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STUDY QUESTION: Does repeat-associated non-AUG (RAN) translation play a role in fragile X-associated primary ovarian insufficiency (FXPOI), leading to the presence of polyglycine containing protein (FMRpolyG)-positive inclusions in ovarian tissue? SUMMARY ANSWER: Ovaries of a woman with FXPOI and of an Fmr1 premutation (PM) mouse model (exCGG-KI) contain intranuclear inclusions that stain positive for both FMRpolyG and ubiquitin. WHAT IS KNOWN ALREADY: Women who carry the FMR1 PM are at 20-fold increased risk to develop primary ovarian insufficiency (FXPOI). A toxic RNA gain-of-function has been suggested as the underlying mechanism since the PM results in increased levels of mRNA containing an expanded repeat, but reduced protein levels of fragile X mental retardation protein (FMRP). Recently, RAN translation has been shown to occur from FMR1 mRNA that contains PM repeat expansions, leading to FMRpolyG inclusions in brain and non-CNS tissues of fragile X-associated tremor/ataxia syndrome (FXTAS) patients. STUDY DESIGN, SIZE, DURATION: Ovaries of a woman with FXPOI and women without PM (controls), and ovaries from wild-type and exCGG-KI mice were analyzed by immunohistochemistry for the presence of inclusions that stained for ubiquitin and FMRpolyG . The ovaries from wild-type and exCGG-KI mice were further characterized for the number of follicles, Fmr1 mRNA levels and FMRP protein expression. The presence of inclusions was also analyzed in pituitaries of a man with FXTAS and the exCGG-KI mice. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human ovaries from a woman with FXPOI and two control subjects and pituitaries from a man with FXTAS and a control subjects were fixed in 4% formalin. Ovaries and pituitaries of wild-type and exCGG mice were fixed in Bouin's fluid or 4% paraformaldehyde. Immunohistochemistry was performed on the human and mouse samples using FMRpolyG, ubiquitin and Fmrp antibodies. Fmr1 mRNA and protein expression were determined in mouse ovaries by quantitative RT-PCR and Western blot analysis. Follicle numbers in mouse ovaries were determined in serial sections by microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: FMRpolyG-positive inclusions were present in ovarian stromal cells of a woman with FXPOI but not in the ovaries of control subjects. The FMRpolyG-positive inclusions colocalized with ubiquitin-positive inclusions. Similar inclusions were also observed in the pituitary of a man with FXTAS but not in control subjects. Similarly, ovaries of 40-week-old exCGG-KI mice, but not wild-type mice, contained numerous inclusions in the stromal cells that stained for both FMRpolyG- and ubiquitin, while the ovaries of 20-week-old exCGG-KI contained fewer inclusions. At 40 weeks ovarian Fmr1 mRNA expression was increased by 5-fold in exCGG-KI mice compared with wild-type mice, while Fmrp expression was reduced by 2-fold. With respect to ovarian function in exCGG-KI mice: (i) although the number of healthy growing follicles did not differ between wild-type and exCGG-KI mice, the number of atretic large antral follicles was increased by nearly 9-fold in 40-week old exCGG-KI mice (P < 0.001); (ii) at 40 weeks of age only 50% of exCGG-KI mice had recent ovulations compared with 89% in wild-type mice (P = 0.07) and (iii) those exCGG-KI mice with recent ovulations tended to have a reduced number of fresh corpora lutea (4.8 ± 1.74 versus 8.50 ± 0.98, exCGG-KI versus wild-type mice, respectively, P = 0.07). LIMITATIONS, REASONS FOR CAUTION: Although FMRpolyG-positive inclusions were detected in ovaries of both a woman with FXPOI and a mouse model of the FMR1 PM, we only analyzed one ovary from a FXPOI subject. Caution is needed to extrapolate these results to all women with the FMR1 PM. Furthermore, the functional consequence of FMRpolyG-positive inclusions in the ovaries for reproduction remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that a dysfunctional hypothalamic-pituitary-gonadal-axis may contribute to FXPOI in FMR1 PM carriers. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from NFXF, ZonMW, the Netherlands Brain Foundation and NIH. The authors have no conflict of interest to declare.
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Ataxia/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Cuerpos de Inclusión Intranucleares/genética , Insuficiencia Ovárica Primaria/genética , Temblor/genética , Expansión de Repetición de Trinucleótido/genética , Adulto , Anciano , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Mutación , PéptidosRESUMEN
OBJECTIVES: To investigate the association between neighbourhood factors and decayed, missing, and filled teeth (dmft) index among preschool children. METHODS: The sample of this cross-sectional study comprised 1,110 children (0-5 years old) clustered in 16 official neighbourhoods of Canoas city, southern Brazil. Multilevel binomial models were used to estimate the association of contextual variables at neighbourhood level (Human Development Index, average income, and public primary health care units) with two oral health outcomes: decayed teeth (dt) and missing or filled teeth (mft), after adjusting for individual variables (gender, age, maternal education, equivalent household income logarithm, household, and point of care). RESULTS: Overall, 24.9% of the sample had dental caries experience (dmft >0), and 92.3% of the dmft was untreated caries. There was no statistical significant association (p > 0.05) of contextual characteristics with the decay component. The teeth of children living in richer areas had 2.87 (95% CI: 1.05-7.86) times more chances of being treated (mft component). Variance attributed to neighbourhood level was estimated as 5.9% (p < 0.01) and 4.1% (p = 0.17) for dt and mft, respectively, in adjusted models. CONCLUSIONS: Intra-urban areas seem homogeneous, with small variability between neighbourhoods, having no contextual effect on untreated dental caries (dt). Contextual variables may influence treatment access (mft) through the use of dental services in preschool children.
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Índice CPO , Caries Dental/diagnóstico , Caries Dental/epidemiología , Brasil/epidemiología , Preescolar , Estudios Transversales , Demografía , Atención Odontológica/estadística & datos numéricos , Caries Dental/patología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Análisis Multinivel , Salud Bucal/estadística & datos numéricos , Factores Socioeconómicos , Población UrbanaRESUMEN
OBJECTIVE: To compare gross and histologic patterns of age-related degeneration within the intervertebral disc and adjacent vertebra between rhesus monkeys and humans. MATERIALS AND METHODS: We examined age-related patterns of disc degeneration from mid-sagittal sections of the intervertebral disc and adjacent vertebral bodies (VB) among six rhesus monkey thoracolumbar and seven human lumbar spines. Gross morphology and histopathology were assessed via the Thompson grading scheme and other degenerative features of the disc and adjacent bone. RESULTS: Thompson grades ranged from 3 through 5 for rhesus monkey discs (T9-L1) and 2 through 5 for the human discs (T12-S1). In both rhesus monkey and human discs, presence of distinct lesions was positively associated with Thompson grade of the overall segment. Degenerative patterns differed for radial tears, which were more prevalent with advanced disc degeneration in humans only. Additionally, compared to the more uniform anteroposterior disc degeneration patterns of humans, rhesus monkeys showed more severe osteophytosis and degeneration on the anterior border of the vertebral column. CONCLUSIONS: Rhesus monkey spines evaluated in the present study appear to develop age-related patterns of disc degeneration similar to humans. One exception is the absence of an association between radial tears and disc degeneration, which could reflect species-specific differences in posture and spinal curvature. Considering rhesus monkeys demonstrate similar patterns of disc degeneration, and age at a faster rate than humans, these findings suggest longitudinal studies of rhesus monkeys may be a valuable model for better understanding the progression of human age-related spinal osteoarthritis (OA) and disc degeneration.
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Envejecimiento/patología , Degeneración del Disco Intervertebral/patología , Vértebras Lumbares/patología , Macaca mulatta , Osteoartritis de la Columna Vertebral/patología , Vértebras Torácicas/patología , Anciano , Animales , Cadáver , Progresión de la Enfermedad , Femenino , Humanos , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Osteoartritis de la Columna Vertebral/diagnóstico por imagen , Radiografía , Índice de Severidad de la Enfermedad , Osteofitosis Vertebral/diagnóstico por imagen , Osteofitosis Vertebral/patología , Vértebras Torácicas/diagnóstico por imagenRESUMEN
Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/myokymia can result from mutations in this gene.
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Ataxia/genética , Fasciculación/genética , Mutación Puntual , Canales de Potasio con Entrada de Voltaje , Canales de Potasio/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Humanos Par 12 , Proteínas de Drosophila , Drosophila melanogaster/genética , Femenino , Genes , Humanos , Canal de Potasio Kv.1.1 , Masculino , Ratones , Datos de Secuencia Molecular , Linaje , Canales de Potasio/química , Canales de Potasio/deficiencia , Canales de Potasio/fisiología , Conformación Proteica , Ratas , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Canales de Potasio de la Superfamilia Shaker , SíndromeRESUMEN
We have examined data on six closely linked microsatellite loci on chromosome 9q34 from 59 Ashkenazi Jewish families with idiopathic torsion dystonia (ITD). Our data show that the vast majority (> 90%) of early-onset ITD cases in the Ashkenazi population are due to a single founder mutation, which we estimate first appeared approximately 350 years ago. We also show that carriers preferentially originate from the northern part of the historic Jewish Pale of settlement (Lithuania and Byelorussia). The recent origin of this dominant mutation and its current high frequency (between 1/6,000 and 1/2,000) suggest that the Ashkenazi population descends from a limited group of founders, and emphasize the importance of genetic drift in determining disease allele frequencies in this population.
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Distonía Muscular Deformante/epidemiología , Distonía Muscular Deformante/genética , Judíos/historia , Judíos/estadística & datos numéricos , Alelos , Mapeo Cromosómico , Cromosomas Humanos Par 9 , Distonía Muscular Deformante/etiología , Europa (Continente)/epidemiología , Frecuencia de los Genes , Marcadores Genéticos , Genética de Población , Historia del Siglo XVII , Humanos , Mutación , Linaje , TiempoRESUMEN
Hallervorden-Spatz syndrome (HSS) (OMIM #234200) is a rare, autosomal recessive neurode-generative disorder with brain iron accumulation as a prominent finding. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals massive iron deposits in the basal ganglia. Systemic and cerebrospinal fluid iron levels are normal, as are plasma levels of ferritin, transferrin and ceruloplasmin. Conversely, in disorders of systemic iron overload, such as haemochromatosis, brain iron is not increased, which suggests that fundamental differences exist between brain and systemic iron metabolism and transport. In normal brain, non-haem iron accumulates regionally and is highest in basal ganglia. Pathologic brain iron accumulation is seen in common disorders, including Parkinson's disease, Alzheimer's disease and Huntington disease. In order to gain insight into normal and abnormal brain iron transport, metabolism and function, our approach was to map the gene for HSS. A primary genome scan was performed using samples from a large, consanguineous family (HS1) (see Fig. 1). While this family was immensely powerful for mapping, the region demonstrating homozygosity in all affected members spans only 4 cM, requiring very close markers in order to detect linkage. The HSS gene maps to an interval flanked by D20S906 and D20S116 on chromosome 20p12.3-p13. Linkage was confirmed in nine additional families of diverse ethnic backgrounds.
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Cromosomas Humanos Par 20 , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Mapeo Cromosómico , Consanguinidad , Femenino , Ligamiento Genético , Marcadores Genéticos , Homocigoto , Humanos , Masculino , LinajeRESUMEN
Early-onset torsion dystonia is a movement disorder, characterized by twisting muscle contractures, that begins in childhood. Symptoms are believed to result from altered neuronal communication in the basal ganglia. This study identifies the DYT1 gene on human chromosome 9q34 as being responsible for this dominant disease. Almost all cases of early-onset dystonia have a unique 3-bp deletion that appears to have arisen idependently in different ethnic populations. This deletion results in loss of one of a pair of glutamic-acid residues in a conserved region of a novel ATP-binding protein, termed torsinA. This protein has homologues in nematode, rat, mouse and humans, with some resemblance to the family of heat-shock proteins and Clp proteases.
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Cromosomas Humanos Par 9 , Distonía Muscular Deformante/genética , Chaperonas Moleculares , Transportadoras de Casetes de Unión a ATP/genética , Edad de Inicio , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas Portadoras/química , Mapeo Cromosómico , Análisis Mutacional de ADN , Tamización de Portadores Genéticos , Ligamiento Genético , Marcadores Genéticos , Humanos , Judíos/genética , Linfocitos , Ratones , Datos de Secuencia Molecular , Mutación Puntual , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Ratas , Proteínas Recombinantes/biosíntesis , Alineación de Secuencia , Eliminación de Secuencia , Homología de Secuencia de Aminoácido , Transcripción GenéticaRESUMEN
PURPOSE: Estimate the incidence of teething symptoms and investigate risk factors at three centers in different regions of Brazil. METHODS: A prospective cohort study enrolled children at birth in the cities of Manaus (northern region), Porto Alegre (southern region) and Salvador (northeast region). Sociodemographic and anthropometric variables were collected at baseline and 6 months. At 12 months, data were collected on the child's health through structured interviews and dental examinations, including the primary outcome: occurrence of signs and symptoms of tooth eruption reported by parents. Statistical analysis involved Poisson regression with robust variance, with calculation of relative risks (RR). RESULTS: The incidence of teething symptoms was 82.4% (238/289). The multivariate analysis revealed a higher occurrence of the outcome in the city of Salvador (RR = 1.39; 95% CI 1.23-1.58), when mother's education was more than 11 years (RR = 1.31; 95% CI 1.04-1.65), when a larger number of individuals resided in the home (RR = 1.15; 95% CI 1.02-1.29), when a smoker resided in the home (RR = 1.16; 95% CI 1.03-1.31) and when the child presented flu or cold in the first year of life (RR = 1.23; 95% CI 1.09-1.38). The most reported symptoms were fever (50.5%), irritability (42.6%), itching (40.8%) and diarrhea (35.3%). Most parents (82%) took some action to alleviate symptoms, including unprescribed systemic medication, such as analgesic, anti-inflammatory and anti-diarrheic agents. CONCLUSION: Reports of teething symptoms were associated with the city investigated, socioeconomic factors of the families and characteristics of the child's health. A high rate of administering unprescribed medication was also found.
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Erupción Dental , Recién Nacido , Niño , Humanos , Estudios de Cohortes , Brasil/epidemiología , Estudios Prospectivos , Factores de RiesgoRESUMEN
Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two- and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies.
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Estrógenos no Esteroides/toxicidad , Sustancias Peligrosas/toxicidad , Fenoles/toxicidad , Animales , Compuestos de Bencidrilo , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Monitoreo del Ambiente , Semivida , Humanos , Ratones , Ratas , Medición de Riesgo , Pruebas de Toxicidad/métodosRESUMEN
The comparison between intensity-modulated proton therapy (IMPT) and volume-modulated arc therapy (VMAT) plans, based on models of normal tissue complication probabilities (NTCP), can support the choice of radiation modality. IMPT irradiation plans for 50 patients with head and neck tumours originally treated with photon therapy have been robustly optimised against density and setup uncertainties. The dose distribution has been calculated with a Monte Carlo (MC) algorithm. The comparison of the plans was based on dose-volume parameters in organs at risk (OARs) and NTCP-calculations for xerostomia, sticky saliva, dysphagia and tube feeding using Langendijk's model-based approach. While the dose distribution in the target volumes is similar, the IMPT plans show better protection of OARs. Therefore, it is not the high dose confirmation that constitutes the advantage of protons, but it is the reduction of the mid-to-low dose levels compared to photons. This work investigates to what extent the advantages of proton radiation are beneficial for the patient's post-therapeutic quality of life (QoL). As a result, approximately one third of the patients examined benefit significantly from proton therapy with regard to possible late side effects. Clinical data is needed to confirm the model-based calculations.
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Modelos Teóricos , Órganos en Riesgo/efectos de la radiación , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Probabilidad , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
Emergency response management and rescue operations concerning the railway network in Germany need special attention and implementation in several ways. The emergency response concerning the German national railway network managed by Deutsche Bahn AG is subject to various rules and regulations which have to be followed precisely. Only by following these rules and procedures is the safety of all emergency staff at the scene ensured. The German national railway network (Deutsche Bahn AG) provides its own emergency response control center, which specializes in managing its response to emergencies and dispatches an emergency response manager to the scene. This person serves as the primary Deutsche Bahn AG representative at the scene and is the only person who is allowed to earth the railway electrical power lines. This article will discuss different emergency situations concerning railway accidents and the emergency medical response to them based on a near collision with a high speed train during a rescue mission close to the railway track. Injury to personnel could only be avoided by chance and luck. The dangers and risks for rescue staff are specified. Furthermore, the article details practical guidelines for rescue operations around the German national railway track system.
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Servicios Médicos de Urgencia/organización & administración , Vías Férreas , Accidentes , Electricidad , Servicios Médicos de Urgencia/legislación & jurisprudencia , Alemania , Guías como Asunto , Vías Férreas/legislación & jurisprudencia , Trabajo de Rescate , RiesgoRESUMEN
The societies of western countries are facing enormous economic and social challenges. Despite a declining population size the number of elderly patients is growing and will lead to an increase in cases of trauma in the near future. In addition, the health care system will have to be financed by a reduced labor force. To realize the ambitious political goal of providing comprehensive medical care an economization of hospital treatment must be achieved. The bottleneck within the surgical specialties in case of efficient scheduling will be the capacity utilization of the operating theatres. Additional separate outpatient operating theatres adjacent to hospitals could be an efficient instrument for using resources and economizing medical procedures. Considering the socio-demographic alterations of our society an adequate discussion regarding the general medical conditions is essential.
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Servicio Ambulatorio en Hospital/organización & administración , Asignación de Recursos/métodos , Asignación de Recursos/organización & administración , Servicio de Cirugía en Hospital/organización & administración , AlemaniaRESUMEN
AIM: To identify factors associated with negative child behaviour in the dental setting. MATERIALS AND METHODS: A cross-sectional study was conducted with a sample of 324 mother-child pairs (children aged 3 to 12 years) seen at a university clinic in Canoas, southern Brazil. Mother's anxiety was measured using the Beck Anxiety Inventory. Oral examinations were performed to determine caries experience (dmft/DMFT index) in the mothers and children. Child behaviour was evaluated at six moments of the dental visit using the Frankl scale. Statistical analysis involved Poisson regression with robust variance. RESULTS: The prevalence of negative child behaviour was 9.3%, with a greater frequency among younger children, those with no previous use of dental services and those whose mothers exhibited a moderate to severe level of anxiety. The multivariable analysis demonstrated that the probability of negative behaviour was 2.4-fold greater among children who had not previous dental services attendance (PR = 2.37, 95% CI:1.13-4.95; p=0.022) and 3.1-fold greater among those whose mothers had a moderate to severe level of anxiety (PR = 3.08, 95% CI:1.64-5.75; p<0.001). CONCLUSION: Mother's anxiety, younger age and no previous history of visiting a dentist are associated with negative behaviour during a dental appointment and therefore merit special attention.
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Caries Dental , Brasil , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Madres , Prevalencia , Factores SocioeconómicosRESUMEN
A common animal model of chemical hepatocarcinogenesis was used to examine the utility of transcriptomic and proteomic data to identify early biomarkers related to chemically induced carcinogenesis. N-nitrosomorpholine, a frequently used genotoxic model carcinogen, was applied via drinking water at 120 mg/L to male Wistar rats for 7 weeks followed by an exposure-free period of 43 weeks. Seven specimens of each treatment group (untreated control and 120 mg/L N-nitrosomorpholine in drinking water) were sacrificed at nine time points during and after N-nitrosomorpholine treatment. Individual samples from the liver were prepared for histological and toxicogenomic analyses. For histological detection of preneoplastic and neoplastic tissue areas, sections were stained using antibodies against the placental form of glutathione-S-transferase (GST-P). Gene and protein expression profiles of liver tissue homogenates were analyzed using RG-U34A Affymetrix rat gene chips and two-dimensional gel electrophoresis-based proteomics, respectively. In order to compare results obtained by histopathology, transcriptomics and proteomics, GST-P-stained liver sections were evaluated morphometrically, which revealed a parallel time course of the area fraction of preneoplastic lesions and gene plus protein expression patterns. On the transcriptional level, an increase of hepatic GST-P expression was detectable as early as 3 weeks after study onset. Comparing deregulated genes and proteins, eight species were identified which showed a corresponding expression profile on both expression levels. Functional analysis suggests that these genes and corresponding proteins may be useful as biomarkers of early hepatocarcinogenesis.
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Neoplasias Hepáticas Experimentales/metabolismo , Hígado/efectos de los fármacos , Nitrosaminas/toxicidad , Animales , Biomarcadores de Tumor/biosíntesis , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Glutatión Transferasa/biosíntesis , Humanos , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/patología , Masculino , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Proteómica , Ratas , Ratas Wistar , ToxicogenéticaRESUMEN
Use of the term "water potential" in place of "diffusion pressure deficit" would improve communication between botanists and scientists in other fields because the concept of potential is familiar to most scientists. Water potential, expressed as PsiW, is the difference in free energy or chemical potential per unit molal volume between pure water and water in cells at the same temperature. The potential of pure water is set at zero; hence the potential of water in cells and solutions is less than zero, or negative. The water potential of a cell is numerically equal to its diffusion pressure deficit, but has a negative sign.
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A new immunosensor for the determination of procalcitonin was developed. A sandwich assay format was implemented on a polymethylmetacrylate optical biochip, opportunely shaped in order to obtain several flow channels and potentially suitable for point of care testing applications. The sandwich format makes use of two new rat monoclonal antibodies. The capture antibody was covalently immobilised on the surface of the plastic chip, and the detection antibody was labelled with DY647 dye. Different combinations of capture and detection antibodies were investigated, and particular attention was devoted in order to avoid the non-specific adsorption. A limit of detection of 0.088 mg L(-1) was achieved within the working range of 0.28-50 mg L(-1) in buffer samples. The assay was also implemented in human serum, and 0.2 and 0.7-25 mg L(-1) were the attained limit of detection and working range, respectively.
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Técnicas Biosensibles , Calcitonina/análisis , Sistemas de Atención de Punto , Precursores de Proteínas/análisis , Péptido Relacionado con Gen de Calcitonina , Polarización de Fluorescencia , Sensibilidad y EspecificidadRESUMEN
This study aimed to evaluate laser fluorescence (LF) for monitoring the initial stage of subsurface de- and remineralization (<150 microm depth). Ninety-six sound blocks of bovine enamel, selected according to surface hardness (SH) and LF were used in two experimental studies, in vitro and in situ. In vitro, blocks were exposed to a demineralizing solution, then remineralized by pH cycling for 6 days. In situ, 10 volunteers wore acrylic palatal appliances, each containing 4 dental enamel blocks that were demineralized for 14 days by exposure to 20% sucrose solution. Following this treatment, blocks were submitted to remineralization for 1 week with fluoride dentifrice (1,100 microg F/g). In both experiments, SH and LH were measured after demineralization and after remineralization. Further, enamel blocks were selected after the demineralization/remineralization steps for measurement of cross-sectional hardness and integrated loss of subsurface hardness (Delta KHN). SH and Delta KHN showed significant differences among the phases in each study. LF values for sound, demineralized and remineralized enamel were: 5.2 +/- 1.1, 8.1 +/- 1.2 and 5.6 +/- 0.8, respectively, in the in vitro study, and 5.3 +/- 0.3, 16.5 +/- 4.7 and 6.5 +/- 2.5, respectively, in the in situ study, values for demineralized enamel being significantly higher than for sound and remineralized enamel in both studies. However, LF was correlated with Delta KHN only in situ. LF was capable of monitoring de- and remineralization in early lesions in situ, when bacteria are presumably present in the caries lesion body, but is not correlated with mineral changes in bacteria-free systems.
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Caries Dental/diagnóstico , Esmalte Dental/efectos de la radiación , Rayos Láser , Desmineralización Dental/diagnóstico , Remineralización Dental , Adulto , Análisis de Varianza , Animales , Bacterias/efectos de la radiación , Biopelículas/efectos de la radiación , Cariostáticos/administración & dosificación , Bovinos , Recuento de Colonia Microbiana , Pruebas de Actividad de Caries Dental/instrumentación , Pruebas de Actividad de Caries Dental/métodos , Esmalte Dental/microbiología , Dentífricos/administración & dosificación , Método Doble Ciego , Fluoruros Tópicos/administración & dosificación , Dureza , Humanos , Espectrometría de Fluorescencia , Desmineralización Dental/microbiología , Diente Artificial , Adulto JovenRESUMEN
AIM: Estimate the prevalence of developmental defects of enamel (DDE) in the primary dentition, describe the distribution among tooth groups and investigate the association with birth weight. METHODS: A cross-sectional study was conducted with a sample of 827 children aged 2-5 years representative of the city of Canela in southern Brazil. Demographic characteristics (gender and age) and birth weight were collected from vaccination cards. The diagnosis of DDE was performed by six trained examiners following the criteria of the Federation Dentaire International. DDE were described both jointly and separately as opacity and hypoplasia. Statistical analysis involved the Chi square test, Mann-Whitney test and Poisson regression with robust variance. RESULTS: The prevalence of DDE was 55.1% (95% CI 51.6-58.5%), with a mean of 3.0 ± 2.2 teeth affected. Opacity was the more frequent defect (50.4%), followed by hypoplasia (15.5%). Distribution of the defects was uneven, with opacity predominant on second molars and hypoplasia predominant on canines and second molars. Children with a low birth weight did not have a greater probability of opacity (PR: 1.13; 95% CI 0.91-1.41), hypoplasia (PR: 1.33; 95% CI 0.80-2.22) or DDE (PR: 1.11; 95% CI 0.91-1.37). CONCLUSION: The prevalence of DDE was high, predominant on second molars and not associated with birth weight. These findings indicate directions for future examination/diagnosis protocols and specific orientations.
Asunto(s)
Hipoplasia del Esmalte Dental , Peso al Nacer , Brasil , Niño , Preescolar , Estudios Transversales , Esmalte Dental , Humanos , Prevalencia , Diente PrimarioRESUMEN
Torsion dystonia is a movement disorder of unknown etiology characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Dystonic movements can be caused by lesions in the basal ganglia, drugs, or gene defects. Several hereditary forms have been described, most of which have autosomal dominant transmission with variable expressivity. In the Ashkenazi Jewish population the defective gene frequency is about 1/10,000. Here, linkage analysis using polymorphic DNA and protein markers has been used to locate a gene responsible for susceptibility to dystonia in a large, non-Jewish kinship. Affected members of this family have a clinical syndrome similar to that found in the Jewish population. This dystonia gene (ITD1) shows tight linkage with the gene encoding gelsolin, an actin binding protein, and appears by multipoint linkage analysis to lie in the q32-q34 region of chromosome 9 between ABO and D9S26, a region that also contains the locus for dopamine-beta-hydroxylase.
Asunto(s)
Cromosomas Humanos Par 9 , Distonía Muscular Deformante/genética , Polimorfismo de Longitud del Fragmento de Restricción , Proteínas de Unión al Calcio/genética , Mapeo Cromosómico , Sondas de ADN , Dopamina beta-Hidroxilasa/genética , Gelsolina , Ligamiento Genético , Marcadores Genéticos , Humanos , Proteínas de Microfilamentos/genética , LinajeRESUMEN
AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma. We describe our early outcome of patients treated with PBT. MATERIALS AND METHODS: Between August 2013 and July 2016, 18 patients with craniopharyngiomas were treated with 54 Cobalt Gray Equivalent (CGE) in 30 fractions over 6 weeks at our centre. The early outcome of 16 patients included in a registry study was analysed. Radiological response was assessed by RECIST criteria and the disease- and treatment-related toxicities were scored according to the CTCAE 4.0. RESULTS: All patients are alive at a median follow-up of 32.6 months (range 9.2-70.6 months) from initial diagnosis. The median age at PBT was 10.2 years (range 5.4-46.9 years). One patient progressed 8.7 months after PBT and subsequently had complete resection of the tumour. At a median follow-up of 18.4 months after PBT, five patients remained in complete remission, four in partial remission and seven with stable disease. The most common adverse effects during PBT were grade 1 (cutaneous in seven patients and fatigue in six patients). There were no treatment-related grade 3 toxicities. CONCLUSIONS: Our early results are encouraging and comparable with the limited literature on PBT for craniopharyngioma.