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BACKGROUND: Risdiplam is an oral small molecule approved for the treatment of patients with spinal muscular atrophy, with approval for use in patients with type 2 and type 3 spinal muscular atrophy granted on the basis of unpublished data. The drug modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN. We aimed to investigate the safety and efficacy of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy. METHODS: In this phase 3, randomised, double-blind, placebo-controlled study, patients aged 2-25 years with confirmed 5q autosomal recessive type 2 or type 3 spinal muscular atrophy were recruited from 42 hospitals in 14 countries across Europe, North America, South America, and Asia. Participants were eligible if they were non-ambulant, could sit independently, and had a score of at least 2 in entry item A of the Revised Upper Limb Module. Patients were stratified by age and randomly assigned (2:1) to receive either daily oral risdiplam, at a dose of 5·00 mg (for individuals weighing =20 kg) or 0·25 mg/kg (for individuals weighing

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No. of bitstreams: 1 Troni_CYN_me_fran.pdf: 1769780 bytes, checksum: 081e231dcda438d8a5ac834e8fb6e670 (MD5) Previous issue date: 2019-09-05 A Lei de Diretrizes Nacionais de Saneamento Básico, importante marco na política de saneamento brasileira, ainda não conseguiu se efetivar em grande parte dos municípios brasileiros e refletir-se em condições adequadas de saneamento, como nos municípios do Médio Vale do Jequitinhonha - piores índices regionais para o estado de Minas Gerais. Em âmbito nacional, o que se observa é que a não elaboração dos Planos Municipais de Saneamento (PMSB) é explicada por vários fatores: falta de recursos financeiros, limitação da capacidade técnica e falta de corpo técnico nas prefeituras. Outro desafio ao planejamento e à efetivação das políticas públicas de saneamento é a superação da tecnicidade e aplicação da intersetorialidade existente com outros campos do planejamento municipal. A fim de superar tal tecnicidade e compreender melhor as particularidades regionais apresenta-se neste trabalho um panorama do saneamento básico na região do Médio Vale do Jequitinhonha, incorporando pontos de vista de atores regionais e municipais. Foi realizada a pesquisa documental aliada à pesquisa quantitativa e qualitativa com aplicação de questionário e entrevistas semiestruturadas com dois grupos de atores sociais. Aplicou-se também o Método de Diagnóstico de Problema utilizado na Gestão Estratégica Pública, a fim de modelizar o problema dos baixos índices de saneamento básico na região. Após a elaboração do fluxograma explicativo de problema foram definidos os nós estratégicos na visão dos atores. Todo material obtido foi analisado e utilizado para melhorar a compreensão sobre o saneamento no Vale. As características regionais do Médio Vale do Jequitinhonha, relacionadas principalmente ao clima e à distribuição de chuvas, o distingue de outras regiões do estado de Minas Gerais fazendo com que haja a necessidade de intervenções diferenciadas, seja a nível estadual, seja a nível federal. Pode-se perceber a ausência de protagonismo municipal em situações como a aceitação das políticas impostas pela Companhia Estadual de Saneamento Básico (CESB) e não participação na elaboração do PMSB. Tais situações implicam na menor capacidade de negociação, resultando na plena aceitação das condições impostas pelas CESB e Governo Estadual, na incapacidade de atender às demandas requeridas pelos munícipes, impedindo até mesmo de instigar a participação popular, pela insegurança em não ter capacidade de corresponder às expectativas criadas. Os municípios devem trabalhar para superar a herança deixada pelo Plano Nacional de Saneamento, tanto pelos gestores quanto pela população e outros atores, a exemplo dos órgãos de controle social, associações de municípios como a do Médio Jequitinhonha (AMEJE) e organizações não governamentais. Sem o protagonismo dos municípios sobre os programas e metas a serem realizados em seu território, fica ainda mais difícil modificar o cenário atual. Diante da centralidade existente anteriormente, percebe-se que há dificuldades por parte dos gestores na compreensão de seu papel. É importante, portanto, que haja a definição clara dos papéis de cada ente, com aprimoramento, conhecimento e empoderamento das partes, para que as ações de cada ator participante no processo possam ser executadas da melhor forma. É necessário que a forma de atuação dos municípios seja mais participativa e esclarecida de forma a ter maior governabilidade sobre a situação. The National Basic Sanitation Guidelines Law, an important milestone in Brazilian sanitation policy, has not yet been effective in most Brazilian municipalities and reflected in adequate sanitation conditions, as in the Middle Valley of Jequitinhonha municipalities - worst regional indexes for the state of Minas Gerais. At the national level, what can be observed is that the non-elaboration of the Municipal Sanitation Plans (PMSB) is explained by several factors: lack of financial resources, limitation of technical capacity and lack of technical staff in the municipalities. Another challenge to planning and implementation of public sanitation policies is to overcome technicality and incorporate existing intersectorialities with other fields of municipal planning. In order to overcome this technicality and better understand its peculiarities, this paper presents an overview of basic sanitation in the Middle Jequitinhonha Valley region, incorporating the views of regional and municipal actors. A documentary research combined with a quantitative and qualitative research with a questionnaire and semi-structured interviews with two groups of social actors. The Problem Diagnosis Method used in Public Strategic Management was applied in order to model the problem of low rates of basic sanitation in the region. After the problem explanatory flowchart elaboration, the strategic nodes were defined. All material obtained was analyzed and used to improve understanding of sanitation in the Valley. The regional characteristics of the Middle Jequitinhonha Valley, mainly related to the climate and the distribution of rainfall, distinguishes it from other regions of Minas Gerais State, requiring distinguished interventions, either at the state level or federal level. It can be noticed the absence of municipal protagonism in situations such as the acceptance of the policies imposed by the State Basic Sanitation Company (CESB) and non-participation in the elaboration of the PMSB. Such situations imply a lower negotiation capacity, resulting in the full acceptance of the conditions imposed by the CESB and the State Government, inability to meet the citizens demands and even preventing from instigating popular participation, due to the insecurity of not being able to respond to the expectations set. Municipalities must work to overcome the inheritance left by the National Sanitation Plan, either by managers, the population and other actors, such as social control agencies, municipal associations such as the one of the Middle Jequitinhonha Valley (AMEJE) and non-governmental organizations. Without its protagonism on the programs and goals to be accomplished in their territory, it is even more difficult to change the current scenario. Given the previously existing centrality, it is clear that there are difficulties for the mayors in understanding their role. Therefore, it is important that there is a clear definition of the roles of each entity, with improvement, knowledge and empowerment of the parties, so that the actions of each actor participating in the process can be performed in the best way. It is necessary that the municipalities actions are more participative and clarified in order to have greater governance over the situation.

Background:. Breast augmentation with autologous fat grafting or hyaluronic acid injection requires minimal loss of healthy tissue. With an increasing trend of breast augmentation with these fillers, accompanying complications have also increased. Patients with complications often complain of induration, cyst formation, calcification, and infection, which require surgical treatment. We will discuss these complications and their surgical treatment through our experience of cases. Methods:. This retrospective study included 20 patients who all required surgical treatment due to breast augmentation complications such as induration, cyst formation, calcification, and infection, and who visited us between May 2007 and June 2018. The patients’ ages ranged from 25 to 63, and the mean age was 39.9. The material used for breast augmentation was fat for 17 cases, and hyaluronic acid, paraffin, and silicon for one case each. The results were analyzed through plastic surgeons at our hospital. Results:. We performed a zigzag incision in the peri-areola margin to 17 of 18 patients for complications of autologous fat grafting and hyaluronic acid injection. The one excluded patient required an adipo-fascial flap from an inframammary fold incision. For one patient with silicon injection complication and one patient with paraffin injection complication, each required mammary gland resection. Conclusions:. A zigzag incision in the peri-areolar margin was useful for treating complications of breast augmentation with autologous fat grafting and hyaluronic acid injection. All cases resulted in inconspicuous fine scars, with high patient satisfaction. However, this incision was insufficient to remove injected silicon and paraffin.

Ultrasonography (US) was recently reported as a reliable modality for diagnosing nasal bone fractures. However, whether US is reliable as a screening tool in the pediatric emergency department (ED) remains unknown. This prospective cohort study had a 2-fold aim: to assess the utility of US in the diagnosis of pediatric nasal bone fracture, and to evaluate the validity of our protocol for managing pediatric nasal bone fractures (Fuchu-Kids algorithm).Among the patients who presented at the ED with facial trauma, those with a suspected nasal bone fracture were enrolled in the study. Patients were treated according to Fuchu-Kids algorithm, and the validity of the protocol using US imaging was evaluated.Among 81 patients who were enrolled during the 1-year study period, 63 patients were able to complete the process described in our protocol for further examination. The diagnostic power of the Fuchu-Kids algorithm had a sensitivity of 91.7%, a specificity of 92.3%, a positive predictive value (PPV) of 88%, and a negative predictive value (NPV) of 94.7%. However, when the performance of US was assessed as a single examination, its sensitivity, specificity, PPV, and NPV were 75%, 92.3%, 85.7%, and 85.7%, respectively.Using our algorithm, the majority of patients with nasal bone fracture were successfully diagnosed and screened out successfully. Repeated US imaging is effective when clinical symptoms persist even if the first US imaging was negative for nasal bone fracture. However, a detailed medical interview and clinical examination are mandatory, regardless of the use of US.

Chiral Ru(salen)(nitrosyl) complex 1 is a useful catalyst for asymmetric aerobic oxidation of alcohols under photo-irradiation. In this study, it was found that addition of β-hydroxy ketone or 1,3-diketone had a significant influence on its asymmetric catalysis. For example, the addition of 1,3-bis(p-bromophenyl)propane-1,3-dione 9 improved the relative reaction ratio in kinetic resolution of simple racemic secondary alcohols up to 30, while the addition gave an adverse effect on desymmetrization of an acyclic meso-1,3-diol. This additive effect was considered to be attributable to the chelate formation of the β-hydroxy ketone or 1,3-diketone with a Ru(salen) complex.

Este trabalho objetivou a avaliacao da qualidade da agua subterrânea no entorno do aterro sanitario do municipio de Visconde do Rio Branco - Minas Gerais. Durante o periodo de setembro de 2010 a outubro de 2011 monitorou-se os parâmetros pH, T, OD, CE, E. coli , coliformes totais, Al, Cd, Cu, Pb, Cr, Fe, Mn, Hg e Zn no lixiviado e nos pocos e, alem destes, a DQO e a DBO no lixiviado e nas aguas das nascentes presentes na area de estudo. Observaram-se teores elevados dos metais Mn, Fe, Al e Hg, bem como contaminacao microbiologica, mais evidentes em periodos chuvosos. Possiveis origens para as inconformidades podem ser problemas na drenagem do lixiviado, no sistema de impermeabilizacao das lagoas e do aterro e na cobertura das celulas. Deve haver maior controle na impermeabilizacao e encerramento das celulas, bem como na construcao e manutencao do sistema de drenagem a fim de que todo lixiviado produzido seja de fato encaminhado as lagoas de tratamento.

PURPOSE. To investigate the morphology and function of photoreceptors in mice with mutation of the FSCN2 gene. METHODS. A mouse line was generated carrying the 208delG mutation (point mutation, or p-type) and another with replacement of exon 1 by the cDNA of a green fluorescent protein (GFP knock-in, or g-type). The expression of retinal mRNA was determined by reverse transcription (RT)-polymerase chain reaction (PCR) and in situ hybridization performed on retinal sections. Morphologic analyses of the retinas were performed by light microscopy (LM) and transmission electron microscopy (TEM) and functional analyses by electroretinogram (ERG). RESULTS. mRNA of FSCN2 was not detected in the retinal mRNA extracted from FSCN2 p/p and FSCN2 g/g mice. Both FSCN2 +/p and FSCN2 +/g mice had progressive photoreceptor degeneration with increasing age detected by LM and structural abnormalities of the outer segment (OS) detected by TEM. Both FSCN2 +/p and FSCN2 +/g mice had depressed rod and cone ERGs that worsened with increasing age. CONCLUSIONS. These results indicate that haploinsufficiency of the FSCN2 gene may hamper maintenance and/or elongation of the OS disks and result in photoreceptor degeneration, as in human autosomal dominant retinitis pigmentosa.

Background Cancer is the leading cause of death in Japan. Recently, the number of patients with lung cancer has been increasing. Most terminal cancer patients wish to die at home, but in fact, most nevertheless die in a hospital. The place of death is important to many patients, and home death may be best in terms of the patients' QOL, family satisfaction, and also regarding the overall cost. Purpose We retrospectively clarified the predictors of home deaths in terminal lung cancer patients. [Patients and Methods] We examined the patients with lung cancer who were introduced to about 30 home palliative care clinics between January 2009 and March 2010. We collected various data from their clinical records as follows; baseline demographics information including sex, PS, stage, and histology, patient's symptoms, patient's desire for home death, the family's wish for the patient's home death, the main caregivers, the number of caregivers, and the presence of a central vein access port (CV port). The survival time and the period of home palliative care were defined as the time from the first visit by the home palliative care team to the date of death, and the period of time after subtracting the total duration of hospitalization from the survival time, respectively. We confirmed the date of home death by a questionnaire given to the home palliative clinics. Results Ninety-one patients were introduced to home palliative care between 1 January 2009 and 31 March 2010, and 78 of them died of lung cancer. Of these 78 patients, 31 died at home (39.7%) and 47 died in a hospital. There were no significant differences in the median survival time between the group of subjects who died in a hospital (53 days) and those who died at home (50 days), and the period of home palliative care in the former (36 days) tended to be shorter than that in the later (50 days). According to a multivariate analysis, the patient's desire for home death and the presence of a CV port were significant factors associated with home death (P = 0.001 and P = 0.041, respectively). Conclusion The patient's desire for home death and the use of a CV port may therefore promote home death in terminal lung cancer patients.

To establish autologous iris pigment epithelial (IPE) cell transplantation in monkey eyes.Autologous IPE cells from three monkeys were obtained by peripheral iridectomy, and cell culture was performed with autologous serum. The cultured cells were labeled with DiI, and transplantation was performed by transvitreal approach to the submacular region of each monkey. Fundus examination, photography, and fluorescein angiography were performed monthly. Histochemical analysis and electron microscopy were also performed six months after transplantation.Auto IPE cells grew well in auto serum. No fluorescein leakage or retinal thickening was observed after submacular transplantation. We demonstrated the presence of autologous IPE cells in the region 6 months after transplantation by histologic and electron microscopic examination. Electron microscopy also demonstrated that the transplanted cells appeared to be less pigmented and to have less mitochondria than did the host retinal pigment epithelial cells. However, some transplanted cells looked as if they embrace the photoreceptor outer segments.Autologous IPE cell culture of the monkey was established using auto serum. Six months after transplantation of the cultured IPE cells, we could still observe the cells in the region. This method may have potential use in human disease that requires autologous cell transplantation to prevent host-graft rejection, and to provide an alternative substance that functions like retinal pigment epithelium.

Background With the recent remarkable developments in anti-cancer agents such as targeted molecular therapies, treating patients with malignancies while keeping a balance among effect, safety, and QOL has become complicated. Methods From the perspective of the role of a board-certified specialist oncology pharmacist, we analyzed the future prospects of medical teams in cancer chemotherapy by examining the current practices of the medical team at our hospital. Results In 2011, our hospital became an authorized base hospital for lung cancer therapy in Osaka Prefecture. The medical team for cancer chemotherapy and supportive therapy at this hospital consists of two medical oncologists, two oncology pharmacists, one certified specialist cancer nurse, one certified cancer chemotherapy nurse, two certified palliative care nurses, and one psychologist. Three departments—thoracic oncology, outpatient chemotherapy, and gynecology—perform cancer chemotherapy. The total number of cancer chemotherapies carried out in 2011 was1433 (thoracic malignancies: 88.4%; breast cancer: 5.1%; gastrointestinal cancer: 6.5%) in outpatients and 1572 (thoracic malignancy: 83.3%; gynecological cancer: 11.8%; gastrointestinal cancer: 4.3%; breast cancer: 0.6%) in inpatients. In 2011, the oncology pharmacist carried out the following important functions in medical team: (i) sitting on a review board four times a year for approval of cancer chemotherapy; (ii) daily management of the ordering system for cancer chemotherapeutic agents; (iii) holding meetings four times a year to educate other specialists about new regimens or anti-cancer agents; (iv) monitoring the dose, schedule and patient's information about cancer chemotherapy to prevent severe toxic effects or treatment death; (v) each day, instructing patients who are receiving cancer chemotherapy; and (vi) consulting daily about side-effects and supportive therapy. Conclusions The oncology pharmacist currently plays an important role in the medical team and will become more important in the future.

A nanoscale heptacobalt complex with an S-shaped folding is created by self-assembly from small building components, trapping the labile [Co(dchpy)2]2− units that are impossible to be isolated as a monomer.

The Kd value of [3H]YM-09151-2, a potent and highly selective dopamine D-2 antagonist, for binding to rat striatum was about 20 pM (half of that for [3H]spiperone and one-fiftieth of that for [3H]raclopride). The Bmax of [3H]YM-09151-2 binding was about 30% higher than that of [3H]raclopride or [3]spiperone. The ratio (bout 3%) of non-specific to specific binding of [3H]YM-09151-2 was smaller than that of [3H]spiperone and [3H]raclopride. The Hill coefficient values of dopamine D-2 antagonists, SCH23390, mianserin and phentolamine for the inhibition of binding of [3H]YM-09151-2 were near 1.0, and their Ki values with [3H]YM-09151-2 were consistent with those for inhibiting [3H]raclopride and [3H]spiperone binding to D-2 receptors. Thus, [3H]YM-09151-2 may be the most suitable ligand for the labelling of dopamine D-2 receptors in the brain.

ヤブラン亜科の1栽培品種と4種,計5系統を供試植物として冠水抵抗性の違いについて比較した。冠水状態においた供試植物の生存率や葉数,根数,葉長,新芽数等の測定結果から,ジャノヒゲ,またはチャボリュウノヒゲ>ノシラン>オオバジャノヒゲ>ヤブランの順で冠水抵抗性があると判断できた。また冠水抵抗性に劣るヤブランやオオバジャノヒゲを冠水し,その水中に人為的に空気を送ると,枯死する個体が少なくなり,生育している個体の生体重や茎数,葉数の値が空気を送らない時に比べて大になった。これらの結果から冠水抵抗性の系統間差異の原因を考察した。, It is known that Ophiopogon japonicus plants are able to survive in areas that remain flooded for long periods. In this study, we investigated differences in resistance to overhead flooding of five strains, all related species of Ophiopogonoideae in the Liliaeae, based on survival rate and measurements of number of leaves, roots, sprouts, and leaf length. Resistance to overhead flooding was shown to be in the following order : Ophiopogon japonicus, O. japonicus 'Nanus', O. jaburan, O. planiscapus and Liriope platyphylla. In O. planiscapus and L. platyphylla plants, their resistance to overhead flooding was lower, and they were found to survive better if the water was aerated. It has been suggested that the difference in resistance to overhead flooding is related to the morphology of the leaves or roots.