks after LDLT in the BCAA group (0.77 ± 0.05 to 0.84 ± 0.06, P = 0.002), but not in the control group (0.78 ± 0.04 to 0.81 ± 0.05).Supplementation with BCAA-enriched nutrients might improve persistent nutritional and metabolic disorders associated with end-stage liver disease in the early post-transplant period, and consequently shorten the post-transplant catabolic phase after LDLT. A larger multicenter trial is needed to confirm these findings.

This open-label clinical study enrolled 10 adults with attenuated Mucopolysaccharidosis II and advanced disease under the direction of the Japan Society for Research on Mucopolysaccharidosis Disorders prior to regulatory approval of idursulfase in Japan. Ten male patients, ages 21-53 years, received weekly intravenous infusions of 0.5 mg/kg idursulfase for 12 months. Significant reductions in lysosomal storage and several clinical improvements were observed during the study (mean changes below). Urinary glycosaminoglycan excretion decreased rapidly within the first three months of treatment and normalized in all patients by study completion (-79.9%). Liver and spleen volumes also showed rapid reductions that were maintained in all patients through study completion (-33.2% and -31.0%, respectively). Improvements were noted in the 6-Minute Walk Test (54.5 m), percent predicted forced vital capacity (3.8 percentage points), left ventricular mass index (-12.4%) and several joint range of motions (8.1-19.0 degrees). Ejection fraction and cardiac valve disease were stable. The sleep study oxygen desaturation index increased by 3.9 events/h, but was stable in 89% (8/9) of patients. Idursulfase was generally well-tolerated. Infusion-related reactions occurred in 50% of patients and were mostly mild with transient skin reactions that did not require medical intervention. Two infusion-related reactions were assessed as serious (urticaria and vasovagal syncope). One patient died of causes unrelated to idursulfase. Anti-idursulfase antibodies developed in 60% (6/10) of patients. In summary, idursulfase treatment appears to be safe and effective in adult Japanese patients with attenuated MPS II. These results are comparable to those of prior studies that enrolled predominantly pediatric, Caucasian, and less ill patients. No new safety risks were identified.

ファブリー病に対して酵素補充療法（ERT）が実用化され，アガルシダーゼアルファ，アガルシダーゼベータの2剤が使用可能である．しかし，透析患者に対してのデータは少ない．特に，アガルシダーゼアルファに関しては血液透析（HD）中投与のデータがないため，HD中投与の可否につき薬物動態の検討を行った．【症例】46歳，男性．26歳時に脳梗塞を発症し，ファブリー病と診断．平成18年7月に血液透析導入，11月よりアガルシダーゼベータによるERTを開始したが，投与関連反応高度のため，平成19年4月よりアガルシダーゼアルファに薬剤を変更．疼痛発作，発汗障害，下痢などの自覚症状はERT開始後1年程度で改善し，心機能の悪化も認めていない．本例に対しHD中，非HD中にERTを行い，薬物動態を検討したが，HD中投与と非HD中投与で，血漿中の酵素活性に差は認めなかった．【まとめ】アガルシダーゼアルファはベータと同様にHD中に投与可能である．また，ERTにより，症状の改善のみならず，心機能維持効果が示唆された．透析患者に対しても，ERTの継続は重要であり，ベータとアルファでの臨床効果の差は認められず，ベータが投与困難な症例に対しアルファへ変更し投与を継続することは効果的であると思われる．

The most appropriate time for screening for Fabry disease (FD) is school age. For this reason, we developed non-invasive methods for measuring urinary alpha-galactosidase A (alpha-gal A) protein, using enzyme-linked immunosorbent assay (ELISA), and for globotriaosylceramide (GL-3), using tandem mass spectrometry (MS/MS). We measured these two biomarkers in the urine of previously diagnosed FD hemizygotes and heterozygotes, and in controls. All the classic FD hemizygotes were clearly distinguished from controls by either method alone, and combining the two assays produced 96% sensitivity for detecting heterozygotes. To assess the utility of these methods for screening school children and adults at high risk of FD, a pilot study was conducted. To distinguish FD from 432 controls, cut-off values for alpha-gal A protein and GL-3 were set at the 5th and 95th centile values of the controls, respectively. Among the high-risk patients, the measurements exceeded the cut-off values for both biomarkers in male and female subjects and were strong indicators for Fabry hemizygotes and heterozygotes. However, we recommend that if the results of the first measurements exceed the cut-off values for only one of these biomarkers, another urine sample should be requested for re-assay to confirm the result.

WOS: 000377110800007, PubMed ID: 26908836, Background Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of beta-glucuronidase (GUS). Patients' phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data. Methods We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease. Results We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS. Conclusions MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy., Ultragenyx Pharmaceutical [16232], This work was supported in part by Ultragenyx Pharmaceutical grant number 16232.

The aim of this work was to evaluate a non-agitated process of bioethanol production from soybean molasses and the kinetic parameters of fermentation using a strain of Saccharomyces cerevisiae (ATCC® 2345). Kinetic experiment was conducted in medium with 30% (w v-1) of soluble solids without supplementation or pH adjustment. The maximum ethanol concentration was in 44 hours, the ethanol productivity was 0.946 g L-1 h-1, the yield over total initial sugars (Y1) was 47.87%, over consumed sugars (Y2) was 88.08% and specific cells production rate was 0.006 h-1. The mathematical polynomial was adjusted to the experimental data and provided very similar parameters of yield and productivity. Based in this study, for one ton of soybean molasses can be produced 103 kg of anhydrous bioethanol.

A total of 216 patients with IEM were treated by allogeneic HSCT in Japan from 1985 until 2010. The results of UCBT have improved, and the OS rate of UCBT (81.9%) was not different from those of RBMT (87.2%) or UBMT (73.9%) in 2000-2010. However, EFS rates in RBMT (73.2%) and UBMT (62.2%) were better than that in UCBT (49.5%), and the difference between RBMT and UCBT was significant (p = 0.01). The EFS rate of patients conditioned by RIC (74.6%) was comparable or slightly better than in those who underwent MAC with irradiation (57.9%) or without irradiation (54.2%) in 2000-2010. A more pronounced trend was observed toward differential EFS for UCBT in 2000-2010: RIC (62.9%), MAC with irradiation (20.0%), and MAC without irradiation (42.1%). The difference between RIC and MAC with irradiation was significant (p < 0.03). In summary, we report a Japanese registry analysis of HSCT for IEM with improving survival in UCBT. The introduction of RIC after 2000 was considered to contribute to this improvement. UCBT could be recommended for those who lack an HLA-identical sibling donor.

Climate change and mitigation measures have three major impacts on food consumption and the risk of hunger: (1) changes in crop yields caused by climate change; (2) competition for land between food crops and energy crops driven by the use of bioenergy; and (3) costs associated with mitigation measures taken to meet an emissions reduction target that keeps the global average temperature increase to 2 °C. In this study, we combined a global computable general equilibrium model and a crop model (M-GAEZ), and we quantified the three impacts on risk of hunger through 2050 based on the uncertainty range associated with 12 climate models and one economic and demographic scenario. The strong mitigation measures aimed at attaining the 2 °C target reduce the negative effects of climate change on yields but have large negative impacts on the risk of hunger due to mitigation costs in the low-income countries. We also found that in a strongly carbon-constrained world, the change in food consumption resulting from mitigation measures depends more strongly on the change in incomes than the change in food prices.

Parte considerável (40-50%) da produção mundial de banana (Musa spp.) é descartada, devido ao manuseio excessivo e armazenamento inadequado, durante e após a colheita. Contudo, estes resíduos podem ser usados com propósitos industriais. Sua polpa é rica em carboidratos, tornando-a excelente matéria-prima para a produção de bebidas fermentadas. O objetivo deste trabalho foi avaliar e comparar, sob parâmetros cinéticos, o desempenho da levedura S. cerevisiae ATCC 2345 na fermentação alcoólica de polpa de banana Prata hidrolisada com agitação (A) e estática (E) e, posteriormente, analisar a acetificação, por processo submerso, do fermentado alcoólico obtido. Foram utilizados frutos de baixo valor comercial em estágio avançado de amadurecimento e/ou com injúrias. A polpa de banana a ser fermentada foi previamente hidrolisada com o complexo enzimático PECTINEX® ULTRA SP-L (0,025 g/100 g). As fermentações alcoólicas foram conduzidas em bioreator (BIOFOCO®) a 30 ºC por 71 h. Os resultados de produtividade em álcool e biomassa e o rendimento em álcool sobre o açúcar total e consumido no processo (A) foram de 1,15 g/L.h; 0,008 g/L.h; 53,91% e 60,21%; e no processo (E), 0,89 g/L.h; 0,004 g/L.h; 68,10% e 72,05%, respectivamente. Os fermentados alcoólicos produzidos apresentaram teor alcoólico de 5,73% (v/v) para o processo (A) e de 6,81% (v/v) para o processo (E). A acetificação foi realizada em bioreator (BIOFOCO®) a 30 ºC por 16 dias, totalizando 7 ciclos, sendo empregado como inóculo “mãe do vinagre”. O vinagre obtido apresentou 4,41 g/100 mL de acidez total titulável e 2,62 g/100 mL de acidez volátil em ácido acético. Os fermentados alcoólicos e acético obtidos foram caracterizados quanto às suas propriedades físico-químicas e compostos voláteis, e apresentaram parâmetros dentro dos estabelecidos pela legislação brasileira. A considerable part (40-50%) of the word production of banana (Musa spp.) is discarded, due to excessive handling and inadequate storage, during and after harvest. However, these wastes could be used for purposes industrial. Its pulp is rich in carbohydrates, making it excellent raw material for the production of fermented beverages. The main of this work was to evaluate and compare, based on kinetic parameters, the behavior of S. cerevisiae ATCC 2345 during alcoholic fermentation with agitation (A) and static process (E) and then to analyze the submerged acetification process of alcoholic fermented beverage obtained. Fruits of low commercial value were used in advanced stage of maturity and/or with injuries. The banana pulp to be fermented was previously hydrolyzed with the enzyme complex PECTINEX® ULTRA SP-L (0,025 g/100 g). The alcoholic fermentations were conducted in bioreactor (BIOFOCO®) at 30 ºC per 71 h. The productivity results on alcohol and biomass and the alcohol yield on total and consumed sugar in process (A) were 1.15 g/L.h; 0.008 g/L.h; 53.91% e 60.21%; and in process (E), 0.89 g/L.h; 0.004 g/L.h; 68.10% e 72.05%, respectively. The alcoholic fermented beverages produced presents an alcohol content of 5.73% (v/v) for process (A) and 6.81% (v/v) for process (E). The acetification was performed by submerged process and it was used as inoculum "mother of vinegar", in bioreactor (BIOFOCO®) at 30 ºC for 16 days, totaling 7 cycles. The vinegar obtained showed 4.41 g/100 mL of titratable acidity and 2.62 g/100 mL of volatile acidity in acetic acid. The alcoholics and acetic fermented were characterized for their physicochemical properties and they presented parameters within the established by Brazilian law.

Agricultural adaptation is necessary to reduce the negative impacts of climate change on crop yields and to maintain food production. However, few studies have assessed the course of adaptation along with the progress of climate change in each of the current major food producing countries. Adaptation pathways, which describe the temporal sequences of adaptations, are helpful for illustrating the timing and intensity of the adaptation required. Here we present adaptation pathways in the current major wheat-producing countries, based on sequential introduction of the minimum adaptation measures necessary to maintain current wheat yields through the 21st century. We considered two adaptation options: (i) expanding irrigation infrastructure; and (ii) switching crop varieties and developing new heat-tolerant varieties. We find that the adaptation pathways differ markedly among the countries. The adaptation pathways are sensitive to both the climate model uncertainty and natural variability of the climate system and the degree of sensitivity differs among countries. Finally, the negative impacts of climate change could be moderated by implementing adaptations steadily according to forecasts of the necessary future adaptations, as compared to missing the appropriate timing to implement adaptations.

Fabry disease is an X-linked sphingolipidosis due to a deficiency of c alpha-galactosidase A, which leads to the accumulation of globotriaosyleeramide (GL-3) in several organs. When recombinant human alpha-galactosidase A is intravenously administered repeatedly before the patient develops permanent tissue damage, there is evidence that the accumulation of GL-3 is decreased in some organs and that the clinical symptoms are alleviated in some patients. However, Fabry disease is rare and many patients are not diagnosed until adulthood after irreversible tissue damage has occurred. Our group has developed a simple and non-invasive screening method for Fabry disease that measures total GL-3 in whole urine samples by tandem mass spectrometry. Using this method, we found that the concentration of GL-3 in whole urine sample from hemizygous patients, including pre-symptomatic young children with classic type Fabry disease, was significantly higher than that in controls. The mean concentration of GL-3 in urine from heterozygotes with symptoms was significantly higher than control concentrations, but GL-3 levels in the urine from 2 out of 8 heterozygotes of classic type Fabry disease were within control levels. An asymptomatic 14-year old hemizygote in the family of a cardiac variant did not have elevated urinary GL-3. Therefore, screening for the classic type and probably renal variant of Fabry disease is possible by measuring urinary GL-3, using our method. The early diagnosis of cardiac variant hemizygotes and some heterozygotes with all types of Fabry disease will not be possible using our method. We propose that this procedure can be used as a reliable, non-invasive, simple method for general and high-risk population screening for hemizygotic patients with, the classic type and probably renal variant of Fabry disease. (c) 2005 Elsevier Inc. All rights reserved.

Fabry's disease is an X-linked inborn error of glycosphingolipid catabolism, resulting from a deficiency in alpha-galactosidase A (alpha-Gal A). A 56-year-old Japanese woman was at first suspected of having hypertrophic cardiomyopathy. The patient and her son had alpha-Gal A activity in leukocytes that was remarkably below the limit of controls. DNA analysis of the alpha-Gal A gene revealed a novel missense mutation at codon 19 in exon 1, resulting in leucine-to-proline substitution. As a result she was confirmed as a classic Fabry heterozygote. Recent advances in enzyme replacement therapy can reverse the storage of glycosphingolipids in Fabry's disease. Thus, in patients with cardiac hypertrophy, it is important to differentiate Fabry's disease from other causes of hypertrophy. Therefore, it is necessary to measure alpha-Gal A activity in all suspected cases and to analyze genetic abnormalities in heterozygotes.