Asunto(s)
Fracturas Abiertas/diagnóstico por imagen , Traumatismos Penetrantes de la Cabeza/diagnóstico por imagen , Hematoma Intracraneal Subdural/diagnóstico por imagen , Fracturas Craneales/diagnóstico por imagen , Deportes Acuáticos/lesiones , Craneotomía , Fracturas Abiertas/cirugía , Traumatismos Penetrantes de la Cabeza/cirugía , Hematoma Intracraneal Subdural/cirugía , Humanos , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica , Fracturas Craneales/cirugíaRESUMEN
Tourette syndrome (TS) is a neurodevelopmental disorder characterised by multiple motor and vocal tics. Co-morbid behavioural problems are common and include obsessive-compulsive disorder, attention-deficit and hyperactivity disorder, depression and anxiety. Both tics and behavioural symptoms tend to have a chronic course and can affect patients' health-related quality of life; however, little is known about the relationship between TS, social status and occupation. We conducted an exploratory study on a clinical sample of 137 adult patients with TS to investigate the association between the core features of TS (both tic severity ratings and behavioural co-morbidities) and socioeconomic class. Both clinician- and patient-reported tic severity ratings were significantly higher amongst unemployed patients, compared to patients in the highest socioeconomic class (P = 0.004 and P < 0.001, respectively). There were no significant differences in socioeconomic class distribution between patients with TS and co-morbid behavioural problems ('TS plus', n = 88) and patients with uncomplicated TS ('pure TS', n = 49) (P = 0.205). Our findings suggest that higher tic severity can have far-reaching consequences on patients' life, as it appears to be selectively associated with unemployment and lower socioeconomic status. These observations prompt further research into the complex relationship between TS and social status.
Asunto(s)
Síndrome de Tourette/epidemiología , Adulto , Comorbilidad , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad , Factores SocioeconómicosRESUMEN
Clinical trials are underway for the treatment of tuberous sclerosis (TSC)-associated tumours using mTOR inhibitors. Here, we show that many of the earliest renal lesions from Tsc1+/- and Tsc2+/- mice do not exhibit mTOR activation, suggesting that pharmacological targeting of an alternative pathway may be necessary to prevent tumour formation. Patients with TSC often develop renal cysts and those with inherited co-deletions of the autosomal dominant polycystic kidney disease (ADPKD) 1 gene (PKD1) develop severe, early onset, polycystic kidneys. Using mouse models, we showed a genetic interaction between Tsc1 and Tsc2 with Pkd1 and confirmed an mTOR-independent pathway of renal cystogenesis. We observed that the Tsc and Pkd1 gene products helped regulate primary cilia length and, consistent with the function of this organelle in modulating cell polarity, found that many dividing pre-cystic renal tubule and hepatic bile duct cells from Tsc1, Tsc2 and Pkd1 heterozygous mice were highly misoriented. We therefore propose that defects in cell polarity underlie TSC and ADPKD-associated cystic disease and targeting of this pathway may be of key therapeutic benefit.