Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids

Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes. In this study, we sought to determine biological and clinical factors associated with treatment response, here indexed by functional improvement in a pre-post examination of a 12-week randomized controlled intervention in individuals at ultra-high risk (UHR) for psychosis. Participants received either long-chain omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of factors specifically relevant to each intervention, and to be able to contrast them, both treatment groups were investigated in parallel. Univariate linear regression analysis indicated that higher levels of erythrocyte membrane α-linolenic acid (ALA; the parent fatty acid of the ω-3 family) and more severe negative symptoms at baseline predicted subsequent functional improvement in the treatment group, whereas less severe positive symptoms and lower functioning at baseline were predictive in the placebo group. A multivariate machine learning analysis, known as Gaussian Process Classification (GPC), confirmed that baseline fatty acids predicted response to treatment in the ω-3 PUFA group with high levels of sensitivity, specificity and accuracy. In addition, GPC revealed that baseline fatty acids were predictive in the placebo group. In conclusion, our investigation indicates that UHR patients with higher levels of ALA may specifically benefit from ω-3 PUFA supplementation. In addition, multivariate machine learning analysis suggests that fatty acids could potentially be used to inform prognostic evaluations and treatment decisions at the level of the individual. Notably, multiple statistical analyses were conducted in a relatively small sample, limiting the conclusions that can be drawn from what we believe to be a first-of-its-kind study. Additional studies with larger samples are therefore needed to evaluate the generalizability of these findings

Genetic polymorphisms in glutathione-S-transferases are associated with anxiety and mood disorders in nicotine dependence

Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence

The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): study protocol for a randomised control trial.

The aim of the Youth Depression Alleviation-Combined Treatment (YoDA-C) study is to determine whether antidepressant medication should be started as a first-line treatment for youth depression delivered concurrently with psychotherapy. Doubts about the use of medication have been raised by meta-analyses in which the efficacy and safety of antidepressants in young people have been questioned, and subsequent treatment guidelines for youth depression have provided only qualified support

Mentoring at the University of Pennsylvania: Results of a Faculty Survey

BACKGROUND: Research suggests mentoring is related to career satisfaction and success. Most studies have focused on junior faculty. OBJECTIVE: To explore multiple aspects of mentoring at an academic medical center in relation to faculty rank, track, and gender. DESIGN: Cross-sectional mail survey in mid-2003. PARTICIPANTS: Faculty members, 1,432, at the University of Pennsylvania School of Medicine MEASUREMENTS: Self-administered survey developed from existing instruments and stakeholders. RESULTS: Response rate was 73% (n = 1,046). Most (92%) assistant and half (48%) of associate professors had a mentor. Assistant professors in the tenure track were most likely to have a mentor (98%). At both ranks, the faculty was given more types of advice than types of opportunities. Satisfaction with mentoring was correlated with the number of types of mentoring received (r = .48 and .53, P < .0001), job satisfaction (r = .44 and .31, P < .0001), meeting frequency (r = .53 and .61, P < .0001), and expectation of leaving the University within 5 years (Spearman r = −.19 and −.18, P < .0001), at the assistant and associate rank, respectively. Significant predictors of higher overall job satisfaction were associate rank [Odds ratio (OR) = 2.04, CI = 1.29–3.21], the 10-point mentoring satisfaction rating (OR = 1.27, CI = 1.17–1.35), and number of mentors (OR = 1.60, CI = 1.20–2.07). CONCLUSIONS: Having a mentor, or preferably, multiple mentors is strongly related to satisfaction with mentoring and overall job satisfaction. Surprisingly, few differences were related to gender. Mentoring of clinician–educators, research track faculty, and senior faculty, and the use of multiple mentors require specific attention of academic leadership and further study

Two-Particle-Self-Consistent Approach for the Hubbard Model

Even at weak to intermediate coupling, the Hubbard model poses a formidable challenge. In two dimensions in particular, standard methods such as the Random Phase Approximation are no longer valid since they predict a finite temperature antiferromagnetic phase transition prohibited by the Mermin-Wagner theorem. The Two-Particle-Self-Consistent (TPSC) approach satisfies that theorem as well as particle conservation, the Pauli principle, the local moment and local charge sum rules. The self-energy formula does not assume a Migdal theorem. There is consistency between one- and two-particle quantities. Internal accuracy checks allow one to test the limits of validity of TPSC. Here I present a pedagogical review of TPSC along with a short summary of existing results and two case studies: a) the opening of a pseudogap in two dimensions when the correlation length is larger than the thermal de Broglie wavelength, and b) the conditions for the appearance of d-wave superconductivity in the two-dimensional Hubbard model.Comment: Chapter in "Theoretical methods for Strongly Correlated Systems", Edited by A. Avella and F. Mancini, Springer Verlag, (2011) 55 pages. Misprint in Eq.(23) corrected (thanks D. Bergeron

Acute wound management: revisiting the approach to assessment, irrigation, and closure considerations

Abstract Background As millions of emergency department (ED) visits each year include wound care, emergency care providers must remain experts in acute wound management. The variety of acute wounds presenting to the ED challenge the physician to select the most appropriate management to facilitate healing. A complete wound history along with anatomic and specific medical considerations for each patient provides the basis of decision making for wound management. It is essential to apply an evidence‐based approach and consider each wound individually in order to create the optimal conditions for wound healing. Aims A comprehensive evidence‐based approach to acute wound management is an essential skill set for any emergency physician or acute care practitioner. This review provides an overview of current evidence and addresses frequent pitfalls. Methods A systematic review of the literature for acute wound management was performed. Results A structured MEDLINE search was performed regarding acute wound management including established wound care guidelines. The data obtained provided the framework for evidence‐based recommendations and current best practices for wound care. Conclusion Acute wound management varies based on the wound location and characteristics. No single approach can be applied to all wounds; however, a systematic approach to acute wound care integrated with current best practices provides the framework for exceptional wound management

Exogenous Glucose Administration Impairs Glucose Tolerance and Pancreatic Insulin Secretion during Acute Sepsis in Non-Diabetic Mice

Objectives:The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT). We next extended our findings using a cecal ligation and puncture (CLP) sepsis model administered early parenteral glucose support.Methods:Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg) in the presence of saline or glucose infusion (100 μL/hr), and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs.Measurements:And MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl) associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL) or sham mice receiving parenteral glucose (113 ± 3 mg/dL) all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml) was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml).Conclusions:The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin secretion, leading to the development of fulminant hyperglycemia. © 2013 Watanabe et al

Altered cardiac autonomic nervous function in depression

Background:Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia.Methods:Individuals (n&thinsp;=&thinsp;53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score &ge;20 and a Zung Self-Rating Depression Scale score&thinsp;&gt;&thinsp;53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals&thinsp;&gt;&thinsp;50 ms different from preceding interval (pNN50). Pearson&rsquo;s correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)).Results:The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P&lt;.05). The mean value of the LF in the depression group was higher than the in control group (P&lt;.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P&lt;.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P&lt;.05), particularly supraventricular arrhythmias.Conclusions:Our findings suggest that depression is accompanied by dysfunction of the cardiac autonomic nervous system, and further, that depression severity is linked to severity of this dysfunction. Individuals with depression appear to be susceptible to premature atrial and/or ventricular disease