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1.
BMC Public Health ; 19(1): 1633, 2019 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-31801512

RESUMEN

BACKGROUND: The border area between French Guiana and Brazil is an active HIV-transmission zone. The aim of the present study was to describe HIV knowledge, risk and the level of stigma among inhabitants of this border area. METHODS: A cross-sectional study was conducted among 621 inhabitants over 18 years of age in the border cities of Saint-Georges-de-l'Oyapock in French Guiana and Oiapoque in Brazil. It was conducted between October 2017 and February 2018. An anonymous standardized questionnaire was filled out by culturally-trained mediators, then analyzed using STATA 12. RESULTS: Almost half (45.9%) of the individuals had a low education level. Participants whose native language was Portuguese or French demonstrated better HIV knowledge than other populations, notably native Amerindian and creole-speaking people. HIV risk behavior was more frequent in men and in younger age groups. People with good HIV knowledge reported having performed more HIV tests in the last year than participants with poor knowledge. The stigma level was high and reported in 74.8% of respondents. CONCLUSIONS: These results illustrate the need for initiatives to improve HIV prevention among autochthonous populations on both sides of this border area. Cross-border collaboration on health policies could produce common key messages adapted to the education level and multi-linguistic populations who live in this area.


Asunto(s)
Infecciones por VIH/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Estigma Social , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Adolescente , Adulto , Factores de Edad , Brasil/epidemiología , Estudios Transversales , Etnicidad/psicología , Etnicidad/estadística & datos numéricos , Femenino , Guyana Francesa/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/psicología , Humanos , Conocimiento , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales , Factores Socioeconómicos , Adulto Joven
2.
Ann Oncol ; 29(8): 1869-1876, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29912274

RESUMEN

Background: Alterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed to inhibit diverse RET fusions, activating mutations and acquired resistance mutations. Patients and methods: Potent anti-RET activity, high selectivity, and central nervous system coverage were confirmed preclinically using a variety of in vitro and in vivo RET-dependent tumor models. Due to clinical urgency, two patients with RET-altered, MKI-resistant cancers were treated with LOXO-292, utilizing rapid dose-titration guided by real-time pharmacokinetic assessments to achieve meaningful clinical exposures safely and rapidly. Results: LOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations; cells engineered to express a KIF5B-RET fusion protein -/+ the RET V804M gatekeeper resistance mutation or the common RET activating mutation M918T; and RET-altered human cancer cell line and patient-derived xenografts, including a patient-derived RET fusion-positive xenograft injected orthotopically into the brain. A patient with RET M918T-mutant medullary thyroid cancer metastatic to the liver and an acquired RET V804M gatekeeper resistance mutation, previously treated with six MKI regimens, experienced rapid reductions in tumor calcitonin, CEA and cell-free DNA, resolution of painful hepatomegaly and tumor-related diarrhea and a confirmed tumor response. A second patient with KIF5B-RET fusion-positive lung cancer, acquired resistance to alectinib and symptomatic brain metastases experienced a dramatic response in the brain, and her symptoms resolved. Conclusions: These results provide proof-of-concept of the clinical actionability of RET alterations, and identify selective RET inhibition by LOXO-292 as a promising treatment in heavily pretreated, multikinase inhibitor-experienced patients with diverse RET-altered tumors.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Carcinoma Neuroendocrino/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-ret/antagonistas & inhibidores , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Adulto , Neoplasias Encefálicas/secundario , Carbazoles/farmacología , Carbazoles/uso terapéutico , Carcinoma Neuroendocrino/patología , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Proteínas de Fusión Oncogénica/antagonistas & inhibidores , Proteínas de Fusión Oncogénica/genética , Piperidinas/farmacología , Piperidinas/uso terapéutico , Prueba de Estudio Conceptual , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-ret/genética , Pirazoles/farmacología , Piridinas/farmacología , Neoplasias de la Tiroides/patología , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Psychol Med ; 44(5): 1087-99, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23866120

RESUMEN

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) often, but not always, persists into adulthood. Investigations of the associations between clinical and biological markers of persistence can shed light on causal pathways. It has been proposed that compensatory improvements in executive neuropsychological functioning are associated with clinical improvements. This is the first study to test this hypothesis prospectively. METHOD: The clinical and neuropsychological functioning of 17 boys with ADHD (mean age 10.45 years at time 1; 14.65 years at time 2) and 17 typically developing (TYP) boys (mean age 10.39 years at time 1; 14.47 years at time 2) was tested on two occasions, 4 years apart. This was done using a battery of standardized neuropsychological tests that included tasks with high and low executive demands. RESULTS: Clinical improvements were observed over time. Neuropsychological performance improvements were also evident, with ADHD boys developing with a similar pattern to TYP boys, but with a developmental lag. Whilst there was an association between reduced symptoms and superior performance at retest for one task with a high executive demand (spatial working memory), this was not seen with two further high executive demand tasks [Stockings of Cambridge and intra-dimensional extra-dimensional (ID/ED) set shifting]. Also, there was no association between change in executive functioning and change in symptoms. Baseline performance on the ID/ED set-shifting task predicted better clinical outcome. Only change in performance on the low executive demand delayed matching-to-sample task predicted better clinical outcome. CONCLUSIONS: These data highlight the importance of longitudinal measurements of cognition, symptoms and treatment response over time in children and adolescents with ADHD.


Asunto(s)
Desarrollo del Adolescente/fisiología , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Progresión de la Enfermedad , Función Ejecutiva/fisiología , Adolescente , Niño , Humanos , Estudios Longitudinales , Masculino
4.
J Endod ; 50(7): 966-975, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38382736

RESUMEN

INTRODUCTION: Diagnostic reference levels (DRLs) are intended to improve patient safety and ensure that patient ionizing radiation doses are as low as reasonably achievable. The purpose of this dosimetry study was to establish regional DRL levels for cone-beam computed tomography (CBCT) imaging for specialty endodontics. Another aim was to compare phantom-measured ionizing radiation dose index 1 (DI1) index doses to the manufacturer-provided dose area product (DAP) radiation output values for each of the CBCT machines studied, to ascertain their degree of correlation. DAP refers to the dose area product, a measure of radiation dose monitoring which represents the dose within the beam times the area within the beam at that position. METHODS: A thimble ionization chamber and polymethyl methacrylate phantom were used to obtain DI1 values using the SEDENTEXTCT method from 21 different CBCT units. DRLs were calculated based on the 75th percentile (third quartile) of the median output values. RESULTS: The proposed DRL from the CBCT units surveyed has a DAP value of 838 mGy cm2 and a DI1 value of 3.924 mGy. DAP versus DI1 values of 500.6 mGy cm2 versus 2.006 mGy, and 838 mGy cm2 versus 3.906 mGy represented the third quartile of the median values for the 4-cm × 4-cm and 5-cm × 5-cm field of views (FOVs), respectively. CONCLUSIONS: The DI1 and DAP values strongly correlated when 3 outlier CBCT machines (J Morita Veraview X800) using a novel 360° (full rotation) acquisition mode were excluded. The importance of selectable exposure parameters as directly related to ionizing radiation output is illustrated among the CBCT units surveyed. Although the actual FOV that is selected is ultimately dictated by the specific clinical requirements, a 4-cm × 4-cm FOV is recommended for specialist endodontics practice, whenever clinically practical, based on the decreased ionizing radiation output, as compared to that from a 5-cm × 5-cm FOV.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Endodoncia , Dosis de Radiación , Humanos , Missouri , Illinois , Niveles de Referencia para Diagnóstico , Fantasmas de Imagen
5.
Nat Genet ; 20(2): 129-35, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9771704

RESUMEN

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.


Asunto(s)
Proteínas Portadoras/genética , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4 , Péptidos y Proteínas de Señalización Intracelular , Trastornos Linfoproliferativos/genética , Mutación , Dominios Homologos src/genética , Antígenos CD , Linfocitos B/inmunología , Linfocitos B/virología , Proteínas Portadoras/metabolismo , Clonación Molecular , Femenino , Ligamiento Genético , Glicoproteínas/metabolismo , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Humanos , Inmunoglobulinas/metabolismo , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/virología , Masculino , Datos de Secuencia Molecular , Linaje , Receptores de Superficie Celular , Alineación de Secuencia , Eliminación de Secuencia , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Miembro 1 de la Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Linfocitos T/inmunología , Linfocitos T/virología , Cromosoma X
6.
Eur J Clin Microbiol Infect Dis ; 31(7): 1551-9, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22167256

RESUMEN

We evaluated Clostridium difficile prevalence rates in 2,807 clinically indicated stool specimens stratified by inpatient (IP), nursing home patient (NH), outpatient (OP), age, gender, and specimen consistency using bacterial culture, toxin detection, and polymerase chain reaction (PCR) ribotyping. Rates were determined based on the detection of toxigenic C. difficile isolates. We identified significant differences in the rates between patient populations and with age. Specimens from NH had a higher rate (46%) for toxigenic C. difficile than specimens from IP (18%) and OP (17%). There were no gender-related differences in the rates. Liquid specimens had a lower rate (15%) than partially formed and soft specimens (25%) and formed specimens (18%) for the isolation of toxigenic C. difficile. The nontoxigenic rate was lowest for NH (4%) and highest for patients<20 years of age (23%). We identified 31 different toxigenic ribotypes from a sampling of 190 isolates that showed the lowest diversity in NH. Fluoroquinolone resistance was observed in 93% of the 027 isolates, all of the 053 isolates, and in four other ribotypes. We observed different rates for toxigenic C. difficile in stratified patient populations, with the highest rate for NH, a low overall nontoxigenic rate, and fluoroquinolone resistance.


Asunto(s)
Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/microbiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Clostridioides difficile/clasificación , Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/genética , Farmacorresistencia Bacteriana , Heces/microbiología , Femenino , Fluoroquinolonas/farmacología , Instituciones de Salud , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Ribotipificación , Factores de Riesgo , Factores Sexuales , Adulto Joven
7.
J Fish Biol ; 80(3): 722-7, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22380566

RESUMEN

This paper reports a new aspect of male signalling in the green swordtail Xiphophorus hellerii. Males are highly ornamented and possess a sword (an extension of the caudal fin), as well as a lateral stripe that has been shown to be a badge of status. Males of one natural population, however, were found to quickly change the colour of their lateral stripe to red when socially dominant over other males and black when subdominant, thereby exploiting the female preference for red stripes while dominant, and avoiding the costs of male aggression while subdominant.


Asunto(s)
Comunicación Animal , Ciprinodontiformes/fisiología , Conducta Social , Predominio Social , Animales , Color , Ciprinodontiformes/anatomía & histología , Femenino , Masculino , Preferencia en el Apareamiento Animal
8.
J Patient Saf ; 18(4): 269-275, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34508038

RESUMEN

OBJECTIVES: The author conducted a study to determine the frequency and types of adverse events associated with endodontic ultrasonic devices as reported to the U.S. Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: Endodontic ultrasonic device-related adverse events reported to the MAUDE database from January 1, 2016, to October 31, 2020, were accessed and reviewed. RESULTS: A total of 1258 adverse event reports were submitted to the FDA MAUDE database, as classified under FDA product code ELC (ultrasonic scaler) during the study period. Among these reports, 403 were specific to the dedicated use of the 2 main types of ultrasonic devices used in endodontic treatment: ultrasonic tip devices and irrigation-related devices. Device malfunction-associated events, consisting primarily of device breakage, comprised 393 of the 1258 adverse event reports, whereas the remaining 10 reports were identified as being patient injury-related reports. CONCLUSIONS: The frequency, root causes, and economic costs of ultrasonic tip device breakage remain largely unstudied. Ultrasonic endodontic device-related adverse events and patient injuries occurring within clinical practice may be underreported at the present time. Consequently, the risks and ultimate impacts to patients from ultrasonic endodontic device breakage, malfunction and unknown cause-related adverse events, and patient injuries during their clinical usage remain largely unknown at the present time. Eight of the 10 patient injury-related reports made to the FDA MAUDE database during the period under study, containing descriptions of varying degrees of injury severity, were associated with an irrigation-related device.


Asunto(s)
Endodoncia , Ultrasonido , Bases de Datos Factuales , Falla de Equipo , Humanos , Estados Unidos , United States Food and Drug Administration
9.
J Autism Dev Disord ; 52(6): 2656-2669, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34196890

RESUMEN

COVID-19 has affected people across the world. The current study examined anxiety and worries during the first UK national lockdown in March 2020. Parents (n = 402) reported on their own anxiety and worries as well as that of their son/daughter with Special Education Needs and Disabilities (SEND) and typically developing (TD) child (n = 186) at three time points. Although both groups showed increased anxiety across the three time points, levels of anxiety in the SEND group, but not the TD siblings, were predicted by awareness about COVID-19. In addition, worries differed between the groups showing that COVID-19 impacts the wellbeing of those with SEND differently to that of their TD siblings.


Asunto(s)
Trastorno del Espectro Autista , COVID-19 , Ansiedad/epidemiología , Niño , Control de Enfermedades Transmisibles , Educación Especial , Humanos , SARS-CoV-2 , Reino Unido/epidemiología
10.
Trials ; 23(1): 357, 2022 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-35477835

RESUMEN

Clinical trial managers play a vital role in the design and conduct of clinical trials in the UK. There is a current recruitment and retention crisis for this specialist role due to a complex set of factors, most likely to have come to a head due to the COVID-19 pandemic. Academic clinical trial units and departments are struggling to recruit trial managers to vacant positions, and multiple influences are affecting the retention of this highly skilled workforce. Without tackling this issue, we face major challenges in the delivery on the Department of Health and Social Care's Future of UK Clinical Research Delivery implementation plan. This article, led by a leading network of and for UK Trial Managers, presents some of the issues and ways in which national stakeholders may be able to address this.


Asunto(s)
Ensayos Clínicos como Asunto , Recursos Humanos , COVID-19 , Ensayos Clínicos como Asunto/organización & administración , Humanos , Pandemias , Proyectos de Investigación
11.
J Am Dent Assoc ; 152(11): 909-918, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34482947

RESUMEN

BACKGROUND: Industry payments made to health care providers can create competing interests. The purpose of this study was to define the overall financial relationships between industry and academic endodontics faculty members, detail any variation in such payment data as related to individual faculty member characteristics and leadership position by institution type, and comment on the potential impacts from conflicts of interest (COIs) created by such relationships. METHODS: The author identified and characterized academic endodontists from information on their institutional websites. The author obtained reported industry payments from 2013 through 2019 from the Centers for Medicare & Medicaid Services Open Payments database. The author also noted the distributions of academic endodontists and industry payments by institution, academic rank, sex, and residency program director position. The author subjected the data to descriptive and nonparametric analyses. RESULTS: Of the 302 academic endodontists included, 240 (80%) accepted reported industry payments totaling $4,260,316.97. Overall, the median of total industry payments for all 302 faculty members was $217.89 (interquartile range [IQR], $34.06-$3,070.00). Among those accepting payments, the median amount was $382.80 (IQR, $110.40-$6,234.00). The top decile of paid academic endodontists received $3,669,291.47 in industry payments (86% of the total), with a median payment of $24,013 (IQR, $17,043-$91,190). Significant sex-associated industry payment differences were seen among the overall faculty and among those with the residency program director position. CONCLUSIONS: Most academic endodontists accept industry payments. Significant sex differences exist in overall faculty member academic rank distribution, leadership role, and accepted median industry payment amounts. COI issues have the potential to arise among academic endodontists when such industry payments are accepted. PRACTICAL IMPLICATIONS: Existing sex disparities in academic endodontics within the United States ideally should be acknowledged. COI issues can arise when academic faculty members accept industry payments. Public knowledge of these conflicts could negatively affect individual faculty members, their institutions, and related areas such as academic publishing. Appropriate faculty member COI disclosure, attestation, annual updates, and transparency are important mitigation measures.


Asunto(s)
Endodoncistas , Caracteres Sexuales , Anciano , Conflicto de Intereses , Revelación , Femenino , Humanos , Masculino , Medicare , Estados Unidos
12.
J Endod ; 47(1): 78-87, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32979435

RESUMEN

INTRODUCTION: Cone-beam computed tomography (CBCT) machines produce relatively low levels of harmful ionizing radiation, as compared with the computed tomography devices used in medical practices. The Carestream CS9600 CBCT imaging device has been recently introduced into the marketplace, and the manufacturer reports the use of an increased x-ray tube voltage (120 kVp) for the device, along with a reduced patient dose that is achieved using added filtration. Independent dosimetry studies are performed to ensure appropriate radiation exposure dose levels are within recommended safety guidelines.The purpose of this study is to independently evaluate and measure the radiation exposure dose performance parameters of the CS9600 CBCT, including its multiple field of view, exposure settings, and filtration options. METHODS: A thimble ionization chamber and PMMA phantom were used to characterize dose index using the established SEDENTEXTCT evaluation method. RESULTS: The phantom-obtained radiation dose index measures ranged from 0.128782-13.848 milligrays (mGy) for the various scanning options evaluated. The field of view, type of filter used, and phantom size all had a direct impact on the relationship between the experimentally obtained dose index measures and the dose area product values reported by the manufacturer. CONCLUSIONS: A strong linear correlation was observed between the experimentally obtained dose index measures and the manufacturer-reported dose area product values. The 0.7 mm Cu filter that has been added to the CS9600 reduced the exposure dose index measures even with the x-ray tube kilovoltage peak (kVp) being increased to 120 kVp, as compared with the 0.15 mm Cu filter at 90 kVp.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Tomografía Computarizada por Rayos X , Humanos , Fantasmas de Imagen , Dosis de Radiación
13.
J Endod ; 47(2): 291-296, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33181168

RESUMEN

INTRODUCTION: Several studies in radiology and medicine have evaluated the satisfaction of search (SOS) error effect in chest radiography, abdominal radiography, osteoradiology, and patients with multiple trauma. No research to date has been published evaluating the possible existence of the SOS error phenomenon made during dental periapical radiograph interpretations. The purpose of the present pilot study was to determine if an SOS error effect exists when dental clinicians interpret periapical radiographs. The null hypothesis was that the detection accuracy will be the same or will improve for the detection of native lesions in the presence of an added abnormality. The alternative hypothesis is that there will be a decrease in detection accuracy for native lesions in the presence of an added abnormality. METHODS: Six images were selected to be part of the present experiment. One of the 6 images served as the positive control, and another image served as the negative control. Four images, each including a single subtle carious lesion, were selected to represent the experimental images. The single subtle carious lesion present within the 4 experimental radiographs served as the native pathology, and an abnormality such as a periapical radiolucency, resorption, inadequate nonideal root canal obturation material, or recurrent carious lesion was artificially inserted into the image as the added pathology. Thus, the second set of images consisted of the same 4 images containing the native pathology including an added pathology that was inserted into the image using Adobe Photoshop CS6 (Adobe, Inc, San Jose, CA). Purposive sampling was obtained from 16 examiners including residents from endodontics and periodontics as well as alumni and faculty from the Saint Louis University Center for Advanced Dental Education, St Louis, MO. Each observer participated as a subject during 2 time-separated sessions. Each session was separated by a minimum period of 3 months' duration in order to prevent memory bias. Before starting each interpretation session, the participants were given verbal instructions. Subjects were instructed to provide a location (by tooth number), identify, and rate the presence of all suspected pathology using a Likert scale of 1-5 (1: definitely normal, 2: probably normal, 3: possibly abnormal, 4: probably abnormal, and 5: definitely abnormal). In the second session, the radiographs that were initially presented containing only the native lesion were presented again with the added abnormality, and vice versa. The observers' reports and confidence ratings were recorded and analyzed. Ratings of 3-5 were considered as being positive for the presence of pathology. RESULTS: A true SOS error occurs when the presence of the native lesion is reported correctly without an added abnormality but is not reported (missed) in the presence of an added abnormality. In our study, a true SOS error occurred in 13 of the 64 interpretation sets (20.31%). There was a total of 64 expected native lesions present within the 4 native images viewed by 16 observers. In the 4 added images, there was a total of 64 expected added findings. In the images containing only native lesions, the observers reported 30 of the 64 expected native lesions. In the images containing an artificially added abnormality, the observers reported 58 of the 64 expected added abnormalities and 25 of the 64 expected native lesions. Observers reported fewer native lesions in the presence of an added abnormality. CONCLUSIONS: The current investigation demonstrated the existence of the SOS effect during periapical radiographic interpretations. In 20.31% of interpretations, a true SOS error occurred. This study is clinically relevant because it can help clinicians in reducing false-negative errors made during radiographic interpretation, thus preventing misdiagnosis.


Asunto(s)
Satisfacción Personal , Errores Diagnósticos , Humanos , Variaciones Dependientes del Observador , Proyectos Piloto , Radiografía
14.
Data Brief ; 39: 107570, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34825034

RESUMEN

The additive manufacturing (AM) of components through laser-blown-powder directed-energy-deposition (LBP-DED) is highly applicable to the repair of aerospace components. Fabrication of superalloys with this technique, as with other AM methods, often encounters complications that include the formation of undesired phases, irregular microstructure and texture leading to anisotropic elastic properties. Heat treatments and other post-processing techniques can be used to mitigate these issues. The collected data demonstrates the effects of different heat treatment protocols on the microstructure, elastic properties, and hardness of LBP-DED IN718. In this study eight different heat treatment were used to investigate the effects of treatment time and temperature. The microstructure was investigated through SEM, with XRD and EDX used for phase analysis. The texture was characterised using SEM coupled with EBSD and the elastic properties were determined from resonant ultrasound spectroscopy.

15.
Clin Endocrinol (Oxf) ; 70(1): 96-103, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19128366

RESUMEN

OBJECTIVE: Homozygous mutations in the gene encoding the pituitary transcription factor PROP1 are associated with combined pituitary hormone deficiency (CPHD) in both mice and humans with a highly variable phenotype with respect to the severity and time of initiation of pituitary hormone deficiency. We have ascertained three pedigrees with PROP1 mutations from a large cohort of patients with variable degrees of CPHD who were screened for mutations in PROP1. RESULTS: Affected individuals from all three pedigrees were found to harbour novel PROP1 mutations. We have identified two siblings in one family who were homozygous for an intronic mutation (c.343-11C > G) that disrupts correct splicing resulting in the loss of exon 3 from the PROP1 transcript. Two siblings from a second, unrelated family are compound heterozygotes for two point mutations in the coding region, a missense mutation (p.R125W) that leads to impaired transcriptional activation, and a deletion of a single nucleotide (c.310delC) resulting in a frameshift and nonfunctional mutant protein. Additionally, we identified a homozygous deletion of the PROP1 locus in two patients born to consanguineous parents. CONCLUSION: Mutations in PROP1 are a frequent cause of familial CPHD. We have described four novel mutations in PROP1 in 3 pedigrees, all resulting in PROP1 deficiency by different mechanisms. The phenotypic variation observed in association with PROP1 mutations both within and between families, together with the evolving nature of hormone deficiencies and sometimes changing pituitary morphology indicates a need for continual monitoring of these patients.


Asunto(s)
Proteínas de Homeodominio/genética , Hipopituitarismo/genética , Hormonas Hipofisarias/deficiencia , Adolescente , Animales , Células CHO , Niño , Preescolar , Estudios de Cohortes , Cricetinae , Cricetulus , Análisis Mutacional de ADN , Femenino , Eliminación de Gen , Humanos , Lactante , Masculino , Linaje
16.
J Exp Psychol Anim Behav Process ; 35(1): 92-8, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19159164

RESUMEN

In two experiments, rats first received preexposure to a rectangular arena in which the geometrically equivalent corner pairs (G1 and G2) were coincident with different luminance characteristics (C1 and C2, respectively). In Experiment 1, rats were then placed in a uniform gray rectangular arena where food was located in one geometrically equivalent pair of corners (G1), but not another (G2). Finally, rats were tested in a square arena with C1 and C2 and preferred to search in C1 rather than C2. In Experiment 2, following preexposure to G1C1 and G2C2, rats received pairings of C1 with food and C2 with no food in a square arena. During testing, rats preferred to search in G1 rather than G2 in a gray rectangular arena. These results demonstrate that reciprocal within-compound associations develop between geometric and luminance information and thereby challenge the view that there is a dedicated geometric module that is impenetrable to information that is not geometric.


Asunto(s)
Percepción de Forma/fisiología , Luz , Memoria , Animales , Alimentos , Aprendizaje , Masculino , Ratas
17.
Genes Immun ; 9(4): 328-33, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18418397

RESUMEN

The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8+ and CD4+ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; approximately 30%) compared to Caucasian Americans (CA; approximately 50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-alpha-2a and ribavirin. We observed carriage of A(*)02 (RR=1.33(1.08-1.64); P=0.008), B(*)58 (RR=1.84(1.24-2.73); P=0.002) and DPB1(*)1701 (RR=1.57(1.09-2.26); P=0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.


Asunto(s)
Antivirales/uso terapéutico , Genes MHC Clase II , Genes MHC Clase I , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Negro o Afroamericano , Alelos , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Genotipo , Hepatitis C Crónica/etnología , Hepatitis C Crónica/virología , Heterocigoto , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Masculino , Polietilenglicoles/administración & dosificación , ARN Viral/genética , Proteínas Recombinantes , Ribavirina/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Carga Viral , Población Blanca
18.
Curr Opin Genet Dev ; 4(5): 709-17, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7849511

RESUMEN

Development of the anterior pituitary gland involves the establishment of five distinct cell lineages which are each characterized by the expression of specific trophic hormone genes. Recent studies of the thyrotrope, somatotrope, and lactotrope cell types have investigated the molecular decisions responsible for the commitment and differentiation of these cell types and have characterized the regulatory mechanisms that govern cell-specific expression of individual hormone genes. In particular, elucidation of the molecular basis of heritable dwarf phenotypes lacking particular pituitary cell lineages, such as the Snell, Jackson, and little dwarf mice, and studies of the regulation of trans-acting factors, including Pit-1, involved in pituitary cell restricted gene activation have begun to delineate the pathways responsible for development of this organ.


Asunto(s)
Adenohipófisis/crecimiento & desarrollo , Animales , Secuencia de Bases , Diferenciación Celular/genética , ADN/genética , Proteínas de Unión al ADN/genética , Regulación del Desarrollo de la Expresión Génica , Humanos , Datos de Secuencia Molecular , Fenotipo , Adenohipófisis/citología , Adenohipófisis/metabolismo , Hormonas Adenohipofisarias/metabolismo , Transducción de Señal , Factor de Transcripción Pit-1 , Factores de Transcripción/genética , Transcripción Genética , Activación Transcripcional
19.
Mol Cell Biol ; 10(8): 3934-44, 1990 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1695319

RESUMEN

Expression of the mammalian muscle regulatory factors MyoD1, myogenin, and MRF4 will convert C3H10T1/2 fibroblasts to stable muscle cell lineages. Recent studies have shown that MyoD1 and myogenin also trans-activate expression of a number of cotransfected contractile protein genes, suggesting that these muscle regulatory factors are involved in controlling terminal differentiation events. The extent and specificity of trans activation by the muscle regulatory factors, however, have not been compared directly. In this study, we found that MyoD1, myogenin, and MRF4 exhibited different trans-activation capacities. In contrast to MyoD1 and myogenin, MRF4 was inefficient in trans-activating most of the genes tested, although conversion of C3H10T1/2 fibroblasts to a myogenic lineage was observed at similar frequencies with all three factors. Addition of basic fibroblast growth factor to cells expressing exogenous muscle regulatory factors inhibited the transcriptional activation of cotransfected genes, demonstrating that MyoD1, myogenin, or MRF4 proteins alone are not sufficient to produce a terminally differentiated phenotype. In all cases, trans activation was dependent on signal transduction pathways that are regulated by fibroblast growth factor. Our observations, coupled with previous studies showing differences in the temporal expression and protein structure of MyoD1, myogenin, and MRF4, suggest that the individual members of the muscle regulatory factor family have distinct biological roles in controlling skeletal muscle development.


Asunto(s)
Diferenciación Celular , Genes Reguladores , Virus del Sarcoma Murino de Moloney/genética , Proteínas Musculares/genética , Proteína MioD , Factores Reguladores Miogénicos , Proteínas Nucleares/genética , Fosfoproteínas/genética , Virus del Sarcoma Murino/genética , Activación Transcripcional , Transfección , Animales , Northern Blotting , Células Cultivadas , Proteínas Contráctiles/genética , Fibroblastos/metabolismo , Expresión Génica , Ratones , Ratones Endogámicos C3H , Proteínas Musculares/metabolismo , Músculos/citología , Miogenina , Proteínas Nucleares/metabolismo , Hibridación de Ácido Nucleico , Fosfoproteínas/metabolismo , ARN/genética , ARN/aislamiento & purificación
20.
Mol Cell Biol ; 9(8): 3576-9, 1989 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2797000

RESUMEN

In this report, we demonstrate that myogenic cultures inhibited from differentiating by treatment with fibroblast growth factor or transforming growth factor beta show reduced levels of MyoD1 mRNA. Although this repression may contribute to the inhibition of myogenesis by growth factors, additional regulatory pathways must be affected, since inhibition still occurs in cultures engineered to constitutively express MyoD1 mRNA.


Asunto(s)
Factores de Crecimiento de Fibroblastos/fisiología , Genes Reguladores , Proteínas Musculares/genética , Transcripción Genética , Factores de Crecimiento Transformadores/fisiología , Diferenciación Celular , Línea Celular , Vectores Genéticos , Desarrollo de Músculos , Músculos/citología , ARN Mensajero/análisis , Transfección , Troponina/genética , Troponina I
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