Tridentate NacNac Tames T-Shaped Nickel(I) Radical.

The reaction of a nickel(II) chloride complex containing a tridentate ß-diketiminato ligand with a picolyl group [2,6-iPr2 -C6 H3 NC(Me)CHC(Me)NH(CH2 py)]Ni(II)Cl (1)] with KSi(SiMe3 )3 conveniently afforded a nickel(I) radical with a T-shaped geometry (2). The compound's metalloradical nature was confirmed through electron paramagnetic resonance (EPR) studies and its reaction with TEMPO, resulting in the formation of a highly unusual three-membered nickeloxaziridine complex (3). When reacted with disulfide and diselenide, the S-S and Se-Se bonds were cleaved, and a coupled product was formed through carbon atom of the pyridine-imine group. The nickel(I) radical activates dihydrogen at room temperature and atmospheric pressure to give the monomeric nickel hydride.

Protecting Sleep Hygiene in the PICU: A Quality Improvement Project.

OBJECTIVES: To increase the number of nights without sleep interruptions for routine tasks in recovering PICU patients. DESIGN: Prospective quality improvement project. SETTING: Single-center, free-standing, tertiary children's hospital. PATIENTS: Patients admitted to the PICU for greater than 72 hours and eligible for early mobilization. INTERVENTIONS: A multidisciplinary sleep hygiene team was created to improve sleep hygiene in critically ill patients eligible for early mobilization. This team rewrote local nursing policies to avoid routine tasks between 11 pm and 5 am . The team provided periodic control chart updates to staff detailing progress made protecting sleep. Discussions of sleep hygiene were added to the daily goal sheet and a sleep hygiene order set was created. Finally, the PICU quality dashboard was modified to show whether a sleep hygiene order set was initiated in eligible patients. MEASUREMENTS AND MAIN RESULTS: Routine tasks were defined as daily chest radiographs, baths, routine tracheostomy care, central line dressing changes, twice daily medications, weights, and Foley care. After a year of data collection, avoidance of routine pupillary examinations was added to the sleep protection criteria. Baseline data was collected for 2 months prior to the creation of the sleep hygiene team. Screening of eligible patients occurred 1 week each month. The data were analyzed utilizing control charts. Baseline data demonstrated 32% of PICU patients without sleep interruptions. The centerline increased to 58% after the initial interventions but dropped to 33% after inclusion of pupillary checks. Following the introduction of the daily goal sheet, sleep hygiene order set, and tracking on the quality board, 49% of patients went without interruptions. CONCLUSIONS: The initiation of a sleep hygiene team along with retiming routine tasks, daily discussions on rounds with the daily goal sheet, introduction of a sleep hygiene order set, and transparent tracking improved the percentage of patients with protected sleep.

Tridentate NacNac Stabilized Tin and Nickel Complexes: Access to a Monomeric Nickel Hydride and Its Catalytic Application.

The transmetalation reaction of picolyl-supported tridentate nacnac germylene monochloride [2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)]GeCl (1) (py = pyridine) with SnCl2 results in an analogous stannylene chloride (2). The three-coordinated stannylenium cation [{2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)}Sn]+ with SnCl3- as a counteranion (3) has been generated through the abstraction of chloride ligand from 2 using an additional equivalent of SnCl2. Instead of forming a donor-acceptor complex, 2 undergoes a facile redox transmetalation reaction with Ni(COD)2 (COD = cyclooctadiene) and CuCl to afford analogous nickel and copper complexes [2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)]MCl [M = Ni (4) and Cu (5)]. The reactions of 4 with potassium tri-sec-butylborohydride (commonly known as K-selectride) and AgSbF6 provide access to monomeric Ni(II) hydride, [2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)]NiH (6) and a Ni(II) cation, [{2,6-iPr2-C6H3NC(Me)CHC(Me)NH(CH2py)}Ni][SbF6] (7), respectively. 6 was found to be an effective catalyst for the hydroboration of amides.

Crystal structure of a 1:1 co-crystal of the anti-cancer drug gefitinib with azelaic acid.

In the title co-crystal, C22H24ClFN4O3·C9H16O4, gefitinib (GTB; systematic name: quinazolin-4-amine) co-crystallizes with azelaic acid (AA; systematic name: nona-nedioic acid). The co-crystal has the monoclinic P21/n centrosymmetric space group, containing one mol-ecule each of GTB and AA in the asymmetric unit. A structure overlay of the GTB mol-ecule in the co-crystal with that of its most stable polymorph revealed a significant difference in the conformation of the morpholine moiety. The significant deviation in the conformation of one of the acidic groups of azelaic acid from its usual linear chain structure could be due to the encapsulation of one acidic group in the pocket formed between the two pincers of GTB namely, the morpholine and phenyl moieties. Both GTB and AA mol-ecules form N-H⋯O, O-H⋯N, C-H⋯O hydrogen bonds with C-H⋯F close contacts along with off-stacked aromatic π-π inter-actions between the GTB mol-ecules.

Use of an Anti-Infective Medication Review Process at Hospital Discharge to Identify Medication Errors and Optimize Therapy.

BACKGROUND: Medication reconciliation is a major patient safety concern, and the impact of a structured process to evaluate anti-infective agents at hospital discharge warrants further review. OBJECTIVE: The aim of this study was to (1) describe a structured, multidisciplinary approach to review anti-infectives at discharge and (2) measure the impact of a stewardship-initiated antimicrobial review process in identifying and preventing anti-infective-related medication errors (MEs) at discharge. METHODS: A prospective study to evaluate adult patients discharged on anti-infectives was conducted from October 2013 to May 2014. The antimicrobial stewardship program (ASP) classified interventions on anti-infective regimens into predefined ME categories. RESULTS: Forty-five patients who were discharged on 59 anti-infective prescriptions were included in the study. The most common indications for anti-infective regimens at discharge were pneumonia (22%, n = 10), bacteremia (18%, n = 8), and skin and soft tissue infections (16%, n = 7). An ME was identified in 42% (n = 19/45) of anti-infective regimens. Seventy percentage of ASP team recommendations were accepted which resulted in an avoidance of MEs in 68% (n = 13/19) of patients with an ME prior to discharge. CONCLUSION: This study describes the outcomes of a stewardship-initiated review process in preventing MEs at discharge. Developing a systematic process for a multidisciplinary ASP team to review all anti-infectives can be a valuable tool in preventing MEs at hospital discharge.

Significant Publications on Infectious Diseases Pharmacotherapy in 2017.

PURPOSE: The most significant peer-reviewed articles pertaining to infectious diseases (ID) pharmacotherapy, as selected by panels of ID pharmacists, are summarized. SUMMARY: Members of the Houston Infectious Diseases Network (HIDN) were asked to nominate peer-reviewed articles that they believed most contributed to the practice of ID pharmacotherapy in 2017, including the areas of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). A list of 33 articles related to general ID pharmacotherapy and 4 articles related to HIV/AIDS was compiled. A survey was distributed to members of the Society of Infectious Diseases Pharmacists (SIDP) for the purpose of selecting 10 articles believed to have made the most significant impact on general ID pharmacotherapy and the single significant publication related to HIV/AIDS. Of 524 SIDP members who responded, 221 (42%) and 95 (18%) members voted for general pharmacotherapy- and HIV/AIDS-related articles, respectively. The highest ranked articles are summarized below. CONCLUSION: Remaining informed on the most significant ID-related publications is a challenge when considering the large number of ID-related articles published annually. This review of significant publications in 2017 may aid in that effort.

A call to action for outpatient antibiotic stewardship.

OBJECTIVES: To address the public health threat of antibiotic resistance, there has been an enhanced call for antibiotic stewardship programs throughout the health care continuum. SUMMARY: While antibiotic stewardship programs have been well described in the inpatient setting, data on effectiveness and guidance on implementing outpatient programs is scarce. Establishing stewardship practices in the outpatient setting is necessary because more than 60% of human antibiotic use occurs in this setting. CONCLUSION: In this article, we highlight the importance and need for stewardship in the outpatient setting, discuss strategies for the development of stewardship teams, and discuss potential metrics that can be used to assess effectiveness of antibiotic stewardship interventions.

Outpatient antibiotic stewardship: Interventions and opportunities.

Improving the use of antibiotics across the continuum of care is a national priority. Data outlining the misuse of antibiotics in the outpatient setting justify the expansion of antibiotic stewardship programs (ASPs) into this health care setting; however, best practices for outpatient antibiotic stewardship (AS) are not yet defined. In a companion article, we focused on recommendations to overcome challenges related to the implementation of an outpatient ASP (e.g., building the AS team and defining program metrics). In this document, we outline AS interventions that have demonstrated success and highlight opportunities to enhance AS in the outpatient arena. This article summarizes examples of point-of-care testing, policies and interventions, and education strategies to improve antibiotic use that can be used in the outpatient setting.

Metacognitive training (MCT) for schizophrenia improves cognitive insight: a randomized controlled trial in a Chinese sample with schizophrenia spectrum disorders.

Metacognitive training (MCT) is a group-based treatment program for people with schizophrenia that targets the cognitive biases thought to contribute to the pathogenesis and maintenance of delusions. Although effective in reducing the severity of delusions, the influence of MCT on cognitive insight, and its feasibility in Chinese culture, has yet to be investigated. The present randomized-controlled trial attempted to address these inconsistencies. A Chinese sample of 80 participants with schizophrenia spectrum disorders was randomized to the eight-module MCT program or continued treatment as usual (TAU). All participants were assessed using the Beck Cognitive Insight Scale, which assesses two components of cognitive insight (self-reflectiveness and self-certainty). Participants in the MCT condition subjectively rated their satisfaction with the training. Retention rates were high after four-weeks of MCT (n = 38) or TAU (n = 39). Clients randomized into the MCT condition rated the program favourably and showed significant improvements in cognitive insight (i.e., increased self-reflectiveness), relative to TAU controls, who exhibited decreases in cognitive insight at follow-up. These findings suggest that the MCT program is not only subjectively efficacious in Chinese samples, but also improves metacognitive awareness of the processes underlying delusional symptoms.

Synthesis, growth and characterization of new borate-mixed crystals of type (NH4)1-xKxB5O8.

New borate-mixed crystals of type (NH4)1-x KxB5O8 were grown from aqueous solution by slow solvent evaporation method. The mixed crystals were confirmed by atomic absorption studies (AAS) and characterized by X-ray diffractometry (XRD), Fourier transform infrared (FT-IR), Fourier transform Raman (FT-Raman), optical absorption and solubility studies. The second harmonic generation efficiencies of the parent and mixed crystals were studied and compared with that of KDP.

Management of chronic obstructive pulmonary disease associated with chronic bronchitis with inhaled fluticasone propionate/salmeterol (ADVAIR DISKUS) 250/50: results of a patient experience trial.

CONTEXT: Chronic obstructive pulmonary disease (COPD) is recognized as a major healthcare problem in the United States and around the world. OBJECTIVE: This survey regarding initial experience in patients with COPD collected feedback about newly initiated therapy with fluticasone propionate/salmeterol (FSC; ADVAIR DISKUS). DESIGN: Three telephone surveys were conducted; Survey 1 prior to initiating therapy with FSC 250/50, and Surveys 2 and 3 at 2 weeks and 30 days after initiating therapy with FSC 250/50, respectively. SETTING: One thousand primary care physicians recruited outpatients into the trial. PATIENTS: Patients were either newly diagnosed with COPD associated with chronic bronchitis or were still experiencing breathing difficulties on an anticholinergic medication. INTERVENTIONS: Patients initiated FSC 250/50 and received a 1-month supply of FSC 250/50 with an albuterol inhaler for rescue use. MAIN OUTCOME MEASURES: Outcome measures were patient perceptions of satisfaction, compliance, and convenience and changes in breathing on 1 (negative) to 9 (positive) point scales. RESULTS: Five hundred sixteen patients completed all 3 surveys. The mean age was 61 years, 63% were female, and 62% had been diagnosed with COPD associated with chronic bronchitis for 3 years or less (Table 1). CONCLUSION: Patients reported high satisfaction, compliance, and convenience with FSC 250/50 within 2 weeks of initiating therapy, all maintained over the trial period. Additionally, patients had positive changes in breathing, including improvements in the ability to breathe upon awakening in the morning.

The efficacy and safety of inhaled fluticasone propionate/salmeterol and ipratropium/albuterol for the treatment of chronic obstructive pulmonary disease: an eight-week, multicenter, randomized, double-blind, double-dummy, parallel-group study.

BACKGROUND: The pathology of chronic obstructive pulmonary disease (COPD) includes both obstructive and inflammatory components. OBJECTIVE: The aim of this study was to confirm the findings of a previous study that compared the efficacy of a combination of 2 short-acting bronchodilators with the use of an inhaled corticosteroid and a long-acting beta-agonist in the treatment of COPD. METHODS: We conducted an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group study of subjects with moderate to severe COPD to compare fluticasone propionate/salmeterol 250/50 microg BID (FSC) with ipratropium/albuterol 36/206 microg QID (IB/ALB). The primary efficacy measure was morning preadministration forced expiratory volume in 1 second (FEV(1)). Secondary measures were morning peak expiratory flow (PEF), 6-hour FEV(1) AUC, percentage of symptom-free nights, Transition Dyspnea Index (TDI) score, and overall daytime symptom score. Additional measures included sleep symptoms, supplemental albuterol use, and nighttime awakenings due to respiratory symptoms. Safety evaluations were based on clinical adverse events and COPD exacerbations. RESULTS: Baseline characteristics were similar between the FSC (n = 180) and IB/ALB (n = 181) groups, including mean age (63.7 and 65.4 years, respectively), mean body weight (81 and 79 kg, respectively), screening pulmonary function (mean [SD], 43.7% [14.2%] and 41.6% [13.4%] of predicted FEV(1)), race (82% and 91% white), and sex (64% and 62% male). FSC resulted in greater improvements in morning preadministration FEV(1), morning PEF, and 6-hour FEV(1) AUC (all, P < 0.001), TDI score (P = 0.026), overall daytime symptom score (P = 0.024), percentage of symptom-free nights (P = 0.010), nighttime awakenings due to respiratory symptoms (P = 0.002), sleep symptom score (P = 0.003), and percentage of days and nights without rescue albuterol use compared with IB/ALB (P = 0.021 and P < 0.001, respectively). Compared with day 1, the FEV(1) AUC at week 8 increased by 0.38 L-h with FSC and decreased by 0.18 L-h with IB/ALB (P < 0.001 between groups). The type and incidence of adverse events were similar between the 2 groups. One or more adverse event was reported for 81 (45%) and 85 (47%) subjects in the FSC and IB/ALB groups, respectively. CONCLUSION: In this 8-week study, subjects with moderate to severe COPD experienced greater improvements in lung function and symptom measures with FSC than with IB/ALB.

A dileucine motif targets E-cadherin to the basolateral cell surface in Madin-Darby canine kidney and LLC-PK1 epithelial cells.

E-cadherin is a major adherens junction protein of epithelial cells, with a central role in cell-cell adhesion and cell polarity. Newly synthesized E-cadherin is targeted to the basolateral cell surface. We analyzed targeting information in the cytoplasmic tail of E-cadherin by utilizing chimeras of E-cadherin fused to the ectodomain of the interleukin-2alpha (IL-2alpha) receptor expressed in Madin-Darby canine kidney and LLC-PK(1) epithelial cells. Chimeras containing the full-length or membrane-proximal half of the E-cadherin cytoplasmic tail were correctly targeted to the basolateral domain. Sequence analysis of the membrane-proximal tail region revealed the presence of a highly conserved dileucine motif, which was analyzed as a putative targeting signal by mutagenesis. Elimination of this motif resulted in the loss of Tac/E-cadherin basolateral localization, pinpointing this dileucine signal as being both necessary and sufficient for basolateral targeting of E-cadherin. Truncation mutants unable to bind beta-catenin were correctly targeted, showing, contrary to current understanding, that beta-catenin is not required for basolateral trafficking. Our results also provide evidence that dileucine-mediated targeting is maintained in LLC-PK(1) cells despite the altered polarity of basolateral proteins with tyrosine-based signals in this cell line. These results provide the first direct insights into how E-cadherin is targeted to the basolateral membrane.

Interleukin-2-induced splenic enlargement.

BACKGROUND: Splenomegaly in patients with cancer raises the suspicion of tumor involvement. Splenic enlargement in the absence of splenic metastases, however, has been reported in patients treated with interleukin-2 (IL-2) immunotherapy. This study characterizes the change in spleen size that occurred in 42 patients treated with IL-2 between 1989 and 1993 for nonhematologic malignancies. METHODS: Computed tomography (CT) scans before and during immunotherapy were available for review on all 42 patients and after immunotherapy on 16 of these patients. The splenic index was measured for each CT by a single reader blinded to the time course of IL-2 therapy. RESULTS: Mean splenic index increased 64.1% from 646 cm3 (standard deviation [SD], 387) pre-IL-2 to 1059 cm3 (SD, 534) during therapy with IL-2 (P < 0.0001). The splenic index remained elevated at 1112 cm3 (SD, 633) after completion of IL-2 therapy. CONCLUSIONS: Splenomegaly, temporally associated with IL-2 therapy for nonhematologic malignancies, is likely to represent a sequela of therapy and not tumor progression.

Respiratory blur in 3D coronary MR imaging.

3D MR imaging of coronary arteries has the potential to provide both high resolution and high signal-to-noise ratio, but it is very susceptible to respiratory artifacts, especially respiratory blurring. Resolution loss caused by respiratory blurring in 3D coronary imaging is analyzed theoretically and verified experimentally. Under normal respiration, the width for any Gaussian point spread function is increased to a new value that is at least several millimeters (about 3-4 mm). In vivo studies were performed to compare respiratory pseudo-gated 3D acquisition with breath-hold 2D acquisition. On average, the overall quality of a pseudo-gated 3D image is worse than that of the corresponding breath-hold 2D image (P = 0.005). In most cases, respiratory blur caused coronary arteries in pseudo-gated 3D data to have lower resolution than in breath-hold 2D data.

Use of a neural network and a multiple regression model to predict histologic grade of astrocytoma from MRI appearances.

Several MRI features of supratentorial astrocytomas are associated with high histologic grade by statistically significant p values. We sought to apply this information prospectively to a group of astrocytomas in the prediction of tumor grade. We used 10 MRI features of fibrillary astrocytomas from 52 patient studies to develop neural network and multiple linear regression models for practical use in predicting tumor grade. The models were tested prospectively on MR images from 29 patients studies. The performance of the models was compared against that of a radiologist. Neural network accuracy was 61% in distinguishing between low and high grade tumors. Multiple linear regression achieved an accuracy of 59%. Assessment of the images by a radiologist yielded 57% accuracy. We conclude that while certain MRI parameters may be statistically related to astrocytoma histologic grade, neural network and linear regression models cannot reliably use them to predict tumor grade.

Coronary MRI with a respiratory feedback monitor: the 2D imaging case.

The inability to return the heart to the same position for all breath-holds during 2D coronary MR imaging can result in imaging different locations than desired. This can lead to problems such as (i) missing a whole vessel, or a part of it, (ii) misaligning segments of vessels imaged in different breath-holds, and (iii) degrading image quality when a single slice is acquired in multiple breath-holds. To reduce inconsistencies in the breath-hold level, we designed a respiratory feedback monitor (RFM) that uses a bellows to monitor the circumference of the subject's chest. When the circumference of the subject's chest is within preset limits, an audio signal alerts subjects to hold their breath at that position. Use of the RFM significantly reduces the problems caused by inconsistent breath-holds and the number of breath-holds for an examination in 2D coronary MR imaging.

Discontinuous genetic variation among mesophilic Naegleria isolates: further evidence that N. gruberi is not a single species.

Naegleria isolates which are currently placed in the type species N. gruberi display great genetic, physiological and morphological heterogeneity. There are two possible interpretations of the nature of this species--that N. gruberi is a species complex or that it is a single continuously variable species. To distinguish between these alternatives, allelic states were determined for 33 loci in 74 new isolates selected to represent wide geographic sources and diverse temperature limits for growth. The results were compared with data for culture collection strains of N. gruberi and other species in the genus. The isolates formed a discontinuous series of clusters, separated by genetic distances similar to those separating the better-characterised taxa N. fowleri, N. lovaniensis, N. jadini, N. australiensis australiensis and N. australiensis italica. Culture collection strains assigned to N. gruberi fell into six distinct clusters, while other clusters were not represented by reference strains. The data are most consistent with the interpretation that N. gruberi is a group of several distinct species, each equivalent to the recently described species in the genus. Naegleria andersoni andersoni and N. andersoni jamiesoni also formed two distinct clusters, equivalent to species. Characteristics temperature limits for growth show that the mesophilic species are ecological as well as genetic entities.

Recursive RF excitation.

We have investigated the properties of a recursive process in which the output signal from a given RF excitation pulse may be used as the input (excitation) pulse of a subsequent iteration. This recursive excitation technique increases contrast and improves feature segmentation for the purpose of motion tracking.