Showing papers by "University of Louisville published in 2011"
TL;DR: It is suggested that intracoronary infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies.
1,312 citations
TL;DR: The substoichiometric MoO(3) core provides a high aspect ratio foundation and enables facile charge transport, while the conformal MoS(2) shell provides excellent catalytic activity and protection against corrosion in strong acids.
Abstract: We synthesize vertically oriented core–shell nanowires with substoichiometric MoO3 cores of ∼20–50 nm and conformal MoS2 shells of ∼2–5 nm. The core–shell architecture, produced by low-temperature sulfidization, is designed to utilize the best properties of each component material while mitigating their deficiencies. The substoichiometric MoO3 core provides a high aspect ratio foundation and enables facile charge transport, while the conformal MoS2 shell provides excellent catalytic activity and protection against corrosion in strong acids.
1,067 citations
TL;DR: Exosomes used to encapsulate curcumin or a signal transducer and activator of transcription 3 (Stat3) inhibitor were delivered noninvasively to microglia cells via an intranasal route and demonstrated that this strategy may provide a noninvasive and novel therapeutic approach for treating brain inflammatory-related diseases.
1,032 citations
TL;DR: Task-specific training with epidural stimulation might reactivate previously silent spared neural circuits or promote plasticity and could be a viable clinical approach for functional recovery after severe paralysis.
945 citations
TL;DR: It is shown that P. gingivalis, at very low colonization levels, triggers changes to the amount and composition of the oral commensal microbiota leading to inflammatory periodontal bone loss, demonstrating that a single, low-abundance species can disrupt host-microbial homeostasis to cause inflammatory disease.
890 citations
TL;DR: In this article, the IL-23 receptor (IL-23R) and transcriptional factor RORγt were found to stimulate dermal γδ T-cells to produce IL-17 that led to disease progression.
846 citations
Emory University1, University of Alabama at Birmingham2, University of Louisville3, St. Luke's Hospital4, Kaiser Permanente5, Mount Sinai St. Luke's and Mount Sinai Roosevelt6, Mayo Clinic7, Ohio State University8, Carolinas Medical Center9, University of Colorado Denver10, Northwestern University11, Advocate Lutheran General Hospital12, University of South Florida13, Rush University Medical Center14, National Institutes of Health15, University of Texas MD Anderson Cancer Center16
TL;DR: In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine andInterleukin-2 than with interleuk in-2 alone.
Abstract: Background Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. Methods We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end p...
801 citations
TL;DR: The technique of meta-analysis (i.e., aggregating findings across multiple studies) is used to address questions about mentoring effectiveness as well as the conditions required for them to achieve optimal positive outcomes for participating youth.
Abstract: The current popularity of mentoring programs notwithstanding, questions remain about their typical effectiveness as well as the conditions required for them to achieve optimal positive outcomes for participating youth. In this report, we use the technique of meta-analysis (i.e., aggregating findings across multiple studies) to address these questions. As backdrop for our analysis, we begin with an overview of recent trends in youth mentoring practice, findings from prior research, and a developmental model of mentoring relationships and their potential effects on young people. Language: en
729 citations
TL;DR: In this article, the authors proposed a framework to integrate biogeochemical processes into designing, implementing, and evaluating the net effectiveness of green infrastructure, and provide examples for GHG mitigation, stormwater runoff mitigation, and improvements in air quality and health.
Abstract: Urban green space is purported to offset greenhouse-gas (GHG) emissions, remove air and water pollutants, cool local climate, and improve public health. To use these services, municipalities have focused efforts on designing and implementing ecosystem-services-based “green infrastructure” in urban environments. In some cases the environmental benefits of this infrastructure have been well documented, but they are often unclear, unquantified, and/or outweighed by potential costs. Quantifying biogeochemical processes in urban green infrastructure can improve our understanding of urban ecosystem services and disservices (negative or unintended consequences) resulting from designed urban green spaces. Here we propose a framework to integrate biogeochemical processes into designing, implementing, and evaluating the net effectiveness of green infrastructure, and provide examples for GHG mitigation, stormwater runoff mitigation, and improvements in air quality and health.
724 citations
TL;DR: These oil degrading indigenous microorganisms played a significant role in reducing the overall environmental impact of both the Exxon Valdez and BP Deepwater Horizon oil spills.
Abstract: Oil biodegradation and bioremediation: A tale of the two worst spills in U. S. history. Ronald M. Atlas, University of Louisville, Louisville KY 40292 Terry C. Hazen, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 Biography Ronald Atlas is Professor of Biology at the University of Louisville. He has over 40 years experience studying the role of microorganisms in oil biodegradation and helped pioneer the field of bioremediation. He has worked extensively on the bioremediation the Exxon Valdez spill. Terry Hazen is DOE BER distinguished scientist in the Earth Sciences Division at Lawrence Berkeley National Laboratory. He has studied oil, chlorinated solvent, and metal and radionuclide bioremediation for more then 30 years. He has been extensively studying the microbial degradation of the BP Deepwater Horizon Spill in the Gulf of Mexico. Abstract The devastating environmental impacts of the Exxon Valdez spill in 1989 and its media notoriety made it a frequent comparison to the BP Deepwater Horizon spill in the popular press in 2010, even though the nature of the two spills and the environments impacted were vastly different. Fortunately, unlike higher organisms that are adversely impacted by oil spills, microorganisms are able to consume petroleum hydrocarbons. These oil degrading indigenous microorganisms played a significant role in reducing the overall environmental impact of both the Exxon Valdez and BP Deepwater Horizon (MC252) oil spills. Introduction to Biodegradation of Petroleum Hydrocarbons Petroleum hydrocarbons in crude oils, such as those released into marine ecosystems by the Exxon Valdez and BP Deepwater Horizon spills, are natural products derived from aquatic algae laid down between 180 and 85 million years ago. Crude oils, composed mostly of diverse aliphatic and aromatic hydrocarbons, regularly escape into the environment from underground reservoirs. Because petroleum hydrocarbons occur naturally in all marine environments there has been time for numerous diverse microorganisms to evolve the capability of utilizing hydrocarbons as sources of carbon and energy for growth. Oil-degrading microorganisms are ubiquitous, but may only be a small proportion of the pre-spill microbial community. Bacteria, archaea, and fungi each have hundreds of species that can degrade petroleum. Most petroleum hydrocarbons are biodegradable under aerobic conditions; though a few compounds found in crude oils, e.g. resins, hopanes, polar molecules, and asphaltenes, have practically imperceptible biodegradation rates. Lighter crudes, such as the oil released from the BP Deepwater Horizon spill, contain a higher proportion of simpler lower molecular weight hydrocarbons that are more readily biodegraded than heavy crudes, such as the oil released from the Exxon Valdez. The polycyclic aromatic hydrocarbons (PAH) are a minor constituent of crude oils; however, they are among the most toxic to plants and animals. Bacteria can convert PAHs completely to biomass, CO 2 , and H 2 O, but they usually require the initial insertion of O 2 via dioxygenase enzymes. Anaerobic degradation of petroleum hydrocarbons can also occur albeit at a much slower rates. Petroleum hydrocarbons can be biodegraded at temperatures below freezing to more than 80°C. Microorganisms require elements other than carbon for
721 citations
TL;DR: Anatomic changes of the lid margin, expressibility of meibomian lipids, gland dropout by meibography, evaporimetry, and meibometry are most commonly used.
Abstract: Recommended definition of MGD: Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease.
Previous definitions and criteria of MGD: There is no firmly established definition of MGD published in the literature. Most researchers have used a criterion-based approach to describe the condition, with combinations of objective findings and measurements. Anatomic changes of the lid margin, expressibility of meibomian lipids, gland dropout by meibography, evaporimetry, and meibometry are most commonly used (Table 1).
Table 1.
Criteria of Meibomian Gland Dysfunction Used in Previous Works
TL;DR: It is found that a high proportion of patients with Parkinson's disease–mild cognitive impairment progress to dementia in a relatively short period of time, and patients at risk of progressing to dementia are at risk.
Abstract: There is controversy regarding the definition and characteristics of mild cognitive impairment in Parkinson's disease. The Movement Disorder Society commissioned a Task Force to critically evaluate the literature and determine the frequency and characteristics of Parkinson's disease-mild cognitive impairment and its association with dementia. A comprehensive PubMed literature review was conducted using systematic inclusion and exclusion criteria. A mean of 26.7% (range, 18.9%-38.2%) of nondemented patients with Parkinson's disease have mild cognitive impairment. The frequency of Parkinson's disease-mild cognitive impairment increases with age, disease duration, and disease severity. Impairments occur in a range of cognitive domains, but single domain impairment is more common than multiple domain impairment, and within single domain impairment, nonamnestic is more common than amnestic impairment. A high proportion of patients with Parkinson's disease-mild cognitive impairment progress to dementia in a relatively short period of time. The primary conclusions of the Task Force are that: (1) Parkinson's disease-mild cognitive impairment is common, (2) there is significant heterogeneity within Parkinson's disease-mild cognitive impairment in the number and types of cognitive domain impairments, (3) Parkinson's disease-mild cognitive impairment appears to place patients at risk of progressing to dementia, and (4) formal diagnostic criteria for Parkinson's disease-mild cognitive impairment are needed.
TL;DR: Tear osmolarity is the best single metric both to diagnose and classify dry eye disease and intereye variability is a characteristic of dry eye not seen in normal subjects.
TL;DR: This work reviews the convergence of miRNAs and NF-κB signaling and dysregulation in human diseases, particularly in cancer and discusses the function and pathological contribution of miR-146,MiR-155, MiR-181b,miR-21, and miR -301a in NF- κB activation and their impact on tumorigenesis.
Abstract: Nuclear factor kB (NF-kB) is a transcriptional factor that regulates a battery of genes that are critical to innate and adaptive immunity, cell proliferation, inflammation, and tumor development. MicroRNAs (miRNAs) are short RNA molecules of 20‐25 nucleotides in length that negatively regulate gene expression in animals and plants primarily by targeting 3 ′ untranslated regions of mRNAs. In this work, we review the convergence of miRNAs and NF-kB signaling and dysregulation of miRNAs and NF-kB activation in human diseases, particularly in cancer. The function of miR-146, miR-155, miR-181b, miR-21, and miR-301a in NF-kB activation and their impact on tumorigenesis are discussed. Given that over 1000 human miRNAs have been identified, rendering miRNAs one of the most abundant classes of regulatory molecules, deciphering their biological function and pathological contribution in NF-kB dysregulation is essential to appreciate the complexity of immune systems and to develop therapeutics against cancer.
University of Marburg1, University of Pittsburgh2, Mayo Clinic3, University of Pennsylvania4, University College London5, University of Louisville6, Case Western Reserve University7, Erasmus University Rotterdam8, VU University Amsterdam9, University of Tübingen10, University of Barcelona11, University of Brescia12, University of Navarra13, National Institutes of Health14, Scripps Research Institute15, University of British Columbia16, University of Washington17, Rutgers University18, University of Giessen19, University of Michigan20, University of Würzburg21, Autonomous University of Madrid22, German Center for Neurodegenerative Diseases23, Karolinska Institutet24, University of California, Los Angeles25, Centre national de la recherche scientifique26, French Institute of Health and Medical Research27, Medical University of Vienna28, Sapienza University of Rome29, University of Antwerp30, Mount Sinai Hospital31, Flinders University32, Harvard University33, University of California, San Diego34, Emory University35, Indiana University36, Rush University Medical Center37, University of Toronto38, Baylor College of Medicine39, University of California, San Francisco40, Ludwig Maximilian University of Munich41, University of Kansas42, Mental Health Research Institute43, University of Göttingen44, Cardiff University45, Newcastle University46, University of Manchester47, Innsbruck Medical University48, Carlos III Health Institute49, University of Saskatchewan50, University of Maryland, Baltimore51, University of Cambridge52, University of Alabama at Birmingham53, Veterans Health Administration54, King's College London55, Johns Hopkins University56, Columbia University57, University of Texas Southwestern Medical Center58, University of Southern California59
TL;DR: Two independent variants in MAPT affecting risk for PSP are confirmed, one of which influences MAPT brain expression and the genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface and for a myelin structural component.
Abstract: Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10−3. We found significant previously unidentified signals (P < 5 × 10−8) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component.
TL;DR: Investigating children's exploratory play after an adult pedagogically demonstrated a function of a toy, after an interrupted pedagogical demonstration, after a naïve adult demonstrated the function, and at baseline shows that children restrict their exploration both after direct instruction to themselves and after overhearing direct instruction given to another child.
TL;DR: The ability of TLRs to engage different intracellular signaling molecules and cross-talk with other regulatory pathways is an important factor in shaping the type, magnitude, and duration of the inflammatory response as discussed by the authors.
Abstract: Toll-like receptors play a critical role in innate immunity by detecting invading pathogens. The ability of TLRs to engage different intracellular signaling molecules and cross-talk with other regulatory pathways is an important factor in shaping the type, magnitude, and duration of the inflammatory response. The present review will cover the fundamental signaling pathways utilized by TLRs and how these pathways regulate the innate immune response to pathogens. Abbreviations: TLR, Toll-like receptor; PRR, pattern recognition receptor; PAMP, pathogen-associated molecular pattern; LPS, lipopolysaccharide; APC, antigen-presenting cell; IL, interleukin; TIR, Toll/IL-1R homology; MyD88, myeloid differentiation factor 88; IFN, interferon; TRIF, TIR-domain-containing adapter-inducing interferon-β; IRAK, IL-1R-associated kinase; TAK1, TGF-β-activated kinase; TAB1, TAK1-binding protein; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B-cells; MAPK, mitogen-activated protein kinase; NLR, NOD-like rece...
[...]
TL;DR: This chapter contains sections titled: Introduction Data-Mining Roots data-mining process large data sets data Warehouses for data Mining business aspects of data mining business Aspects of Data Mining: Why a data-mining project Fails.
Abstract: This chapter contains sections titled: Introduction Data-Mining Roots Data-Mining Process Large Data Sets Data Warehouses for Data Mining Business Aspects of Data Mining: Why a Data-Mining Project Fails Organization of This Book Review Questions and Problems References for Further Study
]]>
TL;DR: The data indicate the critical role of mitochondrial ROS in cardiac hypertrophy and failure and support the potential use of mitochondrial-targeted antioxidants for prevention and treatment of hypertensive cardiomyopathy.
Abstract: Rationale: Mitochondrial dysfunction has been implicated in several cardiovascular diseases; however, the roles of mitochondrial oxidative stress and DNA damage in hypertensive cardiomyopathy are not well understood. Objective: We evaluated the contribution of mitochondrial reactive oxygen species (ROS) to cardiac hypertrophy and failure by using genetic mouse models overexpressing catalase targeted to mitochondria and to peroxisomes. Methods and Results: Angiotensin II increases mitochondrial ROS in cardiomyocytes, concomitant with increased mitochondrial protein carbonyls, mitochondrial DNA deletions, increased autophagy and signaling for mitochondrial biogenesis in hearts of angiotensin II–treated mice. The causal role of mitochondrial ROS in angiotensin II–induced cardiomyopathy is shown by the observation that mice that overexpress catalase targeted to mitochondria, but not mice that overexpress wild-type peroxisomal catalase, are resistant to cardiac hypertrophy, fibrosis and mitochondrial damage induced by angiotensin II, as well as heart failure induced by overexpression of Gαq. Furthermore, primary damage to mitochondrial DNA, induced by zidovudine administration or homozygous mutation of mitochondrial polymerase γ, is also shown to contribute directly to the development of cardiac hypertrophy, fibrosis and failure. Conclusions: These data indicate the critical role of mitochondrial ROS in cardiac hypertrophy and failure and support the potential use of mitochondrial-targeted antioxidants for prevention and treatment of hypertensive cardiomyopathy.
TL;DR: In this article, the authors examined the links between job fit, affective commitment, psychological climate, and employee engagement, and the dependent variables, discretionary effort, and intention to turnover.
Abstract: This correlational study (n = 283) examined the links between job fit, affective commitment, psychological climate, and employee engagement, and the dependent variables, discretionary effort, and intention to turnover. An Internet-based survey battery of six scales was administered to a heterogeneous sampling of organizations from service, technology, healthcare, retail, banking, nonprofit, and hospitality fields. Hypotheses were tested through correlational and hierarchical regression analytic procedures. Job fit, affective commitment, and psychological climate were all significantly related to employee engagement, while employee engagement was significantly related to both discretionary effort and intention to turnover. For the discretionary effort model, the hierarchical regression analysis results suggested that the employees who reported experiencing a positive psychological climate were more likely to report higher levels of discretionary effort. As for the intention to turnover model, the hierarchi...
Vanderbilt University1, Shizuoka University2, Arizona State University3, University of Oxford4, University of Gothenburg5, Pierre-and-Marie-Curie University6, Imperial College London7, McMaster University8, Institute of Science and Technology Austria9, University of Groningen10, Aarhus University11, University of Maryland, College Park12, University of Colorado Boulder13, University of California, Irvine14, University of Exeter15, University of Lausanne16, University of New Mexico17, University of Cambridge18, Australian National University19, University of Houston20, University of Edinburgh21, University of California, Santa Barbara22, Princeton University23, University of Chicago24, Montana State University25, Simon Fraser University26, Villanova University27, Queen's University28, Cornell University29, University of Louisville30, United States Department of Agriculture31, École Normale Supérieure32, University of Sussex33, Ludwig Maximilian University of Munich34, University of Kentucky35, Flinders University36, Michigan State University37, Georgia Institute of Technology38, University of California, Davis39, Pennsylvania State University40, University of Toronto41, University of Sheffield42, University of Regensburg43, University of Helsinki44, University of Vermont45, VU University Amsterdam46, University of Osnabrück47, Harvard University48, Swiss Federal Institute of Aquatic Science and Technology49, University of Copenhagen50, Royal Holloway, University of London51, University of California, Santa Cruz52, University of Arizona53, University of Oklahoma54, University of Texas at Austin55, University of Strasbourg56, University of Bristol57, University of Liverpool58, University of North Carolina at Chapel Hill59, Rice University60, University of Zurich61, University College London62, Newcastle University63, James Cook University64, University of Montpellier65, University of North Carolina at Greensboro66, University of California, Riverside67, ETH Zurich68, University of St Andrews69, William Paterson University70, University of Michigan71, University of Illinois at Urbana–Champaign72, University of Bern73, University of Western Ontario74, University of California, Berkeley75, University of the Ryukyus76, University of Florence77, University of Tennessee78, North Carolina State University79, Humboldt University of Berlin80, Katholieke Universiteit Leuven81, Smithsonian Institution82, University of Nevada, Reno83, San Francisco State University84
TL;DR: It is argued that inclusive fitness theory has been of little value in explained the natural world, and that it has led to negligible progress in explaining the evolution of eusociality, but these arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature.
Abstract: Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues.
TL;DR: Methods for assessing the impact of reactive species on isolated mitochondria are described using representative cell types from renal, cardiovascular, nervous, and tumorigenic model systems while illustrating the application of three protocols to analyze the bioenergetic response of cells to oxidative stress.
Virginia Commonwealth University1, University of Louisville2, Northwestern University3, Indiana University4, University of Erlangen-Nuremberg5, Vanderbilt University Medical Center6, Albany College of Pharmacy and Health Sciences7, Hennepin County Medical Center8, University of Ulm9, University of California, San Diego10, University of Michigan11, University Hospital Heidelberg12, Tufts Medical Center13, Georgetown University Medical Center14, University College Dublin15
TL;DR: The KDIGO Conference highlighted the gaps and focused on crafting paths to the future that will stimulate research and improve the global outcomes of patients with acute and chronic kidney disease.
TL;DR: In this paper, the authors compared four different methods for purifying exosomes for post-isolation analyses, including ExoQuick, ultracentrifugation, chromatography, and DynaBeads.
Abstract: While the existence of exosomes has been known for over three decades, they have garnered recent interest due to their potential diagnostic and therapeutic relevance. The expression and release of specific tumor-derived proteins into the peripheral circulation has served as the centerpiece of cancer screening and diagnosis. Recently, tissue-associated microRNA (miRNA) has been shown to be characteristic of tumor type and developmental origin, as well as exhibit diagnostic potential. Tumors actively release exosomes, exhibiting proteins and RNAs derived from the originating cell, into the peripheral circulation and other biologic fluids. Recently, we have demonstrated the presence of miRNAs within the RNA fraction of circulating tumor-derived exosomes. Currently, in over 75 investigations compiled in ExoCarta, over 2,300 proteins and 270 miRNAs have been linked with exosomes derived from biologic fluids. Our previous work has indicated that these circulating exosomal proteins and miRNAs can serve as surrogates for the tumor cell-associated counterparts, extending their diagnostic potential to asymptomatic individuals. In this chapter, we compare currently utilized methods for purifying exosomes for postisolation analyses. The exosomes derived from these approaches were assessed for quantity and quality of specific RNA populations and specific marker proteins. These results suggest that, while each method purifies exosomal material, circulating exosomes isolated by ExoQuick precipitation produces exosomal RNA and protein with greater purity and quantity than chromatography, ultracentrifugation, and DynaBeads. While this precipitation approach isolates exosomes in general and does not exhibit specificity for the originating cell, the increased quantity and quality of exosomal proteins and RNA should enhance the sensitivity and accuracy of down-stream analyses, such as qRT-PCR profiling of miRNA and mass spectrometric and electrophoretic analyses of exosomal proteins.
TL;DR: Tumor exosomes of tumor origin can be found within neoplastic lesions and in biologic fluids from cancer patients, implying a potential role of these pathways in in vivo tumor progression and systemic paraneoplastic syndromes.
Abstract: Cancer cells, both in vivo and in vitro, have been demonstrated to release membranous structures, defined as microvesicles or exosomes, consisting of an array of macromolecules derived from the originating cells, including proteins, lipids, and nucleic acids. While only recently have the roles of these vesicular components in intercellular communication become elucidated, significant evidence has demonstrated that tumor exosomes can exert a broad array of detrimental effects on the immune system-ranging from apoptosis of activated cytotoxic T cells to impairment of monocyte differentiation into dendritic cells, to induction of myeloid-suppressive cells and T regulatory cells. Immunosuppressive exosomes of tumor origin can be found within neoplastic lesions and in biologic fluids from cancer patients, implying a potential role of these pathways in in vivo tumor progression and systemic paraneoplastic syndromes. Through the expression of molecules involved in angiogenesis promotion, stromal remodeling, signaling pathway activation through growth factor/receptor transfer, chemoresistance, and genetic intercellular exchange, tumor exosomes could represent a central mediator of the tumor microenvironment. By understanding the nature of these tumor-derived exosomes/microvesicles and their roles in mediating cancer progression and modulating the host immune response will significantly impact therapeutic approaches targeting exosomes.
Icahn School of Medicine at Mount Sinai1, University of California, San Francisco2, Pennsylvania State University3, University of Louisville4, Columbia University5, Mayo Clinic6, Boston University7, University of Nebraska Medical Center8, Veterans Health Administration9, Wayne State University10, University of Pittsburgh11
TL;DR: This paper addresses indications for polysomnography in children with suspected sleep related breathing disorders and recommends practices in accordance with the AASM Manual for the Scoring of Sleep and Associated Events.
Abstract: Background There has been marked expansion in the literature and practice of pediatric sleep medicine; however, no recent evidence-based practice parameters have been reported. These practice parameters are the first of 2 papers that assess indications for polysomnography in children. This paper addresses indications for polysomnography in children with suspected sleep related breathing disorders. These recommendations were reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Methods A systematic review of the literature was performed, and the American Academy of Neurology grading system was used to assess the quality of evidence. RECOMMENDATIONS FOR PSG USE: 1. Polysomnography in children should be performed and interpreted in accordance with the recommendations of the AASM Manual for the Scoring of Sleep and Associated Events. (Standard) 2. Polysomnography is indicated when the clinical assessment suggests the diagnosis of obstructive sleep apnea syndrome (OSAS) in children. (Standard) 3. Children with mild OSAS preoperatively should have clinical evaluation following adenotonsillectomy to assess for residual symptoms. If there are residual symptoms of OSAS, polysomnography should be performed. (Standard) 4. Polysomnography is indicated following adenotonsillectomy to assess for residual OSAS in children with preoperative evidence for moderate to severe OSAS, obesity, craniofacial anomalies that obstruct the upper airway, and neurologic disorders (e.g., Down syndrome, Prader-Willi syndrome, and myelomeningocele). (Standard) 5. Polysomnography is indicated for positive airway pressure (PAP) titration in children with obstructive sleep apnea syndrome. (Standard) 6. Polysomnography is indicated when the clinical assessment suggests the diagnosis of congenital central alveolar hypoventilation syndrome or sleep related hypoventilation due to neuromuscular disorders or chest wall deformities. It is indicated in selected cases of primary sleep apnea of infancy. (Guideline) 7. Polysomnography is indicated when there is clinical evidence of a sleep related breathing disorder in infants who have experienced an apparent life-threatening event (ALTE). (Guideline) 8. Polysomnography is indicated in children being considered for adenotonsillectomy to treat obstructive sleep apnea syndrome. (Guideline) 9. Follow-up PSG in children on chronic PAP support is indicated to determine whether pressure requirements have changed as a result of the child's growth and development, if symptoms recur while on PAP, or if additional or alternate treatment is instituted. (Guideline) 10. Polysomnography is indicated after treatment of children for OSAS with rapid maxillary expansion to assess for the level of residual disease and to determine whether additional treatment is necessary. (Option) 11. Children with OSAS treated with an oral appliance should have clinical follow-up and polysomnography to assess response to treatment. (Option) 12. Polysomnography is indicated for noninvasive positive pressure ventilation (NIPPV) titration in children with other sleep related breathing disorders. (Option) 13. Children treated with mechanical ventilation may benefit from periodic evaluation with polysomnography to adjust ventilator settings. (Option) 14. Children treated with tracheostomy for sleep related breathing disorders benefit from polysomnography as part of the evaluation prior to decannulation. These children should be followed clinically after decannulation to assess for recurrence of symptoms of sleep related breathing disorders. (Option) 15. Polysomnography is indicated in the following respiratory disorders only if there is a clinical suspicion for an accompanying sleep related breathing disorder: chronic asthma, cystic fibrosis, pulmonary hypertension, bronchopulmonary dysplasia, or chest wall abnormality such as kyphoscoliosis. (Option) RECOMMENDATIONS AGAINST PSG USE: 16. Nap (abbreviated) polysomnography is not recommended for the evaluation of obstructive sleep apnea syndrome in children. (Option) 17. Children considered for treatment with supplemental oxygen do not routinely require polysomnography for management of oxygen therapy. (Option) Conclusions Current evidence in the field of pediatric sleep medicine indicates that PSG has clinical utility in the diagnosis and management of sleep related breathing disorders. The accurate diagnosis of SRBD in the pediatric population is best accomplished by integration of polysomnographic findings with clinical evaluation.
TL;DR: The effect of the environment on inbreeding depression scales linearly with the magnitude of stress; a population suffers one additional lethal equivalent, on average, for each 30% reduction in fitness induced by the stressful environment.
Abstract: Inbreeding–environment interactions occur when inbreeding leads to differential fitness loss in different environments. Inbred individuals are often more sensitive to environmental stress than are outbred individuals, presumably because stress increases the expression of deleterious recessive alleles or cellular safeguards against stress are pushed beyond the organism's physiological limits. We examined inbreeding–environment interactions, along two environmental axes (temperature and rearing host) that differ in the amount of developmental stress they impose, in the seed-feeding beetle Callosobruchus maculatus. We found that inbreeding depression (inbreeding load, L) increased with the stressfulness of the environment, with the magnitude of stress explaining as much as 66% of the variation in inbreeding depression. This relationship between L and developmental stress was not explainable by an increase in phenotypic variation in more stressful environments. To examine the generality of this experimental result, we conducted a meta-analysis of the available data from published studies looking at stress and inbreeding depression. The meta-analysis confirmed that the effect of the environment on inbreeding depression scales linearly with the magnitude of stress; a population suffers one additional lethal equivalent, on average, for each 30% reduction in fitness induced by the stressful environment. Studies using less-stressful environments may lack statistical power to detect the small changes in inbreeding depression. That the magnitude of inbreeding depression scales with the magnitude of the stress applied has numerous repercussions for evolutionary and conservation genetics and may invigorate research aimed at finding the causal mechanism involved in such a relationship.
TL;DR: There is very little evidence that routine cytologic procedures or imaging improves the ability to detect gynecologic cancer recurrence at a stage that will impact cure or response rates to salvage therapy.
TL;DR: In this paper, the authors reported the results of a prospective study of 20 patients who received a combination of angiotensin-converting enzymes, β-blockers, angiotenin II inhibitors, and aldosterone antagonists followed by the β2-agonist clenbuterol and were regularly tested with the pump at low speed.
Abstract: Background—We have previously shown that a specific combination of drug therapy and left ventricular assist device unloading results in significant myocardial recovery, sufficient to allow pump removal, in two thirds of patients with dilated cardiomyopathy receiving a Heartmate I pulsatile device However, this protocol has not been used with nonpulsatile devices Methods and Results—We report the results of a prospective study of 20 patients who received a combination of angiotensin-converting enzymes, β-blockers, angiotensin II inhibitors, and aldosterone antagonists followed by the β2-agonist clenbuterol and were regularly tested (echocardiograms, exercise tests, catheterizations) with the pump at low speed Before left ventricular assist device insertion, patient age was 352±126 years (16 male patients), patients were on 20±09 inotropes, 7 (35) had an intra-aortic balloon pump, 2 were hemofiltered, 2 were ventilated, 3 had a prior Levitronix device, and 1 had extracorporeal membrane oxygenation C
TL;DR: It is suggested that miR-21 is an Oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing mi R-21.
Abstract: MicroRNA-21 (miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors. Through functional suppression, miR-21 is implicated in practically every walk of oncogenic life: the promotion of cell proliferation, invasion and metastasis, genome instability and mutation, inflammation, replicative immortalization, abnormal metabolism, angiogenesis, and evading apoptosis, immune destruction, and growth suppressors. In particular, miR-21 is strongly involved in apoptosis. In this article, we reviewed the experimentally validated targets of miR-21 and found that two thirds are linked to intrinsic and/or extrinsic pathways of cellular apoptosis. This suggests that miR-21 is an oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing miR-21.