Miracle-dz/UniFAR-FTUs huggingface dataset:
Meta-analysis of Cerebrospinal Fluid Cytokine and Tryptophan Catabolite Alterations in Psychiatric Patients: Comparisons Between Schizophrenia, Bipolar Disorder, and Depression

INTRODUCTION Schizophrenia, bipolar disorder, and major depressive disorder (MDD) have all been associated with immune system dysfunction, including aberrant cerebrospinal fluid (CSF) levels of cytokines and tryptophan catabolites; however, the pattern of alterations has not been compared across disorders. We performed a meta-analysis of CSF cytokine and tryptophan catabolites in patients with these major psychiatric disorders. METHODS Articles were identified by searching Pub Med, PsycInfo, and Web of Science, and the reference lists of these studies. RESULTS Twenty-eight studies met the inclusion criteria (16 schizophrenia, 4 bipolar disorder, and 9 MDD). CSF levels of IL-1β and kynurenic acid were significantly increased in patients with schizophrenia and bipolar disorder compared to healthy controls (P < .001). CSF levels of IL-6 and IL-8 were significantly increased in patients with schizophrenia and MDD compared to healthy controls (P ≤ .013). DISCUSSION There is preliminary evidence for similarities in the pattern of CSF cytokine and tryptophan catabolite alterations across major psychiatric disorders, although findings must be interpreted with caution in light of small numbers of studies/subjects. Many CSF alterations are also concordant with those in the peripheral blood, particularly for schizophrenia. Findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders.
Heterozygous Mutation in CYP2C19 Significantly Increases the Concentration/Dose Ratio of Racemic Citalopram and Escitalopram (S-citalopram)

There is limited documentation of the importance of heterozygous cytochrome P450 (CYP) mutations on drug exposure. This study was designed to evaluate the influence of heterozygous mutations in CYP2C19 on the serum concentration of racemic citalopram and escitalopram (S-citalopram). Eighty-three samples from subjects with determined CYP2C19 and CYP2D6 genotype receiving racemic citalopram or S-citalopram as part of their clinical treatment were collected from a routine therapeutic drug monitoring database. Concentration/dose (C/D) ratios, parent drug/metabolite ratios, and serum concentrations in CYP2C19 homozygous extensive metabolizers (EMs) and heterozygous extensive metabolizers (HEMs) were compared. The median C/D ratio was significantly higher in the HEM group compared with the EM group, both for racemic citalopram (8.0 vs. 4.9, P < 0.01) and S-citalopram (5.3 vs. 2.6, P < 0.01). The median parent drug/metabolite ratio was significantly higher in the HEM group compared with the EM group, both for racemic citalopram (2.9 vs. 1.6, P < 0.01) and for S-citalopram (2.4 vs. 1.2, P < 0.01). A higher median non-dose-corrected serum concentration also was observed in HEMs compared with EMs both for S-citalopram (P < 0.01) and racemic citalopram (P = 0.066). This study shows that the metabolism of racemic citalopram and S-citalopram is significantly impaired in CYP2C19 HEMs. Higher absolute serum concentrations indicate that this is not compensated for by dose reductions in clinical practice.
Utilization of Donors Who have Suffered Cardiopulmonary Arrest and Resuscitation in Intestinal Transplantation

Background. Cardiopulmonary resuscitation (CPR) of a person destined to become an organ donor has been associated with overall poor donor quality, especially for the intestinal donor, as splanchnic vasoconstriction that is intended to preserve coronary and cerebral blood flow may result in clinically relevant intestinal ischemia. Outcomes of recipients who receive intestine grafts that have suffered CPR are unknown. We sought to analyze our clinical experience in using intestinal grafts from donors who suffered cardiopulmonary arrest and resuscitation and to evaluate the outcome of recipients of organs coming from resuscitated donors when compared with recipients of nonresuscitated donors. Methods. We retrospectively analyzed the donor and recipient charts of all of our intestinal transplants with regard to the performance of donor CPR. Results. Sixty-seven intestinal transplants were performed in 65 patients from November 2003 to December 2007. Twelve donors (18%) were identified as having suffered cardiac arrest and subsequent CPR. Mean duration of CPR was 19.3±12.7 min. Terminal laboratory profiles of CPR donors and non-CPR donors were similar. Of the 12 resuscitated grafts, two were used for multivisceral, one for a modified multivisceral, seven for liver–intestine, and two for isolated intestinal transplant. There were no significant differences in outcome parameters such as operative time, blood use, ventilation days, length of stay, time to enteral independence, rejection, enteric bacteremia, and survival between the 12 resuscitated grafts and the 55 nonresuscitated grafts. Conclusion. A donor history of cardiac arrest should not automatically exclude the use of the intestine graft for transplantation.
Changes in blood pressure and cardiac output during maximal isokinetic exercise.

This study was undertaken to determine the blood pressure (BP) and cardiac output (Qc) responses to maximal isokinetic exercise. The subjects (n = 5) performed unilateral knee extension/flexion exercise (knee exercise) and unilateral elbow extension/flexion exercise (elbow exercise) at 0.52, 1.57, and 2.62 rads.sec-1. The BP was monitored using a cannula placed in the radial artery. Heart rate (HR), stroke volume (SV), and Qc were measured by impedance cardiography. In response to isokinetic exercise, HR and Qc increased significantly (p less than .01), while the SV did not. The BP response was characterized by significant increases in systolic, diastolic, and mean arterial pressure (MAP) (p less than .01). The Qc and MAP, responses were not influenced by the exercise velocity. The adjustments in HR, MAP, and rate pressure product (RPP) to the elbow exercise were qualitatively similar to those seen during the knee exercise, but the absolute values achieved were smaller (p less than .05). Compared with maximal dynamic exercise, the HR and SV responses to the knee exercises were lower. The MAP response to isokinetic exercise equaled the highest value achieved during dynamic exercise. Findings from the present study suggest that the cardiovascular stress (the increase in HR, MAP, and RPP) associated with isokinetic exercise is independent of the velocity of movement and is proportional to the active muscle mass.
Urinary lipid and protein oxidation products upon halothane, isoflurane, or sevoflurane anesthesia in humans: potential biomarkers for a subclinical nephrotoxicity

Objective: To investigate whether lipid and protein oxidation products are elevated and correlated with routine clinical markers of hepatic and renal function in patients anesthetized with halothane, isoflurane, or sevoflurane. Methods: Urine and blood samples were collected from patient groups. Excretion of aldehydes, acetone, and o,o’-dityrosine was measured before and after anesthesia. Blood samples were analysed for clinical markers. Results: Urinary concentrations of aldehydes, acetone, o,o’-dityrosine and glucose were significantly increased after anesthesia in halothane and sevoflurane groups earlier than clinical markers. Significant correlations were found in sevoflurane group. Conclusion: Lipid and protein oxidation contributes to subclinical sevoflurane nephrotoxicity. Oxidation products may serve as early biomarkers.
Investigating latitudinal clines for life history and stress resistance traits in Drosophila simulans from eastern Australia

Latitudinal clines have been demonstrated for many quantitative traits in Drosophila and are assumed to be due to climatic selection. However, clinal studies are often performed in species of Drosophila that contain common cosmopolitan inversion polymorphisms that also show clinal patterns. These inversion polymorphisms may be responsible for much of the observed clinal variation. Here, we consider latitudinal clines for quantitative traits in Drosophila simulans from eastern Australia. Drosophila simulans does not contain cosmopolitan inversion polymorphisms, so allows the study of clinal selection on quantitative traits that are not confounded by associations with inversions. Body size showed a strong linear cline for both females and males. Starvation resistance exhibited a weak linear cline in females, whereas chill‐coma recovery exhibited a significant nonlinear cline in females only. No clinal pattern was evident for development time, male chill‐coma recovery, desiccation or heat resistance. We discuss these results with reference to the role inversion polymorphisms play in generating clines in quantitative traits of Drosophila.
HHV‐6, HHV‐7 and HHV‐8 in Solid Organ Transplant Recipients

Epidemiology and risk factors Human herpesvirus 6 (HHV-6) and HHV-7 are lymphotropic b-herpesviruses that infect the majority of humans during the first few years of life. Primary HHV-6 and HHV-7 infections may be asymptomatic or manifest clinically as febrile illness associated with rash, diarrhea, respiratory symptoms, or seizures (1,2). HHV-6 exists as two variants; HHV6A and HHV-6B. The latter variant is responsible for the majority of documented primary infections in children (1) and reactivation events after transplantation (3). HHV-6 and HHV-7 infections result in lifelong latency in mononuclear cells, which eventually serve as reservoirs for endogenous viral reactivation or as potential vectors of transmission to susceptible individuals (4). In less than 1% of infected individuals, HHV-6 persistence occurs as a result of the integration of the virus into the host chromosome (5).
Introduction to Organizational Behaviour Ed. 3

Introduction to Organizational Behaviour, 3e provides a concise and engaging grounding in the core concepts and practical issues of Organizational Behaviour for students with little or no previous experience of business or management. The book adopts a micro-macro approach to OB, starting with the individual through to groups and teams and finishing with the organization. The authors? approach is balanced between a management and psychological perspective, and is pedagogically enhanced with up-to-date illustrative examples, case studies and assessment material. This edition has been thoroughly updated to reflect developments within the field. It includes a new chapter on organization environments - giving special attention to the topical concept of the `knowledge worker? , and dedicates increased coverage to sociological issues such as structure, strategy, power and subjectivity.
Environmental protection without loss of international competitiveness

We develop a two-country Cournot oligopoly model with product differentiation across countries and production-generated pollution. The abatement of pollution by the firms in response to emission taxes is endogenous, and the number of firms can be fixed or there may be free entry and exit of firms in both countries. We propose particular unilateral and multilateral piecemeal policy reforms of emission taxes and production subsidies such that domestic industries will not suffer any loss of international competitiveness (defined in terms of either market share or profits), emission levels will be lower, and welfare could be higher in both countries.
Emergence of penicillin-resistant Streptococcus pneumoniae in southern Ontario, 1993-94.

OBJECTIVE To determine the prevalence of resistance of Streptococcus pneumoniae to penicillin and other antimicrobial agents in metropolitan Toronto. DESIGN Consecutive pneumococcal isolates from different patients were obtained from two private community-based laboratories and from patients assessed in the emergency department of a tertiary-care teaching hospital in Toronto, Ontario between June and December 1993, and between March and October 1994. In vitro susceptibility testing was done by broth microdilution in accordance with National Committee for Clinical Laboratory Standards guidelines. RESULTS Twenty (7.3±3.1%) of 274 pneumococcal isolates were resistant to penicillin; six (30%) isolates had high-level resistance (minimal inhibitory concentration [mic] 2.0 μg/mL or greater); and 14 isolates had intermediate resistance (mic 0.1 to 1.0 μg/mL). Penicillin-resistant strains were also frequently resistant to tetracycline (55%), cotrimoxazole (50%), erythromycin (40%) and cefuroxime (35%). Resistant strains comprised several serotypes: 19F (six isolates), 9V (three), 23F (three), and one each of 6A, 6B, 14, and 19A; four isolates were nontypeable. CONCLUSIONS There has been a recent emergence of penicillin-resistant S pneumoniae in southern Ontario. National and regional surveillance is warranted to determine the extent of the problem elsewhere in Canada.
In vitro study on anti-inflammatory effects of epigallocatechin-3-gallate-loaded nano- and microscale particles

Purpose This study aimed to develop an anti-inflammation system consisting of epigallo-catechin-3-gallate (EGCG) encapsulated in poly(lactide-co-glycolic acid) (PLGA) particles to promote wound healing. Methods Nano- and microscale PLGA particles were fabricated using a water/oil/water emulsion solvent evaporation method. The optimal particle size was determined based on drug delivery efficiency and biocompatibility. The particles were loaded with EGCG. The anti-inflammatory effects of the particles were evaluated in an in vitro cell-based inflammation model. Results Nano- and microscale PLGA particles were produced. The microscale particles showed better biocompatibility than the nanoscale particles. In addition, the microscale particles released ~60% of the loaded drug, while the nanoscale particles released ~50%, within 48 hours. Thus, microscale particles were selected as the carriers. The optimal EGCG working concentration was determined based on the effects on cell viability and inflammation. A high EGCG dose (100 μM) resulted in poor cell viability; therefore, a lower dose (≤50 μM) was used. Moreover, 50 μM EGCG had a greater anti-inflammatory effect than 10 μM concentration on lipopolysaccharide-induced inflammation. Therefore, 50 μM EGCG was selected as the working dose. EGCG-loaded microparticles inhibited inflammation in human dermal fibroblasts. Interestingly, the inhibitory effects persisted after replacement of the drug-loaded particle suspension solution with fresh medium. Conclusion The EGCG-loaded microscale particles are biocompatible and exert a sustained anti-inflammatory effect.
Anticontractile activity of perivascular fat in obese mice and the effect of long-term treatment with melatonin

Aims: It has been demonstrated previously that inflammation in perivascular adipose tissue (PVAT) may be implicated in vascular dysfunction. The aim of this study was to investigate the functional responses of small mesenteric arteries in a hyperphagic animal model of obesity after chronic treatment with melatonin, an endogenous hormone with antioxidant and vasculoprotective properties. Methods and results: Ten obese mice (ob/ob) and 10 control lean mice (CLM) were treated with melatonin 100 mg/kg per day in the drinking water for 8 weeks. Mesenteric small resistance arteries were dissected and mounted on a wire myograph and a concentration-response to norepinephrine was evaluated in vessels with intact PVAT and after PVAT was removed and in the presence of iberiotoxin, a selective blocker of BKCA channels as well as under conditions of induced hypoxia in vitro. The presence of PVAT reduced the contractile response to norepinephrine in both ob/ob and CLM; however, the effect was significantly reduced in ob/ob. The anticontractile effect of PVAT completely disappeared with iberiotoxin preincubation. After melatonin treatment, inflammation was significantly ameliorated, and the contractile response in ob/ob and CLM was significantly reduced when PVAT was removed. Anticontractile effect of PVAT that is lost in obesity can be rescued using melatonin. A reduced expression of adiponectin and adiponectin receptor was observed in perivascular fat of ob/ob, whereas significant increase was observed in ob/ob treated with melatonin. Conclusion: Melatonin seems to exert a protective effect on arteries from both ob/ob and CLM, counteracting the adverse effect of hypoxia and iberiotoxin.
Lifetime risk of symptomatic knee osteoarthritis.

OBJECTIVE To estimate the lifetime risk of symptomatic knee osteoarthritis (OA), overall and stratified by sex, race, education, history of knee injury, and body mass index (BMI). METHODS The lifetime risk of symptomatic OA in at least 1 knee was estimated from logistic regression models with generalized estimating equations among 3,068 participants of the Johnston County Osteoarthritis Project, a longitudinal study of black and white women and men age >or=45 years living in rural North Carolina. Radiographic, sociodemographic, and symptomatic knee data measured at baseline (1990-1997) and first followup (1999-2003) were analyzed. RESULTS The lifetime risk of symptomatic knee OA was 44.7% (95% confidence interval [95% CI] 40.0-49.3%). Cohort members with history of a knee injury had a lifetime risk of 56.8% (95% CI 48.4-65.2%). Lifetime risk rose with increasing BMI, with a risk of 2 in 3 among those who were obese. CONCLUSION Nearly half of the adults in Johnston County will develop symptomatic knee OA by age 85 years, with lifetime risk highest among obese persons. These current high risks in Johnston County may suggest similar risks in the general US population, especially given the increase in 2 major risk factors for knee OA, aging, and obesity. This underscores the immediate need for greater use of clinical and public health interventions, especially those that address weight loss and self-management, to reduce the impact of having knee OA.
Enhancing Driver Car-Following Performance with a Distance and Acceleration Display

A car-following assisting system named the rear window notification display (RWND) was developed, with the aim of improving a driver's manual car-following performance. The RWND presented lead-car acceleration and time headway (THW) (i.e., intervehicle distance divided by the speed of the following car) on the rear window of a lead car, which was driven automatically. A simulator-based experiment with 22 participants showed that the RWND reduced both the mean and standard deviation of THW but did not increase the occurrence of potentially unsafe headways of less than 1 s. The parameter estimation of a common linear car-following model showed that drivers accomplished the performance improvements by adopting higher control gains with respect to intervehicle distance, relative speed, and acceleration. A postexperiment questionnaire revealed that the display was generally not regarded as a distraction nor did participants think that it provided too much information, with means of 4.0 and 2.9, respectively, on a scale from one (completely disagree) to ten (completely agree). The results of this study suggest that the RWND can be used along with Cooperative Adaptive Cruise Control to increase traffic flow without degrading safety.
Comparative effects of two physical activity programs on measured and perceived physical functioning and other health-related quality of life outcomes in older adults.

BACKGROUND Although inactivity is an important contributor to impaired functioning and disability with age, little is known concerning how improvements in physical functioning and well-being in older adults vary with the type of physical activity undertaken. METHODS One hundred three adults age 65 years and older, recruited via population-based methods, were randomized to 12 months of community-based, moderate-intensity endurance and strengthening exercises (Fit & Firm) or stretching and flexibility exercises (Stretch & Flex). A combination of class- and home-based exercise formats was used. Measured and self-rated physical performance along with perceived functioning and well-being were assessed pre- and postintervention. RESULTS Fit & Firm subjects showed greater 12-month improvements in both measured and self-rated endurance and strength compared to Stretch & Flex subjects. Stretch & Flex subjects reported greater improvements in bodily pain, and Stretch & Flex men evidenced greater improvements in flexibility relative to Fit & Firm subjects. Although overall exercise adherence was high in both exercise conditions (approximately 80%), subjects in both conditions showed better adherence to the home- versus class-based portions of their exercise prescriptions. CONCLUSIONS Community-based programs focusing on moderate-intensity endurance and strengthening exercises or flexibility exercises can be delivered through a combination of formats that result in improvement in important functional and well-being outcomes. This represents one of the first studies to report significant improvements in an important quality of life outcome-bodily pain-with a regular regimen of stretching and flexibility exercises in a community-based sample of older adults.
Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974

Significance Targeting the Wnt pathway in cancer is an attractive therapeutic approach. However, success has been limited because of the lack of effective therapeutic agents and the lack of biomarkers to define the patient population that would benefit from such a therapy. Herein, we report the discovery of LGK974, a drug that targets Porcupine, a Wnt-specific acyltransferase. We show that LGK974 potently inhibits Wnt signaling, has strong efficacy in rodent tumor models, and is well-tolerated. We also show that head and neck cancer cell lines with loss-of-function mutations in the Notch signaling pathway have a high response rate to LGK974. Together, these findings provide a strategy and tools for targeting Wnt-driven cancer. Wnt signaling is one of the key oncogenic pathways in multiple cancers, and targeting this pathway is an attractive therapeutic approach. However, therapeutic success has been limited because of the lack of therapeutic agents for targets in the Wnt pathway and the lack of a defined patient population that would be sensitive to a Wnt inhibitor. We developed a screen for small molecules that block Wnt secretion. This effort led to the discovery of LGK974, a potent and specific small-molecule Porcupine (PORCN) inhibitor. PORCN is a membrane-bound O-acyltransferase that is required for and dedicated to palmitoylation of Wnt ligands, a necessary step in the processing of Wnt ligand secretion. We show that LGK974 potently inhibits Wnt signaling in vitro and in vivo, including reduction of the Wnt-dependent LRP6 phosphorylation and the expression of Wnt target genes, such as AXIN2. LGK974 is potent and efficacious in multiple tumor models at well-tolerated doses in vivo, including murine and rat mechanistic breast cancer models driven by MMTV–Wnt1 and a human head and neck squamous cell carcinoma model (HN30). We also show that head and neck cancer cell lines with loss-of-function mutations in the Notch signaling pathway have a high response rate to LGK974. Together, these findings provide both a strategy and tools for targeting Wnt-driven cancers through the inhibition of PORCN.
The External Finance Premium and the Macroeconomy: US post-WWII Evidence

This paper embeds the financial accelerator into a medium-scale DSGE model and estimates it using Bayesian methods. Incorporation of financial frictions enhances the model's description of the main macroeconomic aggregates. The financial accelerator accounts for approximately ten percent of monetary policy transmission. The model-consistent premium for external finance compares well to observable proxies of the premium, such as the high-yield spread. Fluctuations in the external finance premium are primarily driven by investment supply and monetary policy shocks. In terms of recession prediction, false signals of the premium can be given an economic interpretation