Calnexin is an endoplasmic reticulum (ER) lectin that mediates protein folding on the rough ER. Calnexin also interacts with ER calcium pumps that localize to the mitochondria-associated membrane (MAM). Depending on ER homeostasis, varying amounts of calnexin target to the plasma membrane. However, no regulated sorting mechanism is so far known for calnexin. Our results now describe how the interaction of calnexin with the cytosolic sorting protein PACS-2 distributes calnexin between the rough ER, the MAM, and the plasma membrane. Under control conditions, more than 80% of calnexin localizes to the ER, with the majority on the MAM. PACS-2 knockdown disrupts the calnexin distribution within the ER and increases its levels on the cell surface. Phosphorylation by protein kinase CK2 of two calnexin cytosolic serines (Ser554/564) reduces calnexin binding to PACS-2. Consistent with this, a Ser554/564 ➞ Asp phosphomimic mutation partially reproduces PACS-2 knockdown by increasing the calnexin signal on the cell surface and reducing it on the MAM. PACS-2 knockdown does not reduce retention of other ER markers. Therefore, our results suggest that the phosphorylation state of the calnexin cytosolic domain and its interaction with PACS-2 sort this chaperone between domains of the ER and the plasma membrane. INTRODUCTIONA principal function of the ER is chaperone-mediated oxidative folding of newly synthesized proteins, thought to occur close to the translocon on the rER with the help of chaperones (Chen and Helenius, 2000). Recent research has started to view the ER as a multifunctional organelle that comprises distinct domains devoted to specific tasks. Examples are oxidative protein folding that occurs on the rough ER (rER) or lipid synthesis that is associated with the mitochondria-associated membrane (MAM; Vance, 1990;Borgese et al., 2006;Levine and Loewen, 2006). It is also emerging that many ER proteins, including chaperones, localize to multiple ER membrane domains, where they perform distinct functions. Examples are the chaperones calnexin (CNX), calreticulin and ERp44, which interact with the MAM-enriched IP 3 R and SERCA2b, respectively (John et al., 1998;Roderick et al., 2000;Higo et al., 2005).Coat-and receptor-based retention and retrieval mechanisms ensure that ER folding chaperones and oxidoreductases localize to the ER (Teasdale and Jackson, 1996;Duden, 2003;Michelsen et al., 2005). However, in addition to multiple domains of the ER, many ER chaperones such as BiP/ GRP78, PDI , and CNX have also been found on the plasma membrane, suggesting that their intracellular retention and trafficking along the secretory pathway varies (Wiest et al., 1995;Mezghrani et al., 2000;Arap et al., 2004;Misra et al., 2006). For instance, high levels of CNX characterize the plasma membrane of immature thymocytes. Conversely, ER stress can reduce surface CNX (Wiest et al., 1995;Okazaki et al., 2000). Changing the amount of CNX on the plasma membrane could affect cell surface properties and might have implications on phagocytosi...

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OBJECTIVE: To evaluate whether an order set change that halved the initial dose of oxycodone and allowed the remainder to be given 1 hour later, if requested, was associated with reduced opioid use and side effects after cesarean delivery. METHODS: This retrospective, clinical practice study reviewed electronic medical records after implementation of a new order set for cesarean delivery. Oxycodone orders changed from 5 mg (for verbal pain score of 4/10 or lower) and 10 mg (for 5–10/10) to 2.5 mg (for verbal pain score 1–4/10) or 5 mg (for 5–10/10), and the patient requesting pain relief, with a nurse check within 1 hour to administer another 2.5 or 5 mg, respectively, if needed. The primary outcome was opioid use (in intravenous morphine equivalents) in the first 48 hours. Secondary outcomes included incidence and treatment of nausea or vomiting and pruritis, average and peak verbal pain scores within 48 hours, and satisfaction. RESULTS: The records of 1,050 women were examined (542 before and 508 after the change). Opioid use in the first 48 hours was lower after the practice change (median [interquartile range] 10.0 [1.3–25.0] mg before vs 4.4 [0–12.5] mg after; P<.001). A small increase in average verbal pain score occurred (mean [SD] 1.8 [1.0] before vs 2.0 [1.3] after; difference −0.2; 95% CI −0.3 to −0.04). Peak verbal pain score (5.9 [2.0] before vs 6.0 [2.1] after; difference −0.1; 95% CI −0.4 to 0.1) and mean (SD) satisfaction score (97.7 [7.2] before vs 97.1 [7.5] after; difference 0.6, 95% CI −0.5 to 1.6) did not change. Fewer patients reported postoperative nausea or vomiting (30.9% before vs 19.3% after; odds ratio 0.5; 95% CI 0.4 to 0.7). CONCLUSION: Split doses of oxycodone were associated with 56% reduction in 48 hours opioid use after cesarean delivery.

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In Northern Alberta, patients with RA are seen and started on DMARD therapy in a timely fashion. Most of the delay is at the primary care level, suggesting a need for improved education of patients and primary care physicians rather than a formal triage system.

During a cesarean hysterectomy for placenta percreta, transesophageal echocardiography was used to monitor volume status and guide resuscitation. After delivery of the neonate but before massive surgical hemorrhage, a thrombus appeared in the inferior vena cava. Roughly 3 hours later, the patient had hemodynamic changes consistent with an intraoperative pulmonary embolism. Boluses of epinephrine stabilized the patient. An inferior vena cava filter was placed via an in situ internal jugular central venous cannula to prevent further embolic events. We believe transesophageal echocardiography is a useful monitor during surgery for placenta percreta.

The incidence of IOL capture was significantly greater after implantation of a 1-piece IOL than after implantation of a 3-piece IOL during combined cataract extraction and PPV. Posterior synechiae formation was associated with the use of silicone oil, SF(6), or C(3)F(8).

Neuraxial analgesia is the gold standard method for pain relief in labor. Several techniques can optimize both the initiation and maintenance of neuraxial labor analgesia. Initiation techniques such as combined spinal-epidural or dural puncture epidural may offer some advantages over standard epidural insertion. The use of ultrasound to assist with landmarking and optimizing block placement improves neuraxial success, and is particularly useful in certain patient populations. Maintaining labor analgesia with a regimen that includes background programmed intermittent boluses with a patientcontrolled epidural analgesia component affords the best combination of pain relief and avoidance of undesired effects. These techniques are most effective when dilute local anesthetics with lipophilic opioids are utilized.