Safety, Efficacy, and Cost-Analysis of Percutaneous Endoscopic Gastrostomy and Ventriculoperitoneal Shunt Placement in a Simultaneous Surgery.

BACKGROUND: Limited historical data suggest that concomitant placement of both a ventriculoperitoneal (VP) shunt and percutaneous endoscopic gastrostomy (PEG) tube is associated with an increased risk of complications, including VP shunt infections. Here we compare the outcomes and cost difference between 2 groups of patients, one in which a VP shunt and PEG tube were placed in the same operation and the other in which separate operations were performed. METHODS: A total of 10 patients underwent simultaneous placement of a VP shunt and PEG tube. This group was compared with a group of 18 patients that underwent separate placements. Hospital billing charges were used to compare the total cost of the procedures in the 2 groups. RESULTS: Eight of the 10 patients presented with aneurysmal subarachnoid hemorrhage. The average length of stay was 25 ± 2 days for the simultaneous procedure group and 43 ± 7 days for the separate procedures group. The average duration of follow-up was 12 ± 3 months after simultaneous placement. No patient in the simultaneous surgery group had signs of infection or shunt malfunction at last follow-up. The overall complication rate was significantly lower in the simultaneous surgery group. A cost analysis demonstrated significant cost savings by completing both procedures in the same surgical procedure. CONCLUSIONS: Simultaneous placement of a PEG tube and VP shunt is safe, efficacious, and cost-effective. Thus, in patients requiring both a VP shunt and PEG tube, placement of both devices in a single surgical procedure should be considered.

Translational Control by Prion-like Proteins.

Prion-like proteins overlap with intrinsically disordered and low-complexity sequence families. These proteins are widespread, especially among mRNA-binding proteins. A salient feature of these proteins is the ability to form protein assemblies with distinct biophysical and functional properties. While prion-like proteins are involved in myriad of cellular processes, we propose potential roles for protein assemblies in regulated protein synthesis. Since proteins are the ultimate functional output of gene expression, when, where, and how much of a particular protein is made dictates the functional state of a cell. Recent finding suggests that the prion-like proteins offer unique advantages in translation regulation and also raises questions regarding formation and regulation of protein assemblies.

Regulated Intron Removal Integrates Motivational State and Experience.

Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-coding form. The convergence of experience and internal drive transiently increases the spliced protein-coding Orb2A mRNA. A screen identified pasilla, the fly ortholog of mammalian Nova-1/2, as a mediator of Orb2A mRNA processing. A single-nucleotide substitution in the intronic region that reduces Pasilla binding and intron removal selectively impairs long-term memory. We posit that pasilla-mediated processing of unspliced Orb2A mRNA integrates experience and internal state to control Orb2A protein abundance and long-term memory formation.

A phase 2 study of MK-5442, a calcium-sensing receptor antagonist, in postmenopausal women with osteoporosis after long-term use of oral bisphosphonates.

UNLABELLED: In women with osteoporosis treated with alendronate for >12 months and oral bisphosphonates for >3 of the last 4 years, switching to MK-5442, a calcium receptor antagonist, stimulated endogenous parathyroid hormone (PTH) secretion and increased bone turnover marker levels, but produced a decline in bone mineral density (BMD) at all sites. INTRODUCTION: This study assessed the effects of switching from long-term oral bisphosphonate therapy to the calcium-sensing receptor antagonist MK-5442 on BMD and bone turnover markers (BTMs) in post-menopausal women with osteoporosis. METHODS: This randomized, active and placebo-controlled, dose-ranging study enrolled 526 postmenopausal women, who had taken alendronate (ALN) for ≥12 months preceding the trial and any oral bisphosphonate for ≥3 of the preceding 4 years and had spine or hip BMD T-scores ≤-2.5 or ≤-1.5 with ≥1 prior fragility fracture. Women were randomized to continue ALN 70 mg weekly or switch to MK-5442 (5, 7.5, 10, or 15 mg daily) or placebo. RESULTS: Switching from ALN to MK-5442 produced a dose-dependent parathyroid hormone (PTH) pulse of threefold to sixfold above baseline at 1 h, with PTH levels that remained twofold to threefold above baseline at 4 h and returned to baseline by 24 h. Switching to MK-5442 or placebo increased BTM levels compared to baseline within 3 months and MK-5442 10 mg increased BTM levels compared to placebo by 6 months. With all MK-5442 doses and placebo, spine and hip BMD declined from baseline, and at 12 months, BMD levels were below those who continued ALN (all groups P < 0.05 vs ALN). There was also a dose-dependent increase in the incidence of hypercalcemia with MK-5442. CONCLUSION: Switching from ALN to MK-5442 resulted in a pulsatile increase in PTH and increases in BTMs, but a decline in BMD compared with continued ALN. MK-5442 is not a viable option for the treatment of osteoporosis.

Nitric oxide synthase interneurons in the monkey cerebral cortex are subsets of the somatostatin, neuropeptide Y, and calbindin cells.

99%) immunoreactive for somatostatin and neuropeptide Y, but did not express calbindin. The LNOS cells comprised about 30% of the somatostatin cells and about 60% of the neuropeptide Y cells. The SNOS cells were nearly always (87-98%) calbindin-immunoreactive, and were rarely or never labeled with antibodies to somatostatin or neuropeptide Y. The SNOS cells accounted for about 20% of all of the calbindin cells. The findings demonstrate that the two types of nNOS cells can be distinguished by antibodies to calbindin, somatostatin and neuropeptide Y, but none of these markers is found exclusively in nNOS cells. Nevertheless, neuropeptide Y-immunoreactivity provides a useful marker for LNOS cells, because it is very dense in these cells and only light in the interneurons that lack nNOS.