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BACKGROUND: Differences in sexual development (DSD) are rare diseases, which affect the chromosomal, anatomical or gonadal sex differentiation. Although patient education is recommended as essential in a holistic care approach, standardised programmes are still lacking. The present protocol describes the aims, study design and methods of the Empower-DSD project, which developed an age-adapted multidisciplinary education programme to improve the diagnosis-specific knowledge, skills and empowerment of patients and their parents. METHODS: The new patient education programme was developed for children, adolescents and young adults with congenital adrenal hyperplasia, Turner syndrome, Klinefelter syndrome or XX-/or XY-DSD and their parents. The quantitative and qualitative evaluation methods include standardised questionnaires, semi-structured interviews, and participatory observation. The main outcomes (assessed three and six months after the end of the programme) are health-related quality of life, disease burden, coping, and diagnosis-specific knowledge. The qualitative evaluation examines individual expectations and perceptions of the programme. The results of the quantitative and qualitative evaluation will be triangulated. DISCUSSION: The study Empower-DSD was designed to reduce knowledge gaps regarding the feasibility, acceptance and effects of standardised patient education programmes for children and youth with DSD and their parents. A modular structured patient education programme with four generic and three diagnosis-specific modules based on the ModuS concept previously established for other chronic diseases was developed. The topics, learning objectives and recommended teaching methods are summarised in the structured curricula, one for each diagnosis and age group. At five study centres, 56 trainers were qualified for the implementation of the training programmes. A total of 336 subjects have been already enrolled in the study. The recruitment will go on until August 2022, the last follow-up survey is scheduled for February 2023. The results will help improve multidisciplinary and integrated care for children and youth with DSD and their families. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00023096 . Registered 8 October 2020 - Retrospectively registered.
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Educación del Paciente como Asunto , Calidad de Vida , Adolescente , Niño , Humanos , Padres , Desarrollo Sexual , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: The aim of the study was to evaluate psychiatric symptoms among 1022 persons with various disorders of sex development (DSDs). METHODS: The study was a European multicenter cross-sectional clinical evaluation in six countries. The mean (SD) age of participants was 32.1 (13.4) years. The cohort consisted of 325 individuals with Turner syndrome, 219 individuals with Klinefelter syndrome (KS), female individuals with various XY-DSD conditions (107 with and 67 without androgenization), 87 male individuals with XY-DSD conditions, and 221 female individuals with congenital adrenal hyperplasia. The Hospital Anxiety and Depression Scale, the Short Autism Spectrum Quotient, the Adult Attention-Deficit/Hyperactivity Disorder Self-Report Scale, and self-reported mental health history were used to assess psychiatric symptoms. RESULTS: Across the six DSD diagnostic groups, clinical cutoff symptom scores were reached in 19.5% of participants for anxiety, in 7.1% for depression, in 4.1% for attention-deficit/hyperactivity disorder, and in 9.1% for autism. The mean depression and anxiety scores were higher compared with population norms in men with KS and men with XY-DSD. Compared with participants with other DSD conditions, men with KS reported significantly more mental health symptoms. Self-esteem, satisfaction with care, body dissatisfaction, and experiences of shame were associated with psychiatric symptoms in many DSD conditions. CONCLUSIONS: A substantial minority of adults with DSD, with KS in particular, experience psychiatric morbidity. Across DSD conditions, adults may share feelings of shame. Developing a positive self-esteem and body image may be challenging. Multidisciplinary DSD care that involves specialized mental health support can be of important value. TRIAL REGISTRATION: German Clinical Trials Register DRKS00006072.
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Ansiedad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno del Espectro Autista/epidemiología , Depresión/epidemiología , Trastornos del Desarrollo Sexual/epidemiología , Autoimagen , Adolescente , Adulto , Comorbilidad , Estudios Transversales , Europa (Continente)/epidemiología , Femenino , Humanos , Síndrome de Klinefelter/epidemiología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Successful interaction with the environment requires flexible updating of our beliefs about the world. By estimating the likelihood of future events, it is possible to prepare appropriate actions in advance and execute fast, accurate motor responses. According to theoretical proposals, agents track the variability arising from changing environments by computing various forms of uncertainty. Several neuromodulators have been linked to uncertainty signalling, but comprehensive empirical characterisation of their relative contributions to perceptual belief updating, and to the selection of motor responses, is lacking. Here we assess the roles of noradrenaline, acetylcholine, and dopamine within a single, unified computational framework of uncertainty. Using pharmacological interventions in a sample of 128 healthy human volunteers and a hierarchical Bayesian learning model, we characterise the influences of noradrenergic, cholinergic, and dopaminergic receptor antagonism on individual computations of uncertainty during a probabilistic serial reaction time task. We propose that noradrenaline influences learning of uncertain events arising from unexpected changes in the environment. In contrast, acetylcholine balances attribution of uncertainty to chance fluctuations within an environmental context, defined by a stable set of probabilistic associations, or to gross environmental violations following a contextual switch. Dopamine supports the use of uncertainty representations to engender fast, adaptive responses.
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Incertidumbre , Adulto , Monoaminas Biogénicas/farmacología , Encéfalo/fisiología , Humanos , Funciones de Verosimilitud , Modelos TeóricosRESUMEN
BACKGROUND: To investigate the association between the structural quality of care and patient satisfaction with care in individuals with disorders/ differences of sex development (DSD). METHODS: A multicenter cross-sectional comparative study was conducted in 14 clinics in six European countries. We assessed the level of structural quality of care in each center using a self-constructed measure (Center Score) and the level of participant satisfaction with care using the customer satisfaction questionnaire (CSQ-4) and an adopted version of the Youth Health Care - Satisfaction, Utilization & Needs (YHC-SUN-SF). Data were obtained from individuals with Turner Syndrome (261), Klinefelter Syndrome (173), 46, XX congenital adrenal hyperplasia (190) and XY-DSD (257). RESULTS: We found large variations between the scores for structural quality of care both within a diagnostic group and within a country; the overall association between participant satisfaction with the center score was significant. CONCLUSIONS: Comparative effectiveness research across Europe can lead to more insight on beneficial structures and processes and the overall strategy to care for people with rare diseases in general and specific conditions such as disorders/ differences of sex development. Appreciation of higher levels of structural quality of the centers in this study supports the concept of comprehensive care. TRIAL REGISTRATION: German Clinical Trials Register: Registration identification number: DRKS00006072 , date of registration April 17th, 2014. DRKS00006072 (German Clinical Trials Register).
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Trastornos del Desarrollo Sexual/terapia , Calidad de la Atención de Salud/normas , Salud Sexual , Adolescente , Adulto , Estudios Transversales , Trastornos del Desarrollo Sexual/psicología , Europa (Continente) , Femenino , Humanos , Masculino , Satisfacción del Paciente , Calidad de Vida , Enfermedades Raras/terapia , Adulto JovenRESUMEN
We explore the visual world through saccadic eye movements, but saccades also present a challenge to visual processing by shifting externally stable objects from one retinal location to another. The brain could solve this problem in two ways: by overwriting preceding input and starting afresh with each fixation or by maintaining a representation of presaccadic visual features in working memory and updating it with new information from the remapped location. Crucially, when multiple objects are present in a scene the planning of eye movements profoundly affects the precision of their working memory representations, transferring limited memory resources from fixation toward the saccade target. Here we show that when humans make saccades, it results in an update of not just the precision of representations but also their contents. When multiple item colors are shifted imperceptibly during a saccade the perceived colors are found to fall between presaccadic and postsaccadic values, with the weight given to each input varying continuously with item location, and fixed relative to saccade parameters. Increasing sensory uncertainty, by adding color noise, biases updating toward the more reliable input, which is consistent with an optimal integration of presaccadic working memory with a postsaccadic updating signal. We recover this update signal and show it to be tightly focused on the vicinity of the saccade target. These results reveal how the nervous system accumulates detailed visual information from multiple views of the same object or scene. SIGNIFICANCE STATEMENT: This study examines the consequences of saccadic eye movements for the internal representation of visual objects. A saccade shifts the image of a stable visual object from one part of the retina to another. We show that visual representations are built up over these different views of the same object, by combining information obtained before and after each saccade. The weights given to presaccadic and postsaccadic information are determined by the relative reliability of each input. This provides evidence that the visual system combines inputs over time in a statistically optimal way.
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Percepción de Color/fisiología , Memoria a Corto Plazo/fisiología , Movimientos Sacádicos/fisiología , Visión Ocular/fisiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
INTRODUCTION: Published data on prevalence of disturbed eating behavior in youth with type 1 diabetes are heterogeneous. This study assesses the prevalence rate of disturbed eating behavior in a representative German sample of children and adolescents with type 1 diabetes. The prevalence rate is compared to the one published for a national sample of healthy peers. Furthermore prospects as well as limits of a generic screening tool used to identify disturbed eating behavior are compared to those of a diabetes specific screening tool. MATERIAL AND METHODS: A total of 246 children and adolescents (age: 11-19 years) with type 1 diabetes, from 6 pediatric diabetes centers in Germany, completed the generic SCOFF questionnaire and the diabetes specific Diabetes Eating Problem Survey-Revised (DEPS-R) to assess their eating behavior. Prevalence data were compared to representative data from a nationwide survey in Germany (KiGGS-study). RESULTS: A total of 16.3% of the children and adolescents with type 1 diabetes scored above the SCOFF cut-off (≥ 2) (24.2% of the girls and 8.9% of the boys). The percentages in the healthy controls were 28.9% for girls and 15.2% for boys. Compared to this the prevalence of disturbed eating behavior was lower in the diabetes group (p=0.017 and p<0.001). According to the diabetes specific DEPS-R 11.2% of the boys and 13.2% of the girls with type 1 diabetes practiced insulin-purging. The association between SCOFF-scores and the items referring to insulin-purging in DEPS-R, was stronger for girls than for boys (r=0.437 vs. r=0.144). Among the young people with type 1 diabetes DEPS-R-scores showed stronger associations to the quality of metabolic control (HbA1c) than the SCOFF (boys: r=0.357 vs. r=0.217 and girls: r=0.368 vs. r=0.131). DISCUSSION: Children and adolescents with type 1 diabetes are not more frequently affected by disturbed eating behavior than their healthy peers. Particularly boys with type 1 diabetes practicing insulin-purging, are not reliably detected by a generic screening tool. CONCLUSION: As part of long-term care a diabetes specific screening tool should be used to identify adolescents with type 1 diabetes and disturbed eating behavior more reliably.
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Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Adolescente , Niño , Estudios Transversales , Femenino , Alemania/epidemiología , Encuestas Epidemiológicas , Humanos , Masculino , Prevalencia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The major link between the visual and motor systems is via the dorsal stream pathways from visual to parietal and frontal areas of the cortex. Although the pathway appears to be indirect, there is evidence that visual input can reach the motor cortex at relatively short latency. To shed some light on its neural basis, we studied the visuomotor interaction using paired transcranial magnetic stimulation (TMS). Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous in sixteen healthy volunteers. A conditioning stimulus (CS) was applied over the phosphene hotspot of the visual cortex, followed by a test stimulus over the left primary motor cortex (M1) with a random interstimulus interval (ISI) in range 12-40 ms. The effects of paired stimulation were retested during visual and auditory reaction-time tasks (RT). Finally, we measured the effects of a CS on short-interval intracortical inhibition (SICI). At rest, a CS over the occiput significantly (P < 0.001) suppressed test MEPs with an ISI in the range 18-40 ms. In the visual RT, inhibition with an ISI of 40 ms (but not 18 ms) was replaced by a time-specific facilitation (P < 0.001), whereas, in the auditory RT, the CS no longer had any effect on MEPs. Finally, an occipital CS facilitated SICI with an ISI of 40 ms (P < 0.01). We conclude that it is possible to study separate functional connections from visual to motor cortices using paired-TMS with an ISI in the range 18-40 ms. The connections are inhibitory at rest and possibly mediated by inhibitory interneurones in the motor cortex. The effect with an ISI of 40 ms reverses into facilitation during a visuomotor RT but not an audiomotor RT. This suggests that it plays a role in visuomotor integration.
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Corteza Motora/fisiología , Estimulación Magnética Transcraneal , Corteza Visual/fisiología , Adulto , Electroencefalografía , Potenciales Evocados Auditivos/fisiología , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiologíaRESUMEN
Appropriate orientation towards potentially salient novel environmental stimuli requires a system capable of detecting change in the sensorium. Mismatch negativity (MMN), an evoked potential calculated by subtracting the response to a standard repeated stimulus and a rare 'oddball' stimulus, is proposed as such a change detection mechanism. It is most widely studied in the auditory domain, but here we chose to explore the mechanism of somatosensory MMN, and specifically its dependence on the cerebellum. We recorded event-related potentials (ERPs) evoked in response to auditory and sensory stimuli from 10 healthy subjects before and after anodal, cathodal and sham transcranial direct current stimulation (tDCS) of the right cerebellar hemisphere. There was a significant increase in peak amplitude of somatosensory MMN after anodal tDCS (F(1,9) = 8.98, P < 0.02, mean difference anodal pre-post: -1.02 µV) and a significant reduction in peak amplitude of somatosensory MMN after cathodal tDCS (F(1,9) = 7.15, P < 0.03, mean difference cathodal pre-post: 0.65 µV). The amplitude of auditory MMN was unchanged by tDCS. These results reveal the capability of tDCS to cause bidirectional modulation of somatosensory MMN and the dependence of somatosensory MMN on the cerebellum.
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Cerebelo/fisiología , Potenciales Evocados Somatosensoriales , Orientación/fisiología , Anciano , Estimulación Encefálica Profunda , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: The COVID-19 pandemic affected the mental health of children and adolescents in the general population, yet its impact on those with chronic conditions is relatively unknown. This study aimed to compare the incidences of comorbid mental disorders and substance misuse in children and adolescents with type 1 diabetes before and during the pandemic. METHODS: A total of 42,975 patients aged 6-18 years from the multicentre DPV (Diabetes Prospective Follow-up) registry were included. Multivariable regression models were applied to compare newly diagnosed comorbid mental disorders, adjusted for demographic and clinical variables, among them the number of medical visits, during the pre-pandemic period (09/2017-02/2020) and the COVID-19 pandemic period (03/2020-08/2022). RESULTS: Analysing both sexes together, there were no differences in the incidence rates of overall mental disorders between the pandemic and the pre-pandemic period. However, girls showed an increased incidence rate (odds ratio 1.2, CI 1.1-1.3) during the pandemic. Adolescent girls also displayed higher incidence rates of depression, eating disorders, and self-harm. Substance misuse declined overall during the pandemic (odds ratio 0.8, CI 0.7-0.9). CONCLUSIONS: During the COVID-19 pandemic, we found higher incidence rates of overall mental disorders in girls, but not in boys and not in the total study population of children and adolescents with type 1 diabetes. Adolescent girls displayed increased incidence rates of depression, eating disorders, and self-harm. Substance misuse declined substantially. Clinicians should be aware of the high-risk group of adolescent girls during times of increased strain.
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COVID-19 , Diabetes Mellitus Tipo 1 , Trastornos Mentales , Sistema de Registros , Humanos , Adolescente , COVID-19/epidemiología , COVID-19/psicología , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Masculino , Niño , Trastornos Mentales/epidemiología , Incidencia , Comorbilidad , Estudios Prospectivos , SARS-CoV-2 , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/complicaciones , Pandemias , Estudios de SeguimientoRESUMEN
Objective: Evaluation of the participant satisfaction with a newly developed interdisciplinary, modular education program for children, adolescents, and young adults with differences of sex development (DSD) and their parents. Methods: The two-day program including tailored medical information, peer consultation and psychological support aimed to improve diagnosis-specific knowledge and empowerment. Post-training satisfaction was measured using an adapted ZUF-8 questionnaire, scoring from 5 (worst) to a maximum of 26 (best) for persons aged 6-17 and from 10 to 40 points for adults, including 2 open-ended questions. Results: The questionnaire, completed by 89 children (6-13 years), 92 adolescents (14-17 years), 47 young adults (18-24 years), and 345 parents, revealed consistent high satisfaction with the program regardless of age or diagnosis (children 24.4 ± 2.1, adolescents 23.5 ± 2.7; young adults 36.0 ± 4.0, parents 36.6 ± 3.4). Neither sociodemographic factors nor diagnosis burden, shame, or informedness showed relevant associations with satisfaction levels. Participants highlighted exchange and open atmosphere as key satisfaction elements. Conclusion: Satisfaction with the new education program was high in all examined groups. Implementing it in routine care requires further analysis to determine the program's long-term effects on well-being and knowledge. Innovation: The first educational program for young people with DSD addressing their specific challenges through inclusive language, an open approach to sex and gender and the inclusion of self-help groups.
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Selective attention is often considered the "gateway" to visual working memory (VWM). However, the extent to which we can voluntarily control which of an object's features enter memory remains subject to debate. Recent research has converged on the concept of VWM as a limited commodity distributed between elements of a visual scene. Consequently, as memory load increases, the fidelity with which each visual feature is stored decreases. Here we used changes in recall precision to probe whether task-irrelevant features were encoded into VWM when individuals were asked to store specific feature dimensions. Recall precision for both color and orientation was significantly enhanced when task-irrelevant features were removed, but knowledge of which features would be probed provided no advantage over having to memorize both features of all items. Next, we assessed the effect an interpolated orientation-or color-matching task had on the resolution with which orientations in a memory array were stored. We found that the presence of orientation information in the second array disrupted memory of the first array. The cost to recall precision was identical whether the interfering features had to be remembered, attended to, or could be ignored. Therefore, it appears that storing, or merely attending to, one feature of an object is sufficient to promote automatic encoding of all its features, depleting VWM resources. However, the precision cost was abolished when the match task preceded the memory array. So, while encoding is automatic, maintenance is voluntary, allowing resources to be reallocated to store new visual information.
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Atención/fisiología , Percepción de Color/fisiología , Memoria a Corto Plazo/fisiología , Orientación/fisiología , Reconocimiento Visual de Modelos/fisiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Recuerdo Mental , Estimulación Luminosa , Tiempo de Reacción , Adulto JovenRESUMEN
Increasing numbers of healthcare professionals are using smartphones and their associated applications (apps) in daily clinical care. While these medical apps hold great potential for improving clinical practice, little is known about the possible dangers associated with their use. Breaches of patient confidentiality, conflicts of interests and malfunctioning clinical decision-making apps could all negatively impact on patient care. We propose several strategies to enhance the development of evidence-based medical apps while retaining their open nature. The increasing use of medical apps calls for broader discussion across medicine's organising and accrediting bodies. The field of medical apps is currently one of the most dynamic in medicine, with real potential to change the way evidence-based healthcare is delivered in the future. Establishing appropriate regulatory procedures will enable this potential to be fulfilled, while at all times ensuring the safety of the patient.
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Teléfono Celular , Toma de Decisiones Asistida por Computador , Práctica Clínica Basada en la Evidencia , Regulación Gubernamental , Humanos , Seguridad del Paciente , Calidad de la Atención de Salud , Estados Unidos , United States Food and Drug AdministrationRESUMEN
The 2006 Chicago consensus statement of management of disorders/difference of sex development (DSD) has achieved advantages in clinical care and diagnosis for patients and families affect by DSD. This article provides a brief overview of contexts of care for physicians, and points out specific challenges in clinical practice that have arisen from the transformations of the sex/gender system in recent years. We focus on the impact of diagnosis and laboratory measurements. Both laboratory measurements and hormonal therapies still depend on the binary system. One problem is the lack of reference intervals for the different forms of DSD, which means that diversity is often neglected. In the following, we will give a brief insight into this complex topic.
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Post-mortem and in vivo studies provide evidence for a link between reduced plasticity and dysconnectivity in schizophrenia patients. It has been suggested that the association between plasticity and connectivity contributes to the pathophysiology and symptomatology of schizophrenia. However, little is known about the impact of glutamate-dependent long-term depression (LTD)-like cortical plasticity on inter-hemispheric connectivity in schizophrenia patients. The aim of the present study was to investigate LTD-like cortical plasticity following excitability-diminishing cathodal transcranial direct current stimulation (tDCS) of the left primary motor cortex (M1) and its effects on the non-stimulated right M1. Eighteen schizophrenia patients and 18 matched (age, gender, handedness, and smoking status) control subjects were investigated in this study. Corticospinal excitability changes following tDCS and intra-cortical inhibitory circuits were monitored with transcranial magnetic stimulation. On the stimulated hemisphere, cathodal tDCS increased resting motor thresholds (RMT) in both groups and decreased motor-evoked potential (MEP) sizes in healthy controls to a greater extent compared to schizophrenia patients. On the non-stimulated hemisphere, RMTs were increased and MEPs were decreased only in the healthy control group. Our results confirm previous findings of reduced LTD-like plasticity in schizophrenia patients and offer hypothetical and indirect in vivo evidence for an association between LTD-like cortical plasticity and inter-hemispheric connectivity in schizophrenia patients. Moreover, our findings highlight the impact of plasticity on connectivity. Dysfunctional N-methyl D-aspartate receptors or modulation of dopaminergic transmission can explain these findings. Nevertheless, the effects of antipsychotic medication still need to be considered.
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Potenciales Evocados Motores/fisiología , Lateralidad Funcional , Corteza Motora/fisiopatología , Esquizofrenia/patología , Estimulación Magnética Transcraneal , Adulto , Análisis de Varianza , Femenino , Humanos , Masculino , Estadística como Asunto , Adulto JovenRESUMEN
BACKGROUND: Current recommendations define a structured diagnostic process, transparent information, and psychosocial support by a specialized, multi-professional team as central in the care for children and adolescents with genital variations and a suspected difference of sex development (DSD). The active involvement of the child and their parents in shared decision-making should result in an individualized care plan. So far, this process has not been standardized. METHODS: Within the Empower-DSD study, a team of professionals and representatives of patient advocacy groups developed a new diagnostic and information management program based on current recommendations and existing patient information. RESULTS: The information management defines and standardizes generic care elements for the first weeks after a suspected DSD diagnosis. Three different tools were developed: a guideline for the specialized multiprofessional team, a personal health record and information kit for the child with DSD and their family, and a booklet for medical staff not specialized in DSD. CONCLUSIONS: The new information management offers guidance for patients and professionals during the first weeks after a DSD diagnosis is suspected. The developed tools' evaluation will provide further insight into the diagnostic and information-sharing process as well as into all of the involved stakeholders' needs.
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PURPOSE: Mutations in the NR5A1 gene, encoding the transcription factor Steroidogenic Factor-1, are associated with a highly variable genital phenotype in patients with 46,XY differences of sex development (DSD). Our objective was to analyse the pubertal development in 46,XY patients with NR5A1 mutations by the evaluation of longitudinal clinical and hormonal data at pubertal age. METHODS: We retrospectively studied a cohort of 10 46,XY patients with a verified NR5A1 mutation and describe clinical features including the external and internal genitalia, testicular volumes, Tanner stages and serum concentrations of LH, FSH, testosterone, AMH, and inhibin B during pubertal transition. RESULTS: Patients who first presented in early infancy due to ambiguous genitalia showed spontaneous virilization at pubertal age accompanied by a significant testosterone production despite the decreased gonadal volume. Patients with apparently female external genitalia at birth presented later in life at pubertal age either with signs of virilization and/or absence of female puberty. Testosterone levels were highly variable in this group. In all patients, gonadotropins were constantly in the upper reference range or elevated. Neither the extent of virilization at birth nor the presence of Müllerian structures reliably correlated with the degree of virilization during puberty. CONCLUSION: Patients with NR5A1 mutations regardless of phenotype at birth may demonstrate considerable virilization at puberty. Therefore, it is important to consider sex assignment carefully and avoid irreversible procedures during infancy.
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Trastorno del Desarrollo Sexual 46,XY/genética , Pubertad , Desarrollo Sexual , Factor Esteroidogénico 1 , Femenino , Humanos , Mutación , Fenotipo , Pubertad/genética , Estudios Retrospectivos , Factor Esteroidogénico 1/genéticaRESUMEN
BACKGROUND: Jumping-to-conclusions (JTC) is a prominent reasoning bias in schizophrenia (SCZ). While it has been linked to not only psychopathological abnormalities (delusions and impulsive decision-making) but also unstable belief formation, its origin remains unclear. We here directly test to which extend JTC is associated with delusional ideation, impulsive decision-making, and unstable belief formation. METHODS: In total, 45 SCZ patients were compared with matched samples of 45 patients with major depressive disorder (MDD) and 45 healthy controls (HC) as delusions and JTC also occur in other mental disorders and the general population. Participants performed a probabilistic beads task. To test the association of JTC with measures of delusions (Positive and Negative Syndrome Scale [PANSS]positive, PANSSpositive-factor, and Peter Delusions Inventory [PDI]), Bayesian linear regressions were computed. For the link between JTC and impulsive decision-making and unstable beliefs, we conducted between-group comparisons of "draws to decision" (DTD), "decision times" (DT), and "disconfirmatory evidence scores" (DES). RESULTS: Bayesian regression obtained no robust relationship between PDI and DTD (all |R2adj| ≤ .057, all P ≥ .022, all Bayes Factors [BF01] ≤ 0.046; αâadj = .00833). Compared with MDD and HC, patients with SCZ needed more time to decide (significantly higher DT in ambiguous trials: all P ≤ .005, r2 ≥ .216; numerically higher DT in other trials). Further, SCZ had unstable beliefs about the correct source jar whenever unexpected changes in bead sequences (disconfirmatory evidence) occurred (compared with MDD: all P ≤ .004 and all r2 ≥ .232; compared with HC: numerically higher DES). No significant correlation was observed between DT and DTD (all P ≥ .050). CONCLUSIONS: Our findings point toward a relationship of JTC with unstable belief formation and do not support the assumption that JTC is associated with impulsive decision-making.
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Cultura , Toma de Decisiones , Conducta Impulsiva/fisiología , Esquizofrenia/complicaciones , Adulto , Análisis de Varianza , Distribución de Chi-Cuadrado , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Solución de Problemas , Esquizofrenia/fisiopatologíaRESUMEN
The process of encoding a visual scene into working memory has previously been studied using binary measures of recall. Here, we examine the temporal evolution of memory resolution, based on observers' ability to reproduce the orientations of objects presented in brief, masked displays. Recall precision was accurately described by the interaction of two independent constraints: an encoding limit that determines the maximum rate at which information can be transferred into memory and a separate storage limit that determines the maximum fidelity with which information can be maintained. Recall variability decreased incrementally with time, consistent with a parallel encoding process in which visual information from multiple objects accumulates simultaneously in working memory. No evidence was observed for a limit on the number of items stored. Cuing one display item with a brief flash led to rapid development of a recall advantage for that item. This advantage was short-lived if the cue was simply a salient visual event but was maintained if it indicated an object of particular relevance to the task. These cuing effects were observed even for items that had already been encoded into memory, indicating that limited memory resources can be rapidly reallocated to prioritize salient or goal-relevant information.
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Atención , Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Reconocimiento Visual de Modelos/fisiología , Adolescente , Adulto , Percepción de Color/fisiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Orientación , Adulto JovenRESUMEN
BACKGROUND: Impaired probabilistic reasoning and the jumping-to-conclusions reasoning bias are hallmark features of schizophrenia (SCZ), yet the neuropharmacological basis of these deficits remains unclear. Here we tested the hypothesis that glutamatergic neurotransmission specifically contributes to jumping to conclusions and impaired probabilistic reasoning in SCZ. METHODS: A total of 192 healthy participants received either NMDA receptor agonists/antagonists (D-cycloserine/dextromethorphan), dopamine type 2 receptor agonists/antagonists (bromocriptine/haloperidol), or placebo in a randomized, double-blind, between-subjects design. In addition, we tested 32 healthy control participants matched to 32 psychotic inpatients with SCZ-a state associated with compromised probabilistic reasoning due to reduced glutamatergic neurotransmission. All experiments employed two versions of a probabilistic reasoning (beads) task, which required participants to either sample individual amounts of sensory information to infer correct decisions or provide explicit probability estimates for presented sensory information. Our task instantiations assessed both information sampling and explicit probability estimates in different probabilistic contexts (easy vs. difficult conditions) and changing sensory information through random transitions among easy, difficult, and ambiguous trial types. RESULTS: Following administration of D-cycloserine, haloperidol, and bromocriptine, healthy participants displayed data-gathering behavior that was normal compared with placebo and was adequate in the context of all employed task conditions and trial level difficulties. However, healthy participants receiving dextromethorphan displayed a jumping-to-conclusions bias, abnormally increased probability estimates, and overweighting of sensory information. These effects were mirrored in patients with SCZ performing the same versions of the beads task. CONCLUSIONS: Our findings provide novel neuropharmacological evidence linking reduced glutamatergic neurotransmission to impaired information sampling and to disrupted probabilistic reasoning, namely to overweighting of sensory evidence, in patients with SCZ.