Correction to: In vitro schistosomicidal activity of tamoxifen and its effectiveness in a murine model of schistosomiasis at a single dose.

The original published version of this article contains error in Tables 1 and 2. Correct tables are presented here.

Liga de Anatomia Aplicada (LAA): as Múltiplas Perspectivas sobre Participar de uma Liga Acadêmica / League of Applied Anatomy (LAA): Multiple Perspectives on Participation in an Academic League

RESUMO Relata-se a experiência dos membros da Liga Acadêmica de Anatomia Aplicada (LAA) da Universidade do Estado do Rio de Janeiro (Uerj), sejam eles ligantes, gestores ou orientadores. A motivação para esse trabalho reside no desejo de apontar a importância dessas organizações estudantis e seu impacto sobre os alunos, considerando o recente crescimento e criação de diversas ligas. O modelo tradicional de ensino praticado pela maioria das academias no Brasil, caracterizado por uma relação vertical entre professores e alunos, justifica, ao menos em parte, a limitação criativa dos alunos, e consequentemente, dos futuros profissionais. É nesse panorama que as ligas acadêmicas são necessárias, buscando aguçar o espírito crítico dos alunos e tornar palpáveis os assuntos contemplados pela grade curricular tradicional, que, devido aos cronogramas e horários extenuantes, permanecem abstratos e pouco atrativos, contribuindo para a desmotivação e quebra de expectativa dos alunos ingressantes. Nesse sentido, também se busca atender às demandas dos novos acadêmicos, ansiosos pela aplicação prática do conteúdo abordado no ciclo básico. Todas as atividades precisam ser bem organizadas para que atinjam seus objetivos. Assim, os orientadores devem garantir a supervisão, os gestores devem ser bem selecionados, e a divisão de tarefas deve ser efetiva, de modo a conquistar o engajamento dos ligantes. Todo esse trabalho, seja para a produção de conteúdos científicos, seja para a composição de palestras, cursos ou simpósios, influencia diretamente o modo de pensar de cada parte envolvida. Junto a todo o processo descrito, a base para desenvolver as atividades consiste no tripé ensino-pesquisa-extensão, que complementa a aprendizagem, desenvolve a investigação e contribui para a disseminação dos saberes acadêmicos e o cumprimento do dever social. Neste trabalho, é possível entender o impacto que uma liga tem na formação dos estudantes de Medicina e no constante estímulo à atualização do docente. Assim, foram recolhidos depoimentos e aplicados questionários que ratificam a importância da liga no crescimento tanto pessoal, quanto profissional, nas diversas esferas, e como essas atividades extracurriculares têm se mostrado benéficas na aquisição de novas experiências para discentes e docentes.

ABSTRACT This article reports on the experience of members of the Academic League of Applied Anatomy, in Portuguese "Liga de Anatomia Aplicada (LAA)" of Universidade do Estado do Rio de Janeiro (Uerj), whether listeners, organizers or advisers. The motivation behind this article consists in the desire to address the importance of academic organizations and their impact on students, considering the recent growth and inauguration of various leagues. The traditional model of education, practiced in the majority of Brazilian, is characterized by a vertical relationship between the teacher and the students. This view partly the creative limitation imposed on the students and on future professionals. Therefore, Academic Leagues are necessary, as a means of improving, students' critical thinking and solidifying a subject that has already been taught in the curricula but that, due to exhausting schedules and rigid time frames, remains abstract and unappealing to the students, resulting in a lack of motivation and disappointed expectations. The league seeks to meet the demands of recently enrolled students, eager to apply in practice subjects still only seen in theory during the basic cycle of school. However, all the activities need to be well organized if they are to achieve their goals. Teachers must ensure supervision, the league's board of directors must be well-selected, and the division of tasks must be effective, in order to ensure the engagement of all the participants. All this work, whether for the production of scientific content, planning of lectures, courses or symposia, directly impacts the thought processes of all those involved. Alongside the whole process described, the basis of all this evolution is the teaching, research and extension activities, which complement the learning; develop research, and contribute to the dissemination of academic knowledge and the fulfillment of social duty. This paper shows the impact that a league has on the formation of medical students and on the constant encouragement for teachers to update their skills. Therefore, statements were collected and questionnaires conducted, to confirm the importance of the League for personal and professional growth in various spheres, and show how these extracurricular activities have proven to be beneficial in enabling students and teachers to acquire new experiences.

In vitro schistosomicidal activity of tamoxifen and its effectiveness in a murine model of schistosomiasis at a single dose.

Schistosomiasis is a neglected tropical disease affecting 220 million people worldwide. Praziquantel has proven to be effective against this parasitic disease, though there are increasing concerns regarding tolerance/resistance that calls for new drugs. Repurposing already existing and well-known drugs has been a desirable approach since it reduces time, costs, and ethical concerns. The anti-cancer drug tamoxifen (TAM) has been used worldwide for several decades to treat and prevent breast cancer. Previous reports stated that TAM affects Schistosoma hormonal physiology; however, no controlled schistosomicidal in vivo assays have been conducted. In this work, we evaluated the effect of TAM on female and male Schistosoma mansoni morphology, motility, and egg production. We further assessed worm survival and egg production in S. mansoni-infected mice. TAM induced morphological alterations in male and female parasites, as well as in eggs in vitro. Furthermore, in our in vivo experiments, one single dose of intraperitoneal TAM citrate reduced the total worm burden by 73% and led to a decrease in the amount of eggs in feces and low percentages of immature eggs in the small intestine wall. Eggs obtained from TAM citrate-treated mice were reduced in size and presented hyper-vacuolated structures. Our results suggest that TAM may be repurposed as a therapeutic alternative against S. mansoni infections.

Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Current antidepressants used to treat pediatric patients have the disadvantage of limited efficacy and potentially serious side effects. The purpose of this study was to assess the efficacy of vitamin C as an adjuvant agent in the treatment of pediatric major depressive disorder in a six-month, double-blind, placebo-controlled pilot trial. METHODS: The study group (n=12) was given fluoxetine (10-20 mg/day) plus vitamin C (1000 mg/day) and control group (n=12) administered fluoxetine (10-20 mg/day) plus placebo. The data were analyzed by ANOVA and t-test for independent samples. RESULTS: Both groups demonstrated significantly improved scores on the Children's Depression Rating Scale (CDRS), the Children's Depression Inventory (CDI), and the Clinical Global Impression (CGI). ANOVA was significantly different on all clinical measurements (group effect, time effect, and interaction), with the exception of group effect and interaction for CGI. Patients treated for six months with fluoxetine and vitamin C showed a significant decrease in depressive symptoms in comparison to the fluoxetine plus placebo group as measured by the CDRS (t=11.36, P<0.0001) and CDI (t=12.27, P<0.0001), but not CGI (t=0.13, P=0.90). No serious adverse effects were observed. CONCLUSIONS: These preliminary results suggest that vitamin C may be an effective adjuvant agent in the treatment of MDD in pediatric patients.

Automedicação em acadêmicos do curso de medicina / Self-medication in academics from medical school

Objetivo: Avaliar a automedicação em estudantes do curso de Medicina da Universidade de RibeirãoPreto (UNAERP) no ano de 2008. Métodos: Estudo transversal quantitativo, realizado no ano de 2008, no qual 200 alunos do curso de Medicina da UNAERP responderam a um questionário autoaplicado, contendo questões de múltipla escolha sobre a prática da automedicação, no intuito de conhecer aspectos do consumo de medicamentos. Para análise estatística foi empregado o teste de correlação de Pearson. Considerou-se como base o intervalo de confiança de 95%. O estudo foi aprovado pelo Comitê de Ética da UNAERP. Resultados: Observaram-se 58,5% de participantes do sexo feminino. A média de idade foi de 21,5 anos. A prevalência da automedicação foi de 92,0%. As prevalências entre os alunos das diferentes etapas do curso não foram significativamente diferentes: 86,6%, 90,0%, 93,3%,94,4% e 97,1%, respectivamente, entre os alunos do 1º ao 4º ano e internato. A aquisição de medicamentos controlados, sem apresentação da prescrição, ocorreu entre 6,5% dos alunos e 69,5% responderam já terem indicado medicamentos para outras pessoas...

Objective: Evaluate the self-medication by students of University of Medicine of Ribeirão Preto (UNAERP) in 2008. Methods: A quantitative cross-sectional study conducted throughout 2008 in with 200 medicine students, who answered a self-administered questionnaire containing multiple choice questions regarding self-medication and consumption of medicines. Statistical analysis was employed to test Pearson correlation. The confidence interval considered was of 95%. The study was approved by UNAERP Ethics Committee. Results: There were 58.5% of female participants. The age average was 21.5 years old. The prevalence of self-medication was 92.0%. The prevalence among students from different stages of the course was not significantly different: 86.6%, 90.0%, 93.3%, 94.4% and 97.1%, among the students from, respectively, the 1st to 4th year and from the internship...

Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review.

BACKGROUND: Over the past several decades, complementary and alternative medications have increasingly become a part of everyday treatment. With the rising cost of prescription medications and their production of unwanted side effects, patients are exploring herbal and other natural remedies for the management and treatment of psychological conditions. Psychological disorders are one of the most frequent conditions seen by clinicians, and often require a long-term regimen of prescription medications. Approximately 6.8 million Americans suffer from generalized anxiety disorder. Many also suffer from the spectrum of behavioural and physical side effects that often accompany its treatment. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal. METHODS: An electronic and manual search was performed through MEDLINE/PubMed and EBSCO. Articles were not discriminated by date of publication. Available clinical studies published in English that used human participants and examined the anxiolytic potential of dietary and herbal supplements were included. Data were extracted and compiled into tables that included the study design, sample population, intervention, control, length of treatment, outcomes, direction of evidence, and reported adverse events. RESULTS: A total of 24 studies that investigated five different CAM monotherapies and eight different combination treatments and involved 2619 participants met the inclusion criteria and were analyzed. There were 21 randomized controlled trials and three open-label, uncontrolled observational studies. Most studies involved patients who had been diagnosed with either an anxiety disorder or depression (n = 1786). However, eight studies used healthy volunteers (n = 877) who had normal levels of anxiety, were undergoing surgery, tested at the upper limit of the normal range of a trait anxiety scale, had adverse premenstrual symptoms or were peri-menopausal, reported anxiety and insomnia, or had one month or more of elevated generalized anxiety. Heterogeneity and the small number of studies for each supplement or combination therapy prevented a formal meta-analysis. Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence. Any reported side effects were mild to moderate. CONCLUSIONS: Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment.

Biomarkers in psychiatry: drawbacks and potential for misuse.

For more than 20 years, researchers have attempted to identify diagnostic and prognostic biomarkers for psychiatric disorders including schizophrenia, major (unipolar) depression, and bipolar disorder. Advocates of this research contend that identifying such biomarkers will aid in the diagnosis of these disorders, as well as the possible development of effective psychiatric medications to treat them. Currently, there are no diagnostic tests available. This is largely due to the multi-factorial nature of psychiatric disorders. Biomarker testing of individuals is also prohibitively expensive because significant expertise is required to conduct tests and follow-up counseling for the patient is often necessary. It is cautioned that widespread biomarker testing could lead to negative consequences such as discrimination in health insurance and employment, as well as selective abortion.

Schizophrenia pathophysiology: are we any closer to a complete model?

Schizophrenia, a severe brain disorder that involves hallucinations, disordered thinking and deficiencies in cognition, has been studied for decades in order to determine the early events that lead to this neurological disorder. In this review, we interpret the developmental and genetic models that have been proposed and treatment options associated with these models. Schizophrenia was initially thought to be hereditary based on studies of high incidence in certain families. Additionally, studies on specific genes such as ZDHHC8 and DTNBP1 seem to suggest susceptibility to the onset of this disorder. However, no single gene variation has been linked to schizophrenia, and recent evidence on sporadic cases of schizophrenia refutes genetics as being a singular cause of the disease. In addition, current data suggests neurodevelopmental or environmental causes such as viral infections and prenatal/perinatal complications. Before any brain disorder can be understood, however, multiple cognitive neuroscientific models that accommodate evidence from many biomedical research fields should be considered, and unfortunately, many of these models are in the earliest stages of development. Consequently, it makes us question whether we are any closer to an adequate understanding of the pathophysiology of schizophrenia.

Nutritional therapies for mental disorders.

According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD). Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. One way for psychiatrists to overcome this noncompliance is to educate themselves about alternative or complementary nutritional treatments. Although in the cases of certain nutrients, further research needs to be done to determine the best recommended doses of most nutritional supplements, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained.

Antagonistic regulation of beta-globin gene expression by helix-loop-helix proteins USF and TFII-I.

The human beta-globin genes are expressed in a developmental stage-specific manner in erythroid cells. Gene-proximal cis-regulatory DNA elements and interacting proteins restrict the expression of the genes to the embryonic, fetal, or adult stage of erythropoiesis. In addition, the relative order of the genes with respect to the locus control region contributes to the temporal regulation of the genes. We have previously shown that transcription factors TFII-I and USF interact with the beta-globin promoter in erythroid cells. Herein we demonstrate that reducing the activity of USF decreased beta-globin gene expression, while diminishing TFII-I activity increased beta-globin gene expression in erythroid cell lines. Furthermore, a reduction of USF activity resulted in a significant decrease in acetylated H3, RNA polymerase II, and cofactor recruitment to the locus control region and to the adult beta-globin gene. The data suggest that TFII-I and USF regulate chromatin structure accessibility and recruitment of transcription complexes in the beta-globin gene locus and play important roles in restricting beta-globin gene expression to the adult stage of erythropoiesis.

Recruitment of transcription complexes to the beta-globin locus control region and transcription of hypersensitive site 3 prior to erythroid differentiation of murine embryonic stem cells.

Eukaryotic chromosomal DNA is densely packaged in the nucleus and organized into discrete domains of active and inactive chromatin. Gene loci that are activated during the process of cell differentiation undergo changes that result in modifications of specific histone tail residues and in loosening of chromatin structure. The beta-globin genes are expressed exclusively in erythroid cells. High-level expression of these genes is mediated by a locus control region (LCR), a powerful DNA regulatory element composed of several DNase I hypersensitive (HS) sites and located far upstream of the beta-globin genes. Here we show that RNA polymerase II and specific histone modifications that mark transcriptionally active chromatin domains are associated with the LCR core elements HS2 and HS3 in murine embryonic stem cells prior to differentiation along the erythroid lineage. At this stage HS3 is abundantly transcribed. After in vitro differentiation, RNA Polymerase II can also be detected at the embryonic epsilon- and adult beta-globin genes. These results are consistent with the hypothesis that activation of the beta-globin gene locus is initiated by protein complexes recruited to the LCR.

Recruitment of transcription complexes to the beta-globin gene locus in vivo and in vitro.

Erythroid-specific, high level expression of the beta-globin genes is regulated by the locus control region (LCR), composed of multiple DNase I-hypersensitive sites and located far upstream of the genes. Recent studies have shown that LCR core elements recruit RNA polymerase II (pol II). In the present study we demonstrate the following: 1) pol II and other basal transcription factors are recruited to LCR core hypersensitive elements; 2) pol II dissociates from and re-associates with the globin gene locus during replication; 3) pol II interacts with the LCR but not with the beta-globin gene prior to erythroid differentiation in embryonic stem cells; and 4) the erythroid transcription factor NF-E2 facilitates the transfer of pol II from immobilized LCR constructs to a beta-globin gene in vitro. The data are consistent with the hypothesis that the LCR serves as the primary attachment site for the recruitment of macromolecular complexes involved in chromatin structure alterations and transcription of the globin genes.

Characterization of the human beta-globin downstream promoter region.

The human beta-globin gene is abundantly expressed specifically in adult erythroid cells. Stage-specific transcription is regulated principally by promoter proximal cis-regulatory elements. The basal promoter contains a non-canonical TATA-like motif as well as an initiator element. These two elements have been shown to interact with the TFII-D complex. Here we show that in addition to the TATA and initiator elements, conserved E-box motifs are located in the beta-globin downstream promoter. One of the E-box motifs overlaps the initiator and this composite element interacts with USF1 and TFII-I in vitro. Another E-box, located 60 bp 3' to the transcription initiation site, interacts with USF1 and USF2. Mutations of either the initiator or the downstream E-box impair transcription of the beta-globin gene in vitro. Mutations of a putative NF-E2-binding site in the downstream promoter region do not affect transcription in vitro. USF1, USF2, TFII-I and p45 can be crosslinked to a beta-globin promoter fragment in MEL cells in vivo, whereas only TFII-I and USF2 crosslink to the beta-globin gene in K562 cells. The summary data demonstrate that in addition to the well-characterized interactions of the TFII-D complex with the basal promoter, E-box motifs contribute to the efficient formation of transcription complexes on the adult beta-globin gene.

Combining chromatin immunoprecipitation and DNA footprinting: a novel method to analyze protein-DNA interactions in vivo.

A variety of methods are available to analyze protein-DNA interactions in vivo. Two of the most prominent of these methods are chromatin immunoprecipitation (ChIP) and in vivo footprinting. Both of these procedures have specific limitations. For example, the ChIP assay fails to document where exactly a protein binds in vivo. The precipitation of a specific segment of DNA with antibodies directed against DNA-binding proteins does not necessarily indicate that the protein directly interacts with a sequence in the precipitate but could rather reflect protein-protein interactions. Furthermore, the results of in vivo footprinting studies are inconclusive if a DNA sequence is analyzed that is bound by a specific protein in only a certain fraction of cells. Finally, in vivo footprinting does not indicate which protein is bound at a specific site. We have developed a new procedure that combines the ChIP assay and DMS footprinting techniques. Using this method we show here that antibodies specific for USF1 and NF-E2 precipitate the murine beta-globin promoter in MEL cells. DMS footprinting analysis of the DNA precipitated with NF-E2 antibodies revealed a protection over a partial NF-E2-binding site in the beta-globin downstream promoter region. We believe that this novel method will generally benefit investigators interested in analyzing protein-DNA interactions in vivo.