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1.
Int J Dev Disabil ; 70(2): 278-286, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481454

RESUMEN

People with intellectual disability (ID) generally tend to have difficulties expressing their thoughts and feelings verbally. Art-based therapies rely less on cognitive ability and verbal skills and aim to promote mental health. Drama therapy provides a playful framework to communicate problematic issues and to foster social skills. Improvisational theatre (improv) methods applied in therapy settings were reported to show positive effects on social competences and self-esteem. This pilot study investigates the feasibility (N = 24) and appropriateness (n = 12) of an intervention using improv methods in people with mild to moderate ID. Feasibility was measured on the basis of the average participation period, while appropriateness was assessed through a standardised patient satisfaction questionnaire (CSQ-8) and a self-developed questionnaire. The frequency of the applied methods was compared in two subgroups with participants requiring different support. The average participation rate of 19 months indicated a good feasibility. High CSQ-8 scores (M = 27.6/max. 32) and positive feedback on the self-developed questionnaire indicated the overall appropriateness. The frequency analysis of the applied methods reflected the adaptive nature of the intervention. Further research on the efficacy of improv methods contributing to mental health in people with ID is recommended.

2.
Psychiatr Prax ; 50(7): 370-374, 2023 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-37160157

RESUMEN

AUTISM: spectrum disorders (ASD) often remain undiagnosed until adulthood. The aim of this study is to report differential diagnoses (DDX) and comorbidities of adults without intellectual impairment suspected of having an ASD and to test the self-assessment questionnaire Autism Quotient (AQ) for its suitability for screening. METHODS: DDX and comorbidities were recorded with standardized scales in an autism outpatient clinic in 106 individuals. The AQ was tested against the expert judgment of an interdisciplinary case conference using ROC analysis. RESULTS: Affective disorders were common in both groups (48%); other DDX were phobias (33%) and personality disorders (22%). The AQ showed an AUC of 0,527 with sensitivity/specificity of 70%/35%. CONCLUSIONS: Adults suspected of having autism are highly burdened by DDX and comorbidities. An interdisciplinary diagnostic procedure based on standardized scales is useful, whereas the AQ hardly differentiates between persons with and without ASD.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Adulto , Humanos , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/epidemiología , Trastorno Autístico/diagnóstico , Diagnóstico Diferencial , Diclorodifenil Dicloroetileno , Alemania
3.
Theor Appl Genet ; 136(4): 86, 2023 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-36966424

RESUMEN

KEY MESSAGE: Novel QTLs and candidate genes for Sclerotinia-resistance were identified in B. villosa, a wild Brassica species, which represents a new genetic source for improving oilseed rape resistance to SSR. Sclerotinia stem rot (SSR), caused by Sclerotinia sclerotiorum, is one of the most destructive diseases in oilseed rape growing regions. To date, there is no effective genetic resistance against S. sclerotiorum in the B. napus germplasm and knowledge of the molecular plant-fungal interaction is also limited. To identify new resistance resources, we screened a set of wild Brassica species and identified B. villosa (BRA1896) with a high level of Sclerotinia-resistance. Two segregating F2 populations for Sclerotinia-resistance, generated by interspecific crosses between the resistant B. villosa (BRA1896) and the wild susceptible B. oleracea (BRA1909) were assessed for Sclerotinia-resistance. Genetic mapping using a 15-k Illumina Infinium SNP-array resulted in a high-density genetic map containing 1,118 SNP markers and spanning a total genetic length of 792.2 cM. QTL analysis revealed seven QTLs explaining 3.8% to 16.5% of phenotypic variance. Intriguingly, RNAseq-based transcriptome analysis identified genes and pathways specific to B. villosa, of which a cluster of five genes encoding putative receptor-like kinases (RLKs) and two pathogenesis-related (PR) proteins are co-localized within a QTL on chromosome C07. Furthermore, transcriptomic analysis revealed enhanced ethylene (ET)-activated signaling in the resistant B. villosa, which is associated with a stronger plant immune response, depressed cell death, and enhanced phytoalexin biosynthesis compared to the susceptible B. oleracea. Our data demonstrates that B. villosa represents a novel and unique genetic source for improving oilseed rape resistance against SSR.


Asunto(s)
Ascomicetos , Brassica napus , Brassica , Brassica/genética , Mapeo Cromosómico , Brassica napus/genética , Brassica napus/microbiología , Perfilación de la Expresión Génica , Ascomicetos/fisiología , Enfermedades de las Plantas/microbiología
4.
Int J Dev Disabil ; 67(5): 349-365, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34567544

RESUMEN

Autism spectrum disorders (ASD) are often associated with intellectual disability (ID). ASD-specific group concepts usually focus on people on a high functioning level. The Autism-Competence-Group (AutCom) combines a psycho-educative approach with music and dance/movement interventions in adults with ASD and ID. AutCom includes 16 structured 90-minute sessions to foster social and emotional competencies. This study investigates the acceptability and effectiveness of AutCom. Practicability and acceptability were measured based on participation frequency and patient satisfaction (CSQ-8). Efficacy was assessed in a pre-post design (N = 12) based on self- and third-party assessment with a control group matched by gender and level of ID. Primary outcome variables were social and emotional competence, and secondary outcomes were challenging behavior and quality of life. A participation rate of 86% indicated practicability; high CSQ-8 scores (M = 30 of max. 32) indicated acceptability. Significant improvement was found in social competence compared to the control group and emotional competence in the pre-post self-assessment on the AutCom questionnaire. No significant improvement was found in challenging behavior and quality of life. AutCom is shown to be a promising and highly accepted group concept in fostering social and emotional skills in adults with ASD and ID.

5.
J Thorac Dis ; 12(10): 6163-6172, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33209454

RESUMEN

Anatomic resections with bronchial and/or vascular resections and reconstruction, so called sleeve resections were originally performed in patients with impaired cardio-pulmonary reserves. Nowadays, sleeve resections are established surgical procedures of first choice for tracheobronchial pathologies, whenever anatomically and oncologically feasible. Experienced thoracic surgeons have a broad surgical armentarium to avoid a pneumonectomy and the morbidity and mortality associated with it. Sleeve resections are associated with better outcomes in all aspects. Thus, sleeve resection is not an alternative for pneumonectomy and vice versa. In this review article we set out to provide a contemporary overview on this topic.

6.
J Appl Res Intellect Disabil ; 33(3): 542-551, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32048401

RESUMEN

OBJECTIVE: The Scale of Emotional Development-Short (SED-S) is an instrument to assess the level of emotional development (ED) in people with intellectual and developmental disability. Index cases are developed as a didactic tool to standardize the application of the scale. METHOD: In a stepwise process, a European working group from six countries developed five index cases, one for each level of ED. All cases were first scored by 20 raters using the SED-S and then rephrased to reduce inter-rater variations (SD > 0.5). RESULTS: All five index cases yielded overall ratings that matched the intended level of ED. Across the range of ED, Regulating Affect needed rephrasing most to ensure a distinct description within each level of ED. CONCLUSIONS: The tri-lingual, cross-cultural evolution of five index cases contributes to a standardized application of the SED-S and can serve as training material to improve the inter-rater reliability of the SED-S across different cultures and languages.


Asunto(s)
Afecto , Discapacidades del Desarrollo/diagnóstico , Regulación Emocional , Desarrollo Humano , Discapacidad Intelectual/diagnóstico , Pruebas Neuropsicológicas/normas , Psicometría/normas , Adulto , Afecto/fisiología , Comparación Transcultural , Discapacidades del Desarrollo/fisiopatología , Regulación Emocional/fisiología , Europa (Continente) , Desarrollo Humano/fisiología , Humanos , Discapacidad Intelectual/fisiopatología , Psicometría/instrumentación
7.
Mol Plant Pathol ; 20(12): 1645-1661, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31603283

RESUMEN

Verticillium longisporum infects oilseed rape (Brassica napus) and Arabidopsis thaliana. To investigate the early response of oilseed rape to the fungal infection, we determined transcriptomic changes in oilseed rape roots at 6 days post-inoculation (dpi) by RNA-Seq analysis, in which non-infected roots served as a control. Strikingly, a subset of genes involved in abscisic acid (ABA) biosynthesis was found to be down-regulated and the ABA level was accordingly attenuated in 6 dpi oilseed rape as compared with the control. Gene expression analysis revealed that this was mainly attributed to the suppression of BnNCED3-mediated ABA biosynthesis, involving, for example, BnWRKY57. However, this down-regulation of ABA biosynthesis could not be observed in infected Arabidopsis roots. Arabidopsis ABA- defective mutants nced3 and aao3 displayed pronounced tolerance to the fungal infection with delayed and impeded symptom development, even though fungal colonization was not affected in both mutants. These data suggest that ABA appears to be required for full susceptibility of Arabidopsis to the fungal infection. Furthermore, we found that in both 6 dpi oilseed rape and the Arabidopsis nced3 mutant, the salicylic acid (SA) signalling pathway was induced while the jasmonic acid (JA)/ethylene (ET) signalling pathway was concomitantly mitigated. Following these data, we conclude that in oilseed rape the V. longisporum infection triggers a host-specific suppression of the NCED3-mediated ABA biosynthesis, consequently increasing plant tolerance to the fungal infection. We believe that this might be part of the virulence strategy of V. longisporum to initiate/establish a long-lasting compatible interaction with oilseed rape (coexistence), which appears to be different from the infection process in Arabidopsis.


Asunto(s)
Ácido Abscísico/metabolismo , Brassica napus/microbiología , Enfermedades de las Plantas/microbiología , Verticillium/patogenicidad , Arabidopsis/metabolismo , Arabidopsis/microbiología , Brassica napus/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Enfermedades de las Plantas/genética , Raíces de Plantas/metabolismo , Transducción de Señal , Virulencia
8.
Zentralbl Chir ; 144(S 01): S12-S19, 2019 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-31291668

RESUMEN

Arrhythmias are common after pulmonary resection. They often complicate the patient's recovery and can have an effect on the short-term and long-term prognosis. The aim of the following review is to give an overview of risk factors, prevention and therapy of arrhythmias following lung surgery.


Asunto(s)
Arritmias Cardíacas , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Pulmonares , Arritmias Cardíacas/etiología , Humanos , Pronóstico , Procedimientos Quirúrgicos Pulmonares/efectos adversos , Factores de Riesgo
9.
J Autism Dev Disord ; 49(9): 3732-3752, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31161304

RESUMEN

Initial studies have presented the Music-based Scale for Autism Diagnostics (MUSAD) as a promising DSM-5-based observational tool to identify autism spectrum disorder (ASD) in adults with intellectual disability (ID). The current study is the first to address its clinical utility in a new sample of 124 adults with ID (60.5% diagnosed with ASD). The derived diagnostic algorithm differentiated well between individuals with and without ASD (sensitivity 79%, specificity 74%, area under the curve = 0.81). Inter-rater reliability, assessed by the scorings of four independent experts in 22 consensus cases, was excellent (ICC = 0.92). Substantial correlations with scores from other ASD-specific measures indicated convergent validity. The MUSAD yields accurate and reliable scores, supporting comprehensive ASD diagnostics in adults with ID.


Asunto(s)
Algoritmos , Trastorno del Espectro Autista/diagnóstico , Discapacidad Intelectual/diagnóstico , Música/psicología , Pruebas Psicológicas/estadística & datos numéricos , Adulto , Área Bajo la Curva , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
10.
Res Dev Disabil ; 59: 166-175, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27614275

RESUMEN

BACKGROUND: Intellectual disability (ID) is often accompanied by delays in emotional development (ED) that may result in challenging behavior. Insight into emotional functioning is crucial for appropriate diagnostic assessment in adults with ID. However, few standardized assessment instruments are available. AIMS: The aim of this study was to develop a short, psychometrically sound instrument for assessing levels of ED in individuals with ID: The Scale of Emotional Development - Short (SED-S), which can be applied to adults. METHODS AND PROCEDURES: The Scale for ED - Revised2 (SED-R2) was taken as a point of departure. In a first step, the validity and observability of the items (N=556) in the SED-R2 were assessed by 30 experts from Germany, Belgium, and The Netherlands. The SED-S was then constituted in a consecutive consensus process, in which items to be included were selected based on their assessments and subsequently rephrased, and in which the structure and method of administering the new scale were agreed upon. OUTCOMES AND RESULTS: The SED-S consists of 200 binary items describing five levels of emotional functioning (reference ages: 0-12 years) within eight domains: Relating to His/Her Own Body, Relating to Significant Others, Dealing with Change - Object Permanence, Differentiating Emotions, Relating to Peers, Engaging with the Material World, Communicating with Others, and Regulating Affect. CONCLUSIONS AND IMPLICATIONS: The SED-S offers an empirical-based, practical tool to assessing ED in adults with ID. Further research will be needed to meet the requirements of a standardized diagnostic instrument.


Asunto(s)
Desarrollo Infantil , Emociones , Discapacidad Intelectual/psicología , Bélgica , Niño , Preescolar , Consenso , Alemania , Humanos , Lactante , Países Bajos , Psicometría , Encuestas y Cuestionarios
11.
Res Dev Disabil ; 43-44: 123-35, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26183337

RESUMEN

UNLABELLED: The MUSAD was developed as a diagnostic observational instrument in an interactional music framework. It is based on the ICD-10/DSM-5 criteria for autism spectrum disorder (ASD) and was designed to assess adults on a lower level of functioning, including individuals with severe language impairments. This study aimed to evaluate the psychometric properties of the newly developed instrument. METHODS: Calculations were based on a consecutive clinical sample of N=76 adults with intellectual and developmental disabilities (IDD) suspected of ASD. Objectivity, test-retest reliability, and construct validity were calculated and a confirmatory factor analysis was applied to verify a reduced and optimized test version. RESULTS: The structural model showed a good fit, while internal consistency of the subscales was excellent (ω>.92). Item difficulties ranged between .04≤pi≤.82 and item-total correlation from .21 to .85. Objectivity was assessed by comparing the scorings of two external raters based on a subsample of n=12; interrater agreement was .71 (ICC 2, 1). Reliability was calculated for four test repetitions: the average ICC (3, 1) was .69. Convergent ASD measures correlated significantly with the MUSAD, while the discriminant Modified Overt Aggression Scale (MOAS) showed no significant overlap. CONCLUSION: Confirmation of factorial structure and acceptable psychometric properties suggest that the MUSAD is a promising new instrument for diagnosing ASD in adults with IDD.


Asunto(s)
Trastorno Autístico/diagnóstico , Discapacidades del Desarrollo/psicología , Discapacidad Intelectual/psicología , Música , Adolescente , Adulto , Anciano , Trastorno Autístico/complicaciones , Trastorno Autístico/psicología , Estudios de Cohortes , Discapacidades del Desarrollo/complicaciones , Análisis Factorial , Femenino , Humanos , Discapacidad Intelectual/complicaciones , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Adulto Joven
12.
Psychiatr Prax ; 42(3): 140-6, 2015 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-24643768

RESUMEN

BACKGROUND: One in four individuals with intellectual disability (ID) are additionally diagnosed with autism spectrum disorders (ASD) that may not be recognized und thus remain untreated until adulthood. Diagnosing ASD in adults with ID is challenging and there is a lack of specific diagnostic measures. METHODS: The Diagnostic Behavioral Assessment for ASD (DiBAS) is a DSM-5/ICD-10 based caregiver-report screener consisting of 20 Likert-scaled items. This study evaluates the item validities and -difficulties, and the scale's feasibility and validity in a clinical, adult ID sample (N = 91) from 8/2009 to 12/2011. RESULTS: The DiBAS was applicable in all individuals (100 %) and yielded an adequate diagnostic validity reflected by ROC analysis and an AUC of 0.808. Using a cut-point of 30, the sensitivity and specificity values were 83 % and 64 %, the agreement with the final diagnostic classification was 74 %, and Cohen's kappa was 0.469. Single item analysis revealed 12 valid DiBAS variables that predominantly could be assigned to the social interaction and non-verbal communication domains; item difficulties varied from 0.21 to 0.84. The scale's internal consistency was appropriate (Cronbach's alpha 0.749). CONCLUSIONS: The DiBAS is a promising psychometrical sound scale of high feasibility to screen for ASD in adults with ID, which could be further specified by single item analysis.


Asunto(s)
Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/psicología , Técnicas de Observación Conductual/estadística & datos numéricos , Determinación de la Personalidad/estadística & datos numéricos , Adulto , Niño , Comorbilidad , Diagnóstico Tardío , Femenino , Alemania , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/psicología , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/psicología , Psicometría/estadística & datos numéricos , Reproducibilidad de los Resultados
14.
J Chiropr Educ ; 27(2): 158-62, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23957324

RESUMEN

Objective : We evaluated the feasibility of using mobile device technology to allow students to record their own psychomotor skills so that these recordings can be used for self-reflection and formative evaluation. Methods : Students were given the choice of using DVD recorders, zip drive video capture equipment, or their personal mobile phone, device, or digital camera to record specific psychomotor skills. During the last week of the term, they were asked to complete a 9-question survey regarding their recording experience, including details of mobile phone ownership, technology preferences, technical difficulties, and satisfaction with the recording experience and video critique process. Results : Of those completing the survey, 83% currently owned a mobile phone with video capability. Of the mobile phone owners 62% reported having email capability on their phone and that they could transfer their video recording successfully to their computer, making it available for upload to the learning management system. Viewing the video recording of the psychomotor skill was valuable to 88% of respondents. Conclusions : Our results suggest that mobile phones are a viable technology to use for the video capture and critique of psychomotor skills, as most students own this technology and their satisfaction with this method is high.

15.
Res Dev Disabil ; 34(5): 1642-55, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23475013

RESUMEN

Intellectual disability (ID) and autism spectrum disorder (ASD) are frequently co-occurring conditions. Carefully diagnosing ASD in individuals with ID would allow for more tailored clinical interventions that would improve mental health and quality of life. In this study, we evaluated the psychometric properties of the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) in a clinical sample of 79 adults with ID who were suspected of also having ASD. In the testable cases (68%), the ADOS was over-inclusive (specificity 45%) but highly sensitive (100%) of ASD. In the ADI-R, the feasibility was 37%, with a sensitivity of 88% and a specificity of 80%. Previously proposed adaptations of the ADOS algorithm were evaluated, and new items and tasks were suggested. The ADOS and the ADI-R were found to be valuable diagnostic tools for adults with ID. Adjustments of the setting and the tasks may further improve their feasibility and specificity.


Asunto(s)
Trastorno Autístico/diagnóstico , Discapacidad Intelectual/diagnóstico , Psicometría/métodos , Psicometría/normas , Adulto , Algoritmos , Trastorno Autístico/complicaciones , Comunicación , Estudios de Factibilidad , Femenino , Humanos , Discapacidad Intelectual/complicaciones , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Conducta Social
16.
Chiropr Man Therap ; 21(1): 36, 2013 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-24499598

RESUMEN

BACKGROUND: With the development of increasing evidence for the use of manipulation in the management of musculoskeletal conditions, there is growing interest in identifying the appropriate indications for care. Recently, attempts have been made to develop clinical prediction rules, however the validity of these clinical prediction rules remains unclear and their impact on care delivery has yet to be established. The current study was designed to evaluate the literature on the validity and reliability of the more common methods used by doctors of chiropractic to inform the choice of the site at which to apply spinal manipulation. METHODS: Structured searches were conducted in Medline, PubMed, CINAHL and ICL, supported by hand searches of archives, to identify studies of the diagnostic reliability and validity of common methods used to identify the site of treatment application. To be included, studies were to present original data from studies of human subjects and be designed to address the region or location of care delivery. Only English language manuscripts from peer-reviewed journals were included. The quality of evidence was ranked using QUADAS for validity and QAREL for reliability, as appropriate. Data were extracted and synthesized, and were evaluated in terms of strength of evidence and the degree to which the evidence was favourable for clinical use of the method under investigation. RESULTS: A total of 2594 titles were screened from which 201 articles met all inclusion criteria. The spectrum of manuscript quality was quite broad, as was the degree to which the evidence favoured clinical application of the diagnostic methods reviewed. The most convincing favourable evidence was for methods which confirmed or provoked pain at a specific spinal segmental level or region. There was also high quality evidence supporting the use, with limitations, of static and motion palpation, and measures of leg length inequality. Evidence of mixed quality supported the use, with limitations, of postural evaluation. The evidence was unclear on the applicability of measures of stiffness and the use of spinal x-rays. The evidence was of mixed quality, but unfavourable for the use of manual muscle testing, skin conductance, surface electromyography and skin temperature measurement. CONCLUSIONS: A considerable range of methods is in use for determining where in the spine to administer spinal manipulation. The currently published evidence falls across a spectrum ranging from strongly favourable to strongly unfavourable in regard to using these methods. In general, the stronger and more favourable evidence is for those procedures which take a direct measure of the presumptive site of care- methods involving pain provocation upon palpation or localized tissue examination. Procedures which involve some indirect assessment for identifying the manipulable lesion of the spine-such as skin conductance or thermography-tend not to be supported by the available evidence.

17.
Psychiatr Prax ; 39(5): 228-38, 2012 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-22744151

RESUMEN

OBJECTIVE: To specify frequently observed challenging behavior in adults with ID. METHODS: In a sample of individuals with ID and severe behavioral problems (n = 9), we assessed their emotional developmental level using Dosen's scheme for appraisal of emotional development. The clinical characteristics following the arrest of emotional development at various levels were evaluated by standardized behavioral assessments. The results were compared to a control group matched for sex, age, level of ID, and presence of autism spectrum disorder. RESULTS: We observed 3 categories of emotional developmental disorder: (1) Contact disorder (arrest in adaptation phase, 0-6 months, showing self injury, social withdrawal, stereotyped behaviors); (2) disintegrated disorder (arrest in socialization phase, 6-18 months, showing high irritability and aggression), and (3) disorganized disorder (arrest in individuation phase, 18-36 months, showing hyperactivity and attention seeking behavior). The individuals with emotional developmental disorders showed a significant increase in challenging behavior when compared to the control group, especially in terms of hyperactivity, irritability, and overall aggression, and were more often unemployed. CONCLUSIONS: Emotional developmental disorders may lead to severe behavioral problems.


Asunto(s)
Síntomas Afectivos/psicología , Inteligencia Emocional , Discapacidad Intelectual/psicología , Adulto , Síntomas Afectivos/diagnóstico , Síntomas Afectivos/terapia , Estudios de Casos y Controles , Niño , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Trastornos del Conocimiento/terapia , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/terapia , Masculino , Trastorno de la Conducta Social/diagnóstico , Trastorno de la Conducta Social/psicología , Trastorno de la Conducta Social/terapia , Adulto Joven
18.
Mod Pathol ; 25(3): 465-70, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22080060

RESUMEN

Expression of high-risk HPV oncogenes results in a strong overexpression of cellular protein p16(INK4a). Immunohistochemical staining for p16(INK4a) is widely used as diagnostic marker. However, p16(INK4a) upregulation was also described as a biomarker of age. Here we analyzed p16(INK4a) expression in cervical smears to investigate if patient age may influence p16(INK4a)-based cervical cancer diagnosis. p14(ARF) was analyzed as a related supportive biomarker. Cervical scrapes were taken and stored in RNAlater. Total RNA was extracted, and cDNA was analyzed for expression of p16(INK4a) and p14(ARF) relative to ß-actin, by real-time reverse transcriptase PCR SYBR-Green I assays. Patient-derived smears referred as HSIL (n=45) had 6.27-fold higher p16(INK4a) mRNA expression than smears of cytologically normal and HPV-negative persons (n=48). Expression of p14(ARF) was 4.87-fold higher. When women with normal diagnoses were stratified for age, a significantly enhanced p16(INK4a) (2.88-fold) and p14(ARF) (1.9-fold) expression was observed as a consequence of ageing. A significant age-dependent upregulation was also observed in older HSIL patients (2.54-fold). Our study revealed significantly enhanced expression of p16(INK4a)/p14(ARF) mRNA in cervical scrapes referred to as HSIL compared with normal women. An age-dependent bias has to be considered when quantifying these tumor suppressor genes, with respect to cervical cancer development.


Asunto(s)
Envejecimiento/fisiología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Expresión Génica , Proteína p14ARF Supresora de Tumor/genética , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Alphapapillomavirus/aislamiento & purificación , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/patología , ARN Mensajero/análisis , Proteína p14ARF Supresora de Tumor/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/virología
19.
Int J Gynecol Cancer ; 21(9): 1664-71, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21897271

RESUMEN

BACKGROUND: Host genetic characteristics and environmental factors may correlate with risk for cervical cancer development. Here we describe a retrospective screening study for single nucleotide polymorphisms (SNPs) in genetic markers TP53, MTHFR, CYP1A1, and CYP2E1 in 749 patients. METHODS: A multiplex ligation-dependent polymerase chain reaction approach was applied. We used archived material from human papillomavirus tests and correlated SNP genotypes to the corresponding clinical data. Semantic integration was used to identify and evaluate the clinical status from electronic health records. RESULTS: An association with cervical cancer and high-grade dysplasia was found for the rare homozygous CC genotype (rs4646903) in CYP1A1 (odds ratio [OR], 8.862). Odds ratios were also significantly elevated for heterozygous MTHFR CT genotype (rs1801133; OR, 1.457). No significant association was found in TP53 (rs1042522) and CYP2E1 (rs3813867). In addition, we found smokers at higher risk (OR, 2.688) and identified pregnancies as a significant risk factor (OR, 1.54). CONCLUSIONS: Our protocol enables a feasible way for further retrospective large sample size evaluation of potential genetic markers. This study revealed genetic associations of a rare SNP genotype with cervical dysplasia in one of the largest patient sample to date that warrants further investigation.


Asunto(s)
Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , Femenino , Genes p53 , Predisposición Genética a la Enfermedad , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Adulto Joven
20.
Mol Genet Genomics ; 286(3-4): 279-91, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21879293

RESUMEN

A new sensitive method for multiplex gene-specific methylation analysis was developed using a ligation-based approach combined with a TaqMan-based detection and readout employing universal reporter probes. The approach, termed methylation-specific Ligation Detection Reaction (msLDR), was applied to test 16 loci in 8 different colorectal cancer cells in parallel. These loci encode immune regulatory genes involved in T-cell and natural killer cell activation, whose silencing is associated with the development or progression of colorectal cancer. Parallel analysis of HLA-A, HLA-B, STAT1, B2M, LMP2, LMP7, PA28α, TAP1, TAP2, TAPBP, ULBP2 and ULBP3 by msLDR in eight colorectal cancer cell lines showed preferential methylation at the HLA-B, ULBP2 and ULBB3 loci, but not at the other loci. MsLDR was found to represent a suitable and sensitive method for the detection of distinct methylation patterns as validated by conventional bisulphite Sanger sequencing and COBRA analysis. Since gene silencing by epigenetic mechanisms plays a central role during transformation of a normal differentiated somatic cell into a cancer cell, characterization of the gene methylation status in tumours is a major topic not only in basic research, but also in clinical diagnostics. Due to a very simple workflow, msLDR is likely to be applicable to clinical samples and thus comprises a potential diagnostic tool for clinical purposes.


Asunto(s)
Metilación de ADN , Técnicas Genéticas , Presentación de Antígeno/genética , Línea Celular Tumoral , Neoplasias Colorrectales/química , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , ADN de Neoplasias/química , ADN de Neoplasias/genética , Proteínas Ligadas a GPI/genética , Genes MHC Clase I , Técnicas Genéticas/estadística & datos numéricos , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Células Asesinas Naturales/inmunología , Miniaturización , Reacción en Cadena de la Polimerasa/métodos , Linfocitos T/inmunología
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