Honey bees with a drinking problem: potential routes of Nosema ceranae spore transmission.

Nosema apis and N. ceranae are the two causative agents of Nosema disease in adult honey bees (Apis mellifera L.). Nosema apis has been a recognized parasite for over a century and its epizootiology is well known. In contrast, N. ceranae is an emerging parasite of honey bees, which is now globally prevalent and the dominant Nosema spp. in many parts of the world. Despite this, many gaps in our knowledge exist regarding this species. For example, we do not fully understand all of the routes of transmission of N. ceranae among bees, or how long this parasite is capable of surviving in honey bee colonies. Here we investigated the viability and infectivity of N. ceranae spores in water and 2 M sucrose over time after storage at 33, 20, −12 and −20°C. Spores in both 2 M sucrose and water maintained high viability, except in water at −20°C over the course of the 6-week experiment. Infectivity was variable for spores after storage at all four temperatures, but all were infective at the last time point. The results provide evidence for cold tolerance and suggest that both water and 2 M sucrose (fall bee feed) could act as routes of transmission for N. ceranae. This work also contains information that may help influence management recommendations for the parasite.

A Population-Based Study of 90-Day Hospital Cost and Utilization Associated With Robotic Surgery in Colon and Rectal Cancer.

BACKGROUND: The role of robotic surgery in colorectal cancer remains contentious with most data arising from small, single-institution studies. METHODS: Stage I-III colorectal cancer resections from 2008 to 2014 were identified in New York State. Propensity score-adjusted negative binomial models were used to compare cost and utilization between robotic, laparoscopic, and open resections. RESULTS: A total of 12,218 patients were identified. For colectomy, the robotic-to-open conversion rate was 3%, and the laparoscopic-to-open conversion rate was 13%. For rectal resection, the robotic-to-open conversion rate was 7% and the laparoscopic-to-open conversion rate was 32%. In intention-to-treat analysis, there was no significant difference in cost across the surgical approaches, both in overall and stratified analyses. Both laparoscopic and robotic approaches were associated with decreased 90-d hospital utilization compared with open surgery in intention-to-treat analyses. CONCLUSIONS: Robotic and laparoscopic colorectal cancer resections were not associated with a hospital cost benefit after 90 d compared with open but were associated with decreased hospital utilization. Conversion to open resection was common, and efforts should be made to prevent them. Future research should continue to measure how robotic and laparoscopic approaches can add value to the health care system.

Postoperative Mortality After Nonelective Surgery for Inflammatory Bowel Disease Patients in the Era of Biologics.

OBJECTIVE: The aim of the study was to analyze recent trends in the rate of nonelective surgery and corresponding mortality for inflammatory bowel disease (IBD) patients since the rise of biologic use. BACKGROUND: Modern biologic therapy has improved outcomes for IBD, but little is known about the impact on mortality rates after nonelective surgery. METHODS: New York's Statewide Planning & Research Cooperative System was queried for hospital admissions for ulcerative colitis (UC) with concurrent colectomy and Crohn disease (CD) with concurrent small bowel resection or colectomy from 2000 to 2013. Mixed-effects analyses assessed patient, surgeon, and hospital-level factors and hospital-level variation associated with 30-day mortality after nonelective surgery. RESULTS: Between 2000 to 2006 and 2007 to 2013, the number of unscheduled IBD-related admissions increased by 50% for UC and 41% for CD, but no change in the proportion of nonelective surgery cases was observed (UC=38% vs 38%; CD=45% vs 42%) among 15,837 intestinal resections (UC=5,297; CD=10,540). Nonelective surgery mortality rates between 2000 to 2006 and 2007 to 2013 were high and increased for UC (10.2% vs 15%) but decreased for CD (3.3% vs 2.2%). Nonelective surgery in 2007 to 2013 was associated with an 82% increased risk of 30-day mortality in UC cases (odds ratio: 1.82; confidence interval: 1.19-2.62). After controlling for patient-level factors, large hospital-level variation was observed with 23-fold difference in mortality for both UC and CD. CONCLUSIONS: Although nonelective IBD surgery rates have remained stable, associated 30-day mortality for UC has doubled in recent years despite advances in medical management. Current clinical decision-making and care pathways must be further evaluated to improve outcomes in this high-risk population.

Trends in Surgeon-Level Utilization of Sacral Nerve Stimulator Implantation for Fecal Incontinence in New York State.

BACKGROUND: There is a paucity of real-world data regarding surgeon utilization of sacral nerve stimulation for fecal incontinence compared with anal sphincteroplasty. OBJECTIVE: This study aims to examine trends in sacral nerve stimulation use compared with sphincteroplasty for fecal incontinence and surgeon-level variation in progression to implantation of the pulse generator. DESIGN: This is a population-based study. PATIENTS: Patients with fecal incontinence between 2011 and 2014 in New York who underwent stage 1 of the sacral nerve stimulation procedure were selected. For the comparison with sphincteroplasty, patients with fecal incontinence who underwent anal sphincteroplasty between 2008 and 2014 were included. MAIN OUTCOME MEASURES: The main outcomes after sacral nerve stimulation generator placement were unplanned 30-day admission, emergency department visit within 30 days, revision or explant of leads or generator, and 30-day mortality. RESULTS: Six hundred twenty-one patients with fecal incontinence underwent a stage 1 procedure with 79.7% progressing to stage 2. There has been an increase in the number of sacral nerve stimulation cases per year as well as the number of surgeons performing the procedure. The rate of progression to stage 2 among patients treated by colorectal surgeons was 80.2% compared with 77.0% among those treated by noncolorectal surgeons. Among those who completed stage 2, there were 3 (0.5%) unplanned 30-day admissions, 24 (4.4%) emergency department visits within 30 days, and 0 mortalities within 30 days. Thirty-two (6.5%) patients had their leads or pulse generator revised or explanted. There was a significant decrease in annual sphincteroplasty cases and the number of providers performing the procedure starting in 2011. LIMITATIONS: We lacked data regarding patient and physician decision making and the severity of disease. CONCLUSIONS: Sacral nerve stimulation for fecal incontinence is increasing in popularity with an increasing number of surgeons utilizing sacral nerve stimulation for fecal incontinence rather than sphincteroplasty. See Video Abstract at http://links.lww.com/DCR/A450.

Variation in Delayed Time to Adjuvant Chemotherapy and Disease-Specific Survival in Stage III Colon Cancer Patients.

BACKGROUND: There is a paucity of literature quantifying the extent to which time to adjuvant chemotherapy for stage III colon cancer patients varies between individual surgeons, medical oncologists, and hospitals. METHODS: A retrospective cohort study was conducted by merging the New York State Cancer Registry with the Statewide Planning & Research Cooperative System and Medicare claims to identify stage III colon cancer patients from 2004 to 2009 who underwent resection and received adjuvant chemotherapy. Multilevel logistic regression models characterized variation in delayed time to adjuvant chemotherapy (>8 weeks vs. ≤8 weeks). Multilevel competing-risks Cox proportional hazards models assessed the effect of delayed time to adjuvant chemotherapy on disease-specific survival. RESULTS: The proportion of delayed time to adjuvant chemotherapy was 36 % in 1133 patients treated by 516 surgeons and 351 medical oncologists at 163 hospitals. After controlling for case-mix, the majority of the clustering variation (72 %) in delayed time to adjuvant chemotherapy is attributed to differences between medical oncologists. Risk-adjusted surgeon-specific, medical oncologist-specific, and hospital-specific probabilities of delayed time to adjuvant chemotherapy ranged from 30 to 38, 17 to 59, and 27 to 43 %, respectively. Delayed time to adjuvant chemotherapy was associated with disease-specific survival (hazard ratio [HR] 1.24, 95 % confidence interval [CI] 1.07-1.45). CONCLUSIONS: These findings suggest there is substantial variation in time to adjuvant chemotherapy among stage III colon cancer patients. Reasons for delays may be due to system factors that influence individual providers to make varying decisions on the time of initiation. Future research should identify what these factors may be and how to address them to promote better delivery of care.

Is the Distance Worth It? Patients With Rectal Cancer Traveling to High-Volume Centers Experience Improved Outcomes.

BACKGROUND: It is unclear whether traveling long distances to high-volume centers would compensate for travel burden among patients undergoing rectal cancer resection. OBJECTIVE: The purpose of this study was to determine whether operative volume outweighs the advantages of being treated locally by comparing the outcomes of patients with rectal cancer treated at local, low-volume centers versus far, high-volume centers. DESIGN: This was a population-based study. SETTINGS: The National Cancer Database was queried for patients with rectal cancer. PATIENTS: Patients with stage II or III rectal cancer who underwent surgical resection between 2006 and 2012 were included. MAIN OUTCOME MEASURES: The outcomes of interest were margins, lymph node yield, receipt of neoadjuvant chemoradiation, adjuvant chemotherapy, readmission within 30 days, 30-day and 90-day mortality, and 5-year overall survival. RESULTS: A total of 18,605 patients met inclusion criteria; 2067 patients were in the long-distance/high-volume group and 1362 in the short-distance/low-volume group. The median travel distance was 62.6 miles for the long-distance/high-volume group and 2.3 miles for the short-distance/low-volume group. Patients who were younger, white, privately insured, and stage III were more likely to have traveled to a high-volume center. When controlled for patient factors, stage, and hospital factors, patients in the short-distance/low-volume group had lower odds of a lymph node yield ≥12 (OR = 0.51) and neoadjuvant chemoradiation (OR = 0.67) and higher 30-day (OR = 3.38) and 90-day mortality (OR = 2.07) compared with those in the long-distance/high-volume group. The short-distance/low-volume group had a 34% high risk of overall mortality at 5 years compared with the long-distance/high-volume group. LIMITATIONS: We lacked data regarding patient and physician decision making and surgeon-specific factors. CONCLUSIONS: Our results indicate that when controlled for patient, tumor, and hospital factors, patients who traveled a long distance to a high-volume center had improved lymph node yield, neoadjuvant chemoradiation receipt, and 30- and 90-day mortality compared with those who traveled a short distance to a low-volume center. They also had improved 5-year survival. See Video Abstract at http://links.lww.com/DCR/A446.

Long-term Deleterious Impact of Surgeon Care Fragmentation After Colorectal Surgery on Survival: Continuity of Care Continues to Count.

BACKGROUND: Surgical care fragmentation at readmission impacts short-term outcomes. However, the long-term impact of surgical care fragmentation is unknown. OBJECTIVE: The purpose was to evaluate the impact of surgical care fragmentation, encompassing both surgeon and hospital care, at readmission after colorectal surgery on 1-year survival. DESIGN: This was a retrospective cohort study. SETTING: The study included patients undergoing colorectal resection in New York State from 2004 to 2014. PATIENTS: Included were 20,016 patients undergoing colorectal resection who were readmitted within 30 days of discharge and categorized by source-of-care fragmentation. Each readmission was classified by the source of fragmentation: readmission to the index hospital and managed by another provider, readmission to another hospital by the index surgeon, and readmission to another hospital by another provider. Patients readmitted to the index hospital and managed by the index surgeon served as controls. MAIN OUTCOME MEASURES: One-year overall survival and 1-year colorectal cancer-specific survival were the outcomes measured. RESULTS: After propensity adjustment, surgeon care fragmentation was independently associated with decreased survival. In comparison with patients without surgical care fragmentation (patients readmitted to the index hospital and managed by the index surgeon), patients readmitted to the index hospital and managed by another provider had over a 2-fold risk (HR, 2.33; 95% CI, 2.10-2.60) and patients readmitted to another hospital by another provider had almost a 2-fold risk (HR, 1.91; 95% CI, 1.63-2.25) of 1-year mortality. Among 9545 patients with a colorectal cancer diagnosis, surgical care fragmentation was once again associated with decreased survival with patients readmitted to the index hospital and managed by another provider having a HR of 2.12 (95% CI, 1.76-2.56) and patients readmitted to another hospital by another provider having a HR of 1.57 (95% CI, 1.17-2.11) compared with patients readmitted to the index hospital and managed by the index surgeon. LIMITATIONS: Limitations include possible miscoding of data, retrospective design, and selection bias. CONCLUSIONS: After accounting for patient, index hospital, index surgeon, and readmission factors, there is a significant 2-fold decrease in survival associated with surgeon care fragmentation regardless of hospital continuity. See Video Abstract at http://links.lww.com/DCR/A431.

Alogliptin: a new dipeptidyl peptidase-4 inhibitor for type 2 diabetes mellitus.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor in the management of type 2 diabetes mellitus (T2DM). DATA SOURCES: Searches were conducted in MEDLINE (1946-August 2013) and Embase (1974-August 2013) for English language articles using key words alogliptin, SYR-332, Nesina, Oseni, and Kazano. References of articles were reviewed to identify any additional sources. STUDY SELECTION AND DATA EXTRACTION: Articles with adequate sample sizes, evaluating clinically relevant end points were included. DATA SYNTHESIS: Alogliptin is a highly selective and potent competitive inhibitor of DPP-4. The DPP-4 enzyme rapidly inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. GLP-1, which releases postprandial insulin in response to meals, is thought to be deficient in patients with T2DM. Studies evaluating the role of alogliptin in T2DM have shown significant reductions in blood glucose and hemoglobin A1C (A1C) levels. Alogliptin doses of 12.5 to 25 mg once daily reduced A1C by 0.56% to 0.59% as monotherapy. Patients given alogliptin in addition to other antidiabetic agentsexperienced additional A1C lowering of 0.4% to 0.8%. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections, and headache. Alogliptin demonstrates a neutral effect on weight. A large trial evaluating the cardiovascular safety of alogliptin is currently being conducted. CONCLUSIONS: Alogliptin is the fourth DDP-4 inhibitor approved in the US for the treatment of T2DM. It is available alone (Nesina) and in fixed-dose combinations with metformin (Kazano) and pioglitazone (Oseni). It has no demonstrable advantages over other agents in its class.

A tale of two parasites: Responses of honey bees infected with Nosema ceranae and Lotmaria passim.

Nosema ceranae and Lotmaria passim are two commonly encountered digestive tract parasites of the honey bee that have been associated with colony losses in Canada, the United States, and Europe. Though honey bees can be co-infected with these parasites, we still lack basic information regarding how they impact bee health at the individual and colony level. Using locally-isolated parasite strains, we investigated the effect of single and co-infections of these parasites on individual honey bee survival, and their responsiveness to sucrose. Results showed that a single N. ceranae infection is more virulent than both single L. passim infections and co-infections. Honey bees singly infected with N. ceranae reached < 50% survival eight days earlier than those inoculated with L. passim alone, and four days earlier than those inoculated with both parasites. Honey bees infected with either one, or both, parasites had increased responsiveness to sucrose compared to uninfected bees, which could correspond to higher levels of hunger and increased energetic stress. Together, these findings suggest that N. ceranae and L. passim pose threats to bee health, and that the beekeeping industry should monitor for both parasites in an effort correlate pathogen status with changes in colony-level productivity and survival.

Ulipristal acetate for emergency contraception.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of data of ulipristal acetate, a new emergency contraceptive approved for use up to 120 hours after unprotected intercourse. DATA SOURCES: Articles pertaining to the topic were identified and reviewed through searches of PubMed (1994-March 2011) and clinicaltrials.gov, using the key terms ulipristal and CDB-2914. Ella approval documents were obtained and reviewed from Drugs@FDA on the Food and Drug Administration (FDA) Web site. STUDY SELECTION AND DATA EXTRACTION: All published data and FDA approval documents examining pharmacologic, pharmacokinetic, and clinical studies related to ulipristal acetate as an emergency contraceptive were evaluated. Selected studies included 3 randomized trials and 1 meta-analysis. DATA SYNTHESIS: Ulipristal acetate is a progesterone agonist/antagonist emergency contraceptive approved for the prevention of pregnancy to be taken as soon as possible, within 120 hours after unprotected intercourse or a known or suspected contraceptive failure. Based upon results of the Phase 3 clinical trials used to obtain approval, ulipristal acetate administration was at least as effective as levonorgestrel in the reduction of pregnancy rate when studied alone after unprotected intercourse and when taken up to 120 hours after unprotected intercourse. Commonly reported adverse effects associated with ulipristal acetate in trials included headache, breast tenderness, nausea, and abdominal pain. CONCLUSIONS: Ulipristal acetate is effective as an emergency contraceptive for up to 120 hours after unprotected intercourse. Because ulipristal is available only via prescription, it may be covered by insurance. However, the additional factors of travel expenses and time to make and attend a physician appointment must be taken into account when considering use of ulipristal as an emergency contraceptive. Due to the similarity of its structure to mifepristone, controversy regarding ulipristal's mechanism of action has arisen.

Modulation of endogenous antioxidants by zinc and copper in signal crayfish (Pacifastacus leniusculus).

Metal pollution is a long-standing concern and bioindicators are commonly used in ecotoxicological studies to monitor impacted wildlife populations for evidence of sublethal effects. Significant variation in the response of common biomarkers to metals is reported across taxa, thus necessitating careful characterization in model organisms. In this study, we describe the regulation of glutathione S-transferase (GST), glutathione (GSH), and metallothionein (MT) by zinc chloride (0.6, 0.9, 1.2, 2.4, 4.8, 9.6 µg g-1) and copper chloride (0.6, 0.9, 1.2 µg g-1) in signal crayfish (Pacifastacus leniusculus). Zinc chloride did not alter GST activity relative to controls in the hepatopancreas. Crayfish exposed to copper chloride exhibited decreased GST activity at the lowest dose tested (0.6 µg g-1) with no change observed at the higher doses. GSH did not change in response to either metal when sexes were grouped together. MT concentrations increased in response to zinc (2.4, 4.6, and 9.6 µg g-1 doses) and copper (0.6, 0.9, and 1.2 µg g-1 doses) in gill tissue. In tail tissue, MT increased at the 2.4 and 4.8 µg g-1 zinc chloride doses and all the concentrations of copper tested. Sex-specific differences in endogenous antioxidant expression were also analyzed with no clear patterns emerging. We concluded that these endpoints are sensitive to zinc and copper in signal crayfish, although careful interpretation is needed when applying them in field studies given the variation in responses, non-monotonic dose responses, and differences in biotic and abiotic factors that inevitably exist in different aquatic ecosystems.

Rivaroxaban for thromboprophylaxis in patients undergoing major orthopedic surgery.

OBJECTIVE: To review the pharmacology, pharmacokinetics, and clinical efficacy/safety profile of rivaroxaban to inform health-care professionals of this new agent for the prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery. DATA SOURCES: A literature search was performed in PubMed/MEDLINE (1966-March 2010), International Pharmaceutical Abstracts (1970-March 2010), and EMBASE (1990-March 2010), limited to publications in English, using the search terms BAY 59-7939, rivaroxaban, factor Xa inhibitor, hip replacement, and/or knee replacement to identify literature sources. References from retrieved articles were evaluated to identify relevant literature. Unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidance, and advisory committee briefing packets. STUDY SELECTION AND DATA EXTRACTION: All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of rivaroxaban for the prevention of VTE in patients undergoing major orthopedic surgery were included, with preference for clinical data. DATA SYNTHESIS: Rivaroxaban use was significantly more effective for thromboprophylaxis in patients undergoing total knee replacement (TKR) or total hip replacement (THR), compared to enoxaparin for the composite incidence of deep vein thrombosis, nonfatal pulmonary embolism, all-cause mortality, and the rate of major VTE; bleeding events occurred at statistically similar rates. In Phase 3 studies, rivaroxaban 10 mg was administered orally 6-8 hours post-surgery and post-hemostasis. Thereafter, administration was once daily for 35 days in THR and 10-14 days in TKR. CONCLUSIONS: Rivaroxaban has demonstrated comparable safety and superior efficacy to the commonly used low-molecular-weight heparin, enoxaparin. Ongoing and future clinical trials will allow clinicians to further assess the efficacy, safety, and pharmacoeconomics of rivaroxaban.

Nosema ceranae (Microspora: Nosematidae): A Sweet Surprise? Investigating the Viability and Infectivity of N. ceranae Spores Maintained in Honey and on Beeswax.

Nosema disease is a prominent malady among adult honey bees [Apis mellifera L. (Hymenoptera: Apidae)], caused by the microsporidian parasites, Nosema apis Zander (Microspora: Nosematidae) and N. ceranae Fries et al. 1996. The biology of N. apis is well understood, as this parasite was first described over a century ago. As N. ceranae is an emerging parasite of the honey bee, we do not yet understand how long spores of this parasite survive in honey bee colonies, or all the potential modes of transmission among bees. We investigated the viability and infectivity of N. ceranae spores in honey and on beeswax over time after exposure to 33, 20, -12, and -20°C. Spores in honey maintained viability at freezing temperatures for up to 1 yr and remained viable considerably longer than those on beeswax. Based on this evidence, honey may act as an important reservoir for infective spores to initiate or perpetuate N. ceranae infections in honey bee colonies. This work provides information that may help enhance current management recommendations for apiculturalists.

Cerebellospinal Neurons Regulate Motor Performance and Motor Learning.

To understand the neural basis of behavior, it is important to reveal how movements are planned, executed, and refined by networks of neurons distributed throughout the nervous system. Here, we report the neuroanatomical organization and behavioral roles of cerebellospinal (CeS) neurons. Using intersectional genetic techniques, we find that CeS neurons constitute a small minority of excitatory neurons in the fastigial and interpositus deep cerebellar nuclei, target pre-motor circuits in the ventral spinal cord and the brain, and control distinct aspects of movement. CeS neurons that project to the ipsilateral cervical cord are required for skilled forelimb performance, while CeS neurons that project to the contralateral cervical cord are involved in skilled locomotor learning. Together, this work establishes CeS neurons as a critical component of the neural circuitry for skilled movements and provides insights into the organizational logic of motor networks.

The calcium-binding protein cell division cycle 31 of Saccharomyces cerevisiae is a component of the half bridge of the spindle pole body.

Cdc31 mutants of Saccharomyces cerevisiae arrest at the nonpermissive temperature with large buds, G2 DNA content and, a single, abnormally large spindle pole body (SPB) (Byers, B. 1981. Molecular Genetics in Yeast. Alfred Benzon Symposium. 16:119-133). In this report, we show that the CDC31 gene product is essential for cell viability. We demonstrate that purified CDC31 protein binds Ca2+ and that this binding is highly specific. Taken together, three lines of evidence indicate that CDC31 is a component of the SPB. First, CDC31 cofractionates with enriched preparations of SPBs. Second, immunofluorescence staining indicates that CDC31 colocalizes with a known SPB component. Third, immunoelectron microscopy with whole cells and with isolated SPBs reveals that CDC31 is localized to the half bridge of the SPB, which lies immediately adjacent to the SPB plaques. CDC31 was detected mainly at the cytoplasmic side of the half bridge and, therefore, defines a further substructure of the SPB. We suggest that CDC31 is a member of a family of calcium-binding, centrosome-associated proteins from a phylogenetically diverse group of organisms.

The Cdc31p-binding protein Kar1p is a component of the half bridge of the yeast spindle pole body.

KAR1 has been identified as an essential gene which is involved in karyogamy of mating yeast cells and in spindle pole body duplication of mitotic cells (Rose, M. D., and G. R. Fink. 1987. Cell. 48:1047-1060). We investigated the cell cycle-dependent localization of the Kar1 protein (Kar1p) and its interaction with other SPB components. Kar1p is associated with the spindle pole body during the entire cell cycle of yeast. Immunoelectron microscopic studies with anti-Kar1p antibodies or with the monoclonal antibody 12CA5 using an epitope-tagged, functional Kar1p revealed that Kar1p is associated with the half bridge or the bridge of the spindle pole body. Cdc31p, a Ca(2+)-binding protein, was previously identified as the first component of the half bridge of the spindle pole body (Spang, A., I. Courtney, U. Fackler, M. Matzner, and E. Schiebel. 1993. J. Cell Biol. 123:405-416). Using an in vitro assay we demonstrate that Cdc31p specifically interacts with a short sequence within the carboxyl terminal half of Kar1p. The potential Cdc31p-binding sequence of Kar1p contains three acidic amino acids which are not found in calmodulin-binding peptides, explaining the different substrate specificities of Cdc31p and calmodulin. Cdc31p was also able to bind to the carboxy terminus of Nuflp/Spc110p, another component of the SPB (Kilmartin, J. V., S. L. Dyos, D. Kershaw, and J. T. Finch. 1993. J. Cell Biol. 123:1175-1184). The association of Kar1p with the spindle pole body was independent of Cdc31p. Cdc31p, on the other hand, was not associated with SPBs of kar1 cells.

Ustekinumab: treatment of adult moderate-to-severe chronic plaque psoriasis.

OBJECTIVE: To systematically review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of ustekinumab to inform pharmacists and other healthcare professionals of this new biologic therapy for psoriasis. DATA SOURCES: A search of PubMed/MEDLINE, EMBASE, and International Pharmaceutical Abstracts was performed through July 2009, limited to publications in English, using the search terms CNTO-1275, ustekinumab, interleukin-12, interleukin-23, and/or psoriasis to identify literature sources. References from the retrieved articles were also evaluated to identify relevant literature. An abstract from a Congress of the European Academy of Dermatology and Venereology and unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidances, and advisory committee briefing packets. STUDY SELECTION AND DATA EXTRACTION: All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of ustekinumab for the treatment of psoriasis were included, with preference for human data. DATA SYNTHESIS: Ustekinumab, an anti-interleukin-12/23 monoclonal antibody, achieved the primary endpoint of 75% reduction in the Psoriasis Area and Severity Index score in a large proportion of patients in the Phase 3 PHOENIX trials. Commensurate improvements were also seen in the Physician's Global Assessment and Dermatology Life Quality Index scores. These efficacy results were reproduced in the ACCEPT trial, demonstrating superiority of ustekinumab to etanercept. The frequency of adverse events was similar between ustekinumab and placebo; common adverse events reported included nasopharyngitis, upper respiratory tract infection, headache, arthralgia, cough, and injection site reactions. Phase 3 studies indicate that the optimal dosing appears to be 45 mg for patients weighing less than 100 kg or 90 mg for patients weighing more than 100 kg, with both doses administered subcutaneously. In these studies, the second dose was given 4 weeks after the first and then every 8-12 weeks thereafter, based upon response. CONCLUSIONS: Ustekinumab, a promising new therapy, reduces the extent and severity of psoriasis and was well tolerated in clinical trials. Ongoing clinical trials will allow clinicians to further assess the efficacy/safety profile of this novel biologic.

Educational campaign for proper medication disposal.

OBJECTIVE: To assess the effect of an educational intervention on pharmacists' attitudes and knowledge about medication disposal. METHODS: In September 2005, a survey was mailed to 488 registered pharmacists serving as experiential education preceptors to Massachusetts College of Pharmacy and Health Sciences students in 27 states throughout the country. Mailing of this presurvey occurred 2 months before an educational intervention. An identical postsurvey was mailed to the 223 respondents to the presurvey 3 months after the intervention. The main outcome measure was change in pharmacist attitudes and knowledge about medication disposal after educational intervention. RESULTS: 158 pharmacists (32% response rate) completed the pre- and postsurveys. Before the intervention, 47% of pharmacists perceived inappropriate medication disposal to be an environmental problem compared with 57% after the intervention (P = 0.03). Similarly, when asked about medication disposal, 10% correctly indicated that patients could arrange for hazardous waste pick up compared with 20% postintervention (P < 0.01). Conversely, 19% incorrectly indicated that patients should wash medications down the sink compared with 5.6% postintervention (P < 0.01). CONCLUSION: A brief educational intervention is effective at changing pharmacists' attitudes and knowledge of inappropriate and environmentally unsafe medication disposal practices. Pharmacists receiving the educational intervention were more likely to report that they would recommend appropriate methods of medication disposal. Further educational efforts are necessary for improving pharmacists' knowledge regarding safe medication disposal practices.

Decoding Cell Type Diversity Within the Spinal Cord.

To understand fundamental mechanisms of mammalian spinal cord function, it is necessary to reveal the diverse array of constituent spinal "cell types" - populations that can be consistently identified because they share a unique and cohesive set of characteristics. Many parameters can contribute to the definition of a spinal cord cell type, including location, morphology, lineage, electrophysiological properties, circuit features, gene expression patterns, and behavioral contribution. While it is not necessary for all of these features to align completely at all times to identify an individual cell type, a correlation of these characteristics paints a rich portrait of cell identity. This review will summarize recent advances in the identification of mammalian spinal cord neuronal cell types and will highlight the power of transcriptional profiling to identify and characterize the cell types of the spinal cord.