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[PMID]: 26541482
[Au] Autor:Burfeind KG; Michaelis KA; Marks DL
[Ad] Address:Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR, USA; MD/PhD Program, Oregon Health & Science University, Portland, OR, USA.
[Ti] Title:The central role of hypothalamic inflammation in the acute illness response and cachexia.
[So] Source:Semin Cell Dev Biol;54:42-52, 2016 Jun.
[Is] ISSN:1096-3634
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review

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[PMID]: 26733610
[Au] Autor:Vitale C; Falchi L; Ten Hacken E; Gao H; Shaim H; Van Roosbroeck K; Calin G; O'Brien S; Faderl S; Wang X; Wierda WG; Rezvani K; Reuben JM; Burger JA; Keating MJ; Ferrajoli A
[Ad] Address:Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas....
[Ti] Title:Ofatumumab and Lenalidomide for Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia: Correlation between Responses and Immune Characteristics.
[So] Source:Clin Cancer Res;22(10):2359-67, 2016 May 15.
[Is] ISSN:1078-0432
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: We evaluated efficacy and tolerability of the combination of ofatumumab and lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), and explored whether immune system characteristics could influence the response to treatment. EXPERIMENTAL DESIGN: Thirty-four patients were enrolled in this phase II study. Ofatumumab was administered at a dose of 300 mg on day 1, 1,000 mg on days 8, 15, and 22 during course 1, 1,000 mg on day 1 during courses 3-6, and once every other course during courses 7-24 (28-day courses). Oral lenalidomide (10 mg daily) was started on day 9 and continued for as long as a clinical benefit was observed. RESULTS: The overall response rate was 71%. Eight patients (24%) achieved a complete remission (CR) or CR with incomplete recovery of blood counts, including 9% with minimal residual disease-negative CR. The median progression-free survival was 16 months, and the estimated 5-year survival was 53%. The most common treatment-related toxicity was neutropenia (grade >2 in 18% of the 574 patient courses). The most frequent infectious complications were pneumonia and neutropenic fever (24% and 9% of patients, respectively). We observed that patients who achieved a CR had at baseline higher numbers and a better preserved function of T cells and natural killer cells compared with non-responders. CONCLUSIONS: The combination of ofatumumab and lenalidomide is a well-tolerated regimen that induces durable responses in the majority of patients with relapsed/refractory CLL. Our correlative data suggest a role of competent immune system in supporting the efficacy of this treatment. Clin Cancer Res; 22(10); 2359-67. ©2016 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/1078-0432.CCR-15-2476

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[PMID]: 27158977
[Au] Autor:Manso PP; E P Dias de Oliveira BC; Carvalho de Sequeira P; Rodrigues Maia de Souza Y; Dos Santos Ferro JM; da Silva IJ; Gonçalves Caputo LF; Tavares Guedes P; Araujo Cunha Dos Santos A; da Silva Freire M; Bonaldo MC; Pelajo Machado M
[Ad] Address:Laboratório de Patologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil....
[Ti] Title:Kinetic Study of Yellow Fever 17DD Viral Infection in Gallus gallus domesticus Embryos.
[So] Source:PLoS One;11(5):e0155041, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Yellow fever continues to be an important epidemiological problem in Africa and South America even though the disease can be controlled by vaccination. The vaccine has been produced since 1937 and is based on YFV 17DD chicken embryo infection. However, little is known about the histopathological background of virus infection and replication in this model. Here we show by morphological and molecular methods (brightfield and confocal microscopies, immunofluorescence, nested-PCR and sequencing) the kinetics of YFV 17DD infection in chicken embryos with 9 days of development, encompassing 24 to 96 hours post infection. Our principal findings indicate that the main cells involved in virus production are myoblasts with a mesenchymal shape, which also are the first cells to express virus proteins in Gallus gallus embryos at 48 hours after infection. At 72 hours post infection, we observed an increase of infected cells in embryos. Many sites are thus affected in the infection sequence, especially the skeletal muscle. We were also able to confirm an increase of nervous system infection at 96 hours post infection. Our data contribute to the comprehension of the pathogenesis of YF 17DD virus infection in Gallus gallus embryos.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0155041

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[PMID]: 27159023
[Au] Autor:Ten Bosch QA; Singh BK; Hassan MR; Chadee DD; Michael E
[Ad] Address:Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America....
[Ti] Title:The Role of Serotype Interactions and Seasonality in Dengue Model Selection and Control: Insights from a Pattern Matching Approach.
[So] Source:PLoS Negl Trop Dis;10(5):e0004680, 2016 May.
[Is] ISSN:1935-2735
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The epidemiology of dengue fever is characterized by highly seasonal, multi-annual fluctuations, and the irregular circulation of its four serotypes. It is believed that this behaviour arises from the interplay between environmental drivers and serotype interactions. The exact mechanism, however, is uncertain. Constraining mathematical models to patterns characteristic to dengue epidemiology offers a means for detecting such mechanisms. Here, we used a pattern-oriented modelling (POM) strategy to fit and assess a range of dengue models, driven by combinations of temporary cross protective-immunity, cross-enhancement, and seasonal forcing, on their ability to capture the main characteristics of dengue dynamics. We show that all proposed models reproduce the observed dengue patterns across some part of the parameter space. Which model best supports the dengue dynamics is determined by the level of seasonal forcing. Further, when tertiary and quaternary infections are allowed, the inclusion of temporary cross-immunity alone is strongly supported, but the addition of cross-enhancement markedly reduces the parameter range at which dengue dynamics are produced, irrespective of the strength of seasonal forcing. The implication of these structural uncertainties on predicted vulnerability to control is also discussed. With ever expanding spread of dengue, greater understanding of dengue dynamics and control efforts (e.g. a near-future vaccine introduction) has become critically important. This study highlights the capacity of multi-level pattern-matching modelling approaches to offer an analytic tool for deeper insights into dengue epidemiology and control.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pntd.0004680

  5 / 257686 MEDLINE  
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[PMID]: 27152416
[Au] Autor:Hematpoor A; Liew SY; Chong WL; Azirun MS; Lee VS; Awang K
[Ad] Address:Institute of Biological Sciences, Faculty of Science Building, University of Malaya, Kuala Lumpur, Malaysia....
[Ti] Title:Inhibition and Larvicidal Activity of Phenylpropanoids from Piper sarmentosum on Acetylcholinesterase against Mosquito Vectors and Their Binding Mode of Interaction.
[So] Source:PLoS One;11(5):e0155265, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Aedes aegypti, Aedes albopictus and Culex quinquefasciatus are vectors of dengue fever and West Nile virus diseases. This study was conducted to determine the toxicity, mechanism of action and the binding interaction of three active phenylpropanoids from Piper sarmentosum (Piperaceae) toward late 3rd or early 4th larvae of above vectors. A bioassay guided-fractionation on the hexane extract from the roots of Piper sarmentosum led to the isolation and identification of three active phenylpropanoids; asaricin 1, isoasarone 2 and trans-asarone 3. The current study involved evaluation of the toxicity and acetylcholinesterase (AChE) inhibition of these compounds against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae. Asaricin 1 and isoasarone 2 were highly potent against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae causing up to 100% mortality at ≤ 15 µg/mL concentration. The ovicidal activity of asaricin 1, isoasarone 2 and trans-asarone 3 were evaluated through egg hatching. Asaricin 1 and isoasarone 2 showed potent ovicidal activity. Ovicidal activity for both compounds was up to 95% at 25µg/mL. Asaricin 1 and isoasarone 2 showed strong inhibition on acetylcholinesterase with relative IC50 values of 0.73 to 1.87 µg/mL respectively. These findings coupled with the high AChE inhibition may suggest that asaricin 1 and isoasarone 2 are neuron toxic compounds toward Aedes aegypti, Aedes albopictus and Culex quinquefasciatus. Further computational docking with Autodock Vina elaborates the possible interaction of asaricin 1 and isoasarone 2 with three possible binding sites of AChE which includes catalytic triads (CAS: S238, E367, H480), the peripheral sites (PAS: E72, W271) and anionic binding site (W83). The binding affinity of asaricin 1 and isoasarone 2 were relatively strong with asaricin 1 showed a higher binding affinity in the anionic pocket.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0155265

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[PMID]: 27149668
[Au] Autor:Casadevall A
[Ad] Address:Department of Molecular Microbiology and Immunology of the Johns Hopkins School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
[Ti] Title:Thermal Restriction as an Antimicrobial Function of Fever.
[So] Source:PLoS Pathog;12(5):e1005577, 2016 May.
[Is] ISSN:1553-7374
[Cp] Country of publication:United States
[La] Language:eng
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.ppat.1005577

  7 / 257686 MEDLINE  
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[PMID]: 27149385
[Au] Autor:Epelboin L; Nacher M; Mahamat A; Pommier de Santi V; Berlioz-Arthaud A; Eldin C; Abboud P; Briolant S; Mosnier E; Mendonça Gomes Mdo S; Vreden SG; Pierre-Demar M; Lacerda M; Raoult D; Sampaio de Lemos ER; Djossou F
[Ad] Address:Infectious and Tropical Diseases Department, Centre Hospitalier Andrée-Rosemon, Cayenne, French Guiana....
[Ti] Title:Q Fever in French Guiana: Tip of the Iceberg or Epidemiological Exception?
[So] Source:PLoS Negl Trop Dis;10(5):e0004598, 2016 May.
[Is] ISSN:1935-2735
[Cp] Country of publication:United States
[La] Language:eng
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pntd.0004598

  8 / 257686 MEDLINE  
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[PMID]: 27149282
[Au] Autor:Antinori S; Mediannikov O; Corbellino M; Grande R; Parravicini C; Bestetti G; Longhi E; Ricaboni D; Ehounoud CB; Fenollar F; Raoult D; Rimoldi SG
[Ad] Address:Department of Clinical and Biomedical Sciences Luigi Sacco, University of Milano, Milano, Italy....
[Ti] Title:Louse-Borne Relapsing Fever (Borrelia recurrentis) in a Somali Refugee Arriving in Italy: A Re-emerging Infection in Europe?
[So] Source:PLoS Negl Trop Dis;10(5):e0004522, 2016 May.
[Is] ISSN:1935-2735
[Cp] Country of publication:United States
[La] Language:eng
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pntd.0004522

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[PMID]: 27117403
[Au] Autor:Li S; Rissanen I; Zeltina A; Hepojoki J; Raghwani J; Harlos K; Pybus OG; Huiskonen JT; Bowden TA
[Ad] Address:Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK....
[Ti] Title:A Molecular-Level Account of the Antigenic Hantaviral Surface.
[So] Source:Cell Rep;15(5):959-67, 2016 May 3.
[Is] ISSN:2211-1247
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Hantaviruses, a geographically diverse group of zoonotic pathogens, initiate cell infection through the concerted action of Gn and Gc viral surface glycoproteins. Here, we describe the high-resolution crystal structure of the antigenic ectodomain of Gn from Puumala hantavirus (PUUV), a causative agent of hemorrhagic fever with renal syndrome. Fitting of PUUV Gn into an electron cryomicroscopy reconstruction of intact Gn-Gc spike complexes from the closely related but non-pathogenic Tula hantavirus localized Gn tetramers to the membrane-distal surface of the virion. The accuracy of the fitting was corroborated by epitope mapping and genetic analysis of available PUUV sequences. Interestingly, Gn exhibits greater non-synonymous sequence diversity than the less accessible Gc, supporting a role of the host humoral immune response in exerting selective pressure on the virus surface. The fold of PUUV Gn is likely to be widely conserved across hantaviruses.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review

  10 / 257686 MEDLINE  
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[PMID]: 27135829
[Au] Autor:Shahid AS; Ahmed T; Shahunja KM; Kabir S; Chowdhury F; Faruque AS; Das SK; Sarker MH; Bardhan PK; Chisti MJ
[Ad] Address:Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh....
[Ti] Title:Factors Associated with Streptococcal Bacteremia in Diarrheal Children under Five Years of Age and Their Outcome in an Urban Hospital in Bangladesh.
[So] Source:PLoS One;11(5):e0154777, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Although Streptococcal bacteremia is common in diarrheal children with high morbidity and mortality, no systematic data are available on Streptococcal bacteremia in diarrheal children. We sought to evaluate the factors associated with Streptococcal bacteremia in diarrheal children under five years of age and their outcome. METHODS: We used an unmatched case-control design to investigate the associated factors with Streptococcal bacteremia in all the diarrheal children under five years of age through electronic medical record system of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. We had simultaneously used a retrospective cohort design to further evaluate the outcome of our study children. All the enrolled children had their blood culture done between January 2010 and December 2012. Comparison was made among the children with (cases = 26) and without Streptococcal bacteremia (controls = 78). Controls were selected randomly from hospitalized diarrheal children under five years of age. RESULTS: Cases had proportionately higher deaths compared to controls, but it was statistically insignificant (15% vs. 10%, p = 0.49). The cases more often presented with severe dehydration, fever, respiratory distress, severe sepsis, and abnormal mental status compared to the controls (for all p<0.05). In the logistic regression analysis, after adjusting for potential confounders, it has been found that Streptococcal bacteremia in diarrheal children under five years of age was independently associated with nutritional edema (OR: 5.86, 95% CI = 1.28-26.80), hypoxemia (OR: 19.39, 95% CI = 2.14-175.91), fever (OR: 4.44, 95% CI = 1.13-17.42), delayed capillary refill time (OR: 7.00, 95% CI = 1.36-35.93), and respiratory distress (OR: 2.69, 95% CI = 1.02-7.12). CONCLUSIONS AND SIGNIFICANCE: The results of our analyses suggest that diarrheal children under five years of age presenting with nutritional edema, hypoxemia, fever, delayed capillary refill time, and respiratory distress may be at risk of Streptococcal bacteremia. It underscores the importance of identification of these simple clinical parameters for the prompt recognition and management in order to reduce the morbidity and death of such children especially in resource limited settings.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0154777


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