A novel endoplasmic reticulum adaptation is critical for the long-lived Caenorhabditis elegans rpn-10 proteasomal mutant.

The loss of proteostasis due to reduced efficiency of protein degradation pathways plays a key role in multiple age-related diseases and is a hallmark of the aging process. Paradoxically, we have previously reported that the Caenorhabditis elegans rpn-10(ok1865) mutant, which lacks the RPN-10/RPN10/PSMD4 subunit of the 19S regulatory particle of the 26S proteasome, exhibits enhanced cytosolic proteostasis, elevated stress resistance and extended lifespan, despite possessing reduced proteasome function. However, the response of this mutant against threats to endoplasmic reticulum (ER) homeostasis and proteostasis was unknown. Here, we find that the rpn-10 mutant is highly ER stress resistant compared to the wildtype. Under unstressed conditions, the ER unfolded protein response (UPR) is activated in the rpn-10 mutant as signified by increased xbp-1 splicing. This primed response appears to alter ER homeostasis through the upregulated expression of genes involved in ER protein quality control (ERQC), including those in the ER-associated protein degradation (ERAD) pathway. Pertinently, we find that ERQC is critical for the rpn-10 mutant longevity. These changes also alter ER proteostasis, as studied using the C. elegans alpha-1 antitrypsin (AAT) deficiency model, which comprises an intestinal ER-localised transgenic reporter of an aggregation-prone form of AAT called ATZ. The rpn-10 mutant shows a significant reduction in the accumulation of the ATZ reporter, thus indicating that its ER proteostasis is augmented. Via a genetic screen for suppressors of decreased ATZ aggregation in the rpn-10 mutant, we then identified ecps-2/H04D03.3, a novel ortholog of the proteasome-associated adaptor and scaffold protein ECM29/ECPAS. We further show that ecps-2 is required for improved ER proteostasis as well as lifespan extension of the rpn-10 mutant. Thus, we propose that ECPS-2-proteasome functional interactions, alongside additional putative molecular processes, contribute to a novel ERQC adaptation which underlies the superior proteostasis and longevity of the rpn-10 mutant.

Comparison of fluoroscopic operator eye exposures when working from femoral region, side, or head of patient.

Operator radiation exposure is an important occupational hazard compounded over the course of an interventional radiologist's career. This study compared operator radiation dose to the eye and head for different positions around the patient. Compared with cases performed from the femoral region, exposures were 1.8 times higher at the side, and 1.6 times higher at the head, using conventional aprons, table shields, and mobile suspended shields. Exposures were 99% lower when using a suspended personal radiation protection system in all positions. In conclusion, standing at the side or head results in higher head exposures in a conventional setup.

Bowhunter's syndrome diagnosed with provocative digital subtraction cerebral angiography.

Bowhunter's syndrome, also known as rotational occlusion of the vertebral artery, involves posterior circulation ischemia resulting from dynamic compromise of the dominant vertebral artery. This case highlights the importance of provocative digital subtraction angiography in making the diagnosis. A 41-year-old man presented for outpatient neurological evaluation for "lightheadedness" of several years' duration provoked by leftward head rotation. The only abnormality identified on initial magnetic resonance angiography was atresia of the nondominant left vertebral artery. Conventional digital subtraction angiography (DSA) followed by provocative DSA revealed development of a dynamic stenosis of the right vertebral artery involving the extraforaminal segment just superior to the C1 vertebra. Noncontrast computed tomography of the cervical spine confirmed ossification of the posterior right atlanto-occipital membrane leading to a near complete bony arcuate foramen. Following neurosurgical decompression, the patient demonstrated complete resolution of all neurologic symptoms. Bowhunter's syndrome is a unique clinical entity that must be considered in the evaluation of patients with symptoms of posterior circulation ischemia. Provocative DSA remains the preferred modality for definitive diagnosis.

Differential effect of glucocorticoids on abdominal pain induced by morphine.

In patients with unexplained pain after cholecystectomy, morphine often induces pain and may increase plasma aspartate aminotransferase (AST) activity because of exaggerated or prolonged rises in pressure within the biliary system. These anomalous effects of morphine may be mediated by activation of autonomic or related afferent nuclei. In this study, 16 patients with pain and increases in AST after morphine were further studied after pre-treatment with dexamethasone and hydrocortisone. Pre-treatment with dexamethasone decreased scores for pain and nausea and prevented or attenuated increases in plasma AST and glucose; these effects were not observed after pre-treatment with hydrocortisone. Serial changes in plasma concentrations of catecholamines were determined in 8 patients and showed that pre-treatment with dexamethasone, but not hydrocortisone, was associated with lower concentrations of norepinephrine and epinephrine with overall reductions of 53% and 67%, respectively. These observations are consistent with a role for sympatho-adrenomedullary activation in abdominal pain induced by morphine. The different effects of dexamethasone and hydrocortisone raise the possibility that sympatho-adrenomedullary activation after morphine is influenced by the interaction of cortisol with type I glucocorticoid receptors which have a low affinity for dexamethasone and a high affinity for cortisol.

Modified transit dosemeter system for 60 Co rotational therapy.

The transit dosemeter has been used in obtaining inhomogeneity corrections for 60 Co rotational therapy. A modified approach is presented which features a rapid electronic system for determining the average tissue-air ratio (T̄AR̄) for a 360° rotation. Experimental results and early clinical experience show that this system is capable of providing a T̄AR̄ value directly, and more rapidly. It can be readily incorporated in a therapy system which already includes a transit dosemeter.