Showing papers by "University of Tennessee Health Science Center published in 2015"
Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
Case Western Reserve University1, Wake Forest University2, Tulane University3, National Institutes of Health4, United States Department of Veterans Affairs5, University of Alabama at Birmingham6, University of Tennessee Health Science Center7, University of Colorado Boulder8, Veterans Health Administration9, University of Utah10
TL;DR: In this article, the most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain, and the authors propose a target of less than 120 mm Hg.
Abstract: BACKGROUND The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. METHODS We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group. CONCLUSIONS Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).
4,125 citations
TL;DR: The incidence of community-acquired pneumonia requiring hospitalization was highest among the oldest adults and despite current diagnostic tests, no pathogen was detected in the majority of patients.
Abstract: Background Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. Methods We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. Results From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile ...
2,088 citations
Mohammad H. Forouzanfar1, Lily Alexander1, H. Ross Anderson2, Victoria F Bachman1 +718 more•Institutions (295)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
1,656 citations
University of Texas Health Science Center at Houston1, Medical College of Wisconsin2, Oregon Health & Science University3, University of Washington4, University of California, San Francisco5, University of Tennessee Health Science Center6, University of Southern California7, University of Alabama at Birmingham8, University of Cincinnati9, University of Arizona10, University of Toronto11, University of Maryland, Baltimore12, Sunnybrook Health Sciences Centre13, American College of Surgeons14, National Institutes of Health15
TL;DR: In this article, the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1 :1:2 ratio was evaluated.
Abstract: Importance Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. Objective To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Design, Setting, and Participants Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Interventions Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Main Outcomes and Measures Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. Results No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, −4.2% [95% CI, −9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, −3.7% [95% CI, −10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, −5.4% [95% CI, −10.4% to −0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P P Conclusions and Relevance Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. Trial Registration clinicaltrials.gov Identifier:NCT01545232
1,643 citations
TL;DR: The role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway are summarized.
1,229 citations
TL;DR: In this paper, the authors conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts.
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
721 citations
University of Tennessee Health Science Center1, University of Colorado Denver2, University of Kiel3, University of Milan4, University of Manchester5, Harvard University6, University of Copenhagen7, University of Hamburg8, Ghent University9, National University of Singapore10, Mackay Memorial Hospital11
TL;DR: The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL.
Abstract: Purpose To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. Methods A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic p...
680 citations
The American College of Financial Services1, Icahn School of Medicine at Mount Sinai2, Wayne State University3, Emory University4, Cleveland Clinic5, University of California, San Diego6, Ochsner Medical Center7, Louisiana State University8, University of Tennessee Health Science Center9, University of Texas at Dallas10, American Association of Clinical Endocrinologists11, Harvard University12, Baylor College of Medicine13, University of Alabama at Birmingham14, Veterans Health Administration15, University of Washington16, Mayo Clinic17, University of Miami18, University of California, Santa Barbara19, SUNY Downstate Medical Center20, University of Arizona21, Washington University in St. Louis22, University of Southern California23, University of California, Los Angeles24, University of California, Irvine25, Eastern Virginia Medical School26, Cornell University27
TL;DR: These guidelines are a working document that reflects the state of the field at the time of publication and any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.
634 citations
University of Texas MD Anderson Cancer Center1, Duke University2, University of South Florida3, Northwestern University4, University of Tennessee Health Science Center5, City of Hope National Medical Center6, Fox Chase Cancer Center7, University of California, San Diego8, Brigham and Women's Hospital9, Memorial Sloan Kettering Cancer Center10, University of Utah11, University of Michigan12, Roswell Park Cancer Institute13, Mayo Clinic14, Johns Hopkins University15, University of California, San Francisco16, University of Colorado Denver17, Washington University in St. Louis18, University of Alabama at Birmingham19, Stanford University20, University of Nebraska Medical Center21, Seattle Cancer Care Alliance22, Vanderbilt University23, Harvard University24
TL;DR: This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus andEGJ.
Abstract: Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.
379 citations
TL;DR: New insights into genetic factors regulating these mechanisms, as well as cellular factors important for stress adaptation, provide a foundation to better understand the emergence of antifungal drug resistance.
Abstract: As fatalities associated with fungal infections continue to grow as a major global health issue, the need for effective antifungal treatment is crucial. The current number of effective therapeutic drug options, however, is limited. With this, the documented rise in antifungal drug resistance in recent years is a critical concern, as resistance development severely limits the ability to successfully treat fatal infection. In this chapter, we explain the unique mechanisms of action of each antifungal drug class, including the polyenes, azoles, echinocandins, allylamines, flucytosine, griseofulvin, and potassium iodide. Furthermore, we discuss other mechanisms of resistance including biofilms, chromosomal abnormalities, and mitochondrial defects.
Johns Hopkins University1, Seattle Cancer Care Alliance2, University of Utah3, University of California, San Diego4, Fox Chase Cancer Center5, University of Colorado Boulder6, Roswell Park Cancer Institute7, Brigham and Women's Hospital8, Duke University9, University of South Florida10, University of Alabama at Birmingham11, Washington University in St. Louis12, City of Hope National Medical Center13, Vanderbilt University14, University of California, San Francisco15, University of Texas MD Anderson Cancer Center16, Memorial Sloan Kettering Cancer Center17, University of Nebraska Medical Center18, Harvard University19, Yale Cancer Center20, University of Michigan21, Stanford University22, Ohio State University23, Northwestern University24, Mayo Clinic25, University of Tennessee Health Science Center26, National Comprehensive Cancer Network27
TL;DR: Different testing methods currently available for determining whether patients with advanced NSCLC have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations are described.
Abstract: These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations.
TL;DR: It remains controversial whether TNBC in African-American women is a molecularly distinct disease or whether African- American women have a higher incidence of aggressive biology driven by disparities: there is evidence in support of both.
Abstract: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects BRCA1 mutation carriers and young women of African origin. There is evidence that African-American women with TNBC have worse clinical outcomes than women of European descent. However, it is unclear whether survival differences persist after adjusting for disparities in access to health-care treatment, co-morbid disease and income. It remains controversial whether TNBC in African-American women is a molecularly distinct disease or whether African-American women have a higher incidence of aggressive biology driven by disparities: there is evidence in support of both. Understanding the relative contributions of biology and disparities is essential for improving the poor survival rate of African-American women with TNBC.
TL;DR: In this paper, the authors focus on the functional analysis of conserved RNA secondary structures in the 5′ and 3′ of the betacoronavirus genomes and find evidence that an association between the 3′ and 5′UTRs is necessary for subgenomic RNA synthesis, but the basis for this association is not yet clear.
TL;DR: It is demonstrated that E-cig exposure elicits impaired pulmonary anti-microbial defenses and must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.
Abstract: Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7x1011 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.
University of Michigan1, University of Utah2, Johns Hopkins University3, University of Pennsylvania4, Wayne State University5, National Institutes of Health6, University of Toronto7, University of Southern California8, Children's National Medical Center9, Washington University in St. Louis10, University of Texas at Dallas11, Columbia University12, Boston Children's Hospital13, Duke University14, Children's Memorial Hospital15, University of Pittsburgh16, University of California, San Francisco17, Seattle Children's18, University of Rochester19, University of Louisville20, Medical College of Wisconsin21, University of California, Los Angeles22, University of California, Irvine23, University of Minnesota24, Children's of Alabama25, Cincinnati Children's Hospital Medical Center26, Nationwide Children's Hospital27, Loma Linda University28, University of Tennessee Health Science Center29, University of Texas at San Antonio30, University of Arkansas for Medical Sciences31
TL;DR: In this paper, a trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest was conducted, and the primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with at least 70 before cardiac arrest.
Abstract: BackgroundTherapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. MethodsWe conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. ResultsA total of 295 patients underwent randomization. Among the 260 pat...
Pohang University of Science and Technology1, Harvard University2, Jagiellonian University3, Utrecht University4, Lund University5, North Shore-LIJ Health System6, Morehouse School of Medicine7, National Research Council8, Autonomous University of Barcelona9, French Institute of Health and Medical Research10, Semmelweis University11, University of Melbourne12, Cardiff University13, Yale University14, University of Tennessee Health Science Center15, Cedars-Sinai Medical Center16, University of Gothenburg17, University of Oxford18, University of Duisburg-Essen19, La Trobe University20, German Cancer Research Center21, Ghent University22, University of Queensland23, Seoul National University24, London Metropolitan University25, Council of Scientific and Industrial Research26, Mayo Clinic27, Dankook University28, Aalborg University29, Kyung Hee University30, Ewha Womans University31, University of Toronto32, Erasmus University Rotterdam33, University of Pennsylvania34, Temple University35, University of Valencia36, QIMR Berghofer Medical Research Institute37, Université catholique de Louvain38, University of Freiburg39, University of Amsterdam40, Walter and Eliza Hall Institute of Medical Research41, Oswaldo Cruz Foundation42, Federal University of Rio de Janeiro43, Icahn School of Medicine at Mount Sinai44, University of California, Los Angeles45, University of Helsinki46, Queensland University of Technology47, Washington University in St. Louis48, Hiroshima University49, Hannover Medical School50, Umeå University51, Johns Hopkins University52, Ludwig Maximilian University of Munich53
TL;DR: An improved version of EVpedia, a public database for EVs research, is presented, which contains a database of publications and vesicular components, identification of orthologous vesicle components, bioinformatic tools and a personalized function.
Abstract: Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging.
Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research.
Availability and implementation: The web site was implemented in PHP, Java, MySQL and Apache, and is freely available at http://evpedia.info.
Brigham and Women's Hospital1, Ohio State University2, Northwestern University3, University of California, San Francisco4, Vanderbilt University5, Harvard University6, University of Utah7, Fox Chase Cancer Center8, University of California, San Diego9, University of Michigan10, University of Nebraska Medical Center11, Mayo Clinic12, University of Alabama13, City of Hope National Medical Center14, Stanford University15, Roswell Park Cancer Institute16, University of Colorado Boulder17, Washington University in St. Louis18, University of Tennessee Health Science Center19, University of Washington20, Memorial Sloan Kettering Cancer Center21, Duke University22, University of South Florida23, University of Texas MD Anderson Cancer Center24, Johns Hopkins University25
TL;DR: These guidelines focus on sporadic NETs of the pancreas, gastrointestinal tract, lung, and thymus, which are associated with symptoms attributable to hormonal hypersecretion.
Abstract: Neuroendocrine tumors (NETs) comprise a broad family of tumors that may or may not be associated with symptoms attributable to hormonal hypersecretion. The NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine Tumors discuss the diagnosis and management of both sporadic and hereditary NETs. This selection from the guidelines focuses on sporadic NETs of the pancreas, gastrointestinal tract, lung, and thymus.
TL;DR: A PTEN-mTORC2 axis is established that maintains Treg cell stability and coordinates TReg cell–mediated control of effector responses and restores functioning of PTEN -deficient Treg cells.
Abstract: The interplay between effector T cells and regulatory T cells (Treg cells) is crucial for adaptive immunity, but how Treg cells control diverse effector responses is elusive. We found that the phosphatase PTEN links Treg cell stability to repression of type 1 helper T cell (TH1 cell) and follicular helper T cell (TFH cell) responses. Depletion of PTEN in Treg cells resulted in excessive TFH cell and germinal center responses and spontaneous inflammatory disease. These defects were considerably blocked by deletion of interferon-γ, indicating coordinated control of TH1 and TFH responses. Mechanistically, PTEN maintained Treg cell stability and metabolic balance between glycolysis and mitochondrial fitness. Moreover, PTEN deficiency upregulates activity of the metabolic checkpoint kinase complex mTORC2 and the serine-threonine kinase Akt, and loss of this activity restores functioning of PTEN-deficient Treg cells. Our studies establish a PTEN-mTORC2 axis that maintains Treg cell stability and coordinates Treg cell-mediated control of effector responses.
TL;DR: The findings support the use of e health interventions as a treatment option for obesity, but there is insufficient evidence for the effectiveness of eHealth interventions for weight loss maintenance or weight gain prevention.
Abstract: Summary
A systematic review of randomized controlled trials was conducted to evaluate the effectiveness of eHealth interventions for the prevention and treatment of overweight and obesity in adults. Eight databases were searched for studies published in English from 1995 to 17 September 2014. Eighty-four studies were included, with 183 intervention arms, of which 76% (n = 139) included an eHealth component. Sixty-one studies had the primary aim of weight loss, 10 weight loss maintenance, eight weight gain prevention, and five weight loss and maintenance. eHealth interventions were predominantly delivered using the Internet, but also email, text messages, monitoring devices, mobile applications, computer programs, podcasts and personal digital assistants. Forty percent (n = 55) of interventions used more than one type of technology, and 43.2% (n = 60) were delivered solely using eHealth technologies. Meta-analyses demonstrated significantly greater weight loss (kg) in eHealth weight loss interventions compared with control (MD −2.70 [−3.33,−2.08], P < 0.001) or minimal interventions (MD −1.40 [−1.98,−0.82], P < 0.001), and in eHealth weight loss interventions with extra components or technologies (MD 1.46 [0.80, 2.13], P < 0.001) compared with standard eHealth programmes. The findings support the use of eHealth interventions as a treatment option for obesity, but there is insufficient evidence for the effectiveness of eHealth interventions for weight loss maintenance or weight gain prevention.
TL;DR: Systemic scleroderma is one of the most complex systemic autoimmune diseases and the roles played by other ubiquitous molecular entities in influencing the immune system, vasculature, and connective tissue cells are just beginning to be studied and may provide insights into new therapeutic approaches to treat SSc.
Abstract: Systemic scleroderma (SSc) is one of the most complex systemic autoimmune diseases. It targets the vasculature, connective tissue-producing cells (namely fibroblasts/myofibroblasts), and components of the innate and adaptive immune systems. Clinical and pathologic manifestations of SSc are the result of: (1) innate/adaptive immune system abnormalities leading to production of autoantibodies and cell-mediated autoimmunity, (2) microvascular endothelial cell/small vessel fibroproliferative vasculopathy, and (3) fibroblast dysfunction generating excessive accumulation of collagen and other matrix components in skin and internal organs. All three of these processes interact and affect each other. The disease is heterogeneous in its clinical presentation that likely reflects different genetic or triggering factor (i.e., infection or environmental toxin) influences on the immune system, vasculature, and connective tissue cells. The roles played by other ubiquitous molecular entities (such as lysophospholipids, endocannabinoids, and their diverse receptors and vitamin D) in influencing the immune system, vasculature, and connective tissue cells are just beginning to be realized and studied and may provide insights into new therapeutic approaches to treat SSc.
TL;DR: In this paper, the role of miR-21 and its target genes in different cancers, and provide insight into how this oncogenic miRNA regulates cancer cell proliferation, migration, and apoptosis by suppressing the expression of tumor suppressors.
Abstract: MicroRNAs (miRNAs) are small endogenous noncoding RNAs that suppress gene expression at the post-transcriptional level. In the past decade, miRNAs have been extensively studied in a number of different human cancers. MiRNAs have been identified to act both as oncogenes and as tumor suppressors. In addition, miRNAs are associated with the intrinsic resistance of cancer to various forms of therapy, and they are implicated in both tumor progression and metastasis. The characterization of the specific alterations in the patterns of miRNA expression in cancer has great potential for identifying biomarkers for early cancer detection, as well as for potential therapeutic intervention in cancer treatment. In this chapter, we describe the ever-expanding role of miR-21 and its target genes in different cancers, and provide insight into how this oncogenic miRNA regulates cancer cell proliferation, migration, and apoptosis by suppressing the expression of tumor suppressors.
TL;DR: The clinical evidence, current status, and future opportunities of curcumin nanoformulation(s) in the field of medicine are discussed, and a concise summary of the actions required to develop curcuming nanoformulations as pharmaceutical or nutraceutical candidates are presented.
Abstract: Curcumin (diferuloylmethane) is a bioactive and major phenolic component of turmeric derived from the rhizomes of curcuma longa linn For centuries, curcumin has exhibited excellent therapeutic benefits in various diseases Owing to its anti-oxidant and anti-inflammatory properties, curcumin plays a significant beneficial and pleiotropic regulatory role in various pathological conditions including cancer, cardiovascular disease, Alzheimer’s disease, inflammatory disorders, neurological disorders, and so on Despite such phenomenal advances in medicinal applications, the clinical implication of native curcumin is hindered due to low solubility, physico-chemical instability, poor bioavailability, rapid metabolism, and poor pharmacokinetics However, these issues can be overcome by utilizing an efficient delivery system Active scientific research was initiated in 2005 to improve curcumin’s pharmacokinetics, systemic bioavailability, and biological activity by encapsulating or by loading curcumin into nanoform(s) (nanoformulations) A significant number of nanoformulations exist that can be translated toward medicinal use upon successful completion of pre-clinical and human clinical trials Considering this perspective, current review provides an overview of an efficient curcumin nanoformulation for a targeted therapeutic option for various human diseases In this review article, we discuss the clinical evidence, current status, and future opportunities of curcumin nanoformulation(s) in the field of medicine In addition, this review presents a concise summary of the actions required to develop curcumin nanoformulations as pharmaceutical or nutraceutical candidates
TL;DR: It is found that Aim2-deficient mice were hypersusceptible to colonic tumor development and a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer is uncovered.
University of Pennsylvania1, Johns Hopkins University2, University of Maryland, Baltimore3, Emory University4, Rowan University5, Stony Brook University6, McGill University7, University of Tennessee Health Science Center8, Virginia Commonwealth University9, MetroHealth10, Oregon Health & Science University11, University of Michigan12, Case Western Reserve University13, University of Arizona14
TL;DR: It is strongly recommend that patients who present pulseless with signs of life after penetrating thoracic injury undergo EDT, and conditionally recommend against EDT for pulseless patients without signs ofLife after blunt injury.
Abstract: BACKGROUNDWithin the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework, we performed a systematic review and developed evidence-based recommendations to answer the following PICO (Population, Intervention, Comparator, Outcomes) question: should patients who present
Seattle Cancer Care Alliance1, University of Washington2, Memorial Sloan Kettering Cancer Center3, University of South Florida4, Dana Corporation5, University of Michigan6, Fox Chase Cancer Center7, Ohio State University8, Vanderbilt University9, Stanford University10, University of Texas MD Anderson Cancer Center11, University of Colorado Boulder12, Roswell Park Cancer Institute13, University of Utah14, City of Hope National Medical Center15, University of Alabama16, Northwestern University17, Washington University in St. Louis18, Johns Hopkins University19, University of Tennessee Health Science Center20, Duke University21, University of California, San Diego22, National Comprehensive Cancer Network23
TL;DR: The NCCN Guidelines for Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015 are summarized and 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches are highlighted.
Abstract: The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.
TL;DR: Abnormal global longitudinal strain and diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure and may identify a subset of survivors at higher risk for poor clinical cardiac outcomes who may benefit from early medical intervention.
TL;DR: Focusing on the terpenes, the largest class of plant natural products, the basis of terpene diversity is investigated through analysis of multiple sequenced plant genomes and evidence is found for different mechanisms of pathway assembly in eudicots and monocots.
Abstract: Plants produce an array of specialized metabolites, including chemicals that are important as medicines, flavors, fragrances, pigments and insecticides. The vast majority of this metabolic diversity is untapped. Here we take a systematic approach toward dissecting genetic components of plant specialized metabolism. Focusing on the terpenes, the largest class of plant natural products, we investigate the basis of terpene diversity through analysis of multiple sequenced plant genomes. The primary drivers of terpene diversification are terpenoid synthase (TS) “signature” enzymes (which generate scaffold diversity), and cytochromes P450 (CYPs), which modify and further diversify these scaffolds, so paving the way for further downstream modifications. Our systematic search of sequenced plant genomes for all TS and CYP genes reveals that distinct TS/CYP gene pairs are found together far more commonly than would be expected by chance, and that certain TS/CYP pairings predominate, providing signals for key events that are likely to have shaped terpene diversity. We recover TS/CYP gene pairs for previously characterized terpene metabolic gene clusters and demonstrate new functional pairing of TSs and CYPs within previously uncharacterized clusters. Unexpectedly, we find evidence for different mechanisms of pathway assembly in eudicots and monocots; in the former, microsyntenic blocks of TS/CYP gene pairs duplicate and provide templates for the evolution of new pathways, whereas in the latter, new pathways arise by mixing and matching of individual TS and CYP genes through dynamic genome rearrangements. This is, to our knowledge, the first documented observation of the unique pattern of TS and CYP assembly in eudicots and monocots.
TL;DR: Treating women 40 years or older with stage 0 to II breast cancer with HF-WBI appears to yield lower rates of acute toxic effects and quality of life problems and six months after irradiation, as well as less fatigue and less trouble meeting family needs after completing radiation therapy.
Abstract: Importance The most appropriate dose fractionation for whole-breast irradiation (WBI) remains uncertain. Objective To assess acute and 6-month toxic effects and quality of life (QOL) with conventionally fractionated WBI (CF-WBI) vs hypofractionated WBI (HF-WBI). Design, Setting, and Participants Unblinded randomized trial of CF-WBI (n = 149; 50.00 Gy/25 fractions + boost [10.00-14.00 Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56 Gy/16 fractions + boost [10.00-12.50 Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287 women 40 years or older with stage 0 to II breast cancer for whom WBI without addition of a third field was recommended; 76% of study participants (n = 217) were overweight or obese. Patients were enrolled from February 2011 through February 2014 and observed for a minimum of 6 months. Interventions Administration of CF-WBI or HF-WBI. Main Outcomes and Measures Physician-reported acute and 6-month toxic effects using National Cancer Institute Common Toxicity Criteria, and patient-reported QOL using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). All analyses were intention to treat, with outcomes compared using the χ 2 test, Cochran-Armitage test, and ordinal logistic regression. Results Of 287 participants, 149 were randomized to CF-WBI and 138 to HF-WBI. Treatment arms were well matched for baseline characteristics, including FACT-B total score (HF-WBI, 120.1 vs CF-WBI, 118.8; P = .46) and individual QOL items such as somewhat or more lack of energy (HF-WBI, 38% vs CF-WBI, 39%; P = .86) and somewhat or more trouble meeting family needs (HF-WBI, 10% vs CF-WBI, 14%; P = .54). Maximum physician-reported acute dermatitis (36% vs 69%; P P P = .001), hyperpigmentation (9% vs 20%; P = .002), and fatigue (9% vs 17%; P = .02) during irradiation were lower in patients randomized to HF-WBI. The rate of overall grade 2 or higher acute toxic effects was less with HF-WBI than with CF-WBI (47% vs 78%; P P = .01), and patients randomized to HF-WBI reported less lack of energy (23% vs 39%; P P = .01). Multivariable regression confirmed the superiority of HF-WBI in terms of patient-reported lack of energy (odds ratio [OR], 0.39; 95% CI, 0.24-0.63) and trouble meeting family needs (OR, 0.34; 95% CI, 0.16-0.75). Conclusions and Relevance Treatment with HF-WBI appears to yield lower rates of acute toxic effects than CF-WBI as well as less fatigue and less trouble meeting family needs 6 months after completing radiation therapy. These findings should be communicated to patients as part of shared decision making. Trial Registration clinicaltrials.gov Identifier:NCT01266642
TL;DR: A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease.
Abstract: Complement activation has a role in the pathogenesis of IgA nephropathy, an autoimmune disease mediated by pathogenic immune complexes consisting of galactose-deficient IgA1 bound by antiglycan antibodies. Of three complement-activation pathways, the alternative and lectin pathways are involved in IgA nephropathy. IgA1 can activate both pathways in vitro, and pathway components are present in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and mannan-binding lectin, mannan-binding lectin-associated serine proteases 1 and 2, and C4d in the lectin pathway. Genome-wide association studies identified deletion of complement factor H-related genes 1 and 3 as protective against the disease. Because the corresponding gene products compete with factor H in the regulation of the alternative pathway, it has been hypothesized that the absence of these genes could lead to more potent inhibition of complement by factor H. Complement activation can take place directly on IgA1-containing immune complexes in circulation and/or after their deposition in the mesangium. Notably, complement factors and their fragments may serve as biomarkers of IgA nephropathy in serum, urine, or renal tissue. A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease.