Guidelines for hand hygiene recommend the use of alcohol-based hand rubs containing humectants in order to improve dermal tolerance. However, the bactericidal efficacy of pre-surgical hand rubs is negatively a...
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Τρίτη 27 Ιουνίου 2017
Influence of glycerol and an alternative humectant on the immediate and 3-hours bactericidal efficacies of two isopropanol-based antiseptics in laboratory experiments in vivo according to EN 12791
Reconstruction of fluorescence molecular tomography with a cosinoidal level set method
Implicit shape-based reconstruction method in fluorescence molecular tomography (FMT) is capable of achieving higher image clarity than image-based reconstruction method. However, the implicit shape method suf...
http://ift.tt/2sli6Pf
The Complexity of Simple – Bringing Order to Complex Systems by Chris Hicks
The ability to simplify means to eliminate the unnecessary so that the necessary may speak –Hans Hofmann We live in complex times. Resuscitation has gone endovascular, microvascular, mitochondrial. EPR, ED-ECMO, REBOA–it's a fascinating time to be a Resuscitationist. But the more we advance the resuscitation agenda, the more we learn how complex critical illness […]
EMCrit by Chris Hicks.
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Lateral ridge augmentation with two different ratios of deproteinized bovine bone and autogenous bone: A 2-year follow-up of a randomized and controlled trial
Abstract
Background
The optimal ratio of deproteinized bovine bone (DPBB) and autogenous bone (AB) for lateral augmentation is presently unknown.
Purpose
To evaluate implant treatment outcome and radiological graft changes after lateral ridge augmentation with 2 different mixtures of DPBB and AB, 2 years after functional loading.
Materials and methods
Thirteen patients were included in a split mouth, randomized, controlled trial. Four partially edentulous and 10 totally edentulous jaws with an alveolar ridge width of <4 mm were augmented with a graft mixture of 90:10 (DPBB:AB) on one side and 60:40 (DPBB:AB) on the contra lateral side. Graft width changes were measured on CBCT scans at different time points. Implant survival and success rates were calculated. Resonance frequency analysis and marginal bone measurements were performed after 2 years of loading.
Results
The survival rate was 94.4% for implants installed in the 90:10 and 100% for implants installed in the 60:40. There were no statistically significant differences in survival rate or success rate between the mixtures.
The width was 5.7 mm and 6.2 mm, respectively for the 2 groups without any significant difference between the groups after 2 years of loading. There was a significant difference in graft reduction between the groups, 54.4% (90:10) and 37.5% (60:40), respectively. There were no statistically significant differences in implant stability or marginal bone levels at any time points.
Conclusions
The 2 treatment modalities may be successfully used for lateral ridge augmentation and presented good clinical results after 2 years of loading. However, long-term RCTs are required before final conclusions can be provided on this specific topic.
http://ift.tt/2tWmpCC
Sculptors, Architects, and Painters Conceive of Depicted Spaces Differently
Abstract
Sculptors, architects, and painters are three professional groups that require a comprehensive understanding of how to manipulate spatial structures. While it has been speculated that they may differ in the way they conceive of space due to the different professional demands, this has not been empirically tested. To achieve this, we asked architects, painters, sculptors, and a control group questions about spatially complex pictures. Verbalizations elicited were examined using cognitive discourse analysis. We found significant differences between each group. Only painters shifted consistently between 2D and 3D concepts, architects were concerned with paths and spatial physical boundedness, and sculptors produced responses that fell between architects and painters. All three differed from controls, whose verbalizations were generally less elaborate and detailed. Thus, for the case of sculptors, architects, and painters, profession appears to relate to a different spatial conceptualization manifested through a systematically contrasting way of talking about space.
http://ift.tt/2ugWJjw
Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma
Abstract
The oral proteasome inhibitor ixazomib (Ninlaro®) is approved in the USA, EU and Japan in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. In adults with relapsed and/or refractory MM who had received one to three prior therapies, progression-free survival (PFS) was significantly prolonged in patients who received the ixazomib- versus placebo-based triple therapy in the pivotal, global TOURMALINE-MM1 trial and its regional expansion (China continuation study). A significantly longer time to progression and favourable hazard ratios for PFS were observed across all prespecified subgroups, including patients with high cytogenetic risk. Overall response was achieved in a significantly higher proportion of patients receiving ixazomib- than placebo-based treatment. Ixazomib had a manageable tolerability profile in patients with MM. Ixazomib is the first orally-administered proteasome inhibitor approved for patients with MM, and in combination with lenalidomide and dexamethasone represents an important new option for use in patients with relapsed and/or refractory MM who have previously received at least one prior therapy.
http://ift.tt/2ugZiC7
The topical application of low-temperature argon plasma enhances the anti-inflammatory effect of Jaun-ointment on DNCB-induced NC/Nga mice
Jaun-ointment (JO), also known as Shiunko in Japan, is one of the most popular medicinal formulae used in Korean traditional medicine for the external treatment of skin wound and inflammatory skin conditions. ...
http://ift.tt/2sfBeCR
Effect of pomegranate extracts on brain antioxidant markers and cholinesterase activity in high fat-high fructose diet induced obesity in rat model
To investigate beneficial effects of Pomegranate seeds oil (PSO), leaves (PL), juice (PJ) and (PP) on brain cholinesterase activity, brain oxidative stress and lipid profile in high-fat-high fructose diet (HFD...
http://ift.tt/2sZePqL
Reproductive Vocabularies: Interrogating Intersections of Reproduction, Sexualities, and Religion among U.S. Cisgender College Women
Abstract
Although feminists often examine the ways reproduction shapes women's lives, such research typically only focuses on the effects of reproduction after the fact while leaving reproductive decision-making beforehand unexplored. In the present article, we flip this pattern by outlining the "vocabularies of motive" (Mills 1940) cisgender women offer for wanting to engage in or abstain from reproduction. Based on in-depth interviews with 20 class-privileged, cisgender U.S. women in college who possess the resources to forego reproduction, we analyze how they define their reproductive intentions as (a) conforming to social expectations, (b) seeking fulfillment, (c) replicating past experience, and/or (d) rejecting reproduction and parenting. Further, we compare and contrast the reproductive vocabularies of motive offered by heterosexual and bisexual as well as religious and nonreligious cisgender women in our sample. In conclusion, we draw out implications for understanding women's reproductive decision-making and the social construction of reproductive norms.
http://ift.tt/2tjdn4Z
The Antidepressant and Cognitive Improvement Activities of the Traditional Chinese Herb Cistanche
More than ten percent of people suffer from at least one episode of depression and related mental disorders in a lifetime, and depression and related mental disorders are one of the world's greatest public health problems. A multiple system theory holds that dysregulation of the multiple systems underlies the pathogenesis of depression and related mental disorders, and new therapies based on the multiple system dysregulation theory are urgently needed. In this study, the antidepressant effect of decoction from herb Cistanche deserticola Y.C.Ma and Cistanche tubulosa was examined. Herb Cistanche decoction reduced the immobility period significantly in the mouse tail suspension test. Mice treated with herb decoction showed an improved ability of spatial learning and memory in the Morris water maze test. Groups treated herb decoction displayed a downregulated monoamine oxidase (MAO) activity; the dopamine (DA) concentration in the brain was upregulated, indicating herb Cistanche decoction improved the nerve excitability; the serum concentration of corticosterone (CORT) was downregulated, showing that mice benefited from a reduced stress level. Hence, the antidepressant efficacy and mechanism of traditional Chinese herb Cistanche were explored in this study. Herb Cistanche showed a potential to be developed as a complementary and alternative therapy for depression.
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The Perfect Storm of Trauma: The experiences of women who have experienced birth trauma and subsequently accessed residential parenting services in Australia
Publication date: Available online 27 June 2017
Source:Women and Birth
Author(s): Holly S. Priddis, Hazel Keedle, Hannah Dahlen
BackgroundThere appears to be a chasm between idealised motherhood and reality, and for women who experience birth trauma this can be more extreme and impact on mental health. Australia is unique in providing residential parenting services to support women with parenting needs such as sleep or feeding difficulties. Women who attend residential parenting services have experienced higher rates of intervention in birth and poor perinatal mental health but it is unknown how birth trauma may impact on early parenting.Aims and objectivesThis study aims to explore the early parenting experiences of women who have accessed residential parenting services in Australia and consider their birth was traumatic.MethodsIn-depth interviews were conducted with eight women across Australia who had experienced birth trauma and accessed residential parenting services in the early parenting period. These interviews were conducted both face to face and over the telephone. The data was analysed using thematic analysis.FindingsOne overarching theme was identified: "The Perfect Storm of Trauma" which identified that the participants in this study who accessed residential parenting services were more likely to have entered pregnancy with pre-existing vulnerabilities, and experienced a culmination of traumatic events during labour, birth, and in the early parenting period. Four subthemes were identified: "Bringing Baggage to Birth", "Trauma through a Thousand Cuts", "Thrown into the Pressure Cooker", and "Trying to work it all out".ConclusionHow women are cared for during their labour, birth and postnatal period impacts on how they manage early parenthood. Support is crucial for women, including practical parenting support, and emotional support by health professionals and peers.
http://ift.tt/2sZyuXA
A Case of Strongyloidiasis: An Immigrant Healthcare Worker Presenting with Fatigue and Weight Loss
Background. Strongyloides stercoralis is an intestinal nematode parasite classified as a soil-transmitted helminth, endemic in tropical and subtropical regions. Strongyloides stercoralis can remain dormant for decades after the initial infection. Case. We describe a patient who was diagnosed with Strongyloides stercoralis infection three weeks after a left inguinal hernia repair and discuss approaches to prevention, diagnosis, and treatment. Conclusions. Physicians in the United States often miss opportunities to identify patients with chronic strongyloidiasis. Symptoms may be vague and screening tests have limitations. We review current strategies for diagnosis and treatment of chronic intestinal strongyloidiasis in immigrant patients who have significant travel history to tropical regions and discuss the clinical features and management of the infection.
http://ift.tt/2tiJ52w
Efficacy of Sequential Ipilimumab Monotherapy vs Best Supportive Care For Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer
Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase 2 study evaluated the safety and efficacy of ipilimumab monotherapy vs best supportive care among patients with advanced/metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy.<br /><br />Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints included PFS by modified WHO criteria and overall survival (OS). <br /><br />Results: Of 143 patients screened, 57 were randomized to each arm. irPFS with ipilimumab vs BSC was not improved (2.92 months [95% CI, 1.61-5.16] vs 4.90 months [95% CI, 3.45-6.54], HR=1.44; 80% CI, 1.09-1.91; P=0.097), resulting in study cessation. At study closeout, which occurred 8 months after the interim analysis, the median OS durations were 12.7 months (95% CI, 10.5-18.9) and 12.1 months (95% CI, 9.3-not estimable), respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 23% of ipilimumab-treated patients, of which diarrhea (9%) and fatigue (5%) were most frequent, and in 9% of active BSC-treated patients. <br /><br />Conclusions: While ipilimumab at 10 mg/kg was manageable it did not improve irPFS vs BSC. However, comparable median OS of »1 year and a favorable safety profile support the investigation of ipilimumab in combination with other therapies for advanced gastric cancer.
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Diffusion MRI phenotypes predict overall survival benefit from anti-VEGF monotherapy in recurrent glioblastoma: Converging evidence from phase II trials
Purpose: Anti-VEGF therapies remain controversial in the treatment of recurrent glioblastoma (GBM). In the current study we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an overall survival (OS) advantage when treated with cediranib, bevacizumab, cabozantinib, or aflibercept monotherapy at first or second recurrence. These findings were validated using a separate trial comparing bevacizumab with lomustine. <br /><br />Experimental Design: Patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate Phase II clinical trials were included: 1) cediranib (NCT00035656); 2) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); 3) cabozantinib (XL184-201; NCT00704288); 4) aflibercept (VEGF Trap; NCT00369590); and 5) bevacizumab or lomustine (BELOB; NTR1929). Apparent diffusion coefficient (ADC) histogram analysis was performed prior to therapy to estimate "ADCL", the mean of the lower ADC distribution. Pre-treatment ADCL, enhancing volume, and clinical variables were tested as independent prognostic factors for OS. <br /><br />Results: The coefficient of variance (COV) in double baseline ADCL measurements was 2.5% and did not significantly differ (P=0.4537). An ADCL threshold of 1.24 um2/ms produced the largest OS differences between patients (HR~0.5) and patients with an ADCL>1.24 um2/ms had close to double the OS in all anti-VEGF therapeutic scenarios tested. Training and validation data confirmed baseline ADCL was an independent predictive biomarker for OS in anti-VEGF therapies, but not lomustine, after accounting for age and baseline enhancing tumor volume. <br /><br />Conclusions: Pre-treatment diffusion MRI is a predictive imaging biomarker for OS in patients with recurrent GBM treated with anti-VEGF monotherapy at first or second relapse.
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First-in-Human Study of AMG 820, a Monoclonal Anti-Colony-Stimulating Factor 1 Receptor Antibody, in Patients With Advanced Solid Tumors
Purpose: Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and interleukin-34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820.<br /><br />Experimental Design: Adult patients with relapsed or refractory advanced solid tumors received intravenous AMG 820 0.5 mg/kg once weekly or 1.5 to 20 mg/kg every 2 weeks (Q2W) until disease progression, adverse event (AE), or consent withdrawal. <br /><br />Results: Twenty-five patients received ≥1 dose of AMG 820. AMG 820 was tolerated up to 20 mg/kg; the maximum tolerated dose was not reached. One dose-limiting toxicity was observed (20 mg/kg; nonreversible grade 3 deafness). Most patients (76%) had treatment-related AEs; the most common were periorbital edema (44%), increased aspartate aminotransferase (AST; 28%), fatigue (24%), nausea (16%), increased blood alkaline phosphatase (12%), and blurred vision (12%). No patients had serious or fatal treatment-related AEs; 28% had grade ≥3 treatment-related AEs. Grade 3 AST elevations resolved when treatment was withheld. AMG 820 showed linear pharmacokinetics, with minimal accumulation (<2-fold) after repeated dosing. Pharmacodynamic increases in serum CSF1 concentrations and reduced numbers of skin macrophages were observed. Best response was stable disease in 8 patients (32%).<br /><br />Conclusions: AMG 820 was tolerated with manageable toxicities up to 20 mg/kg Q2W. Pharmacodynamic response was demonstrated and limited antitumor activity was observed.
http://ift.tt/2rZZ1Tp
Update on Treatment Options for Advanced Bile Duct Tumours: Radioembolisation for Advanced Cholangiocarcinoma
Abstract
Cholangiocarcinoma is a rare form of gastrointestinal cancer with a poor prognosis. Patients often present with biliary obstruction or non-specific abdominal pain, and a high proportion of patients have advanced disease at initial diagnosis. The goal of this review is to discuss treatment options for patients with advanced bile duct tumours focusing on radioembolisation (RE) and its impact on overall survival. RE provides a therapeutic option for patients with unresectable cholangiocarcinoma. However, although systemic chemotherapy has demonstrated a survival benefit in randomised controlled trials, there is limited supporting evidence for the use of RE in this setting. Studies are mostly limited to single-centre, small cohorts with variable outcome measures. Additionally, patients included in these studies received a variety of previous therapies including chemotherapy, surgery or alternative intra-arterial therapy; therefore, a true assessment of overall survival benefit is difficult.
http://ift.tt/2ugjYdz
Effects of a Preschool Intervention on Physical Activity and Body Composition
To investigate the effect of a preschool physical activity intervention program delivered in licensed childcare settings, with or without a parent-facilitated home component, on children's daily physical activity, sedentary time, and body composition.
http://ift.tt/2ugzSV4
Method of Improved Fuzzy Contrast Combined Adaptive Threshold in NSCT for Medical Image Enhancement
Noises and artifacts are introduced to medical images due to acquisition techniques and systems. This interference leads to low contrast and distortion in images, which not only impacts the effectiveness of the medical image but also seriously affects the clinical diagnoses. This paper proposes an algorithm for medical image enhancement based on the nonsubsampled contourlet transform (NSCT), which combines adaptive threshold and an improved fuzzy set. First, the original image is decomposed into the NSCT domain with a low-frequency subband and several high-frequency subbands. Then, a linear transformation is adopted for the coefficients of the low-frequency component. An adaptive threshold method is used for the removal of high-frequency image noise. Finally, the improved fuzzy set is used to enhance the global contrast and the Laplace operator is used to enhance the details of the medical images. Experiments and simulation results show that the proposed method is superior to existing methods of image noise removal, improves the contrast of the image significantly, and obtains a better visual effect.
http://ift.tt/2sZ8sDH
Role of Vascular Endothelial Cells in Disseminated Intravascular Coagulation Induced by Seawater Immersion in a Rat Trauma Model
Trauma complicated by seawater immersion is a complex pathophysiological process with higher mortality than trauma occurring on land. This study investigated the role of vascular endothelial cells (VECs) in trauma development in a seawater environment. An open abdominal injury rat model was used. The rat core temperatures in the seawater (SW, 22°C) group and normal sodium (NS, 22°C) group declined equivalently. No rats died within 12 hours in the control and NS groups. However, the median lethal time of the rats in the SW group was only 260 minutes. Among the 84 genes involved in rat VEC biology, the genes exhibiting the high expression changes (84.62%, 11/13) on a qPCR array were associated with thrombin activity. The plasma activated partial thromboplastin time and fibrinogen and vWF levels decreased, whereas the prothrombin time and TFPI levels increased, indicating intrinsic and extrinsic coagulation pathway activation and inhibition, respectively. The plasma plasminogen, FDP, and D-dimer levels were elevated after 2 hours, and those of uPA, tPA, and PAI-1 exhibited marked changes, indicating disseminated intravascular coagulation (DIC). Additionally, multiorgan haemorrhagia was observed. It indicated that seawater immersion during trauma may increase DIC, elevating mortality. VECs injury might play an essential role in this process.
http://ift.tt/2sg9233
FDA Partners with ASCO's CancerLinQ [News in Brief]
Alliance gives regulators access to real-world data on impact of newly approved cancer therapies.
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An Automated Critical Event Screening and Notification System to Facilitate Preanesthesia Record Review.
BACKGROUND: Anesthesia information management systems make prior anesthesia records readily available for review when patients return for a subsequent procedure but may create a problem of too much documentation to review in a limited amount of time. We implemented a screening tool to facilitate the identification of critical documentation for review. METHODS: An algorithm was developed to electronically search prior anesthesia records for predefined critical events and flag records containing these events. Our web-based daily case schedule was modified to contain a warning message for any patient on the schedule who has a prior record flagged by the system, in addition to a preexisting hyperlink to view the relevant record. A retrospective analysis was performed to determine the impact of the warning messages on the frequency with which the care team reviewed these records before providing anesthesia care. RESULTS: The screening algorithm flagged 13% of archived cases as critical. There were 3329 and 3369 cases in the 6 months before and after system implementation, respectively, that had prior critical records available for review at that time. One or more of these critical records were viewed before the subsequent case start in 39% vs 59% (P
http://ift.tt/2skvnYr
http://ift.tt/2skvnYr
Anesthetic Management of Narcolepsy Patients During Surgery: A Systematic Review.
BACKGROUND: Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness, sleep paralysis, and/or hypnagogic/hypnopompic hallucinations, and in some cases cataplexy. The response to anesthetic medications and possible interactions in narcolepsy patients is unclear in the perioperative period. In this systematic review, we aim to evaluate the current evidence on the perioperative outcomes and anesthetic considerations in narcolepsy patients. METHODS: Electronic literature search of Medline, Medline in-process, Embase, Cochrane Database of Systematic Reviews databases, international conference proceedings, and abstracts was conducted in November 2015 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guideline. A total of 3757 articles were screened using a 2-stage strategy (title-abstract followed by full text). We included case studies/series, cohort studies, and randomized controlled trials of narcolepsy patients undergoing surgical procedures under anesthesia or sedation. Preoperative narcolepsy symptoms and sleep study data, anesthetic technique, and perioperative complications were extracted. Screening of articles, data extraction, and compilation were conducted by 2 independent reviewers and any conflict was resolved by the senior author. RESULTS: A total of 19 studies including 16 case reports and 3 case series were included and evaluated. The majority of these patients received general anesthesia, whereas a small percentage of patients received regional anesthesia. Reported complications of narcolepsy patients undergoing surgeries were mainly related to autonomic dysregulation, or worsening of narcolepsy symptoms intra/postoperatively. Narcolepsy symptoms worsened only in those patient populations where the preoperative medications were either discontinued or reduced (mainly in obstetric patients). In narcolepsy patients, use of depth of anesthesia monitoring and total intravenous technique may have some advantage in terms of safety profile. Several patients undergoing neurosurgery involving the hypothalamus or third or four ventricles developed new-onset narcolepsy. CONCLUSIONS: We found a paucity of prospective clinical trials in this patient population, as most of the studies were case reports or observational studies. Continuation of preoperative medications, depth of anesthesia monitoring, use of multimodal analgesia with short-acting agents and regional anesthesia techniques were associated with favorable outcomes. Obstetric patients may be at greater risk for worsening narcolepsy symptoms, possibly related to a reduction or discontinuation of medications. For neurosurgical procedures involving the hypothalamus or third and fourth ventricle, postoperative considerations should include monitoring for symptoms of narcolepsy. Future studies are needed to better define perioperative risks associated with anesthesia and surgery in this population of patients. (C) 2017 International Anesthesia Research Society
http://ift.tt/2sPh29G
http://ift.tt/2sPh29G
Intraoperative Detection of Persistent Endoleak by Detecting Residual Spontaneous Echocardiographic Contrast in the Aneurysmal Sac During Thoracic Endovascular Aortic Repair.
Persistent endoleaks may lead to adverse events after endovascular aortic repair. We prospectively examined the relationship between intraoperative residual spontaneous echocardiographic contrast (SEC) within the aneurysmal sac and the incidence of postoperative endoleaks in 60 patients undergoing thoracic endovascular aortic repair. Patients with SEC had a higher incidence of postoperative endoleaks than did patients without SEC within a few days postoperatively (60.0% vs 12.5%, respectively; P
http://ift.tt/2sPzPC0
http://ift.tt/2sPzPC0
Validation of a Real-Time Minute-to-Minute Urine Output Monitor and the Feasibility of Its Clinical Use for Patients Undergoing Cardiac Surgery.
Acute kidney injury after cardiac surgery is associated with increased morbidity and mortality. Methods for measuring urine output in real time may better ensure renal perfusion perioperatively in contrast to the current standard of care where urine output is visually estimated after empiric epochs of time. In this study, we describe an accurate method for monitoring urine output continuously during cardiopulmonary bypass. This may provide a means for setting patient-specific targets for blood pressure and cardiopulmonary bypass flow as a potential strategy to reduce the risk for acute kidney injury. (C) 2017 International Anesthesia Research Society
http://ift.tt/2skRvl8
http://ift.tt/2skRvl8
Evaluation and Design of Genome-Wide CRISPR/SpCas9 Knockout Screens
The adaptation of CRISPR/SpCas9 technology to mammalian cell lines is transforming the study of human functional genomics. Pooled libraries of CRISPR guide RNAs (gRNAs) targeting human protein-coding genes and encoded in viral vectors have been used to systematically create gene knockouts in a variety of human cancer and immortalized cell lines, in an effort to identify whether these knockouts cause cellular fitness defects. Previous work has shown that CRISPR screens are more sensitive and specific than pooled library shRNA screens in similar assays, but currently there exists significant variability across CRISPR library designs and experimental protocols. In this study, we re-analyze 17 genome-scale knockout screens in human cell lines from three research groups using three different genome-scale gRNA libraries. Using the Bayesian Analysis of Gene Essentiality (BAGEL) algorithm to identify essential genes, we refine and expand our previously defined set of human core essential genes from 360 to 684 genes. We use this expanded set of reference Core Essential Genes (CEG2) plus empirical data from six CRISPR knockout screens to guide the design of a sequence-optimized gRNA library, the Toronto KnockOut version 3.0 (TKOv3) library. We then demonstrate the high effectiveness of the library relative to reference sets of essential and nonessential genes as well as other screens using similar approaches. The optimized TKOv3 library, combined with the CEG2 reference set, provide an efficient, highly optimized platform for performing and assessing gene knockout screens in human cell lines.
http://ift.tt/2rZOfMZ
Genome-Wide Associations for Water-Soluble Carbohydrate Concentration and Relative Maturity in Wheat Using SNP and DArT Marker Arrays
Improving water-use efficiency by incorporating drought avoidance traits into new wheat varieties is an important objective for wheat breeding in water-limited environments. This study uses genome wide association studies (GWAS) to identify candidate loci for water-soluble carbohydrate accumulation, an important drought-avoidance characteristic in wheat. Phenotypes from a multi-environment trial with experiments differing in water availability and separate single nucleotide polymorphism (SNP) and diversity arrays technology (DArT) marker sets were used to perform the analyses. Significant associations for water-soluble carbohydrate accumulation were identified on chromosomes 1A, 1B, 1D, 2D and 4A. Notably, these loci did not collocate with the major loci identified for relative maturity. Loci on chromosome 1D collocated with markers previously associated with the high molecular weight glutenin Glu-D1 locus. Genetic x environmental interactions impacted the results strongly, with significant associations for carbohydrate accumulation only identified in the water-deficit experiments. The markers associated with carbohydrate accumulation may be useful for marker assisted selection of drought tolerance in wheat.
http://ift.tt/2tiSJ52
Two Variants in SLC24A5 Are Associated with "Tiger-Eye" Iris Pigmentation in Puerto Rican Paso Fino Horses
A unique eye color, called tiger-eye, segregates in the Puerto Rican Paso Fino Horse breed and is characterized by a bright yellow, amber, or orange iris. Pedigree analysis identified a simple autosomal recessive mode of inheritance for this trait. A genome-wide association study with 24 individuals identified a locus on ECA 1 reaching genome wide significance (Pcorrected =1.32 x 10-5). This ECA1 locus harbors the candidate gene, Solute Carrier Family 24 (Sodium/Potassium /Calcium Exchanger), Member 5 (SLC24A5), with known roles in pigmentation in humans, mice, and zebrafish. Humans with compound heterozygous mutations in SLC24A5 have oculocutaneous albinism type 6 (OCA6) which is characterized by dilute skin, hair, and eye pigmentation as well as ocular anomalies. Twenty tiger-eye horses were homozygous for a non-synonymous mutation in Exon 2 (p.Phe91Tyr) of SLC24A5 (called here Tiger-eye 1), which is predicted to be deleterious to protein function. Additionally, eight of the remaining 12 tiger-eye horses heterozygous for the p.Phe91Tyr variant were also heterozygous for a 628bp deletion encompassing all of Exon 7 of SLC24A5 (c.875-340_1081+82del) which we will call here the Tiger-eye 2 allele. None of the 122 brown-eyed horses were homozygous for either tiger-eye associated allele or were compound heterozygotes. Further, neither variant was detected in 196 horses from four related breeds, not known to have the tiger-eye phenotype. Here we propose that two mutations in SLC24A5 affect iris pigmentation in tiger-eye Puerto Rican Paso Fino horses. Further, unlike OCA6 in humans, the Tiger-eye 1 mutation in its homozygous state or as a compound heterozygote (Tiger-eye 1/ Tiger-eye 2), do not appear to cause ocular anomalies or change in coat color in the Puerto Rican Paso Fino horse.
http://ift.tt/2s0ixPu
Frozen shoulder and risk of cancer: a population-based cohort study
Frozen shoulder and risk of cancer: a population-based cohort study
British Journal of Cancer 117, 144 (27 June 2017). doi:10.1038/bjc.2017.146
Authors: Alma B Pedersen, Erzsébet Horváth-Puhó, Vera Ehrenstein, Mikael Rørth & Henrik T Sørensen
http://ift.tt/2pZ5zk7
Second-line pazopanib in patients with relapsed and refractory small-cell lung cancer: a multicentre phase II study of the Hellenic Oncology Research Group
Second-line pazopanib in patients with relapsed and refractory small-cell lung cancer: a multicentre phase II study of the Hellenic Oncology Research Group
British Journal of Cancer 117, 8 (27 June 2017). doi:10.1038/bjc.2017.137
Authors: F Koinis, S Agelaki, V Karavassilis, N Kentepozidis, E Samantas, S Peroukidis, P Katsaounis, E Hartabilas, I I Varthalitis, I Messaritakis, G Fountzilas, V Georgoulias & A Kotsakis
http://ift.tt/2qpYWds
CBF1 is clinically prognostic and serves as a target to block cellular invasion and chemoresistance of EMT-like glioblastoma cells
CBF1 is clinically prognostic and serves as a target to block cellular invasion and chemoresistance of EMT-like glioblastoma cells
British Journal of Cancer 117, 102 (27 June 2017). doi:10.1038/bjc.2017.157
Authors: D Maciaczyk, D Picard, L Zhao, K Koch, D Herrera-Rios, G Li, V Marquardt, D Pauck, T Hoerbelt, W Zhang, D M Ouwens, M Remke, T Jiang, H J Steiger, J Maciaczyk & U D Kahlert
http://ift.tt/2qGJcVb
Randomised controlled trial of early prophylactic feeding vs standard care in patients with head and neck cancer
Randomised controlled trial of early prophylactic feeding vs standard care in patients with head and neck cancer
British Journal of Cancer 117, 15 (27 June 2017). doi:10.1038/bjc.2017.138
Authors: Teresa E Brown, Merrilyn D Banks, Brett G M Hughes, Charles Y Lin, Lizbeth M Kenny & Judith D Bauer
http://ift.tt/2rer5Wt
MicroRNA-211-5p suppresses tumour cell proliferation, invasion, migration and metastasis in triple-negative breast cancer by directly targeting SETBP1
MicroRNA-211-5p suppresses tumour cell proliferation, invasion, migration and metastasis in triple-negative breast cancer by directly targeting SETBP1
British Journal of Cancer 117, 78 (27 June 2017). doi:10.1038/bjc.2017.150
Authors: Liang-liang Chen, Zhou-jing Zhang, Zhan-bo Yi & Jian-jun Li
http://ift.tt/2qH1rJU
Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach
Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach
British Journal of Cancer 117, 25 (27 June 2017). doi:10.1038/bjc.2017.144
Authors: Yukinori Kurokawa, Han-Kwang Yang, Haruhiko Cho, Min-Hee Ryu, Toru Masuzawa, Sook Ryun Park, Sohei Matsumoto, Hyuk-Joon Lee, Hiroshi Honda, Oh Kyoung Kwon, Takashi Ishikawa, Kyung Hee Lee, Kazuhito Nabeshima, Seong-Ho Kong, Toshio Shimokawa, Jeong-Hwan Yook, Yuichiro Doki, Seock-Ah Im, Seiichi Hirota, Seokyung Hahn, Toshirou Nishida & Yoon-Koo Kang
http://ift.tt/2rNCoSg
A meta-analysis of CXCL12 expression for cancer prognosis
A meta-analysis of CXCL12 expression for cancer prognosis
British Journal of Cancer 117, 124 (27 June 2017). doi:10.1038/bjc.2017.134
Authors: Harsh Samarendra, Keaton Jones, Tatjana Petrinic, Michael A Silva, Srikanth Reddy, Zahir Soonawalla & Alex Gordon-Weeks
http://ift.tt/2rNQ9ka
A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus)
A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus)
British Journal of Cancer 117, 33 (27 June 2017). doi:10.1038/bjc.2017.145
Authors: Glen J Weiss, Jordan Waypa, Lisa Blaydorn, Jessica Coats, Kayla McGahey, Ashish Sangal, Jiaxin Niu, Cynthia A Lynch, John H Farley & Vivek Khemka
http://ift.tt/2sAYZC9
Hallmarks of response to immune checkpoint blockade
Hallmarks of response to immune checkpoint blockade
British Journal of Cancer 117, 1 (27 June 2017). doi:10.1038/bjc.2017.136
Authors: Alexandria P Cogdill, Miles C Andrews & Jennifer A Wargo
http://ift.tt/2pZ4AjZ
High-energy particle beam and gamma radiation exposure, familial relatedness and cancer in mice
High-energy particle beam and gamma radiation exposure, familial relatedness and cancer in mice
British Journal of Cancer 117, 41 (27 June 2017). doi:10.1038/bjc.2017.141
Authors: Pavel Chernyavskiy, Elijah F Edmondson, Michael M Weil & Mark P Little
http://ift.tt/2res9tk
MicroRNA-7 suppresses the homing and migration potential of human endothelial cells to highly metastatic human breast cancer cells
MicroRNA-7 suppresses the homing and migration potential of human endothelial cells to highly metastatic human breast cancer cells
British Journal of Cancer 117, 89 (27 June 2017). doi:10.1038/bjc.2017.156
Authors: Yu-Xin Cui, Robyn Bradbury, Valentina Flamini, Bo Wu, Nicola Jordan & Wen G Jiang
http://ift.tt/2rqpGcD
Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
British Journal of Cancer 117, 51 (27 June 2017). doi:10.1038/bjc.2017.151
Authors: Miika Martikainen, Janne Ruotsalainen, Johanna Tuomela, Pirkko Härkönen, Magnus Essand, Jari Heikkilä & Ari Hinkkanen
http://ift.tt/2rBSthj
Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells
Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells
British Journal of Cancer 117, 113 (27 June 2017). doi:10.1038/bjc.2017.133
Authors: Jenni Nikkilä, Rahul Kumar, James Campbell, Inger Brandsma, Helen N Pemberton, Fredrik Wallberg, Kinga Nagy, Ildikó Scheer, Beata G Vertessy, Artur A Serebrenik, Valentina Monni, Reuben S Harris, Stephen J Pettitt, Alan Ashworth & Christopher J Lord
http://ift.tt/2reBC3Z
Inhibition of autophagy prevents cadmium-induced prostate carcinogenesis
Inhibition of autophagy prevents cadmium-induced prostate carcinogenesis
British Journal of Cancer 117, 56 (27 June 2017). doi:10.1038/bjc.2017.143
Authors: Deeksha Pal, Suman Suman, Venkatesh Kolluru, Sophia Sears, Trinath P Das, Houda Alatassi, Murali K Ankem, Jonathan H Freedman & Chendil Damodaran
http://ift.tt/2sBxoAS
Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia
Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia
British Journal of Cancer 117, 136 (27 June 2017). doi:10.1038/bjc.2017.148
Authors: Sanjiban Chakrabarty, Vinay Koshy Varghese, Pranoy Sahu, Pradyumna Jayaram, Bhadravathi M Shivakumar, Cannanore Ganesh Pai & Kapaettu Satyamoorthy
http://ift.tt/2rkcQyO
Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC
Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC
British Journal of Cancer 117, 65 (27 June 2017). doi:10.1038/bjc.2017.140
Authors: Carina Strell, Karin Jessica Norberg, Artur Mezheyeuski, Jonas Schnittert, Praneeth R Kuninty, Carlos Fernández Moro, Janna Paulsson, Nicolai Aagaard Schultz, Dan Calatayud, Johannes Matthias Löhr, Oliver Frings, Caroline Sophie Verbeke, Rainer Lothar Heuchel, Jai Prakash, Julia Sidenius Johansen & Arne Östman
http://ift.tt/2rklgGF
Subcutaneous adiposity is an independent predictor of mortality in cancer patients
Subcutaneous adiposity is an independent predictor of mortality in cancer patients
British Journal of Cancer 117, 148 (27 June 2017). doi:10.1038/bjc.2017.149
Authors: Maryam Ebadi, Lisa Martin, Sunita Ghosh, Catherine J Field, Richard Lehner, Vickie E Baracos & Vera C Mazurak
http://ift.tt/2sBfzS7
Pharmacokinetics and pharmacodynamics-based mathematical modeling identifies an optimal protocol for metronomic chemotherapy
Metronomic chemotherapy is usually associated with better tolerance than conventional chemotherapy, and encouraging response rates have been reported in various settings. However, clinical development of metronomic chemotherapy has been hampered by a number of limitations, including the vagueness of its definition and the resulting empiricism in protocol design. In this study, we developed a pharmacokinetic/pharmacodynamic (PK/PD) mathematical model that identifies in silico the most effective administration schedule for gemcitabine monotherapy. This model is based upon four biological assumptions regarding the mechanisms of action of metronomic chemotherapy, resulting in a set of 6 minimally parameterized differential equations. Simulations identified daily 0.5-1 mg/kg gemcitabine as an optimal protocol to maximize anti-tumor efficacy. Both metronomic protocols (0.5 and 1 mg/kg/day for 28 days) were evaluated in chemoresistant neuroblastoma-bearing mice and compared with the standard MTD protocol (100 mg/kg once a week for 4 weeks). Systemic exposure to gemcitabine was 14 times lower in the metronomic groups compared with the standard group. Despite this, metronomic gemcitabine significantly inhibited tumor angiogenesis and reduced tumor perfusion and inflammation in vivo, while standard gemcitabine did not. Furthermore, metronomic gemcitabine yielded a 40-50% decrease in tumor mass at the end of treatment as compared to control mice (p=0.002; ANOVA on Ranks with Dunn's Test), while standard gemcitabine failed to significantly reduce tumor growth. Stable disease was maintained in the metronomic groups for up to 2 months after treatment completion (67-72% reduction in tumor growth at study conclusion, p>0.001; ANOVA on Ranks with Dunn's Test). Collectively, our results confirmed the superiority of metronomic protocols in chemoresistant tumors in vivo. <p>MAJOR FINDING: our study demonstrates the potential of PK/PD mathematical modeling to optimize metronomic chemotherapy protocols, which can be tested in non-clinical models and future clinical trials.
http://ift.tt/2ug0DsS
Inhibiting p53 acetylation reduces cancer chemotoxicity
Chemotoxicity due to unwanted p53 activation in the bone marrow remains an unmet clinical challenge. Doxorubicin, a first-line chemotherapy drug, often causes myelosuppression in patients, thus limiting its effectiveness. In this study, we discovered that C646, a reversible p300 inhibitor, downregulates p53 transcription and selectively protects non-cancerous cells from p53-dependent apoptosis. C646 treatment blocked acetylation of specific lysine residues that regulate p53 activity. Exploitation of differential p53 genetic backgrounds between human hematopoietic and colorectal cancer cells improved the therapeutic index of doxorubicin with C646 cotreatment. C646 administration in mice afflicted with p53 mutant tumors protected them from doxorubicin-induced neutropenia and anemia while retaining anti-tumor efficacy. We deduce that temporary and reversible inhibition of p53 acetylation in cancer subjects, especially those with p53-mutant tumors, may protect them from severe chemotoxicity while allowing treatment regimens to effectively proceed.
http://ift.tt/2tiSXst
Nrf2 mutagenic activation drives hepatocarcinogenesis
Nrf2, a master regulator of oxidative stress, is considered a prominent target for prevention of hepatocellular carcinoma (HCC), one of the leading causes of cancer-related deaths worldwide. Here we report that Nrf2 deficient mice resisted diethylnitrosamine (DEN)-induced hepatocarcinogenesis without affecting P450-mediated metabolic activation of DEN. Nrf2 expression, nuclear translocation, and transcriptional activity were enhanced in liver tumors. Overactivated Nrf2 was required for hepatoma growth in DEN-induced HCC. Following DEN treatment, Nrf2 genetic disruption reduced expression of pentose phosphate pathway (PPP)-related enzymes, the depletion of which has been associated with an amelioration of HCC incidence. Conversely, enhanced Nrf2 activity was attributable to alterations in the ability to bind its endogenous inhibitor Keap1. Our findings provide a mechanistic rationale for Nrf2 blockade to prevent and possibly treat liver cancer.
http://ift.tt/2uggmIg
Ischemic Cardiac Events Following Treatment of the Internal Mammary Nodal Region Using Contemporary Radiation Planning Techniques
There is increasing evidence supporting the oncologic benefit of internal mammary nodal (IMN) radiation in select patients, yet the associated cardiac radiation exposure and possible cardiac injury with IMN treatment is of concern. In this study, we highlight the importance of minimizing cardiac exposure and use of computed-tomography-based radiation planning when including a limited IMN field in the target volume (interspaces 1-3).
http://ift.tt/2skk02r
Proliferation index of different Gleason pattern 4 histomorphologies and associated pattern 3 adenocarcinoma of the prostate
Gleason grade is one of the most powerful prognostic indicators for adenocarcinoma of the prostate. A higher proliferation index of prostatic adenocarcinoma has been demonstrated in numerous studies to be significantly associated with more aggressive behavior. To date, the proliferation index of the different Gleason pattern 4 histomorphologies, including cribriform, fused glands, and poorly-formed glands, has not been determined. The aim of this investigation was to quantitate and compare the proliferation index, as assessed by Ki67 labeling index, of different Gleason pattern 4 histomorphologies.
http://ift.tt/2tiE3mf
EZH2 upregulation correlates with tumor invasiveness, proliferation, and angiogenesis in human pituitary adenomas
Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb repressive complex 2 (PRC2), which epigenetically represses genes involved in tumorigenesis and is highly expressed in tumors. However, no studies have investigated EZH2 expression and its clinical significance in human pituitary adenomas (PAs). Therefore, we examined the expression pattern of EZH2 in PAs and studied the correlations between protein expression and invasiveness, proliferation, angiogenesis, hormone functioning, and some other factors.
http://ift.tt/2ugoJUe
Quantifying Decreased Radiation Exposure From Modern CT Scan Technology and Surveillance Programs of Germ Cell Tumors.
Introduction: Upgrading computerized tomography (CT) scanners to iterative reconstruction techniques (IRT) decreases radiation dose. This reduction, combined with changes in surveillance protocols in clinical stage I testicular cancer (CS1TC) measurably decrease the lifetime attributable risk (LAR) of dying of radiation-associated cancer. Materials and Methods: This IRB-approved study enrolled 24 CS1TC patients who had CT scans on the same Toshiba Aquilion 64 CT before and after IRT software installation. Dose-length product and CT dose index volume were recorded. A physicist calculated effective doses. Radiation doses were compared using the Wilcoxon signed rank test. Median effective dose per scan was multiplied by scan number based on 16 versus 7 scans in 5-year AS protocols to calculate estimated cumulative dose (ECD). LAR of dying of radiation-associated solid tumor was estimated using ECD for a single exposure at age 35 with the excess absolute risk transport model from the BEIR VII analysis of long-term atomic bomb survivors. Results: Median preupgrade and postupgrade effective doses were 12.5 and 7.7 mSv, respectively (P
http://ift.tt/2ti8n07
http://ift.tt/2ti8n07
Patterns of Adjuvant Therapy Utilization in Uterine Carcinosarcoma Stages I to III: A National Cancer Database Analysis.
Objective: The objective of this study is to characterize patterns of utilization of adjuvant chemotherapy (CT) and radiotherapy (RT) in the posthysterectomy management of uterine carcinosarcoma (UCS) in the United States. Materials and Methods: We queried the National Cancer Database for women diagnosed with UCS between 2004 and 2012 and undergoing hysterectomy. Logistic regression was performed to identify sociodemographic, facility-specific, and treatment-related predictors of receiving multiagent chemotherapy, external beam radiotherapy (EBRT), or brachytherapy (BT). Results: In total 4272 patients were included, with 2 in 5 (40.5%) receiving no adjuvant therapy. Regarding RT, 2357 (55.1%) received neither EBRT nor BT, 929 (21.7%) received EBRT alone, 518 (12.1%) received BT alone, and 468 (11.0%) received EBRT+BT. Most women (70.8%) received no CT, a minority (1.5%) received single-agent CT, and the rest (27.8%) received multiagent chemotherapy. Logistic regression demonstrated disparities in receipt of adjuvant therapies by age, diagnosis year, insurance, facility volume, facility type, stage, and margin status, with patients with positive surgical margins less likely to receive BT. Conclusions: Following hysterectomy for UCS, a large proportion of women receives no CT and no RT in the United States. Multispecialty evaluation is critical for individualization of therapy and may address disparities in this aggressive disease. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2ug0vtt
http://ift.tt/2ug0vtt
Capecitabine and Celecoxib as a Promising Therapy for Thymic Neoplasms.
Objectives: For patients with unresectable or metastatic thymic epithelial neoplasms, few therapy options are available and outcomes are poor. This case series demonstrates that the combination of capecitabine and celecoxib may be a promising therapeutic option for these patients. Materials and Methods: The current report describes the outcomes of 5 patients with thymic neoplasms treated on a drug-drug interaction study of capecitabine and celecoxib in patients with advanced solid malignancies (NCT01705106) conducted at the University of Chicago, plus a sixth patient treated with the same regimen outside of the protocol. Results: Six patients with thymic neoplasms were treated with capecitabine 1000 mg/m2 twice daily and celecoxib 200 mg twice daily, day 1 to day 14 on a 21-day cycle. This included 3 patients with thymic carcinoma, 1 with thymic neuroendocrine tumor, and 2 with thymomas. Objective response rates were noted in 3 of 6 patients. Two of the 3 thymic carcinoma patients had complete responses, and the third had a partial response. Best response for the other patients included stable disease for both thymoma patients and progressive disease for the thymic neuroendocrine patient. Other than grade 3 palmar-plantar erythrodysesthesia, which developed in 4 of 6 patients and required dose reductions, the regimen was well tolerated. Conclusions: This case series suggests that capecitabine plus celecoxib may be an effective and well-tolerated treatment option for patients with thymic carcinoma. Further studies should be carried out to establish the efficacy of capecitabine plus celecoxib in thymic carcinoma, and to determine whether monotherapy with capecitabine would be similarly effective. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2tiON41
http://ift.tt/2tiON41
Predictors of Local Recurrence in Patients With Myxofibrosarcoma.
Objectives: Myxofibrosarcoma (MFS) is reported to have a higher risk of local recurrence (LR) following definitive surgical excision relative to other soft tissue sarcomas. We reviewed our clinical experience treating MFS to investigate predictors of LR. Materials and Methods: We retrospectively reviewed treatment outcomes for MFS patients treated at our institution between 1999 and 2015. A total of 52 patients were identified. Median age was 65 years (range, 21 to 86 y). Site of disease was: upper extremity (27%), lower extremity (46%), trunk (15%), pelvic (8%), and head and neck (4%). Patients had low, intermediate, high-grade, and unknown grade in: 23%, 8%, 67%, and 2% of tumors, respectively. Tumors were categorized as 5 cm (56%), or unknown size (9%). In total, 71% received radiotherapy: 19% preoperative, 50% postoperative, and 2% both. All patients underwent surgery. Margins were negative in 71%, close/positive in 21%, and unknown in 8%. In total, 27% of patients received chemotherapy. Univariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR. Results: Median follow-up time was 2.9 years (range, 0.4 to 14.3 y). The 3-year actuarial LR, distant metastasis, and overall survival were: 31%, 15%, and 87%, respectively. Predictors of LR were patient age greater than or equal to the median of 65 years (hazard ratio, 13.46, 95% confidence interval, 1.71-106.18, P=0.013), and having close/positive tumor margins (hazard ratio, 3.4, 95% confidence interval, 1-11.53, P=0.049). Conclusions: In this institutional series of MFS older age and positive/close margins were significantly associated with a higher risk of LR. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2seYukE
http://ift.tt/2seYukE
Bile Acid Deficiency in Subgroup of Patients With Irritable Bowel Syndrome With Constipation Based on Biomarkers in Serum and Fecal Samples
Short-term administration of delayed-release chenodeoxycholic acid to patients with irritable bowel syndrome with constipation (IBS-C) accelerates colonic transit and reduces symptoms. A preliminary study has shown that patients with IBS-C have reduced levels of bile acids (BAs) in feces and reduced synthesis of BA. We compared levels of primary and secondary BAs in fecal samples collected over a 48-hr period from patients with IBS-C on a diet that contained 100 g fat per day, and compared them will levels in samples from healthy volunteers (controls).
http://ift.tt/2sfrusE
Treatment with Biologic Agents has not Reduced Surgeries among Patients with Crohn’s Disease with Short Bowel Syndrome
Little is known about the effects of biologic agents used to treat Crohn's disease (CD) on its long-term complications, such as short bowel syndrome and intestinal failure (SBS-IF). We evaluated trends in small bowel resections and health care utilization among patients with CD with and without SBS-IF.
http://ift.tt/2sYLj4r
Potassium Phosphate and Succinylcholine Chloride by PharMEDium Services: Recall - Lack of Sterility Assurance
Audience: Pharmacy [Posted 06/27/2017] ISSUE: PharMEDium Services is conducting a limited, voluntary recall due to Hospira Inc.'s ("Hospira") June 15, 2017 recall announcement that microbial growth was detected during a routine simulation...
http://ift.tt/2tijHth
Potassium Phosphate and Succinylcholine Chloride by PharMEDium Services: Recall - Lack of Sterility Assurance
Audience: Pharmacy [Posted 06/27/2017] ISSUE: PharMEDium Services is conducting a limited, voluntary recall due to Hospira Inc.'s ("Hospira") June 15, 2017 recall announcement that microbial growth was detected during a routine...
http://ift.tt/2tijHth
Recurrence of cystic echinococcosis in an endemic area: a retrospective study
Cystic echinococcosis (CE) is a chronic, complex and neglected zoonotic disease. CE occurs worldwide. In humans, it may result in a wide spectrum of clinical manifestations, ranging from asymptomatic infection...
http://ift.tt/2tisfA8
Multi-state models for the analysis of time-to-treatment modification among HIV patients under highly active antiretroviral therapy in Southwest Ethiopia
Highly active antiretroviral therapy (HAART) has shown a dramatic change in controlling the burden of HIV/AIDS. However, the new challenge of HAART is to allow long-term sustainability. Toxicities, comorbidity...
http://ift.tt/2ufFsH9
Comparison of apoptosis in human primary pulmonary endothelial cells and a brain microvascular endothelial cell line co-cultured with Plasmodium falciparum field isolates
Plasmodium falciparum infection can progress unpredictably to severe forms including respiratory distress and cerebral malaria. The mechanisms underlying the variable natural course of...
http://ift.tt/2tipRtj
Hydraulic retention time and pH affect the performance and microbial communities of passive bioreactors for treatment of acid mine drainage
For acceleration of removing toxic metals from acid mine drainage (AMD), the effects of hydraulic retention time (HRT) and pH on the reactor performance and microbial community structure in the depth direction...
http://ift.tt/2sOQANs
Comparison of duplex PCR and phenotypic analysis in differentiating Candida dubliniensis from Candida albicans from oral samples
Candida dubliniensis shares a wide range of phenotypic characteristics with Candida albicans including a common trait called germ tube positivity. Hence, laboratory differentiation of the...
http://ift.tt/2skdpFm
Intensive Management and Natural Genetic Variation in Red Deer ( Cervus elaphus )
Abstract
The current magnitude of big-game hunting has outpaced the natural growth of populations, making artificial breeding necessary to rapidly boost hunted populations. In this study, we evaluated if the rapid increase of red deer (Cervus elaphus) abundance, caused by the growing popularity of big-game hunting, has impacted the natural genetic diversity of the species. We compared several genetic diversity metrics between 37 fenced populations subject to intensive management and 21 wild free-ranging populations. We also included a historically protected population from a national park as a baseline for comparisons. Contrary to expectations, our results showed no significant differences in genetic diversity between wild and fenced populations. Relatively lower genetic diversity was observed in the protected population, although differences were not significant in most cases. Bottlenecks were detected in both wild and fenced populations, as well as in the protected population. Assignment tests identified individuals that did not belong to their population of origin, indicating anthropogenic movement. We discuss the most likely processes, which could have led to the observed high levels of genetic variability and lack of differentiation between wild and fenced populations and suggest cautionary points for future conservation. We illustrate our comparative approach in red deer. However, our results and interpretations can be largely applicable to most ungulates subject to big-game hunting as most of them share a common exploitation–recovery history as well as many ecological traits.http://ift.tt/2sOxS8T
Contrasting Patterns of Gene Flow for Amazonian Snakes That Actively Forage and Those That Wait in Ambush
Abstract
Knowledge of genetic structure, geographic distance and environmental heterogeneity can be used to identify environmental features and natural history traits that influence dispersal and gene flow. Foraging mode is a trait that might predict dispersal capacity in snakes, because actively foragers typically have greater movement rates than ambush predators. Here, we test the hypothesis that 2 actively foraging snakes have higher levels of gene flow than 2 ambush predators. We evaluated these 4 co-distributed species of snakes in the Brazilian Amazon. Snakes were sampled along an 880 km transect from the central to the southwest of the Amazon basin, which covered a mosaic of vegetation types and seasonal differences in climate. We analyzed thousands of single nucleotide polymorphisms to compare patterns of neutral gene flow based on isolation by geographic distance (IBD) and environmental resistance (IBR). We show that IBD and IBR were only evident in ambush predators, implying lower levels of dispersal than the active foragers. Therefore, gene flow was high enough in the active foragers analyzed here to prevent any build-up of spatial genotypic structure with respect to geographic distance and environmental heterogeneity.http://ift.tt/2sOg8KO
Identification of an Early Male-Killing Agent in the Oriental Tea Tortrix, Homona magnanima
Abstract
Arthropods are frequently infected with inherited symbionts, which sometimes confer fitness benefits on female hosts or manipulate host reproduction. Early male killing, in which infected males die during embryogenesis, is induced by some bacteria, such as Wolbachia and Spiroplasma. A female-biased sex ratio has been found in Homona magnanima, collected from a tea plantation in Japan. Here, we examined the male-killing trait in H. magnanima and identified the agent that induces early male killing. The sex ratio distortion (SR) strain produced only females and no males, and its egg hatch rate was significantly lower than that of the normal (N) strain. The N strain was infected with only Wolbachia, whereas the SR strain was infected with both Wolbachia and Spiroplasma. Antibiotic treatment with 0.10% tetracycline restored the 1:1 sex ratio in the SR strain. Females treated with 0.05% tetracycline were positive for Spiroplasma but not for Wolbachia and showed a female-biased sex ratio, whereas Wolbachia-positive females did not revert to male killing. When inoculated with a homogenate of the SR strain female, females infected with only Spiroplasma produced female-biased offspring. Sequence analysis of the 16S rRNA gene revealed that Spiroplasma sp. of H. magnanima belonged to the ixodetis clade. These results indicate that Spiroplasma was responsible for male killing in H. magnanima. Late male killing is induced in H. magnanima by an RNA-like virus, and therefore this is the first case in which different male-killing agents expressed at different times in the life cycle have been found within one host species.http://ift.tt/2sjA8kX
Captive Ancestry Upwardly Biases Estimates of Relative Reproductive Success
Abstract
Supplementation programs, which release captive-born individuals into the wild, are commonly used to demographically bolster declining populations. In order to evaluate the effectiveness of these programs, the reproductive success of captive-born individuals released into the wild is often compared to the reproductive success of wild-born individuals in the recipient population (relative reproductive success, RRS). However, if there are heritable reductions in fitness associated with captive breeding, gene flow from captive-born individuals into the wild population can reduce the fitness of the wild population. Here, we show that when captive ancestry in the wild population reduces mean population fitness, estimates of RRS are upwardly biased, meaning that the relative fitness of captive-born individuals is over-estimated. Furthermore, the magnitude of this bias increases with the length of time that a supplementation program has been releasing captive-born individuals. This phenomenon has long-term conservation impacts since management decisions regarding the design of a supplementation program and the number of individuals to release can be based, at least in part, on RRS estimates. Therefore, we urge caution in the interpretation of relative fitness measures when the captive ancestry of the wild population cannot be precisely measured.http://ift.tt/2sOoDFp
Constraints on the F ST –Heterozygosity Outlier Approach
Abstract
The FST–heterozygosity outlier approach has been a popular method for identifying loci under balancing and positive selection since Beaumont and Nichols first proposed it in 1996 and recommended its use for studies sampling a large number of independent populations (at least 10). Since then, their program FDIST2 and a user-friendly program optimized for large datasets, LOSITAN, have been used widely in the population genetics literature, often without the requisite number of samples. We observed empirical datasets whose distributions could not be reconciled with the confidence intervals generated by the null coalescent island model. Here, we use forward-in-time simulations to investigate circumstances under which the FST–heterozygosity outlier approach performs poorly for next-generation single nucleotide polymorphism (SNP) datasets. Our results show that samples involving few independent populations, particularly when migration rates are low, result in distributions of the FST–heterozygosity relationship that are not described by the null model implemented in LOSITAN. In addition, even under favorable conditions LOSITAN rarely provides confidence intervals that precisely fit SNP data, making the associated P-values only roughly valid at best. We present an alternative method, implemented in a new R package named fsthet, which uses the raw empirical data to generate smoothed outlier plots for the FST–heterozygosity relationship.http://ift.tt/2sjJE7t
Understanding the Genomic Basis of Adaptive Response to Variable Osmotic Niches in Freshwater Prawns: A Comparative Intraspecific RNA-Seq Analysis of Macrobrachium australiense
Abstract
Understanding the molecular basis of adaptive response to variable environmental conditions is a central goal of evolutionary biology. Here, we sought to identify potential outlier single nucleotide polymorphisms (SNPs) in 3 wild populations of a freshwater prawn (Macrobrachium australiense) that are exposed to differing osmotic niches by using a comparative transcriptomics approach. De novo assembly of approximately 542 million (75 nt) pair end reads collected from 10 individuals revealed 123396 longer contigs/transcripts of variable length, that showed 97.38% transcriptome assembly completeness. Differential gene expression analysis of major osmoregulatory genes revealed that calreticulin, Na+/H+ exchanger, and V-type (H+) ATPase showed the highest expression levels in the Blunder Creek (low ionic) population, while Crustacean cardiovascular peptide (CCP), Na+/K+-ATPase, Na+/K+/2Cl− co-transporter (NKCC) and Na+/HCO3− exchanger showed the highest expression levels in the Bulimba Creek (higher ionic) population. In total, 16 gene ontology term categories were functionally enriched among the 3 studied populations. We identified 4144 raw and 835 high quality filtered SNPs in the 3 M. australiense populations, of which 84 SNPs were identified as outliers. Outliers were detected in 4 important osmoregulatory genes that include: calreticulin, Na+/H+ exchanger, Na+/K+-ATPase, and V-type-(H+)-ATPase. All outliers in the osmoregulatory genes were located in noncoding regulatory regions (untranslated regions) of the gene. We hypothesize that the outlier SNPs identified here in M. australiense populations exposed naturally to different osmotic conditions influence specific gene expression patterns that allow individuals to respond to local environmental conditions.http://ift.tt/2sOrjD7
Estimating Inbreeding Rates in Natural Populations: Addressing the Problem of Incomplete Pedigrees
Abstract
Understanding and estimating inbreeding is essential for managing threatened and endangered wildlife populations. However, determination of inbreeding rates in natural populations is confounded by incomplete parentage information. We present an approach for quantifying inbreeding rates for populations with incomplete parentage information. The approach exploits knowledge of pedigree configurations that lead to inbreeding coefficients of F = 0.25 and F = 0.125, allowing for quantification of Pr(I|k): the probability of observing pedigree I given the fraction of known parents (k). We developed analytical expressions under simplifying assumptions that define properties and behavior of inbreeding rate estimators for varying values of k. We demonstrated that inbreeding is overestimated if Pr(I|k) is not taken into consideration and that bias is primarily influenced by k. By contrast, our new estimator, incorporating Pr(I|k), is unbiased over a wide range of values of k that may be observed in empirical studies. Stochastic computer simulations that allowed complex inter- and intragenerational inbreeding produced similar results. We illustrate the effects that accounting for Pr(I|k) can have in empirical data by revisiting published analyses of Arabian oryx (Oryx leucoryx) and Red deer (Cervus elaphus). Our results demonstrate that incomplete pedigrees are not barriers for quantifying inbreeding in wild populations. Application of our approach will permit a better understanding of the role that inbreeding plays in the dynamics of populations of threatened and endangered species and may help refine our understanding of inbreeding avoidance mechanisms in the wild.http://ift.tt/2sjyfEI
Neutral Genetic Processes Influence MHC Evolution in Threatened Gopher Tortoises ( Gopherus polyphemus )
Abstract
Levels of adaptive genetic variation influence how species deal with environmental and ecological change, but these levels are frequently inferred using neutral genetic markers. Major histocompatibility complex (MHC) genes play a key role in the adaptive branch of the immune system and have been used extensively to estimate levels of adaptive genetic variation. Parts of the peptide binding region, sites where MHC molecules directly interact with pathogen and self-proteins, were sequenced from a MHC class I (95/441 tortoises) and class II (245/441 tortoises) gene in threatened and nonthreatened populations of gopher tortoises (Gopherus polyphemus), and adaptive genetic variation at MHC genes was compared to neutral genetic variation derived from 10 microsatellite loci (441 tortoises). Genetic diversity at the MHC class II locus and microsatellites was greater in populations in the nonthreatened portion of the gopher tortoise's range (MHC class II difference in mean A = 8.11, AR = 0.79, HO = 0.51, and HE = 0.16; microsatellite difference in mean A = 1.05 and AR = 0.47). Only MHC class II sequences showed evidence of positive selection (dN/dS > 1, Z = 1.81, P = 0.04). Historical gene flow as estimated with Migrate-N was greater than recent migration estimated with BayesAss, suggesting that populations were better connected in the past when habitat was less fragmented. MHC genetic differentiation was correlated with microsatellite differentiation (Mantel r = 0.431, P = 0.001) suggesting neutral genetic processes are influencing MHC evolution, and advantageous MHC alleles could be lost due to genetic drift.http://ift.tt/2sOQZj3
Color-Biased Dispersal Inferred by Fine-Scale Genetic Spatial Autocorrelation in a Color Polymorphic Salamander
Abstract
Behavioral traits can be influenced by predation rates of color morphs, potentially leading to reduced boldness or increased escape behaviors in one color morph. The red-backed salamander, Plethodon cinereus, is a small terrestrial salamander whose color morphs have different diets and select different microhabitats, but little is known about potential differences in dispersal behaviors. We used fine-scale genetic spatial autocorrelation to examine 122 P. cinereus in a color-polymorphic population at 10 microsatellite loci in order to generate estimates of spatial genetic structure for each color morph. Differences in spatial genetic structure have been used extensively to infer within-population sex-biased dispersal but have never been used to test for dispersal differences between other groups within populations such as color morphs. We found evidence for color-biased dispersal, but not sex-biased dispersal. Striped salamanders had significant positive genetic structure in the shortest distance classes indicating philopatry. In contrast, unstriped salamanders showed a lack of spatial genetic structure at shorter distances and higher than expected genetic similarity at further distances, as expected if they are dispersing from their natal site. These results show that genetic methods typically used for sex-biased dispersal can be used to investigate differences in dispersal between morphs that vary discretely in polymorphic populations, such as color morphs.http://ift.tt/2sjyeRa
Phenotypic and Genetic Analysis of the Leopard Complex Spotting in Noriker Horses
Abstract
Genetic analyses of coat colors are frequently restricted to subjectively categorized phenotype information. The aim of this study was to develop a method to numerically quantify the variability of leopard complex (LP) spotting phenotypes introducing tools from image analysis. Generalized Procrustes analysis eliminates systematic errors due to imaging process. The binarization of normalized images and the application of principal component analysis (PCA) on the derived pixel matrices, transform pixel information into numerical data space. We applied these methods on 90 images to ascertain the specific leopard patterns within the Noriker breed. Furthermore, we genotyped a representative sample of 191 Noriker horses for the known LP spotting associated loci. Ninety-seven percentage of the genotyped leopard spotted horses were heterozygous for LP and had at least one copy of the PATN1 allele. However, the remaining pattern variation was great, indicating other genetic factors influencing the expression of LP spotting. Based upon this data, we estimated effect sizes of the modifier PATN1, and additional factors including sex, age, base color, and spotting phenotype of parents. The PCA of the pixel matrix resulted in 2 significant components accounting for 51% of the variation. Applying a linear model, we identified significant effects for age groups and base color on the first and second components, while for sex and parents' LP phenotype significant effects were found on 4 additional components.http://ift.tt/2sOrONr
Effects of Sample Size and Full Sibs on Genetic Diversity Characterization: A Case Study of Three Syntopic Iberian Pond-Breeding Amphibians
Abstract
Accurate characterization of genetic diversity is essential for understanding population demography, predicting future trends and implementing efficient conservation policies. For that purpose, molecular markers are routinely developed for nonmodel species, but key questions regarding sampling design, such as calculation of minimum sample sizes or the effect of relatives in the sample, are often neglected. We used accumulation curves and sibship analyses to explore how these 2 factors affect marker performance in the characterization of genetic diversity. We illustrate this approach with the analysis of an empirical dataset including newly optimized microsatellite sets for 3 Iberian amphibian species: Hyla molleri, Epidalea calamita, and Pelophylax perezi. We studied 17–21 populations per species (total n = 547, 652, and 516 individuals, respectively), including a reference locality in which the effect of sample size was explored using larger samples (77–96 individuals). As expected, FIS and tests for Hardy–Weinberg equilibrium and linkage disequilibrium were affected by the presence of full sibs, and most initially inferred disequilibria were no longer statistically significant when full siblings were removed from the sample. We estimated that to obtain reliable estimates, the minimum sample size (potentially including full sibs) was close to 20 for expected heterozygosity, and between 50 and 80 for allelic richness. Our pilot study based on a reference population provided a rigorous assessment of marker properties and the effects of sample size and presence of full sibs in the sample. These examples illustrate the advantages of this approach to produce robust and reliable results for downstream analyses.http://ift.tt/2sjFT29
Asymmetric Hybridization in Cattails ( Typha spp.) and Its Implications for the Evolutionary Maintenance of Native Typha latifolia
Abstract
Cattails (Typha spp.) have become an increasingly dominant component of wetlands in eastern North America and this dominance is largely attributable to the high frequency of Typha × glauca, the hybrid of native Typha latifolia and putatively introduced Typha angustifolia. Hybridization in this group is asymmetric, with T. angustifolia nearly always the maternal parent of F1 hybrids. However, the magnitude of hybrid infertility and whether mating asymmetries extend to the formation of advanced-generation hybrids have not been examined. We used hand-crosses to measure seed set and germination success. We found that mating asymmetries extend to the formation of back-crosses, with ~0 seeds set when T. latifolia was pollinated by hybrid cattails. Seed set was unaffected by pollen source for T. × glauca or T. angustifolia. However, seed production by T. angustifolia was consistently high while that of T. × glauca was variable and when pollinated by other T. × glauca more than 75% lower than for any other intraspecific cross indicating reduced hybrid fertility. We used these results to parameterize a model of hybrid zone evolution in which mating patterns and fertility were governed by interactions between alleles at nuclear and cytoplasmic loci. The model revealed that asymmetric mating and reduced hybrid fertility should favor the maintenance of T. latifolia over T. angustifolia compared to null expectations. However, the model also indicated restrictive conditions for the long-term maintenance of T. latifolia within populations, indicating that asymmetric mating might only stall rather than prevent the displacement of native cattails by hybrids.http://ift.tt/2sjjzpk
Is Empiricism Empirically False? Lessons from Early Nervous Systems
Abstract
Recent work on skin-brain thesis (de Wiljes et al. 2015; Keijzer 2015; Keijzer et al. 2013) suggests the possibility of empirical evidence that empiricism is false. It implies that early animals need no traditional sensory receptors to be engaged in cognitive activity. The neural structure required to coordinate extensive sheets of contractile tissue for motility provides the starting point for a new multicellular organized form of sensing. Moving a body by muscle contraction provides the basis for a multicellular organization that is sensitive to external surface structure at the scale of the animal body. In other words, the nervous system first evolved for action, not for receiving sensory input. Thus, sensory input is not required for minimal cognition; only action is. The whole body of an organism, in particular its highly specific animal sensorimotor organization, reflects the bodily and environmental spatiotemporal structure. The skin-brain thesis suggests that, in contrast to empiricist claims that cognition is constituted by sensory systems, cognition may be also constituted by action-oriented feedback mechanisms. Instead of positing the reflex arc as the elementary building block of nervous systems, it proposes that endogenous motor activity is crucial for cognitive processes. In the paper, I discuss the issue whether the skin-brain thesis and its supporting evidence can be really used to overthrow the main tenet of empiricism empirically, by pointing out to cognizing agents that fail to have any sensory apparatus.
http://ift.tt/2sOqPNv
FDA Expands Approval of Ceritinib for ALK-Positive Non-Small Cell Lung Cancer
The FDA has approved the targeted therapy ceritinib as an initial treatment for patients with lung cancer that has a mutation in the ALK gene.
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Health, Wealth, and the U.S. Senate
The Better Care Reconciliation Act (BCRA), as the U.S. Senate calls the health care bill released by a small working group of Republican senators last week, is not designed to lead to better care for Americans. Like the House bill that was passed in early May, the American Health Care Act (AHCA),…
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Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
http://ift.tt/2thDEjG
Different dissecting orders of the pulmonary bronchus and vessels during right upper lobectomy are associated with surgical feasibility and postoperative recovery for lung cancer patients
Right upper lobectomy (RUL) for lung cancer with different dissecting orders involves the most variable anatomical structures, but no studies have analyzed its effects on postoperative recovery. This study com...
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Detection of microRNA Expression in Peritoneal Membrane of Rats Using Quantitative Real-time PCR
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Inducible T7 RNA Polymerase-mediated Multigene Expression System, pMGX
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MLKL, the Protein that Mediates Necroptosis, Also Regulates Endosomal Trafficking and Extracellular Vesicle Generation
When phosphorylated by RIPK3, MLKL triggers necroptotic death. Yoon et al. show that MLKL also contributes to endosomal trafficking and generation of extracellular vesicles. This function is independent of RIPK3 but can be enhanced by it, yielding phospho-MLKL release within the vesicles, thereby apparently withholding death mediation by MLKL.
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Race and risk of metastases and survival after radical prostatectomy: Results from the SEARCH database
BACKGROUND
Black race is associated with prostate cancer (PC) diagnosis and poor outcome. Previously, the authors reported that black men undergoing radical prostatectomy (RP) in equal-access hospitals had an increased risk of biochemical disease recurrence (BCR), but recurrences were equally aggressive as those occurring in white men. The authors examined the association between race and long-term outcomes after RP.
METHODS
Data regarding 1665 black men (37%) and 2791 white men (63%) undergoing RP were analyzed. Using Cox models, the authors tested the association between race and BCR, BCR with a prostate-specific antigen (PSA) doubling time <9 months (aggressive disease recurrence), metastases, PC-specific death, and overall death.
RESULTS
At a median follow-up of 102 months, 1566 men (35%) developed BCR, 217 men (5%) experienced aggressive disease recurrence, 193 men (4%) developed metastases, and 1207 men (27%) had died, 107 of whom (2%) died of PC. White men were older and had a lower preoperative PSA level, a lower biopsy and pathological grade group, and more capsular penetration but less seminal vesicle invasion and positive surgical margins versus black men (all P<.05). Black men were found to have a more recent surgery year (P<.001). On univariable analysis, black race was associated with increased BCR (P = .003) and reduced overall death (P = .017). On multivariable analysis, black race was not found to be associated with BCR (hazard ratio [HR], 1.07; P = .26), aggressive recurrence (HR, 1.14; P = .42), metastasis (HR, 1.24; P = .21), PC-specific death (HR, 1.03; P = .91), or overall death (HR, 1.03; P = .67).
CONCLUSIONS
Among men undergoing RP at equal-access centers, although black men were found to have an increased risk of BCR, they had similar risks of aggressive disease recurrence, metastasis, and PC-specific death compared with white men, and the risk of BCR was found to be similar after controlling for risk parameters. Longer follow-up is needed to confirm these findings. Cancer 2017. © 2017 American Cancer Society.
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The Hospital Anxiety and Depression Scale (HADS) and the 9-item Patient Health Questionnaire (PHQ-9) as screening instruments for depression in patients with cancer
BACKGROUND
Depression screening in patients with cancer is recommended by major clinical guidelines, although the evidence on individual screening tools is limited for this population. Here, the authors assess and compare the diagnostic accuracy of 2 established screening instruments: the depression modules of the 9-item Patient Health Questionnaire (PHQ-9) and the Hospital Anxiety and Depression Scale (HADS-D), in a representative sample of patients with cancer.
METHODS
This multicenter study was conducted with a proportional, stratified, random sample of 2141 patients with cancer across all major tumor sites and treatment settings. The PHQ-9 and HADS-D were assessed and compared in terms of diagnostic accuracy and receiver operating characteristic (ROC) curves for Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnosis of major depressive disorder using the Composite International Diagnostic Interview for Oncology as the criterion standard.
RESULTS
The diagnostic accuracy of the PHQ-9 and HADS-D was fair for diagnosing major depressive disorder, with areas under the ROC curves of 0.78 (95% confidence interval, 0.76-0.79) and 0.75 (95% confidence interval, 0.74-0.77), respectively. The 2 questionnaires did not differ significantly in their areas under the ROC curves (P = .15). The PHQ-9 with a cutoff score ≥7 had the best screening performance, with a sensitivity of 83% (95% confidence interval, 78%-89%) and a specificity of 61% (95% confidence interval, 59%-63%). The American Society of Clinical Oncology guideline screening algorithm had a sensitivity of 44% (95% confidence interval, 36%-51%) and a specificity of 84% (95% confidence interval, 83%-85%).
CONCLUSIONS
In patients with cancer, the screening performance of both the PHQ-9 and the HADS-D was limited compared with a standardized diagnostic interview. Costs and benefits of routinely screening all patients with cancer should be weighed carefully. Cancer 2017. © 2017 American Cancer Society.
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Survivorship and the chronic cancer patient: Patterns in treatment-related effects, follow-up care, and use of survivorship care plans
BACKGROUND
The survivorship needs of patients living with chronic cancer (CC) and their use of survivorship care plans (SCPs) have been overlooked and underappreciated.
METHODS
A convenience sample of 39,088 SCPs completed for cancer survivors with an Internet-based SCP tool was examined; it included 5847 CC survivors (15%; CC was defined as chronic leukemia and/or recurrent/metastatic cancer of another nature). Patient-reported treatment effects and follow-up care patterns were compared between CC survivors and survivors treated with curative intent (CI). Responses from a follow-up survey regarding SCP satisfaction and use were reviewed.
RESULTS
CC survivors had greater odds of experiencing multiple treatment-related effects than survivors treated with CI; these effects included fatigue, cognitive changes, dyspnea, peripheral neuropathy, lymphedema, and erectile dysfunction. Nearly half of CC survivors were managed by an oncologist alone, and they were less likely than CI patients to be comanaged by a primary care provider and an oncologist. Fewer SCPs were generated by health care providers (HCPs) for CC survivors versus CI survivors. A smaller proportion of CC users versus CI users rated their experience and satisfaction with the SCP tool as very good or excellent, and CC users were less likely to share the HCP summary with their health care team.
CONCLUSIONS
A substantial number of CC survivors, often considered incurable but treatable, seek survivorship support. Tools to facilitate participation, communication, and coordination of care are valuable for these patients, and future iterations of SCPs should be designed to address the particular circumstances of living with CC. Cancer 2017. © 2017 American Cancer Society.
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Socioeconomic factors affect the selection of proton radiation therapy for children
BACKGROUND
Proton radiotherapy remains a limited resource despite its clear potential for reducing radiation doses to normal tissues and late effects in children in comparison with photon therapy. This study examined the impact of race and socioeconomic factors on the use of proton therapy in children with solid malignancies.
METHODS
This study evaluated 12,101 children (age ≤ 21 years) in the National Cancer Data Base who had been diagnosed with a solid malignancy between 2004 and 2013 and had received photon- or proton-based radiotherapy. Logistic regression analysis was used to evaluate patient, tumor, and socioeconomic variables affecting treatment with proton radiotherapy versus photon radiotherapy.
RESULTS
Eight percent of the patients in the entire cohort received proton radiotherapy, and this proportion increased between 2004 (1.7%) and 2013 (17.5%). Proton therapy was more frequently used in younger patients (age ≤ 10 years; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.2) and in patients with bone/joint primaries and ependymoma, medulloblastoma, and rhabdomyosarcoma histologies (P < .05). Patients with metastatic disease were less likely to receive proton therapy (OR, 0.4; 95% CI, 0.3-0.6). Patients with private/managed care were more likely than patients with Medicaid or no insurance to receive proton therapy (P < .0001). A higher median household income and educational attainment were also associated with increased proton use (P < .001). Patients treated with proton therapy versus photon therapy were more likely to travel more than 200 miles (13% vs 5%; P < .0001).
CONCLUSIONS
Socioeconomic factors affect the use of proton radiotherapy in children. Whether this disparity is related to differences in the referral patterns, the knowledge of treatment modalities, or the ability to travel for therapy needs to be further clarified. Improving access to proton therapy in underserved pediatric populations is essential. Cancer 2017. © 2017 American Cancer Society.
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Race-specific molecular alterations correlate with differential outcomes for black and white endometrioid endometrial cancer patients
BACKGROUND
The objective of this study was to identify molecular alterations associated with disease outcomes for white and black patients with endometrioid endometrial cancer (EEC).
METHODS
EEC samples from black (n = 17) and white patients (n = 13) were analyzed by proteomics (liquid chromatography–tandem mass spectrometry) and transcriptomics (RNA-seq). Coordinate alterations were validated with RNA-seq data from black (n = 49) and white patients (n = 216). Concordantly altered candidates were further tested for associations with race-specific progression-free survival (PFS) in black (n = 64) or white patients (n = 267) via univariate and multivariate Cox regression modeling and log-rank testing.
RESULTS
Discovery analyses revealed significantly altered candidate proteins and transcripts between black and white patients, suggesting modulation of tumor cell viability in black patients and cell death signaling in black and white patients. Eighty-nine candidates were validated as altered between these patient cohorts, and a subset significantly correlated with differential PFS. White-specific PFS candidates included serpin family A member 4 (SERPINA4; hazard ratio [HR], 0.89; Wald P value = .02), integrin subunit α3 (ITGA3; HR, 0.76; P = .03), and Bet1 Golgi vesicular membrane trafficking protein like (BET1L; HR, 0.48; P = .04). Black-specific PFS candidates included family with sequence similarity 228 member B (FAM228B; HR, 0.13; P = .001) and HEAT repeat containing 6 (HEATR6; HR, 4.94; P = .047). Several candidates were also associated with overall survival (SERPINA4 and ITGA3) as well as PFS independent of disease stage, grade and myometrial invasion (SERPINA4, BET1L and FAM228B).
CONCLUSIONS
This study has identified and validated molecular alterations in tumors from black and white EEC patients, including candidates significantly associated with altered disease outcomes within these patient cohorts. Cancer 2017. © 2017 American Cancer Society.
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Young adult survivors of childhood acute lymphoblastic leukemia show evidence of chronic inflammation and cellular aging
BACKGROUND
Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation.
METHODS
Plasma inflammatory cytokines were measured using a cytometric bead array in 87 asymptomatic young adult survivors of childhood ALL (median age, 25 years; age range, 18-35 years) who attended annual follow-up clinic and compared with healthy, age-matched and sex-matched controls. Leukocyte telomere length (LTL) was measured using Southern blot analysis.
RESULTS
Survivors had significant elevation of plasma interleukin-2 (IL-2), IL-10, IL-17a, and high-sensitivity C-reactive protein levels (all P < .05). A raised high-sensitivity C-reactive protein level (>0.8 mg/dL) was related to increased odds of having metabolic syndrome (odds ratio, 7.256; 95% confidence interval, 1.501-35.074). Survivors also had significantly shorter LTL compared with controls (median, 9866 vs 10,392 base pairs; P = .021). Compared with published data, LTL in survivors was similar to that in healthy individuals aged 20 years older. Survivors who received cranial irradiation had shorter LTL compared with those who had not (P = .013).
CONCLUSIONS
Asymptomatic young adult survivors of childhood ALL demonstrate a biologic profile of chronic inflammation and telomere attrition, consistent with an early onset of cellular processes that drive accelerated aging. These processes may explain the premature development of age-related chronic conditions in childhood cancer survivors. Understanding their molecular basis may facilitate targeted interventions to disrupt the accelerated aging process and its long-term impact on overall health. Cancer 2017. © 2017 American Cancer Society.
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Dual-labelled antibodies for flow and mass cytometry: A new tool for cross-platform comparison and enrichment of target cells for mass cytometry
Antibody conjugates applicable in both conventional flow and mass cytometry would offer interesting options for cross-platform comparison, as well as the enrichment of rare target cells by conventional flow cytometry (FC) sorting prior to deep phenotyping by mass cytometry (MC). Here, we introduce a simple method to generate dual fluorochrome/metal-labelled antibodies by consecutive orthogonal labelling. First we compared different fluorochrome-conjugated antibodies specific for CD4, such as FITC, Vio667, VioGreen or VioBlue for their compatibility with the conventional secondary MAXPAR® labelling protocol. After labelling with 141Pr, the fluorescence emission spectra of all fluorochromes investigated retained their characteristics, and CD4 dual conjugates (DCs) provided consistent results in immune phenotyping assays performed by FC and MC. The phenotypical composition of CD4+ T-cells was maintained after enrichment by FC sorting using different CD4 DCs. Finally, magnetic cell depletion was combined with FC sorting using CD19-VioBlue-142Nd, CD20-VioGreen-147Sm, CD27-Cy5-167Er and CD38-Alexa488-143Nd DC to enrich rare human plasmablasts (PBs) to purities >80%, which allowed a subsequent deep phenotyping by MC. In conclusion, DCs have been successfully established for direct assay comparison between FC and MC, and help to minimise MC data acquisition time for deep phenotyping of rare cell subsets.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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