NDUFV2 pseudogene (NDUFV2P1) contributes to mitochondrial complex I deficits in schizophrenia.

Mitochondria together with other cellular components maintain a constant crosstalk, modulating transcriptional and posttranslational processes. We and others demonstrated mitochondrial multifaceted dysfunction in schizophrenia, with aberrant complex I (CoI) as a major cause. Here we show deficits in CoI activity and homeostasis in schizophrenia-derived cell lines. Focusing on a core CoI subunit, NDUFV2, one of the most severely affected subunits in schizophrenia, we observed reduced protein level and functioning, with no change in mRNA transcripts. We further show that NDUFV2 pseudogene (NDUFV2P1) expression is increased in schizophrenia-derived cells and in postmortem brain specimens. In schizophrenia and controls pooled samples, NDUFV2P1 level demonstrated a significant inverse correlation with NDUFV2 pre- and matured protein level and with CoI-driven cellular respiration. Our data suggest a role for a pseudogene in its parent-gene regulation and possibly in CoI dysfunction in schizophrenia. The abnormal expression of the pseudogene may be one element of a vicious circle in which CoI deficits lead to mitochondrial dysfunction potentially affecting genome-wide regulation of gene expression, including the expression of pseudogenes.

Role of Doppler ultrasonography in the triage of acute scrotum in the emergency department.

OBJECTIVE: The purpose of this study was to examine the triage role of scrotal Doppler ultrasonography (DUS) as the primary preoperative diagnostic tool in patients presenting to the emergency department (ED) with acute scrotum. METHODS: Patients who presented to the ED with acute scrotum and underwent scrotal DUS in the ultrasound unit over a 3-year period (2004-2007) were included in the study. Patient characteristics, DUS findings, and clinical management were retrospectively collected and reviewed. Doppler ultrasonographic diagnoses were compared with histopathologic findings for patients who underwent exploration and with final diagnoses at the time of discharge for patients undergoing medical treatment. RESULTS: A total of 620 consecutive patients with 669 DUS examinations were included. The most common scrotal DUS diagnoses were epididymitis, hydrocele, varicocele, and orchitis. Scrotal trauma was present in 77 cases. Hospitalization followed the initial ED evaluation for 155 patients; 68 underwent surgery. Testicular torsion was ultrasonographically suspected in 20 patients and confirmed in 18. Scrotal malignancy was incidentally diagnosed in 13 patients and testicular hematoma in 8. Doppler ultrasonography for the diagnosis of testicular torsion had 94% sensitivity, 96% specificity, 95.5% accuracy, an 89.4% positive predictive value (PPV), and a 98% negative predictive value (NPV). Doppler ultrasonography for the diagnosis of testicular malignancy had 92% sensitivity, 95% specificity, 94% accuracy, a 78.5% PPV, and a 98% NPV. CONCLUSIONS: Scrotal DUS is a highly sensitive preoperative diagnostic tool, thereby validating its routine use in the initial triage of patients with acute scrotum presenting to the ED.