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1.
Mar Drugs ; 20(2)2022 Jan 29.
Article in English | MEDLINE | ID: mdl-35200640

ABSTRACT

Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (-)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos.


Subject(s)
Anthelmintics , Laurencia , Molluscacides , Sesquiterpenes , Animals , Anthelmintics/isolation & purification , Anthelmintics/pharmacology , Larva , Laurencia/chemistry , Molluscacides/isolation & purification , Molluscacides/pharmacology , Schistosoma mansoni/drug effects , Schistosomiasis/drug therapy , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Spiro Compounds/isolation & purification , Spiro Compounds/pharmacology
2.
J Mol Evol ; 86(3-4): 190-203, 2018 04.
Article in English | MEDLINE | ID: mdl-29556740

ABSTRACT

Horizontal gene transfer (HGT) has a major impact on the evolution of prokaryotic genomes, as it allows genes evolved in different contexts to be combined in a single genome, greatly enhancing the ways evolving organisms can explore the gene content space and adapt to the environment. A systematic analysis of HGT in a large number of genomes is of key importance in understanding the impact of HGT in the evolution of prokaryotes. We developed a method for the detection of genes that potentially originated by HGT based on the comparison of BLAST scores between homologous genes to 16S rRNA-based phylogenetic distances between the involved organisms. The approach was applied to 697 prokaryote genomes and estimated that in average approximately 15% of the genes in prokaryote genomes originated by HGT, with a clear correlation between the proportion of predicted HGT genes and the size of the genome. The methodology was strongly supported by evolutionary relationships, as tested by the direct phylogenetic reconstruction of many of the HGT candidates. Studies performed with Escherichia coli W3110 genome clearly show that HGT proteins have fewer interactions when compared to those predicted as vertical inherited, an indication that the number of protein partners imposes limitations to horizontal transfer. A detailed functional classification confirms that genes related to protein translation are vertically inherited, whereas interestingly, transport and binding proteins are strongly enriched among HGT genes. Because these genes are related to the cell exchange with their environment, their transfer most likely contributed to successful adaptation throughout evolution.


Subject(s)
Evolution, Molecular , Gene Transfer, Horizontal , Genome, Bacterial , Prokaryotic Cells , Bacteria/genetics , Escherichia coli/genetics , Phylogeny , RNA, Ribosomal, 16S/genetics
3.
Entropy (Basel) ; 20(3)2018 Mar 14.
Article in English | MEDLINE | ID: mdl-33265285

ABSTRACT

Measuring the dependence between random variables is one of the most fundamental problems in statistics, and therefore, determining the joint distribution of the relevant variables is crucial. Copulas have recently become an important tool for properly inferring the joint distribution of the variables of interest. Although many studies have addressed the case of continuous variables, few studies have focused on treating discrete variables. This paper presents a nonparametric approach to the estimation of joint discrete distributions with bounded support using copulas and Bernstein polynomials. We present an application in real obsessive-compulsive disorder data.

4.
Ecotoxicol Environ Saf ; 110: 208-15, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25259848

ABSTRACT

A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies.


Subject(s)
Biomphalaria/drug effects , Chromium/toxicity , Embryonic Development/drug effects , Fresh Water , Mutagens/toxicity , Animals , Biological Assay/methods , Biomphalaria/embryology , Biomphalaria/growth & development , Daphnia/genetics , Ecotoxicology/methods , Embryo, Nonmammalian , Mutagenicity Tests/methods , Potassium Dichromate/toxicity
5.
Psychiatry Res Neuroimaging ; 336: 111733, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37913655

ABSTRACT

Specific brain activation patterns during fear conditioning and the recall of previously extinguished fear responses have been associated with obsessive-compulsive disorder (OCD). However, further replication studies are necessary. We measured skin-conductance response and blood oxygenation level-dependent responses in unmedicated adult patients with OCD (n = 27) and healthy participants (n = 22) submitted to a two-day fear-conditioning experiment comprising fear conditioning, extinction (day 1) and extinction recall (day 2). During conditioning, groups differed regarding the skin conductance reactivity to the aversive stimulus (shock) and regarding the activation of the right opercular cortex, insular cortex, putamen, and lingual gyrus in response to conditioned stimuli. During extinction recall, patients with OCD had higher responses to stimuli and smaller differences between responses to conditioned and neutral stimuli. For the entire sample, the higher the response delta between conditioned and neutral stimuli, the greater the dACC activation for the same contrast during early extinction recall. While activation of the dACC predicted the average difference between responses to stimuli for the entire sample, groups did not differ regarding the activation of the dACC during extinction recall. Larger unmedicated samples might be necessary to replicate the previous findings reported in patients with OCD.


Subject(s)
Fear , Obsessive-Compulsive Disorder , Adult , Humans , Fear/physiology , Extinction, Psychological/physiology , Brain/diagnostic imaging , Mental Recall/physiology , Obsessive-Compulsive Disorder/diagnostic imaging
6.
Psychiatry Res ; 312: 114567, 2022 06.
Article in English | MEDLINE | ID: mdl-35490573

ABSTRACT

This study aimed to identify the factors associated with a delay in treatment-seeking among patients with obsessive-compulsive disorder (OCD), a disabling neuropsychiatric disorder. To achieve this purpose, we conducted a cross-sectional study examining latency to treatment (LTT) and its associated correlates in 863 patients with OCD. We defined LTT as the time lag between the awareness of discomfort and/or impairment caused by symptoms and the beginning of OCD-specific treatment. To determine the socio-demographic and clinical characteristics associated with LTT, we built an interval-censored survival model to simultaneously assess the relationship between all variables, representing the best fit to our data format. The results of our study showed that approximately one-third of OCD patients sought treatment within two years of symptom awareness, one-third between two and nine years, and one-third after ten or more years. Median LTT was 4.0 years (mean = 7.96, SD = 9.54). Longer LTT was associated with older age, early onset of OCD symptoms, presence of contamination/cleaning symptoms and full-time employment. Shorter LTT was associated with the presence of aggression symptoms and comorbidity with hypochondriasis. The results of our study confirm the understanding that LTT in OCD is influenced by several interdependent variables - some of which are modifiable. Strategies for reducing LTT should focus on older patients, who work in a full-time job, and on individuals with early onset of OCD and contamination/cleaning symptoms.


Subject(s)
Obsessive-Compulsive Disorder , Comorbidity , Cross-Sectional Studies , Humans , Hypochondriasis/epidemiology , Obsessive-Compulsive Disorder/diagnosis
7.
J Clin Psychopharmacol ; 31(6): 763-8, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22020357

ABSTRACT

Obsessive-compulsive disorder patients who do not improve sufficiently after treatment with a selective serotonin reuptake inhibitor might improve further if other drugs were added to the treatment regimen. The authors present a double-blind, placebo-controlled trial comparing the efficacy of adding quetiapine or clomipramine to a treatment regimen consisting of fluoxetine. Between May 2007 and March 2010, a total of 54 patients with a primary diagnosis of obsessive-compulsive disorder, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and a current Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of at least 16, the score having dropped by less than 35% after fluoxetine monotherapy, were allocated to 1 of 3 arms (n = 18 per arm): quetiapine + fluoxetine (≤200 and ≤40 mg/d, respectively), clomipramine + fluoxetine (≤75 and ≤40 mg/d, respectively), or placebo + fluoxetine (≤80 mg/d of fluoxetine). Follow-up was 12 weeks. The Y-BOCS scores were the main outcome measure. No severe adverse events occurred during the trial, and 40 patients (74%) completed the 12-week protocol. The Y-BOCS scores (mean [SD]) were significantly better in the placebo + fluoxetine and clomipramine + fluoxetine groups than in the quetiapine + fluoxetine group (final: 18 [7] and 18 [7], respectively, vs 25 [6], P < 0.001) (reduction from baseline: -6.7 [confidence interval {CI}, -9.6 to -3.8; and -6.5 [CI, -9.0 to -3.9], respectively, vs -0.1 [CI, -2.9 to 2.7], P < 0.001; number needed to treat = 2.4). The clomipramine-fluoxetine combination is a safe and effective treatment for fluoxetine nonresponders, especially those who cannot tolerate high doses of fluoxetine. However, the period of monotherapy with the maximum dose of fluoxetine should be extended before a combination treatment strategy is applied.


Subject(s)
Clomipramine/therapeutic use , Dibenzothiazepines/therapeutic use , Fluoxetine/therapeutic use , Obsessive-Compulsive Disorder/drug therapy , Adolescent , Adult , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Clomipramine/administration & dosage , Clomipramine/adverse effects , Dibenzothiazepines/administration & dosage , Dibenzothiazepines/adverse effects , Double-Blind Method , Drug Therapy, Combination , Fluoxetine/administration & dosage , Fluoxetine/adverse effects , Follow-Up Studies , Humans , Middle Aged , Quetiapine Fumarate , Selective Serotonin Reuptake Inhibitors/administration & dosage , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/therapeutic use , Treatment Outcome , Young Adult
8.
J Pediatr Gastroenterol Nutr ; 51(4): 477-80, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20562724

ABSTRACT

AIM: The aim of the study was to evaluate the association between Helicobacter pylori infection and iron deficiency (ID) in adolescents attending a public school. PATIENTS AND METHODS: From March to June 2001, a cross-sectional study was conducted among adolescents (10-16 years) enrolled in a single public school in São Paulo, Brazil. Of 400 eligible students, 195 agreed to participate, but 1 was excluded due to sickle cell disease. A blood sample was collected from each subject to measure hemoglobin and ferritin. H pylori status was investigated with the C-urea breath test. All of the subjects with either anemia or ID were given iron therapy. RESULTS: H pylori prevalence was 40.7% (79/194), being higher in male subjects (45/90 vs 34/104, P = 0.014). There was no relation between infection and nutritional status. Abnormally low serum ferritin was observed in 12 subjects, half of whom were positive for H pylori (odds ratio [OR] 1.49, 95% confidence interval [CI] 0.38-5.81). The median serum ferritin was 33.6 ng/mL (interquartile range 23.9-50.9) in infected subjects and 35.1 ng/mL (interquartile range 23.7-53.9) in uninfected subjects. Anemia was detected in 2% (4/194) of the students, half of whom were infected (OR 1.47, 95% CI 0.1-20.6). The mean hemoglobin value in infected subjects was 13.83 g/dL ± 1.02 versus 14 g/dL ± 1.06 in uninfected subjects. CONCLUSIONS: The study was not able to find a relation between H pylori infection and ID or anemia.


Subject(s)
Anemia, Iron-Deficiency/epidemiology , Helicobacter Infections/epidemiology , Helicobacter pylori/isolation & purification , Adolescent , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/microbiology , Brazil/epidemiology , Breath Tests , Child , Comorbidity , Cross-Sectional Studies , Female , Ferritins/blood , Helicobacter Infections/blood , Helicobacter Infections/microbiology , Humans , Male , Odds Ratio , Prevalence , Sex Distribution
9.
Braz J Psychiatry ; 31(2): 131-5, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19578685

ABSTRACT

OBJECTIVE: Evidence from family and molecular genetic studies support the hypothesis of involvement of immunologic mechanisms in the pathophysiology of obsessive-compulsive disorder. The nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 1 (NFKBIL1) has been suggested as a modulator of the immunological system. Given the importance of NFKBIL1 in the immunological response, the present study investigated the -62A/T polymorphism (rs2071592), located in the promoter region of its gene (NFKBIL1), as a genetic risk factor for the development of obsessive-compulsive disorder. METHOD: The -62A/T NFKBIL1 polymorphism was investigated in a sample of 111 patients who met DSM-IV criteria for obsessive-compulsive disorder and 272 healthy age- and gender-matched controls. RESULTS: There were no differences in genotypic distributions between patients and controls (chi2 = 0.98; 2 d.f.; p = 0.61). DISCUSSION: Despite these negative findings, more comprehensive polymorphism coverage within the NFKBIL1 is warranted in larger samples. Populations with different ethnic backgrounds should also be studied. CONCLUSION: The results of the present investigation do not provide evidence for the association between the -62A/T NFKBIL1 polymorphism and obsessive-compulsive disorder in this Brazilian sample.


Subject(s)
Histocompatibility Antigens Class II/genetics , Obsessive-Compulsive Disorder/genetics , Polymorphism, Genetic , Adaptor Proteins, Signal Transducing , Adult , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Male
10.
Clinics (Sao Paulo) ; 74: e789, 2019.
Article in English | MEDLINE | ID: mdl-31664424

ABSTRACT

The aim of this study was to estimate the prevalence of low-back pain (LBP) and to identify the level of functional disability in elderly individuals in different populations. From January 1985 to October 2018, a search was performed using the following databases: Embase, LILACS, SciELO, Scopus, Medline, and the Web of Science. The descriptors were low-back pain, back pain, lower-back pain, prevalence, and elderly in Portuguese and English. Two independent reviewers conducted a search for studies and evaluated their methodological quality. The search strategy returned 2186 titles, and 35 were included in this review. The studies evaluated 135,059 elderly individuals aged between 60 and 102 years, and the prevalence of LBP ranged from 21% to 75%. The levels of functional disability, as well as functional difficulties, activities of daily living, and physical capacity, were identified in 60% of the studies. This review indicated a high prevalence of LBP in elderly individuals and functional disability that affects factors important for independence. However, the studies used different methodologies, suggesting that more studies be conducted with scientific accuracy, methodological quality, and low risk of bias to contribute to the proposal of preventive actions for elderly populations.


Subject(s)
Activities of Daily Living , Low Back Pain/epidemiology , Aged , Aged, 80 and over , Chronic Pain , Humans , Middle Aged , Prevalence
11.
Cells ; 8(12)2019 12 04.
Article in English | MEDLINE | ID: mdl-31817155

ABSTRACT

Breast cancer stromal compartment, may influence responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy (neoCT) in locally advanced breast cancer (LABC). The tumor samples were collected from 44 patients with LABC (29 estrogen receptor (ER) positive and 15 ER negative) before the start of any treatment. Neoadjuvant chemotherapy consisted of doxorubicin and cyclophosphamide, followed by paclitaxel. Response was defined as downstaging to maximum ypT1a-b/ypN0. The stromal cells, mainly composed of fibroblast and immune cells, were microdissected from fresh frozen tumor samples and gene expression profile was determined using Agilent SurePrint G3 Human Gene Expression microarrays. Expression levels were compared using MeV (MultiExperiment Viewer) software, applying SAM (significance analysis of microarrays). To classify samples according to tumor response, the order of median based on confidence statements (MedOr) was used, and to identify gene sets correlated with the phenotype downstaging, gene set enrichment analysis (GSEA). Nine patients presented disease downstaging. Eleven sequences (FDR 17) were differentially expressed, all of which (except H2AFJ) more expressed in responsive tumors, including PTCHD1 and genes involved in abnormal cytotoxic T cell physiology, TOX, LY75, and SH2D1A. The following four pairs of markers could correctly classify all tumor samples according to response: PTCHD1/PDXDC2P, LOC100506731/NEURL4, SH2D1A/ENST00000478672, and TOX/H2AFJ. Gene sets correlated with tumor downstaging (FDR < 0.01) were mainly involved in immune response or lymphocyte activation, including CD47, LCK, NCK1, CD24, CD3E, ZAP70, FOXP3, and CD74, among others. In locally advanced breast cancer, stromal cells may present specific features of immune response that may be associated with chemotherapy response.


Subject(s)
Breast Neoplasms/drug therapy , Drug Resistance, Neoplasm/genetics , Stromal Cells/metabolism , Transcriptome , Adult , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cancer-Associated Fibroblasts/metabolism , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Drug Administration Schedule , Female , Humans , Middle Aged , Neoadjuvant Therapy , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use
12.
Mutat Res ; 654(1): 58-63, 2008 Jun 30.
Article in English | MEDLINE | ID: mdl-18579435

ABSTRACT

The single cell gel electrophoresis or the comet assay was established in the freshwater snail Biomphalaria glabrata. For detecting DNA damage in circulating hemocytes, adult snails were irradiated with single doses of 2.5, 5, 10 and 20 Gy of (60)Co gamma radiation. Genotoxic effect of ionizing radiation was detected at all doses as a dose-related increase in DNA migration. Comet assay in B. glabrata demonstrated to be a simple, fast and reliable tool in the evaluation of genotoxic effects of environmental mutagens.


Subject(s)
Biological Assay/methods , Biomphalaria , DNA Damage , Environmental Monitoring/methods , Animals , Biomphalaria/genetics , Biomphalaria/radiation effects , Comet Assay , Dose-Response Relationship, Radiation , Gamma Rays , Hemolymph/radiation effects , Sensitivity and Specificity
13.
J Int Med Res ; 44(6): 1359-1375, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27834300

ABSTRACT

Objective To describe the protocol of the SURgically induced Metabolic effects on the Human GastroIntestinal Tract (SURMetaGIT) study, a clinical pan-omics study exploring the gastrointestinal tract as a central organ driving remission of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB). The main points considered in the study's design and challenges faced in its application are detailed. Methods This observational, longitudinal, prospective study involved collection of gastrointestinal biopsy specimens, faeces, urine, and blood from 25 obese women with T2DM who were candidates for RYGB (20 patients for omics assessment and 5 for omics validation). These collections were performed preoperatively and 3 and 24 months postoperatively. Gastrointestinal transcriptomics; faecal metagenomics and metabolomics; plasma proteomics, lipidomics, and metabolomics; and biochemical, nutritional, and metabolic data were assessed to identify their short- and long-term correlations with T2DM remission. Results Data were collected from 20 patients before and 3 months after RYGB. These patients have nearly completed the 2-year follow-up assessments. The five additional patients are currently being selected for omics data validation. Conclusion The multi-integrated pan-omics approach of the SURMetaGIT study enables integrated analysis of data that will contribute to the understanding of molecular mechanisms involved in T2DM remission after RYGB.


Subject(s)
Diabetes Mellitus, Type 2/blood , Gastric Bypass , Gastrointestinal Tract/metabolism , Obesity, Morbid/blood , Proteome/metabolism , Transcriptome , Adult , Biopsy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/surgery , Diabetes Mellitus, Type 2/urine , Feces/chemistry , Feeding Behavior , Female , Gastrointestinal Tract/physiopathology , Gastrointestinal Tract/surgery , Humans , Longitudinal Studies , Metabolome , Middle Aged , Obesity, Morbid/complications , Obesity, Morbid/surgery , Obesity, Morbid/urine , Prospective Studies , Proteome/genetics , Remission Induction , Research Design , Weight Loss
14.
DNA Res ; 12(1): 27-38, 2005 Feb 28.
Article in English | MEDLINE | ID: mdl-16106750

ABSTRACT

A collection of 237,954 sugarcane ESTs was examined in search of signal transduction genes. Over 3500 components involved in several aspects of signal transduction, transcription, development, cell cycle, stress responses and pathogen interaction were compiled into the Sugarcane Signal Transduction (SUCAST) Catalogue. Sequence comparisons and protein domain analysis revealed 477 receptors, 510 protein kinases, 107 protein phosphatases, 75 small GTPases, 17 G-proteins, 114 calcium and inositol metabolism proteins, and over 600 transcription factors. The elements were distributed into 29 main categories subdivided into 409 sub-categories. Genes with no matches in the public databases and of unknown function were also catalogued. A cDNA microarray was constructed to profile individual variation of plants cultivated in the field and transcript abundance in six plant organs (flowers, roots, leaves, lateral buds, and 1st and 4th internodes). From 1280 distinct elements analyzed, 217 (17%) presented differential expression in two biological samples of at least one of the tissues tested. A total of 153 genes (12%) presented highly similar expression levels in all tissues. A virtual profile matrix was constructed and the expression profiles were validated by real-time PCR. The expression data presented can aid in assigning function for the sugarcane genes and be useful for promoter characterization of this and other economically important grasses.


Subject(s)
Gene Expression Profiling , Saccharum/genetics , Signal Transduction/genetics , Transcription, Genetic , Computational Biology , Expressed Sequence Tags , Microarray Analysis , Polymerase Chain Reaction , Reproducibility of Results , Species Specificity
15.
Mutat Res ; 536(1-2): 145-54, 2003 Apr 20.
Article in English | MEDLINE | ID: mdl-12694755

ABSTRACT

Mutagens in the environment may represent a long-term risk for ecosystems. The reproductive potential of populations can be affected by alterations in the fecundity and offspring viability caused by germ cell mutations. Despite the ecological relevance of these effects, there are few studies on germ cell mutagenicity in natural populations. Biomphalaria glabrata was chosen for this study because of the scarcity of data on freshwater invertebrates and the ecological importance of this group. The aim of this study was to establish a germ cell mutagenicity test in B. glabrata by using a similar approach to that used in the dominant lethal test in rodents. Mitomycin C was used as a direct mutagen and cyclophosphamide as a mutagen that requires metabolic activation. Wild-type snails were exposed for 10 days to three concentrations of each agent and crossed with non-exposed albino snails at the end of the treatment. The total frequencies of malformations were analyzed in the offspring of wild-type snails; among the offspring of albino snails, only the heterozygous wild-type embryos were analyzed for malformations. Both agents induced germ cell mutations. The analysis of the offspring of the wild-type snails showed an effect of the exposure up to approximately 5 days after the end of the treatment with cyclophosphamide; the effect of mitomycin C was observed until 45 days after the end of the exposure. There was an increase in the frequencies of malformations in the wild-type offspring of the non-exposed albino snails crossed with the wild-type snails exposed to both agents. The dominant lethal test in B. glabrata proposed in this work is easy to perform, efficient, specific and sensitive in the evaluation of germ cell mutations induced by reference mutagens. The possibility of expanding its use to environmental biomonitoring studies seems very promising and worth trying.


Subject(s)
Biomphalaria/genetics , Environmental Monitoring/methods , Genes, Dominant , Mutagens/toxicity , Animals , Biomphalaria/drug effects , Biomphalaria/embryology , Crosses, Genetic , Cyclophosphamide/toxicity , Dose-Response Relationship, Drug , Embryo, Nonmammalian/abnormalities , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/pathology , Female , Fresh Water , Germ Cells/drug effects , Male , Mitomycin/toxicity , Mutagenicity Tests/methods , Mutation
16.
Sao Paulo Med J ; 122(6): 252-8, 2004 Nov 04.
Article in English | MEDLINE | ID: mdl-15692719

ABSTRACT

CONTEXT: Fibromyalgia is a syndrome characterized by chronic, diffuse musculoskeletal pain, and by a low pain threshold at specific anatomical points. The syndrome is associated with other symptoms such as fatigue, sleep disturbance, morning stiffness and anxiety. Because of its chronic nature, it often has a negative impact on patients' quality of life. OBJECTIVE: To assess the quality of life and anxiety level of patients with fibromyalgia. TYPE OF STUDY: Cross-sectional. SETTING: Rheumatology outpatient service of Hospital das Clínicas (Medical School, Universidade de São Paulo). METHODS: This study evaluated 80 individuals, divided between test and control groups. The test group included 40 women with a confirmed diagnosis of fibromyalgia. The control group was composed of 40 healthy women. Three questionnaires were used: two to assess quality of life (FIQ and SF-36) and one to assess anxiety (STAI). They were applied to the individuals in both groups in a single face-to-face interview. The statistical analysis used Student's t test and Pearson's correlation test (r), with a significance level of 95%. Also, the Pearson chi-squared statistics test for homogeneity, with Yates correction, was used for comparing schooling between test and control groups. RESULTS: There was a statistically significant difference between the groups (p = 0.000), thus indicating that fibromyalgia patients have a worse quality of life and higher levels of anxiety. The correlations between the three questionnaires were high (r = 0.9). DISCUSSION: This study has confirmed the efficacy of FIQ for evaluating the impact of fibromyalgia on the quality of life. SF-36 is less specific than FIQ, although statistically significant values were obtained when analyzed separately, STAI showed lower efficacy for discriminating the test group from the control group. The test group showed worse quality of life than did the control group, which was demonstrated by both FIQ and SF-36. Even though STAI was a less efficient instrument, it presented significant results, showing that fibromyalgia patients presented higher levels of anxiety, both on the state and trait scales. Thus, patients with fibromyalgia had higher levels of tension, nervousness, preoccupation and apprehension, and higher propensity towards anxiety. CONCLUSION: The three instruments utilized showed efficiency in evaluating fibromyalgia patients. FIQ was found to be the most efficient instrument for discriminating and assessing the impact of fibromyalgia on their quality of life. It can be concluded that such patients have a worse quality of life and higher levels of anxiety.


Subject(s)
Anxiety/psychology , Fibromyalgia/psychology , Quality of Life , Epidemiologic Methods , Female , Humans , Middle Aged , Pain Measurement , Personality Inventory/standards , Psychometrics/standards , Surveys and Questionnaires/standards
17.
Clinics ; 74: e789, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039548

ABSTRACT

The aim of this study was to estimate the prevalence of low-back pain (LBP) and to identify the level of functional disability in elderly individuals in different populations. From January 1985 to October 2018, a search was performed using the following databases: Embase, LILACS, SciELO, Scopus, Medline, and the Web of Science. The descriptors were low-back pain, back pain, lower-back pain, prevalence, and elderly in Portuguese and English. Two independent reviewers conducted a search for studies and evaluated their methodological quality. The search strategy returned 2186 titles, and 35 were included in this review. The studies evaluated 135,059 elderly individuals aged between 60 and 102 years, and the prevalence of LBP ranged from 21% to 75%. The levels of functional disability, as well as functional difficulties, activities of daily living, and physical capacity, were identified in 60% of the studies. This review indicated a high prevalence of LBP in elderly individuals and functional disability that affects factors important for independence. However, the studies used different methodologies, suggesting that more studies be conducted with scientific accuracy, methodological quality, and low risk of bias to contribute to the proposal of preventive actions for elderly populations.


Subject(s)
Humans , Middle Aged , Aged , Aged, 80 and over , Activities of Daily Living , Low Back Pain/epidemiology , Prevalence , Chronic Pain
18.
PLoS One ; 9(7): e101656, 2014.
Article in English | MEDLINE | ID: mdl-25006670

ABSTRACT

The influence of genetic factors may contribute to the poor prognosis of breast cancer (BC) at a very young age. However BRCA1/2 mutations could not explain the majority of cases arising in these patients. MicroRNAs (miRs) have been implicated in biological processes associated with BC. Therefore, we investigated differences in miRs expression between tumors from young patients (≤35 years) with sporadic or familial history and non-carriers of BRCA1/2 mutations. Thirty-six young Brazilian patients were divided into 2 groups: sporadic (NF-BC) or familial breast cancer (F-BC). Most of the samples were classified as luminal A and B and the frequency of subtypes did not differ between familial or sporadic cases. Using real time qPCR and discriminant function analysis, we identified 9 miRs whose expression levels rather than miR identity can discriminate between both patient groups. Candidate predicted targets were determined by combining results from miRWalk algorithms with mRNA expression profiles (n = 91 differently expressed genes). MiR/mRNA integrated analysis identified 91 candidate genes showing positive or negative correlation to at least 1 of the 9 miRs. Co-expression analysis of these genes with 9 miRs indicated that 49 differentially co-expressed miR-gene interactions changes in F-BC tumors as compared to those of NF-BC tumors. Out of 49, 17 (34.6%) of predicted miR-gene interactions showed an inverse correlation suggesting that miRs act as post-transcriptional regulators, whereas 14 (28.6%) miR-gene pairs tended to be co-expressed in the same direction indicating that the effects exerted by these miRs pointed to a complex level of target regulation. The remaining 18 pairs were not predicted by our criteria suggesting involvement of other regulators. MiR-mRNA co-expression analysis allowed us to identify changes in the miR-mRNA regulation that were able to distinguish tumors from familial and sporadic young BC patients non-carriers of BRCA mutations.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Ductal, Breast/metabolism , MicroRNAs/metabolism , Adult , Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/genetics , Female , Genes, BRCA1 , Genes, BRCA2 , Humans , MicroRNAs/genetics , Transcriptome , Young Adult
19.
Article in English | LILACS | ID: biblio-894380

ABSTRACT

Dear Editor I have read an article recently published in "Medical Express", "Writing Good English: Is scientific English a Latin Language in Disguise?" With respect to the statistical analyses, I have some comments. I would like to point out that ANOVA, the statistical treatment used to compare the incidence of Latin/Greek words in English against Portuguese texts, is not appropriate for the data analyzed. The reason is very simple: the sample space of a normal distribution is the whole real set of numbers extending from −∞ to +∞. In contrast, the sample space of a proportion π extends from zero to one. Another point is that the beta distribution is symmetric only when (π = ½ - beta). The beta distribution, considered here, is one of the adequate distributions to analyze proportions. Asymmetry grows as π moves away from ½. The author kindly provided me with the raw data allowing me to reanalyze the results within his focus. I came up with the results shown in Figure 3A which may be advantageously compared with Figure 3 of the article. Adding another technical argument and having adopted the beta distribution, I found that the log-odds, ln (π / 1 - π ),are normally distributed allowing us to apply standard statistical methods. My decision was to use confidence intervals to clearly illustrate the differences between English and Portuguese on the use of Latin/Greek words. I call the attention to the fact that the intervals for Portuguese are more asymmetric than the ones for English which are close to ½. To obtain the intervals for proportions the inverse transformations were taken from log-odds to proportions. These transformations through the log-odds made the distribution of the proportions be described as Logistic-Normal, as painstakingly discussed in: Aitchison J. (2003), The Statistical Analysis of Compositional Data, Blackburn Press.


Subject(s)
Humans , Communications Media/statistics & numerical data , Language , Incidence , Analysis of Variance , Data Interpretation, Statistical
20.
J Crit Care ; 28(1): 62-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23228727

ABSTRACT

PURPOSE: During the mechanical ventilation weaning process, the spontaneous breathing trial (SBT) is the confirmatory test of patients' capability to breathe unassisted. However, the SBT interobserver agreement rate (its reliability) is unknown, and our objective was to evaluate it. MATERIALS AND METHODS: This is a prospective, multicentric and observational study. Patients were included when the SBT criteria were fulfilled. Two physicians and 2 respiratory therapists (RTs) rated each SBT. The SBT interobserver agreement was measured using κ statistic and also the percentage of agreement with its 95% credible interval (CrI) calculated by a Bayesian inference. RESULTS: Ninety-three distinct physicians and 91 distinct RTs rated 130 SBTs. The κ coefficient was 0.46 for physicians and 0.57 for RT, indicating a moderate interobserver agreement rate. The percentage of agreement was 87.7% between physicians (95% CrI, 81.0%-92.3%) and 86.2% between RT (95% CrI, 79.2%-91.1%). The physicians' and RT' percentage of agreement were not statistically different (P = .71). CONCLUSIONS: The SBT interobserver agreement rate is only moderate for physicians and RT. The percentage of agreement between 2 different SBT observers is 79.2% to 92.3%. Therefore, a relevant percentage of patients will have different extubation decisions depending on the SBT observer.


Subject(s)
Respiratory Function Tests , Ventilator Weaning , Adult , Allied Health Personnel , Bayes Theorem , Humans , Likelihood Functions , Observer Variation , Physicians , Prospective Studies , Reproducibility of Results
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