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There has been recent interest in understanding the role that sleep disturbance plays in patients at Clinical High Risk for psychosis (CHR). We assessed sleep disturbance in 194 CHR patients and 66 healthy control subjects and their relationship to symptoms (positive, negative and general functioning). Patients experienced significantly more sleep disturbance than healthy control subjects and their sleep disturbance was related to greater positive and negative symptoms and worse overall functioning. Targeting sleep disturbance in CHR individuals may provide alternative means of treating the CHR syndrome., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Importance: Blood transfusion can be a lifesaving treatment for the surgical patient, yet transfusion-related immunomodulation may underlie the association of allogeneic transfusion with increased perioperative morbidity and possibly poorer long-term oncologic outcomes., Objective: To evaluate trends in transfusion rates for major abdominal oncologic resections to assess changes in recent clinical practice (given the accumulating evidence of the deleterious effects of blood transfusion)., Design, Setting, and Participants: Retrospective review of a population-based registry of all hospitals participating in the American College of Surgeons National Surgical Quality Improvement Project (2005-2013 Participant Use Data Files), which was queried for patients who underwent major resection of a pancreatic, hepatic, or gastric malignant tumor. Data analysis was performed from July to August 2015., Main Outcome and Measures: The primary outcome was the transfusion of any quantity of packed red blood cells. Transfusion rates were calculated for the perioperative period, which was defined as the time from the start of surgery to 72 hours after surgery. Secondary outcomes included wound infection, myocardial infarction, and renal insufficiency, and the rates of these complications were calculated as well. Trend analysis was performed for each year of data to evaluate for changes over the study period., Results: A total of 19 680 patients (median age, 65.0 years [interquartile range, 57.0-73.0 years]) were identified, of whom 5900 (30.0%) received a blood transfusion (of 13 657 patients who underwent a pancreatic resection, 4074 required transfusion [29.8%]; of 1605 patients who underwent a gastric resection, 378 required transfusion [23.6%]; and of 4418 patients who underwent a hepatic resection, 1448 required transfusion [32.8%]). There was a significant trend toward decreasing rates of transfusion during the study period (z = -7.89, P < .001), which corresponded to an absolute 6.1% decrease in the rate of transfusion of packed red blood cells from 2005 to 2013 (ie, from 32.8% to 26.7%). There was no significant change in the rates of postoperative wound infection or renal insufficiency during this time period, but there was an increased rate of perioperative myocardial infarction during the study period (0.33% absolute increase; z = 3.15, P = .002)., Conclusions and Relevance: Over 9 years of contemporary practice, a trend of less perioperative blood transfusions for oncologic abdominal surgery was observed. Further studies are needed to assess whether these trends reflect changes in operative techniques, hospital cohorts, or transfusion thresholds.

Aim: Social cognition impairment is a hallmark of schizophrenia and contains multiple domains. The domain of social inference has been relatively understudied in schizophrenia and its risk states., Methods: Social inference was assessed in 60 clinical high-risk (CHR) patients and 28 healthy control subjects, using the video social inference task. We hypothesized a deficit in social inference in CHR participants and examined predictive value for psychosis transition., Results: Social inference was positively associated with increasing age. Social inference did not differ significantly between CHR patients and controls, or predict transition to psychosis., Conclusions: Few studies have examined social inference of individuals at clinical high risk for psychosis, and findings have been inconclusive. Additional studies using a variety of measures of social inference in CHR participants are recommended., (© 2014 Wiley Publishing Asia Pty Ltd.)

Background and Objectives: When performed at select centers, minimally invasive gastrectomy (MIG) for gastric adenocarcinoma is associated with reduced perioperative morbidity, and similar oncologic outcomes as compared to open gastrectomy (OG). Utilization of, and outcomes associated with, MIG in the United States have not been characterized., Methods: The National Cancer Database (2010-2011) was queried for AJCC pStage IB-IIIC patients who underwent curative-intent OG (n = 2,303) or MIG (n = 331). Multivariable models identified factors associated with MIG utilization, R0 resection rates, and adequate lymph node staging (LNS)., Results: MIG was more frequently utilized for T1/T2 (P < 0.001), N0 (P = 0.022), and stage IB (P = 0.001) tumors. MIG was associated with shorter hospital stay (P < 0.001), equivalent lymph node examination (P = 0.337) and superior rates of R0 resection (P = 0.011) compared with OG. In patients undergoing MIG, R0 resection was associated with performance of near-total/total gastrectomy (OR 3.90, 95%CI 1.10-13.9) and tumors < 5 cm (OR 2.78, 95%CI 1.07-7.26). Adequate LNS was associated with surgery at academic (OR 1.99, 95%CI 1.19-3.32) or high-volume facilities (OR 2.97, 95%CI 1.59-5.54), tumor size ≥ 5 cm (OR 1.85, 95%CI 1.10-3.11), and node positivity (OR 1.75, 95%CI 1.04-2.93)., Conclusions: MIG is selectively utilized in cases with favorable tumor characteristics. In such cases, short-term oncologic outcomes are equivalent to those achieved with OG. Worse oncologic outcomes in specific subgroups underscore opportunities for quality improvement., (© 2015 Wiley Periodicals, Inc.)

Background: The majority of individuals with schizophrenia and other psychotic illnesses have had suicidal ideation at some point during the illness. However, little is known about the variation in level and intensity of suicidal ideation and symptoms in the attenuated stage of psychotic illness. Our aims were to assess prevalence of suicidal ideation in this at risk group, and to examine the severity and intensity of suicidal ideation, and their relation to symptoms., Methods: Suicidal ideation was assessed in 42 clinical high-risk participants using the Columbia Suicide Severity Rating Scale (C-SSRS). We hypothesized that prevalence rates would be similar to what was found in previous studies, and individuals with suicidal ideation would have higher positive and negative symptoms, with poorer functioning. We assessed levels of severity and intensity of suicidal ideation related to these symptoms, and examined how depressive symptoms affected these relationships., Results: Nearly half (42.9%) of participants reported having current suicidal ideation. We found no relationship to positive symptoms. However, severity and intensity of suicidal ideation were found to be related to negative symptoms and level of functioning. When controlling for depressive symptoms during exploratory analysis, this relationship still emerged., Conclusions: This study adds to the literature demonstrating the complex nature of suicidal ideation in psychotic illness. The C-SSRS has shown to be helpful in determining relationships between severity and intensity in suicidal ideation in relation to specific symptoms in a research setting., (Published by Elsevier B.V.)

Literature suggests that social maladjustment is predictive of psychosis. We assessed 70 clinical high risk (CHR) patients for social maladjustment. There were no significant differences between patients with a positive or negative family history, suggesting that the relationship between social maladjustment and psychosis found in the recent literature may not translate to a relationship between social maladjustment and family history of psychosis in a CHR population., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Bacterial pneumonia remains a significant burden worldwide. Although an inflammatory response in the lung is required to fight the causative agent, persistent tissue-resident neutrophils in non-resolving pneumonia can induce collateral tissue damage and precipitate acute lung injury. However, little is known about mechanisms orchestrated in the lung tissue that remove apoptotic neutrophils to restore tissue homeostasis. In mice infected with Klebsiella pneumoniae, a bacterium commonly associated with hospital-acquired pneumonia, we show that interleukin (IL)-10 is essential for resolution of lung inflammation and recovery of mice after infection. Although IL-10(-/-) mice cleared bacteria, they displayed increased morbidity with progressive weight loss and persistent lung inflammation in the later phase after infection. A source of tissue IL-10 was found to be resident CD11b(+)Gr1(int)F4/80(+) cells resembling myeloid-derived suppressor cells (MDSCs) that appeared with a delayed kinetics after infection. These cells efficiently efferocytosed apoptotic neutrophils, which was aided by IL-10. The lung neutrophil burden was attenuated in infected signal transducer and activator of transcription 1 (STAT1)(-/-) mice with concomitant increase in the frequency of the MDSC-like cells and lung IL-10 levels. Thus, inhibiting STAT1 in combination with antibiotics may be a novel therapeutic strategy to address inefficient resolution of bacterial pneumonia.

Recently, Nicolaou and Baran independently synthesized optically active 4-substituted 2-cyclohexenones via an efficient LiOH-mediated intramolecular aldol condensation. Thus far, application of their cyclization approach has been limited to ketoaldehydes where the R-group is branched. It is demonstrated that the LiOH-mediated cyclization, when applied to substrates containing unbranched R-groups, results in significant erosion of optical purity. A mechanistic justification is provided, and a set of neutral, organocatalyzed conditions is identified that enables cyclization with little loss in optical purity.

Myeloid-derived suppressor cells (MDSCs) have been investigated largely in the context of tumor progression. In contrast to the negative connotation of MDSCs in cancer immunity, our laboratory has recently reported on the development and role of pulmonary MDSC-like cells (CD11b(+)Gr1(int)F4/80(+)) in the regulation of allergic airway inflammation. These regulatory cells were expanded in a TLR4/MyD88-dependent manner and were both phenotypically and morphologically similar to those described in the tumor microenvironment. Although bacterial lipopolysaccharide (LPS) was initially described as an adjuvant in the development of allergic inflammation, subsequent studies showed that this is true only at relatively low doses of LPS. A high dose of LPS was shown to actually suppress eosinophilic airway inflammation. In our efforts to understand the mechanism underlying LPS-mediated suppression of allergic airway disease, we recently showed that LPS induces MDSC-like cells in the lung tissue in a dose-dependent manner, with increased accumulation of the cells at high doses of LPS. In contrast to lung dendritic cells (DCs), the MDSC-like cells did not traffic to the lung-draining lymph nodes, allowing them to act in a dominant fashion over DCs in the regulation of Th2 responses. The MDSC-like cells were found to blunt the ability of the lung DCs to upregulate GATA-3 or to promote STAT5 activation in primed Th2 cells, both transcription factors having critical roles in Th2 effector function. Thus, a complete understanding of the generation and regulation of the lung MDSCs would provide novel options for therapeutic interventions.

In humans, the bacterial product lipopolysaccharide (LPS) has been associated with protection from allergic diseases such us asthma. However, in mouse models of allergic asthma, differential effects of LPS have been noted based on the dose. A low dose of LPS promotes Th2 responses and allergic disease but a high dose has been associated with suppression of allergic airway inflammation. Our recent work has described the ability of LPS to increase the frequency of CD11b+Gr1(int)F4/80+(abbreviated as Gr1(int) cells) cells in the lung tissue of mice in a dose-dependent fashion that is dependent on TLR4 and the TLR adaptor protein, MyD88. Both phenotypically and morphologically, the cells were found to have similarities with mycloid-derived suppressor cells. Adoptive transfer of LPS-induced Gr1(int) cells suppressed allergen-induced airway inflammation suggesting regulatory functions of the cells in allergic asthma. Although the Gr1(int) cells are detectable in the lung tissue of LPS-treated mice, they are barely detectable in the lung-draining lymph nodes (Lns) or in the airway lumen. This causes selective enrichment of these cells over dendritic cells (Dcs) in the tissue which upon LPS stimulation migrate to lung-draining LNs. The Gr1(int) cells were found to blunt the ability of the lung DCs to upregulate GATA-3 or to promote STAT5 activation in primed Th2 cells, both transcription factors having critical roles in TH2 effector function. Thus, a complete understanding of the generation and regulation of the Gr1(int) cells would provide new avenues to either promote or delete these cells for disease-specific immunoregulation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In humans, environmental exposure to a high dose of lipopolysaccharide (LPS) protects from allergic asthma, the immunological underpinnings of which are not well understood. In mice, exposure to a high LPS dose blunted house dust mite-induced airway eosinophilia and T-helper 2 (Th2) cytokine production. Although adoptively transferred Th2 cells induced allergic airway inflammation in control mice, they were unable to do so in LPS-exposed mice. LPS promoted the development of a CD11b(+)Gr1(int)F4/80(+) lung-resident cell resembling myeloid-derived suppressor cells in a Toll-like receptor 4 and myeloid differentiation factor 88 (MyD88)-dependent manner that suppressed lung dendritic cell (DC)-mediated reactivation of primed Th2 cells. LPS effects switched from suppressive to stimulatory in MyD88(-/-) mice. Suppression of Th2 effector function was reversed by anti-interleukin-10 (IL-10) or inhibition of arginase 1. Lineage(neg) bone marrow progenitor cells could be induced by LPS to develop into CD11b(+)Gr1(int)F4/80(+)cells both in vivo and in vitro that when adoptively transferred suppressed allergen-induced airway inflammation in recipient mice. These data suggest that CD11b(+)Gr1(int)F4/80(+) cells contribute to the protective effects of LPS in allergic asthma by tempering Th2 effector function in the tissue.

The rate of the proline-catalyzed alpha-aminoxylation of aldehydes is significantly increased in the presence of a bifunctional urea. Structure-activity relationship data indicate that both an amine and a urea are crucial for rate enhancement. The evidence presented herein suggests that this rate enhancement originates from the hydrogen bonding interaction between the bifunctional urea and an oxazolidinone intermediate to increase the rate of enamine formation. Proline derivatives that are incapable of forming oxazolidinones exhibit no rate enhancement in the presence of the bifunctional urea. The rate enhancement is general for a variety of aldehydes, and the faster reactions do not reduce yields or selectivities.

In this paper, we describe the development and application of a multistep one-pot reaction that is made possible by the site isolation of two otherwise incompatible catalysts. We prepared a microencapsulated amine catalyst by interfacial polymerization and used it in conjunction with a nickel-based catalyst for the transformation of an aldehyde to a Michael adduct via a nitroalkene intermediate. The amine-catalyzed conversion of an aldehyde to a nitroalkene was found to proceed through an imine rather than a nitroalcohol. Kinetic studies indicated that the reaction is first order in both the nickel catalyst and the shell of the encapsulated amine catalyst. Furthermore, we provide evidence against interaction between amine and nickel catalysts and present kinetic data that demonstrates that there is a rate enhancement of the Michael addition due to the urea groups on the surface of the microencapsulated catalyst. We applied our one-pot reaction to the development of a new synthetic route for pregabalin that proceeds with an overall yield of 74%.

We present a new microencapsulated catalyst and report its use in a tandem multicatalyst reaction. Using an encapsulation technique, we developed an active, site-isolated amine catalyst that is capable of catalyzing the addition of nitromethane to an aldehyde. When a second Lewis acid catalyst is added, the nitroalkene intermediate is trapped and converted to the corresponding Michael adduct. We show that if the amine catalyst is not encapsulated, the two catalysts cannot function together. Moreover, if the two reactions are performed in sequence rather than in tandem, the first reaction results in an undesired dinitro product and the desired Michael adduct is not formed.

A highly enriched sarcolemma preparation was isolated by differential centrifugation of a canine ventricular homogenate followed by centrifugation of a membrane fraction layered over 22% (w/v) sucrose. Ouabain binding, ouabain-sensitive potassium phosphatase activity and 5'-nucleotidase activity were enriched 19--27 fold over the homogenate whereas Ca2+-ATPase and succinate dehydrogenase activities were 0.75 and 0.36, respectively, of that for the homogenate. The isolation procedure was relatively rapid and yielded about 2.0 mg protein/100 g of ventricular muscle. The highest salt concentration used in the procedure was 0.6 M KCl and no detergents were employed. Initial characterization studies suggested that the sarcolemma-enriched fraction consists predominantly if not totally of freely permeable membrane vesicles and that the sarcolemma does not manifest a Ca2+-ATPase activity, at least within the limits of the assay procedures employed. This preparation was concluded to be about 1.5- to 4-fold more highly enriched with sarcolemmal markers than preparations obtained by previously published procedures. Accordingly, the preparation provides an improved basis for the probe of calcium movements that occur across the sarcolemma in association with the excitation-contraction-relaxation sequence of the mammalian myocardial cell.