American Psychiatric Nurses Association Position: Staffing Inpatient Psychiatric Units.

OBJECTIVE: An American Psychiatric Nurses Association (APNA) task force reviewed current staffing research to revise and update the 2011 APNA "Staffing inpatient psychiatric units" position paper and provide recommendations to the APNA Board of Directors on how psychiatric mental health (PMH) nurses might champion the staffing needs of inpatient psychiatric units. METHODS: Current research on staffing and nursing practice in inpatient psychiatric units was reviewed as well as variables believed to influence staffing and nursing practice, such as consumer needs and workplace culture. Since current nurse staffing principles emphasize nursing value and how that value is connected to outcomes, the literature search included a focus on staffing and related patient outcomes. RESULTS: PMH nurses are critical to the safety and quality of care in inpatient psychiatric units. However, there are little existing data on the relationship between staffing levels and even common adverse events such as staff injury and restraint of patients. Furthermore, there is scant research conducted on inpatient psychiatric units that informs optimal staffing models or establishes links between staffing and patient outcomes. CONCLUSIONS: Consistent with current evidence, the universal use of a single method or model of determining staffing needs (e.g., nursing hours per, case mix index, or mandatory ratios) is not recommended. PMH nurses should champion systematic evaluation of staffing on their inpatient units against select patient, nurse, and system outcomes. A data repository of PMH nurse-sensitive outcomes is necessary to benchmark unit performance and staffing.

Development and characterization of an immortalized swine respiratory cell line for influenza A virus research.

Introduction: Swine serve as an important intermediate host species for generating novel influenza A viruses (IAVs) with pandemic potential because of the host's susceptibility to IAVs of swine, human and avian origin. Primary respiratory cell lines are used in IAV research to model the host's upper respiratory tract in vitro. However, primary cell lines are limited by their passaging capacity and are time-consuming for use in industry and research pipelines. We were interested in developing and characterizing a biologically relevant immortalized swine respiratory cell line that could be used for efficient propagation and characterization of swine IAV isolates. Methods: Lung tissue for the generation of primary swine respiratory cells were isolated from the bronchi of an 8-week-old Yorkshire/Hampshire pig, which were immortalized by transduction of the SV40 T antigen using a lentivirus vector. The transduction of the SV40 T antigen was confirmed by Real Time RT-PCR in cells passaged greater than twenty times. Results: Immortalized swine respiratory cells expressed primarily α2,6 sialic acid receptors and were susceptible to both swine and human IAVs, with swine viruses exhibiting higher replication rates. Notably, infection with a swine H3N2 isolate prompted increased IL-6 and IL-1α protein secretion compared to a seasonal human H3N2 virus. Even after 20 passages, the immortalized cells maintained the primary respiratory cell phenotype and remained permissive to IAV infection without exogenous trypsin. Discussion: In summary, our developed immortalized swine respiratory cell line offers an alternative in vitro substrate for studying IAV replication and transmission dynamics in pigs, overcoming the limitations of primary respiratory cells in terms of low passage survivability and cost.

Universal Pediatric Suicide Risk Screening in a Health Care System: 90,000 Patient Encounters.

BACKGROUND: Suicidal behavior is increasing among US youths. Contact with the health care system is common in the months before suicide. OBJECTIVE: To assess the characteristics of suicide risk among youths presenting for health care, universal screening results from a large hospital system were analyzed. METHODS: A retrospective analysis of the Ask Suicide-Screening Questions tool administered to patients aged 10-17 years in a hospital system including an emergency department, inpatient medical units, and primary care clinics was conducted. Demographic and clinical data from 3 years of encounters were analyzed. RESULTS: The sample consisted of 91,580 pediatric encounters, predominantly white Hispanic and women, with one third speaking Spanish. Across health care settings, 2.9% of encounters produced positive suicide risk screens, with the highest rate in the emergency department (8.5%). Acute positive screens, indicating imminent risk for suicidal behavior, accounted for 0.3% of all encounters. Approximately one-fourth (27.6%) of encounters for psychiatric presenting problems screened positive compared with 2.3% for nonpsychiatric encounters. Higher rates of positive screens were present among encounters for psychiatric presenting problems across all settings. Positive screens were less common among preteen (1.8%) than adolescent (3.1%) encounters (χ2 = 65.50, P < 0.001). CONCLUSIONS: Universal screening detected suicide risk in approximately 3% of pediatric health care encounters. Screening identified risk in encounters among preteen and adolescent patients, with a higher prevalence of positive screens in encounters for youths presenting with psychiatric problems and for emergency department visits. Acute positive screens were rare, occurring in less than half of 1 percent of encounters.

Development and Implementation of a Universal Suicide Risk Screening Program in a Safety-Net Hospital System.

BACKGROUND: Many individuals who die by suicide present for nonbehavioral health care prior to death. The risk is often undetected. Universal suicide screening in health care may improve risk recognition. A quality improvement project involving a universal suicide screening program was designed and developed in a large safety-net health care system. METHODS: The steps in developing and implementing this quality improvement program were gathering intelligence, examining resources, designing the screening program, creating a clinical response, constructing an electronic health record screening protocol, clinical workforce education, and program implementation. This project used the Columbia-Suicide Severity Rating Scale, Clinical Practice Screener-Recent, and a preliminary clinical decision support system. RESULTS: Prevalence data on suicide risk levels are provided for 328,064 adult encounters from the first six months of the screening program. Approximately half of the screens were completed in the outpatient clinics, more than 40% in the emergency department (ED), and slightly less than 5% in the hospital inpatient units. In the ED, 6.3% of the screens were positive, as were 1.6% in the inpatient units, and 2.1% in the outpatient clinics. The odds of a positive suicide screening in the ED was 4.29 times higher than the inpatient units and 3.13 times higher than the outpatient clinics. CONCLUSION: A new quality improvement program for universal suicide screening was successfully implemented in a large safety-net health care system. The burden to the system from universal screening was not overwhelming and was managed effectively through thoughtful allocation of clinical resources.

African-American teen girls grieve the loss of friends to homicide: meaning making and resilience.

Few studies have examined the bereavement experiences of African-American teen girls who have mourned the loss of friends due to homicide. This qualitative study examined such bereavement experiences with a sample of 20 African-American teen girls, ages 16-19, living in a large northeastern U.S. city. Meaning making, adolescent developmental theory, ideas regarding traumatic loss, and resilience provided a framework to understand how these teens coped with the tragic loss of a friend. The teen girls in this study demonstrated resilience in their ability to adequately "move on" with their lives. They remained achievement oriented and sustained meaningful relationships with family, valued friends, and others. Early, metaphysical, and motivational meaning constructions contributed to the teens' resilience.

PduL is an evolutionarily distinct phosphotransacylase involved in B12-dependent 1,2-propanediol degradation by Salmonella enterica serovar typhimurium LT2.

Salmonella enterica degrades 1,2-propanediol (1,2-PD) in a coenzyme B(12)-dependent manner. Previous enzymatic assays of crude cell extracts indicated that a phosphotransacylase (PTAC) was needed for this process, but the enzyme involved was not identified. Here, we show that the pduL gene encodes an evolutionarily distinct PTAC used for 1,2-PD degradation. Growth tests showed that pduL mutants were unable to ferment 1,2-PD and were also impaired for aerobic growth on this compound. Enzyme assays showed that cell extracts from a pduL mutant lacked measurable PTAC activity in a background that also carried a pta mutation (the pta gene was previously shown to encode a PTAC enzyme). Ectopic expression of pduL corrected the growth defects of a pta mutant. PduL fused to eight C-terminal histidine residues (PduL-His(8)) was purified, and its kinetic constants were determined: the V(max) was 51.7 +/- 7.6 micromol min(-1) mg(-1), and the K(m) values for propionyl-PO(4)(2-) and acetyl-PO(4)(2-) were 0.61 and 0.97 mM, respectively. Sequence analyses showed that PduL is unrelated in amino acid sequence to known PTAC enzymes and that PduL homologues are distributed among at least 49 bacterial species but are absent from the Archaea and Eukarya.

Biochemical evidence that the pduS gene encodes a bifunctional cobalamin reductase.

Salmonella enterica degrades 1,2-propanediol (1,2-PD) by a pathway that requires coenzyme B(12) (adenosylcobalamin; AdoCbl). The genes specifically involved in 1,2-PD utilization (pdu) are found in a large contiguous cluster, the pdu locus. Earlier studies have indicated that this locus includes genes for the conversion of vitamin B(12) (cyanocobalamin; CNCbl) to AdoCbl and that the pduO gene encodes an ATP : cob(I)alamin adenosyltransferase which catalyses the terminal step of this process. Here, in vitro evidence is presented that the pduS gene encodes a bifunctional cobalamin reductase that catalyses two reductive steps needed for the conversion of CNCbl into AdoCbl. The PduS enzyme was produced in high levels in Escherichia coli. Enzyme assays showed that cell extracts from the PduS expression strain reduced cob(III)alamin (hydroxycobalamin) to cob(II)alamin at a rate of 91 nmol min(-1) mg(-1) and cob(II)alamin to cob(I)alamin at a rate of 7.8 nmol min(-1) mg(-1). In contrast, control extracts had only 9.9 nmol min(-1) mg(-1) cob(III)alamin reductase activity and no detectable cob(II)alamin reductase activity. Thus, these results indicated that the PduS enzyme is a bifunctional cobalamin reductase. Enzyme assays also showed that the PduS enzyme reduced cob(II)alamin to cob(I)alamin for conversion into AdoCbl by purified PduO adenosyltransferase. Moreover, studies in which iodoacetate was used as a chemical trap for cob(I)alamin indicated that the PduS and PduO enzymes physically interact and that cob(I)alamin is sequestered during the conversion of cob(II)alamin to AdoCbl by these two enzymes. This is likely to be important physiologically, since cob(I)alamin is extremely reactive and would need to be protected from unproductive by-reactions. Lastly, bioinformatic analyses showed that the PduS enzyme is unrelated in amino acid sequence to enzymes of known function currently present in GenBank. Hence, results indicate that the PduS enzyme represents a new class of cobalamin reductase.

Purification and initial characterization of the Salmonella enterica PduO ATP:Cob(I)alamin adenosyltransferase.

The PduO enzyme of Salmonella enterica is an ATP:cob(I)alamin adenosyltransferase that catalyzes the final step in the conversion of vitamin B(12) to coenzyme B(12). The primary physiological role of this enzyme is to support coenzyme B(12)-dependent 1,2-propanediol degradation, and bioinformatic analysis has indicated that it has two domains. Here the PduO adenosyltransferase was produced in Escherichia coli, solubilized from inclusion bodies, purified to apparent homogeneity, and partially characterized biochemically. The K(m) values of PduO for ATP and cob(I)alamin were 19.8 and 4.5 microM, respectively, and the enzyme V(max) was 243 nmol min(-1) mg of protein(-1). Further investigations showed that PduO was active with ATP and partially active with deoxy-ATP, but lacked measurable activity with other nucleotides. (31)P nuclear magnetic resonance established that triphosphate was a product of the PduO reaction, and kinetic studies indicated a ternary complex mechanism. A series of truncated versions of the PduO protein were produced in Escherichia coli, partially purified, and used to show that adenosyltransferase activity is associated with the N-terminal domain. The N-terminal domain was purified to near homogeneity and shown to have biochemical properties and kinetic constants similar to those of the full-length enzyme. This indicated that the C-terminal domain was not directly involved in catalysis or substrate binding and may have another role.

Zoniporide: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1).

The sodium-hydrogen exchanger isoform-1 (NHE-1) plays an important role in the myocardial response to ischemia-reperfusion; inhibition of this exchanger protects against ischemic injury, including reduction in infarct size. Herein we describe a novel, potent, and highly selective NHE-1 inhibitor, zoniporide (CP-597,396; [1-(quinolin-5-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl] guanidine). Zoniporide inhibits human NHE-1 with an IC(50) of 14 nM, has >150-fold selectivity vs. other NHE isoforms, and potently inhibits ex vivo NHE-1-dependent swelling of human platelets. This compound is well tolerated in preclinical animal models, exhibits moderate plasma protein binding, has a t(1/2) of 1.5 h in monkeys, and has one major active metabolite. In both in vitro and in vivo rabbit models of myocardial ischemia-reperfusion injury, zoniporide markedly reduced infarct size without adversely affecting hemodynamics or cardiac function. In the isolated heart (Langendorff), zoniporide elicited a concentration-dependent reduction in infarct size (EC(50) = 0.25 nM). At 50 nM it reduced infarct size by 83%. This compound was 2.5-20-fold more potent than either eniporide or cariporide (EC(50)s of 0.69 and 5.11 nM, respectively), and reduced infarct size to a greater extent than eniporide. In open chest, anesthetized rabbits, zoniporide also elicited a dose-dependent reduction in infarct size (ED(50) = 0.45 mg/kg/h) and inhibited NHE-1-mediated platelet swelling (93% inhibition at 4 mg/kg/h). Furthermore, zoniporide attenuated postischemic cardiac contractile dysfunction in conscious primates, and reduced both the incidence and duration of ischemia-reperfusion-induced ventricular fibrillation in rats. Zoniporide represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.