Narrowing the gap of personalized medicine in emerging countries: the case of multiple endocrine neoplasias in Brazil

The finished version of the human genome sequence was completed in 2003, and this event initiated a revolution in medical practice, which is usually referred to as the age of genomic or personalized medicine. Genomic medicine aims to be predictive, personalized, preventive, and also participative (4Ps). It offers a new approach to several pathological conditions, although its impact so far has been more evident in mendelian diseases. This article briefly reviews the potential advantages of this approach, and also some issues that may arise in the attempt to apply the accumulated knowledge from genomic medicine to clinical practice in emerging countries. The advantages of applying genomic medicine into clinical practice are obvious, enabling prediction, prevention, and early diagnosis and treatment of several genetic disorders. However, there are also some issues, such as those related to: (a) the need for approval of a law equivalent to the Genetic Information Nondiscrimination Act, which was approved in 2008 in the USA; (b) the need for private and public funding for genetics and genomics; (c) the need for development of innovative healthcare systems that may substantially cut costs (e.g. costs of periodic medical follow-up); (d) the need for new graduate and postgraduate curricula in which genomic medicine is emphasized; and (e) the need to adequately inform the population and possible consumers of genetic testing, with reference to the basic aspects of genomic medicine

Landscape statistics of the p-spin Ising model

The statistical properties of the local optima (metastable states) of the infinite range Ising spin glass with p-spin interactions in the presence of an external magnetic field h are investigated analytically. The average number of optima as well as the typical overlap between pairs of identical optima are calculated for general p. Similarly to the thermodynamic order parameter, for p>2 and small h the typical overlap q_t is a discontinuous function of the energy. The size of the jump in q_t increases with p and decreases with h, vanishing at finite values of the magnetic field.Comment: 12 pages,te

RET haplotype, not linked to the C620R activating mutation, associated with Hirschsprung disease in a novel MEN2 family

Hirschsprung disease is a congenital form of aganglionic megacolon that results from cristopathy. Hirschsprung disease usually occurs as a sporadic disease, although it may be associated with several inherited conditions, such as multiple endocrine neoplasia type 2. The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15–20% of sporadic cases of Hirschsprung disease. The prevalence of Hirschsprung disease in multiple endocrine neoplasia type 2 cases was recently determined to be 7.5% and the co-occurrence of Hirschsprung disease and multiple endocrine neoplasia type 2 has been reported in at least 22 families so far. It was initially thought that Hirschsprung disease could be due to disturbances in apoptosis or due to a tendency of the mutated RET receptor to be retained in the Golgi apparatus. Presently, there is strong evidence favoring the hypothesis that specific inactivating haplotypes play a key role in the fetal development of congenital megacolon/Hirschsprung disease. In the present study, we report the genetic findings in a novel family with multiple endocrine neoplasia type 2: a specific RET haplotype was documented in patients with Hirschsprung disease associated with medullary thyroid carcinoma, but it was absent in patients with only medullary thyroid carcinoma. Despite the limited number of cases, the present data favor the hypothesis that specific haplotypes not linked to RET germline mutations are the genetic causes of Hirschsprung disease

Narrowing the gap of personalized medicine in emerging countries: the case of multiple endocrine neoplasias in Brazil

The finished version of the human genome sequence was completed in 2003, and this event initiated a revolution in medical practice, which is usually referred to as the age of genomic or personalized medicine. Genomic medicine aims to be predictive, personalized, preventive, and also participative (4Ps). It offers a new approach to several pathological conditions, although its impact so far has been more evident in mendelian diseases. This article briefly reviews the potential advantages of this approach, and also some issues that may arise in the attempt to apply the accumulated knowledge from genomic medicine to clinical practice in emerging countries. The advantages of applying genomic medicine into clinical practice are obvious, enabling prediction, prevention, and early diagnosis and treatment of several genetic disorders. However, there are also some issues, such as those related to: (a) the need for approval of a law equivalent to the Genetic Information Nondiscrimination Act, which was approved in 2008 in the USA; (b) the need for private and public funding for genetics and genomics; (c) the need for development of innovative healthcare systems that may substantially cut costs (e.g. costs of periodic medical followup); (d) the need for new graduate and postgraduate curricula in which genomic medicine is emphasized; and (e) the need to adequately inform the population and possible consumers of genetic testing, with reference to the basic aspects of genomic medicine

Effectiveness of silver nitrate compared to talc slurry as pleural sclerosing agent in rabbits. Influence of concomitant intrapleural lidocaine

Não está ainda definido, qual o agente ideal para a produção de uma pleurodese efetiva. O talco é o agente mais freqüentemente utilizado apesar de suas manifestações colaterais. Outra possibilidade é o nitrato de prata, largamente usado no passado. OBJETIVOS: Determinar a influência da injeção intrapleural de lidocaina na produção de pleurodese com nitrato de prata, definir o efeito da lidocaina na maturação das fibras colágenas e confirmar que a pleurodese produzida pelo nitrato de prata é mais potente que a conseqüente à injeção intrapleural de talco. MÉTODOS: Foram estudados três grupos de 8 coelhos. Dois receberam nitrato de prata a 0,5%; em um deles, foi injetado previamente 0,5 ml de lidocaina a 2%. O terceiro grupo recebeu 2 ml de talco (400 mg/kg). Os animais foram sacrificados após 28 dias da injeção intrapleural e as cavidades pleurais examinadas macroscopicamente, analisando-se a presença de fusão entre os folhetos pleurais e microscopicamente avaliando-se a inflamação e a fibrose. Quantificou-se o total de colágeno na pleura e a distribuição de fibras finas e grossas, utilizando-se a coloração de pricrosirius. RESULTADOS: Nos dois grupos em que se injetou nitrato de prata (s/ lidocaina: 3.5 + 0.3 e com lidocaina: 3.2 + 0.3), a pleurodese macroscópica (scala 0 - 4) foi significantemente (p = 0.001) melhor do que a pleurodese resultante do talco (1.6 + 0.2). A média da fibrose pleural induzida pelo nitrato de prata (3.5 + 0.2) foi significantemente (p = 0.004) mais acentuada do que a produzida por talco (1.9 + 0.1). A instilação prévia de lidocaina determinou tendência a diminuir a quantidade de fibrose (3.1 + 0.4). A média (10³mm²) do colágeno pleural foi significantemente (p = 0.009) maior nos coelhos que receberam nitrato de prata (116.9 + 22.7) do que naqueles que receberam talco (10.7 + 3.4). A injeção de lidocaina reduziu discretamente o colágeno (80.1 + 30.3). A distribuição das fibras colágenas não foi diferente entre os grupos estudados. CONCLUSÃO: Este modelo animal confirma que, o nitrato de prata injetado no espaço pleural mais efetivo do que o talco na produção de pleurodese. A injeção intrapleural de lidocaina determina uma tendência a reduzir a quantidade de colágeno, mas não muda a efetividade da sínfise pleural ou modifica a maturação do colágeno.The ideal agent for producing pleurodesis has not been identified. Talc, the most commonly used, poses several problems. Another possibility is silver nitrate, which was widely used in the past. PURPOSE: To determine the influence of the intrapleural instillation of lidocaine in producing a pleurodesis with silver nitrate, to define the effect of lidocaine in the maturation of the collagen fibers, and to confirm that the pleurodesis after silver nitrate is stronger than after talc. METHODS: We studied three groups of 8 rabbits. Two groups received 0.5% silver nitrate; in one we had previously injected 0.5 ml of 2% lidocaine. The third group received 400 mg/kg talc (2 ml). The animals were sacrificed 28 days after the injection, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of inflammation and fibrosis. The total amount of pleural collagen and the distribution of thick and thin collagen fibers were quantified. Collagen was identified using picrosirius red stain. RESULTS: In the two groups that received silver nitrate (without lidocaine: 3.5 + 03 and with lidocaine: 3.2 + 0.3), the macroscopic pleurodesis (scale 0 -- 4) was significantly (p = 0.001) better than that resulting from talc (1.6 + 0.2). The mean degree of pleural fibrosis induced by silver nitrate (3.5 + 0.2) was significantly (p = 0.004) higher than that induced by talc (1.9 + 0.1). The previous instillation of lidocaine resulted in a tendency for decreased amounts of fibrosis (3.1 + 0.4). The mean amount (10³mm²) of pleural collagen was significantly (p = 0.009) greater in the rabbits that received silver nitrate (116.9 + 22.7) than in those that received talc (10.7 + 3.4). The injection of lidocaine slightly reduced the collagen (80.1 + 30.3). The distribution of collagen fibers did not differ among the groups. CONCLUSION: This rabbit model clearly confirms that intrapleural silver nitrate is more effective than talc for producing pleurodesis. The previous intrapleural instillation of lidocaine results in a decreasing trend in the amount of collagen, but does not change the effectiveness of the pleural fusion or modify the process of collagen maturation

Structural glass on a lattice in the limit of infinite dimensions

We construct a mean field theory for the lattice model of a structural glass and solve it using the replica method and one step replica symmetry breaking ansatz; this theory becomes exact in the limit of infinite dimensions. Analyzing stability of this solution we conclude that the metastable states remain uncorrelated in a finite temperature range below the transition, but become correlated at sufficiently low temperature. We find dynamic and thermodynamic transition temperatures as functions of the density and construct a full thermodynamic description of a typical physical process in which the system gets trapped in one metastable state when cooled below vitrification temperature. We find that for such physical process the entropy and pressure at the glass transition are continuous across the transition while their temperature derivatives have jumps.Comment: 4 pages, 2 figure

A Decade of Implantation of the Bachelor’s Degree in Electrical Engineering in the Western Amazon

This paper deals with the implementation of the Bachelor\u27s Degree in Electrical Engineering in Western Amazonia, as well as it presents an analysis of the academic performance of students in the Basic and Professional Core. The Federal University of Rondônia Foundation (UNIR), located in Porto Velho, Brazil, started the activities of the course in 2007 and continues to invest in the infrastructure and qualification of human resources in order to stimulate technological development in the region. Analyzing the performance data of the academics regarding the degree of difficulty established from the curricular offer, it is possible to infer some answers. In the course of the analysis, the databases emerged by taking note, such as students who only enroll and do not attend the course, among others. The disciplines diverged into two segments, Basic Core (NB) and Professional Core (NP). The data refers to the grades obtained by the students in all the disciplines studied and offered by the Academic Electrical Engineering Department (DAEE) in the period from 2007/1 to 2016/2. Along the analysis, two graphs demonstrated the evaluation. The analysis of the academic performance of students in the subjects during the NB and NP reinforces the result obtained in the Program for International Student Assessment (PISA), since Brazil has not obtained progress in science, reading, and mathematics averages. The results obtained indicate the necessity of effective measures in primary and secondary education since the deficit propagated to superior levels

Alstonine as an Antipsychotic: Effects on Brain Amines and Metabolic Changes

Managing schizophrenia has never been a trivial matter. Furthermore, while classical antipsychotics induce extrapyramidal side effects and hyperprolactinaemia, atypical antipsychotics lead to diabetes, hyperlipidaemia, and weight gain. Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement. Alstonine is an indole alkaloid identified as the major component of a plant-based remedy used in Nigeria to treat the mentally ill. Alstonine presents a clear antipsychotic profile in rodents, apparently with differential effects in distinct dopaminergic pathways. The aim of this study was to complement the antipsychotic profile of alstonine, verifying its effects on brain amines in mouse frontal cortex and striatum. Additionally, we examined if alstonine induces some hormonal and metabolic changes common to antipsychotics. HPLC data reveal that alstonine increases serotonergic transmission and increases intraneuronal dopamine catabolism. In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels. Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications