Preliminary core sets of measures for disease activity and damage assessment in juvenile systemic lupus erythematosus and juvenile dermatomyositis

Objective. To identify preliminary core sets of outcome variables for disease activity and damage assessment in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). Methods. Two questionnaire surveys were mailed to 267 physicians from 46 different countries asking each member to select and rank the response variables used when assessing clinical response in patients with JSLE or JDM. Next, 40 paediatric rheumatologists from 34 countries met and, using the nominal group technique, selected the domains to be included in the disease activity and damage core sets for JSLE and JDM. Results. A total of 41 response variables for JSLE and 37 response variables for JDM were selected and ranked through the questionnaire surveys. In the consensus conference, domains selected for both JSLE and JDM activity or damage core sets included the physician and parent/patient subjective assessments and a global score tool. Domains specific for JSLE activity were the immunological tests and the kidney function parameters. Concerning JDM, functional ability and muscle strength assessments were indicated for both activity and damage core sets, whereas serum muscle enzymes were included only in the activity core set. A specific paediatric domain called 'growth and development' was introduced in the disease damage core set for both diseases and the evaluation of health-related quality of life was advised in order to capture the influence of the disease on the patient lifestyle. Conclusions. We developed preliminary core sets of measures for disease activity and damage assessment in JSLE and JDM. The prospective validation of the core sets is in progress.

Caracterização fisionômica de fragmentos vegetacionais do distrito de Rubião Júnior, minicípio de Botucatu, São Paulo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Dysregulation of Anti-Inflammatory Annexin A1 Expression in Progressive Crohns Disease

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Potencial de contribuição e importância socioambiental dos 'catadores autônomos' de Rio Claro (SP) para o programa de coleta seletiva municipal

The Urban Solid Residues are the rests of human activity, popularly known by trash and considered by population like useless, undesirable and disposable. On the other hand, for the waste pickers, solid residues are the beginning of a cycle: they see in the other's people trash the only income, an economic value. Currently, in brazilian cities, one million collectors act, alone or in cooperatives, socially excluded by the work they do. The National Policy of Solid Residues (PNRS), instituted in 2010, established guidelines to the execution of integrated residues management, with should be practiced by city halls and other governmental institutions. This policy has, besides other things, goals of residues reduction and inclusion of waste pickers in the mechanism of selective collect and recycling. However, this and other public policies created for residue management are benefic only for cooperated waste pickers. That could negatively affect most of this class, since 90% are waste pickers working in a precarious way on the country's streets. This study has for objective show that most of waste pickers that work in a precarious way on the brazilian territory has a huge potential for the solid residues recycling chain and how they should be valued for the environmental services they provide, so they can be included with dignity on the society, ensuring economic and social benefits for this workers. The methodology adopted was based on the amount of residue collected by the 44 cooperated members of the Rio Claro‟s waste pickers cooperative to estimate the potential of collect and recycling did by 210 autonomous waste pickers who are active on city streets. It was observed that the cooperative collects the equivalent of 10.2% of all recyclable residues generated by city population. However, with the potential that these autonomous waste pickers have, which together could contribute 465 tonnes of solid residues per month, or 5,570 tons a year...

Potencial de contribuição e importância socioambiental dos 'catadores autônomos' de Rio Claro (SP) para o programa de coleta seletiva municipal

The Urban Solid Residues are the rests of human activity, popularly known by trash and considered by population like useless, undesirable and disposable. On the other hand, for the waste pickers, solid residues are the beginning of a cycle: they see in the other's people trash the only income, an economic value. Currently, in brazilian cities, one million collectors act, alone or in cooperatives, socially excluded by the work they do. The National Policy of Solid Residues (PNRS), instituted in 2010, established guidelines to the execution of integrated residues management, with should be practiced by city halls and other governmental institutions. This policy has, besides other things, goals of residues reduction and inclusion of waste pickers in the mechanism of selective collect and recycling. However, this and other public policies created for residue management are benefic only for cooperated waste pickers. That could negatively affect most of this class, since 90% are waste pickers working in a precarious way on the country's streets. This study has for objective show that most of waste pickers that work in a precarious way on the brazilian territory has a huge potential for the solid residues recycling chain and how they should be valued for the environmental services they provide, so they can be included with dignity on the society, ensuring economic and social benefits for this workers. The methodology adopted was based on the amount of residue collected by the 44 cooperated members of the Rio Claro‟s waste pickers cooperative to estimate the potential of collect and recycling did by 210 autonomous waste pickers who are active on city streets. It was observed that the cooperative collects the equivalent of 10.2% of all recyclable residues generated by city population. However, with the potential that these autonomous waste pickers have, which together could contribute 465 tonnes of solid residues per month, or 5,570 tons a year...

PIK3CA exon 20 mutations are associated with poor prognosis in breast cancer patients

OBJECTIVES: The phosphatidylinositol 3-kinase/AKT axis is an important cell-signaling pathway that mediates cell proliferation and survival, two biological processes that regulate malignant cell growth. The phosphatidylinositol 3-kinase CA gene encodes the p110 alpha subunit of the phosphatidylinositol 3-kinase protein. There are phosphatidylinositol 3-kinase CA mutations in several types of human tumors, and they are frequently observed in breast cancer. However, these mutations have not been investigated in Brazilian breast cancer patients. METHODS: PCR-SSCP and direct DNA sequencing were performed to identify phosphatidylinositol 3-kinaseCA exon 9 and exon 20 mutations in 86 patients with sporadic breast cancer. The relationships between PIK3CA mutations and patient clinicopathological characteristics and survival were analyzed. The presence of the TP53 mutation was also examined. RESULTS: Twenty-three (27%) of the 86 primary breast tumors contained PIK3CA mutations. In exons 9 and 20, we identified the hotspot mutations E542K, E545K, and H1047R, and we identified two new missense mutations (I1022V and L1028S) and one nonsense (R992X) mutation. Phosphatidylinositol 3-kinase CA exon 20 mutations were associated with poor overall survival and TP53 gene mutations. CONCLUSIONS: Phosphatidylinositol 3-kinase CA mutations are common in tumors in Brazilian breast cancer patients, and phosphatidylinositol 3-kinase CA and TP53 mutations are not mutually exclusive. Phosphatidylinositol 3-kinase CA exon 20 mutations are associated with poor survival, and they may be useful biomarkers for identifying breast cancer patients with aggressive tumors and for predicting the response to treatment with PI3K pathway inhibitors.

Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria

Objective: To study the activation of an inflammatory cascade through leukocyte mRNA expression of TLR2, TLR4, MyD88, and pro-inflammatory cytokines in individuals with childhood onset type 1 diabetes. Design and methods: Seventy-six type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old were recruited. Type 1 diabetic patients (DM1) were considered to have good (DM1G) or poor (DM1P) glycemic control according to the values of glycated hemoglobin. TLR2, TLR4, MyD88, interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) mRNA expressions were measured in peripheral blood leukocytes (PBL) by real-time polymerase chain reaction (PCR). Urea, creatinine, albumin, and total protein serum levels were determined. Urinary albumin-to-creatinine ratio (ACR) was calculated. Results: DM1 and DM1P patients showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose concentrations (208 and 226 mg/ dL, respectively) compared to NG (Glycated hemoglobin: 7% and glucose: 76 mg/ dL) (p < 0.05). PBL mRNA expressions of TLR2, MyD88, IL-1 beta, IL-6, and TNF-alpha were higher in DM1 and TLR2, IL-1 beta, and IL-6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum albumin and total protein were lower, while serum urea and ACR were higher in comparison to NG (p < 0.05). However, these differences compared to NG were more pronounced in DM1P, which included nine individuals with microalbuminuria. Conclusions: Increased mRNA expression of TLR2, MyD88, and pro-inflammatory cytokines in leukocytes of patients with childhood onset type 1 diabetes indicates the development of a TLR2-mediated pro-inflammatory process, which may also be associated with an early inflammatory process in the kidney and the occurrence of microalbuminuria.

The Natural Cell-Penetrating Peptide Crotamine Targets Tumor Tissue in Vivo and Triggers a Lethal Calcium-Dependent Pathway in Cultured Cells

Our goal was to demonstrate the in vivo tumor specific accumulation of crotamine, a natural peptide from the venom of the South American rattlesnake Crotalus durissus terrificus, which has been characterized by our group as a cell penetrating peptide with a high specificity for actively proliferating cells and with a concentration-dependent cytotoxic effect. Crotamine cytotoxicity has been shown to be dependent on the disruption of lysosomes and subsequent activation of intracellular proteases. In this work, we show that the cytotoxic effect of crotamine also involves rapid intracellular calcium release and loss of mitochondrial membrane potential as observed in real time by confocal microscopy. The intracellular calcium overload induced by crotamine was almost completely blocked by thapsigargin. Microfluorimetry assays confirmed the importance of internal organelles, such as lysosomes and the endoplasmic reticulum, as contributors for the intracellular calcium increase, as well as the extracellular medium. Finally, we demonstrate here that crotamine injected intraperitoneally can efficiently target remote subcutaneous tumors engrafted in nude mice, as demonstrated by a noninvasive optical imaging procedure that permits in vivo real-time monitoring of crotamine uptake into tumor tissue. Taken together, our data indicate that the cytotoxic peptide crotamine can be used potentially for a dual purpose: to target and detect growing tumor tissues and to selectively trigger tumor cell death.

Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?

Background:The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression. Methods Human Immature Dental Pulp Stem Cells (hIDPSC) were transplanted into 4 littermate dogs aged 28 to 40 days by either arterial or muscular injections. Two non-injected dogs were kept as controls. Clinical translation effects were analyzed since immune reactions by blood exams and physical scores capacity of each dog. Samples from biopsies were checked by immunohistochemistry (dystrophin markers) and FISH for human probes. Results and Discussion We analyzed the cells' ability in respect to migrate, engraftment, and myogenic potential, and the expression of human dystrophin in affected muscles. Additionally, the efficiency of single and consecutive early transplantation was compared. Chimeric muscle fibers were detected by immunofluorescence and fluorescent in situ hybridisation (FISH) using human antibodies and X and Y DNA probes. No signs of immune rejection were observed and these results suggested that hIDPSC cell transplantation may be done without immunosuppression. We showed that hIDPSC presented significant engraftment in GRMD dog muscles, although human dystrophin expression was modest and limited to several muscle fibers. Better clinical condition was also observed in the dog, which received monthly arterial injections and is still clinically stable at 25 months of age. Conclusion Our data suggested that systemic multiple deliveries seemed more effective than local injections. These findings open important avenues for further researches.

Ensino superior e voto: análise do comportamento eleitoral da comunidade uspiana em 2010

O objetivo deste artigo é apresentar os resultados de uma pesquisa eleitoral realizada nos Campi da USP-Capital pelo Centro de Estudos das Negociações Internacionais (CAENI) e pelo Instituto Júnior de Pesquisas Sociais (IJPS) durante o período de campanha do segundo turno da eleição presidencial de 2010. Discutimos o processo de amostragem e a implicação de pesquisar sobre um universo de pessoas mais escolarizadas e jovens do que a população total. Mostraremos que é mais fácil isolar um comportamento prospectivo nessas condições do que em uma amostra onde o universo é a população de eleitores inteira do país.

Bogomilismo e dualismo iranico. Il "neomanicheismo"

L’idea che il bogomilismo sia “in una qualche maniera” da riconnettere al manicheismo è di per sè molto antica. Fin da quando giunsero le prime voci su questa nuova eresia che si era diffusa in terra bulgara, i bogomili vennero etichettati come manichei. Non necessariamente però chi è più vicino ad un fenomeno, sia nello spazio sia nel tempo, vede meglio i suoi contorni, le sue implicazioni e la sua essenza. Altri campi di studio ci insegnano che la natura umana tende a inquadrare ciò che non è noto all’interno degli schemi del “già conosciuto”: è così che spesso nomi di popoli si fissano al territorio divenendo concetti geografici anche quando i popoli cambiano; non a caso tutta la regione che si estendeva ad est della Germania veniva definita Sarmazia ed i numerosi popoli che si muovevano al seguito ed agli ordini del gran qan venivano chiamati Tartari; analogamente in semantica possiamo assistere al posizionamento di etichette consolidate e particolari su “oggetti” che ne condividono tratti pur essendo sotto molti aspetti del tutto estranei a quella che si potrebbe definire la matrice: il terrorista islamico che si fa esplodere viene chiamato sui giornali kamikaze e non casualmente lo tsunami porta questo nome: l’onda anomala che può sconvolgere coste distanti migliaia di chilometri dall’epicentro di un terremoto sottomarino ricorda la più familiare onda di porto. Se il continuo riconnettere il bogomilismo al manicheismo delle fonti antiche rappresenta un indizio, ma non necessariamente una prova di certa connessione, la situazione si è notevolmente complicata nel corso del XX secolo. Dobbiamo al principe Obolensky l’introduzione del termine neomanicheismo per indicare le eresie di carattere dualistico sviluppatesi dal X secolo in avanti sul territorio europeo con particolare riferimento al bogomilismo. Il termine dal 1948 in avanti è stato ripetutamente utilizzato più o meno a proposito in svariati lavori a volte pubblicati in sedi editoriali d’eccellenza apparsi in Europa occidentale e nell’est europeo. Il problema principale resta definire il valore da attribuire al termine “neomanicheismo”: indica un forte dualismo religioso in generale, ben diffuso e studiato da tempo ad esempio nei lavori del Bianchi dedicati ai popoli siberiani e mongoli, oppure presuppone una reale catena di connessioni che ci conducono fino al manicheismo vero e proprio? A fronte di chi sostiene che il bogomilismo, così come l’eresia catara, può essere spiegato semplicemente come fenomeno interno al cristianesimo sulla base di un’interpretazione contrastante da quella ufficiale dei testi sacri vi è chi ritiene che sia stato un contatto diretto con gli ambienti manichei a generare le caratteristiche proprie del bogomilismo. Da qui nasce la parte più affascinante della ricerca che porta all’individuazione di possibili contatti attraverso gli spostamenti delle popolazioni, alla circolazione delle idee all’interno di quello che fu il commonwealth bizantino ed all’individuazione di quanto sia rimasto di tutto ciò all’interno della dottrina bogomila. Il lavoro è suddiviso in tre capitoli, preceduti dalla bibliografia e seguiti da un indice analitico dei nomi di persona e luogo. Il primo capitolo prende in esame le fonti sul bogomilismo, il tempo ed il luogo in cui si è manifestato e la sua evoluzione. Il secondo analizza la dottrina bogomila, i suoi possibili contatti con le dottrine iraniche ed i possibili canali di trasmissione delle idee. Il terzo capitolo è costituito da una serie di racconti popoloari bulgari di matrice dualistica e da testi antico slavi usati dai bogomili. La maggior parte di questi testi viene presentata per la prima volta qui in traduzione italiana.