Heme oxygenase-1 enhances renal mitochondrial transport carriers and cytochrome C oxidase activity in experimental diabetes

Up-regulation of heme oxygenase (HO-1) by either cobalt protoporphyrin (CoPP) or human gene transfer improves vascular and renal function by several mechanisms, including increases in antioxidant levels and decreases in reactive oxygen species (ROS) in vascular and renal tissue. The purpose of the present study was to determine the effect of HO-1 overexpression on mitochondrial transporters, cytochrome c oxidase, and anti-apoptotic proteins in diabetic rats (streptozotocin, (STZ)-induced type 1 diabetes). Renal mitochondrial carnitine, deoxynucleotide, and ADP/ATP carriers were significantly reduced in diabetic compared with nondiabetic rats (p<0.05). The citrate carrier was not significantly decreased in diabetic tissue. CoPP administration produced a robust increase in carnitine, citrate, deoxynucleotide, dicarboxylate, and ADP/ATP carriers and no significant change in oxoglutarate and aspartate/ glutamate carriers. The increase in mitochondrial carriers (MCs) was associated with a significant increase in cytochrome c oxidase activity. The administration of tin mesoporphyrin (SnMP), an inhibitor of HO-1 activity, prevented the restoration of MCs in diabetic rats. Human HO-1 cDNA transfer into diabetic rats increased both HO-1 protein and activity, and restored mitochondrial ADP/ ATP and deoxynucleotide carriers. The increase in HO-1 by CoPP administration was associated with a significant increase in the phosphorylation of AKT and levels of BcL-XL proteins. These observations in experimental diabetes suggest that the cytoprotective mechanism of HO-1 against oxidative stress involves an increase in the levels of MCs and anti-apoptotic proteins as well as in cytochrome c oxidase activity

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

&lt;p&gt;Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.&lt;/p&gt; &lt;p&gt;Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.&lt;/p&gt

A reduced integer programming model for the ferry scheduling problem

We present an integer programming model for the ferry scheduling problem, improving existing models in various ways. In particular, our model has reduced size in terms of the number of variables and constraints compared to existing models by a factor of approximately O(n), where n being the number of ports. The model also handles efficiently load/unload time constraints, crew scheduling and passenger transfers. Experiments using real world data produced high quality solutions in 12 hours using CPLEX 12.4 with a performance guarantee of within 15% of optimality, on average. This establishes that using a general purpose integer programming solver is a viable alternative in solving the ferry scheduling problem of moderate size.Comment: To appear in Public Transpor

The impact of the implementation of work hour requirements on residents' career satisfaction, attitudes and emotions

BACKGROUND: To assess the impact of work hours' limitations required by the Accreditation Council for Graduate Medical Education (ACGME) on residents' career satisfaction, emotions and attitudes. METHODS: A validated survey instrument was used to assess residents' levels of career satisfaction, emotions and attitudes before and after the ACGME duty hour requirements were implemented. The "pre" implementation survey was distributed in December 2002 and the "post" implementation one in December 2004. Only the latter included work-hour related questions. RESULTS: The response rates were 56% for the 2002 and 72% for the 2004 surveys respectively. Although career satisfaction remained unchanged, numerous changes occurred in both emotions and attitudes. Compared to those residents who did not violate work-hour requirements, those who did were significantly more negative in attitudes and emotions. CONCLUSION: With the implementation of the ACGME work hour limitations, the training experience became more negative for those residents who violated the work hour limits and had a small positive impact on those who did not violate them. Graduate medical education leaders must innovate to make the experiences for selected residents improved and still maintain compliance with the work hour requirements

A mid year comparison study of career satisfaction and emotional states between residents and faculty at one academic medical center

BACKGROUND: The Accreditation Council for Graduate Medical Education's (ACGME) new requirements raise multiple challenges for academic medical centers. We sought to evaluate career satisfaction, emotional states, positive and negative experiences, work hours and sleep among residents and faculty simultaneously in one academic medical center after implementation of the ACGME duty hour requirements. METHODS: Residents and faculty (1330) in the academic health center were asked to participate in a confidential survey; 72% of the residents and 66% of the faculty completed the survey. RESULTS: Compared to residents, faculty had higher levels of satisfaction with career choice, competence, importance and usefulness; lower levels of anxiousness and depression. The most positive experiences for both groups corresponded to strong interpersonal relationships and educational value; most negative experiences to poor interpersonal relationships and issues perceived outside of the physician's control. Approximately 13% of the residents and 14% of the faculty were out of compliance with duty hour requirements. Nearly 5% of faculty reported working more than 100 hours per week. For faculty who worked 24 hour shifts, nearly 60% were out of compliance with the duty-hour requirements. CONCLUSION: Reasons for increased satisfaction with career choice, positive emotional states and experiences for faculty compared to residents are unexplained. Earlier studies from this institution identified similar positive findings among advanced residents compared to more junior residents. Faculty are more frequently at risk for duty-hour violations. If patient safety is of prime importance, faculty, in particular, should be compliant with the duty hour requirements. Perhaps the ACGME should contain faculty work hours as part of its regulatory function

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions

Cue-Reactors: Individual Differences in Cue-Induced Craving after Food or Smoking Abstinence

Background: Pavlovian conditioning plays a critical role in both drug addiction and binge eating. Recent animal research suggests that certain individuals are highly sensitive to conditioned cues, whether they signal food or drugs. Are certain humans also more reactive to both food and drug cues? Methods: We examined cue-induced craving for both cigarettes and food, in the same individuals (n = 15 adult smokers). Subjects viewed smoking-related or food-related images after abstaining from either smoking or eating. Results: Certain individuals reported strong cue-induced craving after both smoking and food cues. That is, subjects who reported strong cue-induced craving for cigarettes also rated stronger cue-induced food craving. Conclusions: In humans, like in nonhumans, there may be a ‘‘cue-reactive’ ’ phenotype, consisting of individuals who are highly sensitive to conditioned stimuli. This finding extends recent reports from nonhuman studies. Further understanding this subgroup of smokers may allow clinicians to individually tailor therapies for smoking cessation

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability