Although the selection of patients is known to be a powerful factor affecting the results of clinical trials, little is known about recruitment issues. Many patients with schizophrenia who are screened for a clinical trial of an investigational antipsychotic are ultimately not included in the study. Therefore, the question arises of whether the results obtained by studying a selected group of patients are really representative of the general population of patients with schizophrenia. The authors studied possible reasons for selective sampling in 200 patients who were consecutively admitted to inpatient units of Innsbruck's Department of Psychiatry with a diagnosis of schizophreniform or schizophrenic disorder over a time period of 33 months. Apart from demographic data and a psychopathologic rating (using the Brief Psychiatric Rating Scale), the authors recorded whether or not a patient was included in a phase III study and whether or not those were not included would have theoretically been eligible for such a study. Twenty-seven patients were finally recruited for a clinical trial. These patients were younger, on average, had a more recent onset of illness, and had experienced fewer psychotic episodes in the past. A history of noncompliance with previous treatment and the refusal of consent were the most common reasons for not including theoretically eligible patients in a clinical trial.

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Outcome in schizophrenia is multidimensional and consists of clinical and psychosocial domains. Difficulties in affect recognition are a hallmark of schizophrenia, but there is little research investigating the consequences of this deficit on patients' psychosocial status. This cross-sectional study examined the relationship of facial affect recognition and treatment outcomes in terms of psychopathology, quality of life (QOL), and psychosocial functioning. We investigated 40 regular attendees of a specialized schizophrenia outpatient clinic who had been stable both from a symptomatic and a medication perspective for a minimum of 6 months and 40 healthy volunteers who were chosen to match patients in age, sex, and education. Affect recognition was positively associated with patients' level of education and negatively with increasing age. Deficits in this area corresponded to the severity of negative and affective symptoms as well as to poor work and global functioning. These findings suggest that affect recognition is an important aspect of psychosocial functioning in stable outpatients with schizophrenia.

Hypoxia is a common pathogenic stress, which requires adaptive activation of the Hypoxia-inducible transcription factor (HIF). In concert transcriptional HIF targets enhance oxygen availability and simultaneously reduce oxygen demand, enabling survival in a hypoxic microenvironment. Here, we describe the characterization of a new HIF-1 target gene, Rab20, which is a member of the Rab family of small GTP-binding proteins, regulating intracellular trafficking and vesicle formation. Rab20 is directly regulated by HIF-1, resulting in rapid upregulation of Rab20 mRNA as well as protein under hypoxia. Furthermore, exogenous as well as endogenous Rab20 protein colocalizes with mitochondria. Knockdown studies reveal that Rab20 is involved in hypoxia induced apoptosis. Since mitochondria play a key role in the control of cell death, we suggest that regulating mitochondrial homeostasis in hypoxia is a key function of Rab20. Furthermore, our study implicates that cellular transport pathways play a role in oxygen homeostasis. Hypoxia-induced Rab20 may influence tissue homeostasis and repair during and after hypoxic stress.

Loss-of-function mutations of the epithelial sodium channel (ENaC) may contribute to pulmonary symptoms resembling those of patients with atypical cystic fibrosis (CF). Recently, we identified a loss-of-function mutation in the α-subunit of ENaC (αF61L) in an atypical CF patient without mutations in CFTR. To investigate the functional effect of this mutation, we expressed human wild-type αβγ-ENaC or mutant α _F61Lβγ-ENaC in Xenopus laevis oocytes. The αF61L mutation reduced the ENaC mediated whole-cell currents by ñ90%. In contrast, the mutation decreased channel surface expression only by ñ40% and did not alter the single-channel conductance. These findings indicate that the major effect of the mutation is a reduction of the average channel open probability (P_o). This was confirmed by experiments using the βS520C mutant ENaC which can be converted to a channel with a P_o of nearly one, and by experiments using chymotrypsin to proteolytically activate the channel. These experiments revealed that the mutation reduced the average P_o of ENaC by ñ75%. Na⁺ self inhibition of the mutant channel was significantly enhanced, but the observed effect was too small to account for the large reduction in average channel P_o. The ENaC-activator S3969 partially rescued the loss-of-function phenotype of the αF61L mutation. We conclude that the αF61L mutation may contribute to respiratory symptoms in atypical CF patients.