Mcleodsigmon3027

Poor HRQL assessed after coronary revascularization appears to be a powerful predictor of rehospitalization over a 3-year period.The CAF01 adjuvant has previously been shown to be safe for human use and to be a potent adjuvant for several vaccine antigens. In the present work, we sought to optimize the Leishmania amazonensis antigens (LaAg) intranasal vaccine in an attempt to enhance the protective immune responses against Leishmania (infantum) chagasi by using the CAF01 association. LaAg/CAF01 vaccinated mice that were challenged 15 days after booster dose with L. (infantum) chagasi showed a significant reduction in their parasite burden in both the spleen and liver, which is associated with an increase in specific production of IFN-γ and nitrite, and a decrease in IL-4 production. In addition, LaAg/CAF01 intranasal delivery was able to increase lymphoproliferative immune responses after parasite antigen recall. These results suggest the feasibility of using the intranasal route for the delivery of crude antigens and of a human-compatible adjuvant against visceral leishmaniasis.

To determine the causative role of the REDD (regulated in development and DNA damage)-1 protein, a known negative regulator of mTOR kinase, in changes in muscle protein synthesis induced by acute alcohol administration.

Adult female REDD1(-/-) or wild-type (WT) mice were injected IP with ethanol (alcohol; 3 g/kg BW) or saline and the skeletal muscle was removed 1 h later. In vivo protein synthesis was assessed as were selected endpoints related to the activation of mTOR and protein degradation.

Acute alcohol decreased muscle protein synthesis similarly in WT and REDD1(-/-) mice. In contrast, mTORC1 signaling was largely unaffected by either EtOH or genotype as evidenced by the lack of change in the phosphorylation of its downstream targets, S6K1 T(389) and 4E-BP1 S(65). Although alcohol decreased p62 and ULK1 S(757) protein in muscle from WT and REDD1(-/-) mice, there was no change in LC3B lipidation, or beclin1, Atg7 and Atg12 protein suggesting no change in autophagy. MuRF1 and atrogin-1 mRNAs were elevated in alcohol-treated REDD1(-/-) mice compared with WT mice suggesting activation of the ubiquitin proteasome activity. While there was no genotype or alcohol effect on plasma corticosterone, REDD1(-/-) mice failed to demonstrate the alcohol-induced hyperinsulinemia seen in WT mice.

REDD1 does not appear to play a role in the acute alcohol-mediated decrease in protein synthesis or mTOR activity, but may contribute to the regulation of ubiquitin-proteasome mediated protein breakdown.

REDD1 does not appear to play a role in the acute alcohol-mediated decrease in protein synthesis or mTOR activity, but may contribute to the regulation of ubiquitin-proteasome mediated protein breakdown.

Local plaque macrophage proliferation and monocyte production in hematopoietic organs promote progression of atherosclerosis. Therefore, noninvasive imaging of proliferation could serve as a biomarker and monitor therapeutic intervention.

To explore (18)F-FLT positron emission tomography-computed tomography imaging of cell proliferation in atherosclerosis.

(18)F-FLT positron emission tomography-computed tomography was performed in mice, rabbits, and humans with atherosclerosis. In apolipoprotein E knock out mice, increased (18)F-FLT signal was observed in atherosclerotic lesions, spleen, and bone marrow (standardized uptake values wild-type versus apolipoprotein E knock out mice, 0.05 ± 0.01 versus 0.17 ± 0.01, P<0.05 in aorta; 0.13 ± 0.01 versus 0.28 ± 0.02, P<0.05 in bone marrow; 0.06 ± 0.01 versus 0.22 ± 0.01, P<0.05 in spleen), corroborated by ex vivo scintillation counting and autoradiography. Flow cytometry confirmed significantly higher proliferation of macrophages in aortic lesions and hematopoietic stem and progenitor cells in the spleen and bone marrow in these mice. In addition, (18)F-FLT plaque signal correlated with the duration of high cholesterol diet (r(2)=0.33, P<0.05). Aortic (18)F-FLT uptake was reduced when cell proliferation was suppressed with fluorouracil in apolipoprotein E knock out mice (P<0.05). In rabbits, inflamed atherosclerotic vasculature with the highest (18)F-fluorodeoxyglucose uptake enriched (18)F-FLT. In patients with atherosclerosis, (18)F-FLT signal significantly increased in the inflamed carotid artery and in the aorta.

(18)F-FLT positron emission tomography imaging may serve as an imaging biomarker for cell proliferation in plaque and hematopoietic activity in individuals with atherosclerosis.

(18)F-FLT positron emission tomography imaging may serve as an imaging biomarker for cell proliferation in plaque and hematopoietic activity in individuals with atherosclerosis.

Over the past several decades, Hodgkin lymphoma (HL) has become a highly treatable lymphoid malignancy with excellent response rates and long-term disease-free survival. Late-toxicities, however, continue to be an area of significant concern. Recent studies have evaluated novel approaches to limit long-term toxicity without adversely impacting short-term survival. While early or interim PET scan has been correlated with PFS and OS in HL, the modification of therapy based on interim PET (response-adapted therapy) has been evaluated in retrospective and prospective cohorts. This paper will review evidence for the role of response-adapted therapy in HL.

Data from completed and ongoing retrospective and prospective cohorts of HL patients were reviewed utilizing pubmed and clinicaltrials.org and pertinent studies culled to compile this review article.

While response-adapted therapy represents a promising area of research which may ultimately become standard-of-care, current data does not unequivocally endorse this approach, which should be used with caution outside of a clinical trial.

While response-adapted therapy represents a promising area of research which may ultimately become standard-of-care, current data does not unequivocally endorse this approach, which should be used with caution outside of a clinical trial.

This meta-analysis has been conducted to determine the risk of elevated transaminases associated with immune checkpoint inhibitors use in patients with cancer.

Studies eligible for our analysis included randomized Phase II and III trials of patients with cancer on ipilimumab, nivolumab, pembrolizumab, tremelimumab and pidilizumab, which describe events of elevated transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)].

Initial database search revealed 210 relevant citations. After excluding noneligible studies, 10 trials were considered eligible for the quantitative synthesis. The RR of all-grade elevated ALT and AST was 2.36 (95% CI 1.20-4.66; p = 0.01) and 1.53 (95% CI 0.73-3.22; p = 0.26), respectively, whereas for high-grade elevated ALT and AST, it was 11.27 (95% CI 5.38-23.63; p < 0.0001) and 4.9 (95% CI 2.97-8.09; p < 0.0001), respectively.

Our study has shown that the use of immune checkpoint inhibitors has a causal relationship to an increased risk of high-grade elevated ALT and AST. Clinicians using these agents should be attentive of this risk.

Our study has shown that the use of immune checkpoint inhibitors has a causal relationship to an increased risk of high-grade elevated ALT and AST. Clinicians using these agents should be attentive of this risk.

A new pricing policy was introduced in Korea in April 2012 with the aim of strengthening competition among off-patent drugs by eliminating price gaps between originators and generics.

Examine the effect of newly implemented pricing policy.

Retrospectively examining the effects through extracting from the National Health Insurance claims data a 30-month panel dataset (January 2011-June 2013) containing consumption data in four major therapeutic classes (antihypertensives, lipid-lowering drugs, antiulcerants and antidepressants). Proxies for market competition were examined before and after the policy.

The new pricing policy did not enhance competition among off-patent drugs. In fact, price dispersion significantly decreased as opposed to the expected change. Originator-to-generic utilization increased 6.12 times (p = 0.000) after the new policy.

The new pricing policy made no impact on competition among off-patent drugs. Competition in the off-patent market cannot be enhanced unless both supply and demand side measures are coordinated.

The new pricing policy made no impact on competition among off-patent drugs. Competition in the off-patent market cannot be enhanced unless both supply and demand side measures are coordinated.

In Colombia, Rhodnius prolixus and Triatoma dimidiata are the main domestic triatomine species known to transmit T. cruzi. However, there are multiple reports of T. cruzi transmission involving secondary vectors. In this work, we carried out an eco-epidemiological study on Margarita Island, located in the Caribbean region of Colombia, where Chagas disease is associated with non-domiciliated vectors.

To understand the transmission dynamics of Trypanosoma cruzi in this area, we designed a comprehensive, multi-faceted study including the following (i) entomological evaluation through a community-based insect-surveillance campaign, blood meal source determination and T. cruzi infection rate estimation in triatomine insects; (ii) serological determination of T. cruzi prevalence in children under 15 years old, as well as in domestic dogs and synanthropic mammals; (iii) evaluation of T. cruzi transmission capacity in dogs and Didelphis marsupialis, and (iv) genetic characterization of T. ALK inhibitor cruzi isolates targetingiated vectors where active human infection exists. There is an ongoing need to control peridomestic T. maculata populations and to implement continuous reservoir surveillance strategies with community participation.

This study reveals the role of peridomestic T. maculata and dogs in T. cruzi persistence in this region and presents evidence that D. marsupialis are a reservoir mediating peridomestic-zoonotic cycles. This picture reflects the complexity of the transmission dynamics of T. cruzi in an endemic area with non-domiciliated vectors where active human infection exists. There is an ongoing need to control peridomestic T. maculata populations and to implement continuous reservoir surveillance strategies with community participation.The objective of the study was to examine changes in coping and their predictors in patients in the chronic phase after an acquired brain injury with prominent neuropsychiatric symptoms. Patients with brain injury were recruited from consecutive admissions to the outpatient clinics of four mental health centers in the Netherlands. Patients received psychoeducation and/or one or more individual treatment sessions that were not targeting coping styles. Forty-two patients and thirty-two significant others participated. Patients reported a significantly greater use of passive and avoidance coping than both the general population and patients with brain injury without neuropsychiatric symptoms. There were statistically significant increases in avoidance coping between T1 and T2 (t = 2.0; p  less then  0.05). Less neuropsychiatric symptoms at T1 were associated with increases in avoidance coping, and more neuropsychiatric symptoms were associated with decreases in avoidance coping (β = -3.3; p  less then  0.001). Patients' underestimation of their deficits at T1 was associated with greater increases in active coping (β = -2.