Base genética de la cistinuria, heterogeneidad genética

La cistinuria es una aminoaciduria que se transmite de forma autosómica rececesiva. Clínicamente se distinguen 3 formas de cistinuria, tipos I, II y III. Inicialmente identificamos un gen, implicado en el transporte de cistina y aminoácidos básicos, rBAT como responsable de esta enfermedad. Hasta la fecha se han identificado 22 mutaciotles en rBAT responsables de cistinuria. Mediante estudios de mutaciones y ligamiento genético en familias con cistinuria hemos podido demostrar que la enfermedad es heterogénea. Sólo la cistinuria de tipo I se debe a mutaciones en rBAT, mientras otros genes serán responsables de los tipos II y III. Actualmente estamos realizando estudios de exclusión genética en familias tipo no I, que nos permitirían asignar las regiones cromosómicas en las que se encuentran el gen o los genes responsables de cistinuria tipo II y/o III, paso previo para poder aislar y caracterizar dichos genes.

Desenvolvimento dos frutos de pêssego 'Aurora' e nectarina 'Sunraycer' no sul de Santa Catarina

O desenvolvimento do fruto de pessegueiro é resultado da diferenciação e do crescimento das paredes do ovário após a fecundação. A persistência e o crescimento do fruto na planta dependem das relações exatas entre os hormônios auxina, giberelina e citocinina que condicionam o desenvolvimento dos frutos, caracterizado por uma curva dupla sigmoide, com três estádios distintos. O presente trabalho teve por objetivo conhecer o comportamento dos frutos e das sementes do pêssego Aurora e da Nectarina Sunraycer durante todo o seu ciclo de desenvolvimento. O crescimento dos frutos e das sementes durante o ciclo foi determinado semanalmente, coletando-se 30 frutos de dez diferentes plantas em ramos previamente identificados. As sementes foram separadas do fruto para a determinação do peso fresco (PF) e do peso seco (PS). O crescimento dos frutos da variedade Sunraycer dá-se de forma contínua e acelerada desde a floração até a maturação, sugerindo um curto período ou a inexistência do Estágio II de crescimento. Para a variedade Aurora, a curva de crescimento é diferenciada nos três estádios (I, II e III). O raleio dos frutos deve ser feito até o início do estádio II, para a variedade Aurora e Sunraycer. As sementes das variedades Aurora e Sunraycer atingem seu tamanho máximo no estágio I de crescimento do fruto. O aumento de peso seco na semente, para a variedade Sunraycer, é praticamente inexistente no estádio III, enquanto para a variedade Aurora ocorre o maior aumento de peso seco que vai até a maturação do fruto.

Adjuvant radiotherapy for gastric carcinoma: 10 years follow-up of 244 cases from a single institution.

BACKGROUND: Postoperative chemoradiotherapy (CRT) of gastric carcinoma improves survival among high- risk patients. This study was undertaken to analyse long-term survival probability and the impact of certain covariates on the survival outcome in affected individuals. MATERIALS AND METHODS: Between January 2000 and December 2005, 244 patients with gastric cancer underwent adjuvant radiotherapy (RT) in our institution. Data were retrieved retrospectively from patient files and analysed with SPSS version 21.0. RESULTS: A total of 244 cases, with a male to female ratio of 2.2:1, were enrolled in the study. The median age of the patients was 52 years (range, 20-78 years). Surgical margin status was positive or close in 72 (33%) out of 220 patients. Postoperative adjuvant RT dose was 46 Gy. Median follow-up was 99 months (range, 79-132 months) and 23 months (range, 2-155 months) for surviving patients and all patients, respectively. Actuarial overall survival (OS) probability for 1-, 3-, 5- and 10-year was 79%, 37%, 24% and 16%, respectively. Actuarial progression free survival (PFS) probability was 69%, 34%, 23% and 16% in the same consecutive order. AJCC Stage I-II disease, subtotal gastrectomy and adjuvant CRT were significantly associated with improved OS and PFS in multivariate analyses. Surgical margin status or lymph node dissection type were not prognostic for survival. CONCLUSIONS: Postoperative CRT should be considered for all patients with high risk of recurrence after gastrectomy. Beside well-known prognostic factors such as stage, lymph node status and concurrent chemotherapy, the type of gastrectomy was an important prognostic factor in our series. With our findings we add to the discussion on the definition of required surgical margin for subtotal gastrectomy. We consider that our observations in gastric cancer patients in our clinic can be useful in the future randomised trials to point the way to improved outcomes.

Quantificação da divergência genética entre acessos de goibeira por meio da estratégia Ward-MLM

O presente trabalho teve como objetivo quantificar a divergência genética entre 138 acessos de goiabeira procedentes do banco de germoplasma da Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF), com base em descritores morfológicos, agronômicos e físico-químicos, por meio do procedimento Ward - Modified Location Model (MLM). Para tanto, foram avaliados 13 descritores, sendo cinco qualitativos (coloração da polpa, superfície do fruto, formato do fruto ao final do pedúnculo, largura do pescoço e uniformidade da cor da polpa) e oito quantitativos (massa média do fruto, diâmetro longitudinal do fruto, diâmetro transversal do fruto, rendimento da polpa, teor de sólidos solúveis totais, acidez do fruto, relação teor de sólidos solúveis totais e acidez do fruto e teor de ácido ascórbico). Detectou-se ampla variabilidade genética pelos dados morfológicos, agronômicos e físico-químicos nos 138 acessos de goiaba. Pelo procedimento da função da verossimilhança, determinou-se oito o número ideal de grupos, com um valor de incremento de 67,51. O grupo III foi considerado o mais distante, enquanto os grupos I, II, IV, V e VI, os mais próximos. O procedimento Ward-MLM é uma ferramenta útil para detectar divergência genética e agrupar os acessos utilizando, simultaneamente, variáveis qualitativas e quantitativas.

May increasing incidence of breast cancer be related to overdiagnosis? : a population-based study

Background: Breast cancer is the first cause of cancer in women in Switzerland. While breast cancer mortality has sharply decreased in the two last decades in Switzerland, the incidence of breast cancer has increased during the same period. Various reasons for this increase have been hypothesized, such as the increase in the prevalence of obesity, the use of postmenauposal hormone replacement therapy, or a later age for having a first child. Overdiagnosis secondary to screening and any other forms of early detection procedures could be also involved. Analyses of breast cancer by stage can help evaluate if overdiagnosis could have contributed to the increase in the incidence of breast cancer. Methods: We used data from the Valais cancer registry at the Observatoire valaisan de la santé (www.ovs.ch). This population based registry collects data on all new (incident) cases of cancer diagnosed in women living in one canton of Switzerland, Valais. Cancers are coded according to the International Classification of Diseases for Oncology (ICD-O-3) and the stages are coded according to the TNM classification. Information on breast cancer stage (in situ: 0; invasive: I, II, III, IV) was available for all cases recorded between 1993 and 2011 (N=4246). Standardized rates of breast cancer were computed (direct standardization on European population).

Nutrição mineral e produção de abacaxizeiro 'Pérola', em função das relações K/N na adubação

A adubação do abacaxizeiro deve contemplar a reposição das quantidades de N e K absorvidas pela planta e exportadas pelos frutos e mudas, e o estabelecimento de relações adequadas entre as doses destes nutrientes. Este trabalho objetivou avaliar o efeito de diferentes relações K/N na adubação sobre a nutrição mineral e a produção de abacaxizeiro 'Pérola', em solos de Tabuleiros Costeiros da Paraíba. O experimento foi conduzido em delineamento experimental em blocos casualizados com 13 tratamentos e três repetições. Os tratamentos resultaram da combinação de quatro relações K/N (0,85:1; 1:1; 2:1 e 3:1), duas doses de N (7,2 e 10,8 g planta-1), quatro tratamentos adicionais (relação K/N de 2:1 na maior dose de N, variando-se a fonte, o parcelamento, a época e a forma de aplicação das doses de N e K) e uma testemunha absoluta (sem adubação). O aumento das relações K/N eleva o peso da folha 'D', os teores de K e os valores das relações K/N e K/Mg; reduz os teores de N e não afeta os teores de P, Ca e a relação K/Ca. O aumento das relações K/N não influencia no peso médio, na produtividade e no percentual de frutos das classes I, II e III. A utilização de sulfato de K, o parcelamento das doses de N e K, na forma de KCl, em cinco aplicações, e a aplicação de metade das doses de N e K via foliar na relação 2:1 aumentam o peso da folha 'D', o teor foliar de N e os valores de peso médio, produtividade e percentual de frutos da classe II.

Outcomes After Liver Resection for Hepatic Alveolar Echinococcosis: A Single-Center Cohort Study.

BACKGROUND: Switzerland is a region in which alveolar echinococcosis (AE) is endemic. Studies evaluating outcomes after liver resection (LR) for AE are scarce. The aim of this study was to assess the short- and long-term outcomes of AE patients after LR in a single tertiary referral center. METHODS: We retrospectively analyzed data pertaining to all patients with liver AE who were treated with LR at our institution between January 1992 and December 2013. Patient demographics, intraoperative data, extent of LR procedures (major vs. minor LR), postoperative outcomes, and negative histological margin (R0) resection rate were recorded in a database. Recurrence rates after LR were analyzed. RESULTS: LR was performed in 59 patients diagnosed with hepatic AE (56 complete surgeries, 3 reduction surgeries). Postoperative morbidity and mortality were observed in 34 % (25 % grade I-II, 9 % grade III-IV) and 2 % of the patients, respectively. R0 (complete) resection rate was 71 % (n = 42), and R1/R2 resection rate was 29 % (n = 17). Extra-hepatic recurrence occurred in 1 case (lung) after R0 resection. In cases of R1/R2 resection, 7 intra-hepatic disease progressions occurred with a median time of 10 months (IQR 6-11 months). Long-term (more than 1 year) benzimidazole treatment stabilized the disease in 64 % (9/14) of patients with R1 status. The overall survival rate was 97 %. CONCLUSIONS: Liver AE can be safely and definitively treated with LR, provided that R0 resection is achieved. In cases of R1 resection, benzimidazole therapy seems to be effective in stabilizing the intra-hepatic disease and preventing extra-hepatic recurrence.

Development, physical-chemical stability and release studies of four alcohol-free spironolactone suspensions for use in pediatrics

Dissolution studies have become of great significance because, in most cases, drug dissolution is the rate-limiting step in the absorption process. As occurs with solid oral dosage forms, heterogeneous disperse systems (suspensions) could also have some problems with their in vitro dissolution. The objective of this study was to evaluate influence of the excipients on the release of spironolactone from four alcohol free suspensions (pharmaceutical compounding) of spironolactone 5 mg/mL suitable for pediatric use. Also the comparison of the physical and chemical stability of the suspensions stored at 4, 25 and 40 ºC over a 60- day period has been studied. Rheological behavior, particle size, a prediction of long-term physical stability, pH and assay of spironolactone by HPLC were assessed at prefixed times. The dissolution profile of each suspension was determined and compared with that of the commercial tablets. A microbiological study of the best formula was also performed. Chemically, the four spironolactone suspensions were stable for 60 days stored at three temperatures; Suspension IV had optimum pH values and the highest recovery percentage. In terms of physical stability, sedimentation occurred in Suspension IV and flotation of spironolactone in Suspensions I, II and III. Suspension III had the highest viscosity and the slowest drug release. Suspension IV was also microbiologically stable for 60 days. In conclusion, Suspension IV had the best properties and the least suitable form was Suspension III, as its high viscosity made it difficult to achieve homogeneous redispersion, and it had the slowest dissolution profile.

Social Cognition and Behavior in Relationship Context

Social information processing (SIP; Crick & Dodge, 1994) and social-cognitive learning theories have been often used to understand children’s problem behaviors, such as aggression. According to these theories, children’s thinking guides their subsequent behaviors. Although most of us agree that social behavior and underlying thought processes are context-dependent, personality and social development researchers have usually engaged in searching for stable patterns of dispositions and behaviors, ignoring (or treating as error) the variance across different situations and relationship types. This, however, can result in erroneous conclusions and question the interpretation of previous findings. Four studies were conducted to explore the influence of relationship context on children’s social-cognitive evaluations and behavior. Samples were fourth to sixth graders from Estonia and Finland. Social cognitions were assessed by presenting children with hypothetical vignettes where the previously identified relationship partner’s behavior had a negative consequence for the child (Studies I, II, and IV), followed by questions measuring different social-cognitive processes (e.g., hostile attributions, behavioral strategies, outcome expectations and self-efficacy beliefs for aggression). In addition, in Studies II and IV, children provided information about their behavior within a specific relationship context. In Study III, an affective priming paradigm was employed where participants were presented with a short display of photographs of children’s liked and disliked classmates, and unknown peers. The results of this thesis suggest that children’s thinking and behavior are largely influenced by the affective valence of the relationship. Moreover, cognitions guide behavior within the relationship. The current findings offer a fruitful avenue for studying the heterogeneity of peer interactions.

International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus.

BACKGROUND: Clinical guidelines are essential in implementing and maintaining nationwide stage-specific diagnostic and therapeutic standards. In 2011, the first German expert consensus guideline defined the evidence for diagnosis and treatment of early and locally advanced esophagogastric cancers. Here, we compare this guideline with other national guidelines as well as current literature. METHODS: The German S3-guideline used an approved development process with de novo literature research, international guideline adaptation, or good clinical practice. Other recent evidence-based national guidelines and current references were compared with German recommendations. RESULTS: In the German S3 and other Western guidelines, adenocarcinomas of the esophagogastric junction (AEG) are classified according to formerly defined AEG I-III subgroups due to the high surgical impact. To stage local disease, computed tomography of the chest and abdomen and endosonography are reinforced. In contrast, laparoscopy is optional for staging. Mucosal cancers (T1a) should be endoscopically resected "en-bloc" to allow complete histological evaluation of lateral and basal margins. For locally advanced cancers of the stomach or esophagogastric junction (≥T3N+), preferred treatment is preoperative and postoperative chemotherapy. Preoperative radiochemotherapy is an evidence-based alternative for large AEG type I-II tumors (≥T3N+). Additionally, some experts recommend treating T2 tumors with a similar approach, mainly because pretherapeutic staging is often considered to be unreliable. CONCLUSIONS: The German S3 guideline represents an up-to-date European position with regard to diagnosis, staging, and treatment recommendations for patients with locally advanced esophagogastric cancer. Effects of perioperative chemotherapy versus chemoradiotherapy are still to be investigated for adenocarcinoma of the cardia and the lower esophagus.

Bosniak classification of renal cystic lesions according to multidetector computed tomography findings

Renal cystic lesions are usually diagnosed in the radiologists' practice and therefore their characterization is crucial to determine the clinical approach to be adopted and prognosis. The Bosniak classification based on computed tomography findings has allowed for standardization and categorization of lesions in increasing order of malignancy (I, II, IIF, III and IV) in a simple and accurate way. The present iconographic essay developed with multidetector computed tomography images of selected cases from the archives of the authors' institution, is aimed at describing imaging findings that can help in the diagnosis of renal cysts.