Background. We aimed to evaluate the correlation of platelet-to-lymphocyte ratio (PLR) with prognosis and clinicopathological characteristics of breast cancer. Methods. The PubMed and Embase databases were searched. Hazard ratio (HR) with 95% confidence interval (CI) was used to summarize disease-free survival (DFS) and overall survival (OS). Odds ratio (OR) was used to summarize tumor clinicopathological characteristics. Results. High PLR was associated with poor DFS and OS (DFS: HR = 1.47, 95% CI = 1.16–1.85, and Tau2 = 0.070; OS: HR = 1.88, 95% CI = 1.27–2.80, and Tau2 = 0.192). A Galbraith plot indicated that the studies by Allan et al. and Cihan et al. contributed the heterogeneity of DFS and OS, respectively. There were significant differences in the incidence of high PLR between stage II–IV and stage I groups (OR = 1.86, 95% CI = 1.20–2.90, and Tau2
http://ift.tt/2xOqIB9
Τετάρτη 30 Αυγούστου 2017
High Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Breast Cancer: A Meta-Analysis
Expression Levels and Clinical Significance of miR-21-5p, miR-let-7a, and miR-34c-5p in Laryngeal Squamous Cell Carcinoma
Objective. Altered microRNAs (miRNAs) expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). The aim of this study was to determine the role and clinical value of three LSCC-related miRs, such as miR-21-5p, miR-let-7a, and miR-34c-5p in a homogeneous cohort of patients with primary LSCC treated by primary surgery. Methods. Expression levels of miR-21-5p, miR-let-7a, and miR-34c-5p were detected in 43 pairs of LSCC and adjacent normal tissues by reverse-transcription quantitative PCR. Overall survival and disease-free survival were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results. miR-21-5p is significantly upregulated, while miR-let-7a is significantly downregulated in LSCC tumor tissues compared with the corresponding adjacent normal tissues. The downregulation of miR-34c-5p expression significantly correlated with a shorter disease-free survival and, in the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. Conclusions. miR-21-5p, miR-let-7a, and miR-34c-5p seem to play a critical role in LSCC carcinogenesis and might have a diagnostic and prognostic clinical value. The miR-let-7a levels could have a predictive role for lymph node metastases and miR-34c-5p might be a promising biomarker of patient outcome.
http://ift.tt/2wU70av
Interactive Segmentation of Pancreases in Abdominal Computed Tomography Images and Its Evaluation Based on Segmentation Accuracy and Interaction Costs
The present paper proposed an interactive segmentation method of pancreases in abdominal computed tomography (CT) images based on the anatomical knowledge of medical doctors and the statistical information of pancreas shapes. This segmentation method consisted of two phases: training and testing. In the training phase, pancreas regions were manually extracted from sample CT images for training, and then a probabilistic atlas (PA) was constructed from the extracted regions. In the testing phase, a medical doctor selected seed voxels for a pancreas and background in a CT image for testing by use of our graphical user interface system. The homography transformation was used to fit the PA to the seeds. The graph cut technique whose data term was weighted by the transformed PA was applied to the test image. The seed selection, the atlas transformation, and the graph cut were executed iteratively. This doctor-in-the-loop segmentation method was applied to actual abdominal CT images of fifteen cases. The experimental results demonstrated that the proposed method was more accurate and effective than the conventional graph cut.
http://ift.tt/2xOyUBr
CT Scanning in Identification of Sheep Cystic Echinococcosis
Objective. We aim to determine the efficiency of CT in identification of cystic echinococcosis in sheep. Methods. Fifty-three sheep with liver cysts confirmed by ultrasonography were subject to CT scan to evaluate the number, size, and type of the cysts in liver and lung, confirmed using necropsy. The correlation of numbers between liver cysts and lung cysts was calculated using Pearson analysis. Results. Necropsy indicated a 98% consensus on size, location, number, and activity compared with CT scan. The viable cysts were 53.1% and 50.6% in the liver and lung, respectively. Among the cysts in liver, 35.5%, 9.5%, 5.7%, 10.2%, and 39.1% were Types CE1, CE2, CE3, CE4, and CE5, respectively. The cysts in the lungs, 17.4%, 26.9%, 12.1%, 11.6%, and 32.1%, were Types CE1, CE2, CE3, CE4, and CE5, respectively. A significant correlation was noticed between the number of cysts in liver and those in lung (, ). Conclusions. CT scan is a suitable tool in determining the size and type of cystic hydatid cysts in both liver and lung of sheep. A significant correlation was noticed between the numbers in liver and lung, indicating that lung infection was likely due to the expansion of liver cyst burden pressure.
http://ift.tt/2wTUl7A
Biophysics of Biochemical Signaling in Dendritic Spines: Implications in Synaptic Plasticity
Dendritic spines are mushroom-shaped postsynaptic compartments that host biochemical signal cascades important for synaptic plasticity and, ultimately, learning and memory. Signaling events in spines involve a signaling network composed of hundreds of signaling proteins interacting with each other extensively. Synaptic plasticity is typically induced by Ca2+ elevation in spines, which activates a variety of signaling pathways. This leads to changes in the actin cytoskeleton and membrane dynamics, which in turn causes structural and functional changes of the spine.
http://ift.tt/2xNEqUO
Biophysics of Biochemical Signaling in Dendritic Spines: Implications in Synaptic Plasticity
Dendritic spines are mushroom-shaped postsynaptic compartments that host biochemical signal cascades important for synaptic plasticity and, ultimately, learning and memory. Signaling events in spines involve a signaling network composed of hundreds of signaling proteins interacting with each other extensively. Synaptic plasticity is typically induced by Ca2+ elevation in spines, which activates a variety of signaling pathways. This leads to changes in the actin cytoskeleton and membrane dynamics, which in turn causes structural and functional changes of the spine.
http://ift.tt/2xNEqUO
Robot-Assisted Training of Arm and Hand Movement Shows Functional Improvements for Incomplete Cervical Spinal Cord Injury.
http://ift.tt/2x71DEc
Effectiveness of a Group Physiotherapy Intervention in Nontraumatic, Inoperable Painful Shoulder: A Randomized Clinical Trial.
http://ift.tt/2vGitpS
A Novel Approach to Overcome Movement Artifact When Using a Laser Speckle Contrast Imaging System for Alternating Speeds of Blood Microcirculation
http://ift.tt/2vGeNoc
Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients
Abstract
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.
http://ift.tt/2xynBOs
Spatial and temporal epithelial ovarian cancer cell heterogeneity impacts Maraba virus oncolytic potential
Abstract
Background
Epithelial ovarian cancer exhibits extensive interpatient and intratumoral heterogeneity, which can hinder successful treatment strategies. Herein, we investigated the efficacy of an emerging oncolytic, Maraba virus (MRBV), in an in vitro model of ovarian tumour heterogeneity.
Methods
Four ovarian high-grade serous cancer (HGSC) cell lines were isolated and established from a single patient at four points during disease progression. Limiting-dilution subcloning generated seven additional subclone lines to assess intratumoral heterogeneity. MRBV entry and oncolytic efficacy were assessed among all 11 cell lines. Low-density receptor (LDLR) expression, conditioned media treatments and co-cultures were performed to determine factors impacting MRBV oncolysis.
Results
Temporal and intratumoral heterogeneity identified two subpopulations of cells: one that was highly sensitive to MRBV, and another set which exhibited 1000-fold reduced susceptibility to MRBV-mediated oncolysis. We explored both intracellular and extracellular mechanisms influencing sensitivity to MRBV and identified that LDLR can partially mediate MRBV infection. LDLR expression, however, was not the singular determinant of sensitivity to MRBV among the HGSC cell lines and subclones. We verified that there were no apparent extracellular factors, such as type I interferon responses, contributing to MRBV resistance. However, direct cell-cell contact by co-culture of MRBV-resistant subclones with sensitive cells restored virus infection and oncolytic killing of mixed population.
Conclusions
Our data is the first to demonstrate differential efficacy of an oncolytic virus in the context of both spatial and temporal heterogeneity of HGSC cells and to evaluate whether it will constitute a barrier to effective viral oncolytic therapy.
http://ift.tt/2gr0O2R
LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia
Abstract
Background
Long Interspersed Nuclear Elements-1 (LINEs-1) methylation from white blood cells (WBCs) DNA has been proposed as biomarker associated with different types of cancer. The aim of the present study was to investigate the degree of WBCs LINE-1 methylation, according to high-risk Human Papilloma Virus (hrHPV) status in a healthy population, and the association with high-grade Cervical Intraepithelial Neoplasia (CIN2+) in hrHPV positive women.
Methods
Women with abnormal cervical cells were enrolled and classified by histological diagnosis and hrHPV infection. A structured questionnaire was used to obtain information on socio-demographic variables and lifestyle factors. LINE-1 methylation level in WBCs was measured by pyrosequencing-based methylation analysis after bisulfite conversion.
Results
Among 252 women diagnosed with normal cervical epithelium, with regard to LINE-1 methylation level no significant difference was observed between hrHPV positive and hrHPV negative women, also adjusting for known risk factors of infection. The association between WBCs LINE-1 methylation and CIN2+ status was analyzed in hrHPV positive women. The median value of LINE-1 methylation levels was higher in cases (CIN2+) than in controls (75.00% versus 73.17%; p = 0.002). For a one-unit increase in LINE-1 methylation level, the odds of being diagnosed with CIN2+ increased by 10%, adjusting for known factors related to LINE-1 methylation (adjOR: 1.10; 95% CI:1.01–1.20; p = 0.032). The Receiver-Operating Characteristic (ROC) curve analysis identified the cut-off value of 73.8% as the best threshold to separate cases from controls (sensitivity: 63.4% and specificity: 61.8%).
Conclusions
LINE-1 methylation status in WBCs DNA may represent a cost-effective and tissue-accessible biomarker for high-grade CIN in hrHPV positive women. However, LINE-1 hypermethylation cannot be considered specific for cervical cancer (CC) and a model based solely on LINE-1 methylation levels has limited performance. Further investigations are necessary to propose and validate a novel methylation biomarker panel, based on LINE-1 methylation and other differentially methylated regions, for the screening of women at risk of CC.
http://ift.tt/2wjiBOO
Comprehensive genomic profiling in routine clinical practice leads to a low rate of benefit from genotype-directed therapy
Abstract
Background
Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options.
Methods
Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT.
Results
A total of 125 pediatric and adult patients with a histologically confirmed diagnosis of malignancy were included. Among these, 106 samples were from adult patients, and 19 samples were from pediatric patients. The median age was 54 years for adults. The majority had stage IV malignancy (53%) and were pretreated with 2–3 lines of therapy (45%). The median age was 8 years for pediatric patients. The majority had brain tumors (47%) and had received none or 1 line of therapy (58%) when the profiling was requested. A total of 111 (92%) patients had genomic alterations and were candidates for GDT either via on/off-label use or a clinical trial (phase 1 through 3). Fifteen patients (12%) received GDT based on these results including two patients who were referred for genomically matched phase 1 clinical trials. Three patients (2%) derived benefit from their GDT that ranged from 2 to 6 months of stable disease.
Conclusions
CGP revealed potential treatment options in the majority of patients profiled. However, multiple barriers to therapy were identified, and only a small minority of the patients derived benefit from GDT.
http://ift.tt/2gqPweU
An Integrated System to Remotely Trigger Intracellular Signal Transduction by Upconversion Nanoparticle-mediated Kinase Photoactivation
In this protocol, caged protein kinase A (PKA), a cellular signal transduction bioeffector, was immobilized on a nanoparticle surface, microinjected into the cytosol, and activated by the upconverted UV light from near-infrared (NIR) irradiation, inducing downstream stress fiber disintegration in the cytosol.
http://ift.tt/2grptnT
Modified Stem Cells Deliver Chemotherapy to Metastatic Tumors
Researchers have used modified stem cells to deliver a cancer drug selectively to metastatic breast cancer tumors in mice. The stem cells target metastatic tumors by homing in on the stiff environment that typically surrounds them.
http://ift.tt/2vKOjRB
A systematic synthesis of direct costs to treat and manage tuberculosis disease applied to California, 2015
The cost of treating and managing cases of active tuberculosis (TB) disease—from diagnosis to treatment completion—is needed by agencies working on public health budgets, resource allocation and cost-effective...
http://ift.tt/2vsi8LL
Perceptions of human papillomavirus vaccination of adolescent schoolgirls in western Uganda and their implications for acceptability of HPV vaccination: a qualitative study
Human papillomavirus (HPV) vaccination has been perceived in diverse ways some of which encourage its uptake while others could potentially deter its acceptability. This study explored community member's perce...
http://ift.tt/2gpKbVh
Forced Air Thermal Regulating Systems: Healthcare Provider Letter - Information About Use
Audience: Surgery, Nursing, Anesthesia [Posted 08/30/2017] ISSUE: The FDA is reminding health care providers that using thermoregulation devices during surgery, including forced air thermoregulating systems, have been demonstrated to result in less...
http://ift.tt/2gqaCu0
Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients
Abstract
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.
http://ift.tt/2xynBOs
Novel Object Recognition Test for the Investigation of Learning and Memory in Mice
The object recognition test (ORT) is a simple and efficient assay for evaluating learning and memory in mice. The methodology is described below.
http://ift.tt/2vFJQAE
Forced Air Thermal Regulating Systems: Healthcare Provider Letter - Information About Use
Audience: Surgery, Nursing, Anesthesia [Posted 08/30/2017] ISSUE: The FDA is reminding health care providers that using thermoregulation devices during surgery, including forced air thermoregulating systems, have been demonstrated to result in less...
http://ift.tt/2gqaCu0
On the Structure of Cortical Microcircuits Inferred from Small Sample Sizes
The structure in cortical microcircuits deviates from what would be expected in a purely random network, which has been seen as evidence of clustering. To address this issue, we sought to reproduce the nonrandom features of cortical circuits by considering several distinct classes of network topology, including clustered networks, networks with distance-dependent connectivity, and those with broad degree distributions. To our surprise, we found that all of these qualitatively distinct topologies could account equally well for all reported nonrandom features despite being easily distinguishable from one another at the network level. This apparent paradox was a consequence of estimating network properties given only small sample sizes. In other words, networks that differ markedly in their global structure can look quite similar locally. This makes inferring network structure from small sample sizes, a necessity given the technical difficulty inherent in simultaneous intracellular recordings, problematic. We found that a network statistic called the sample degree correlation (SDC) overcomes this difficulty. The SDC depends only on parameters that can be estimated reliably given small sample sizes and is an accurate fingerprint of every topological family. We applied the SDC criterion to data from rat visual and somatosensory cortex and discovered that the connectivity was not consistent with any of these main topological classes. However, we were able to fit the experimental data with a more general network class, of which all previous topologies were special cases. The resulting network topology could be interpreted as a combination of physical spatial dependence and nonspatial, hierarchical clustering.
SIGNIFICANCE STATEMENT The connectivity of cortical microcircuits exhibits features that are inconsistent with a simple random network. Here, we show that several classes of network models can account for this nonrandom structure despite qualitative differences in their global properties. This apparent paradox is a consequence of the small numbers of simultaneously recorded neurons in experiment: when inferred via small sample sizes, many networks may be indistinguishable despite being globally distinct. We develop a connectivity measure that successfully classifies networks even when estimated locally with a few neurons at a time. We show that data from rat cortex is consistent with a network in which the likelihood of a connection between neurons depends on spatial distance and on nonspatial, asymmetric clustering.
http://ift.tt/2vFqw6A
Feedback Inhibition Shapes Emergent Computational Properties of Cortical Microcircuit Motifs
Cortical microcircuits are very complex networks, but they are composed of a relatively small number of stereotypical motifs. Hence, one strategy for throwing light on the computational function of cortical microcircuits is to analyze emergent computational properties of these stereotypical microcircuit motifs. We are addressing here the question how spike timing-dependent plasticity shapes the computational properties of one motif that has frequently been studied experimentally: interconnected populations of pyramidal cells and parvalbumin-positive inhibitory cells in layer 2/3. Experimental studies suggest that these inhibitory neurons exert some form of divisive inhibition on the pyramidal cells. We show that this data-based form of feedback inhibition, which is softer than that of winner-take-all models that are commonly considered in theoretical analyses, contributes to the emergence of an important computational function through spike timing-dependent plasticity: The capability to disentangle superimposed firing patterns in upstream networks, and to represent their information content through a sparse assembly code.
SIGNIFICANCE STATEMENT We analyze emergent computational properties of a ubiquitous cortical microcircuit motif: populations of pyramidal cells that are densely interconnected with inhibitory neurons. Simulations of this model predict that sparse assembly codes emerge in this microcircuit motif under spike timing-dependent plasticity. Furthermore, we show that different assemblies will represent different hidden sources of upstream firing activity. Hence, we propose that spike timing-dependent plasticity enables this microcircuit motif to perform a fundamental computational operation on neural activity patterns.
http://ift.tt/2vENxq7
Segregation of Visual Response Properties in the Mouse Superior Colliculus and Their Modulation during Locomotion
The superior colliculus (SC) receives direct input from the retina and integrates it with information about sound, touch, and state of the animal that is relayed from other parts of the brain to initiate specific behavioral outcomes. The superficial SC layers (sSC) contain cells that respond to visual stimuli, whereas the deep SC layers (dSC) contain cells that also respond to auditory and somatosensory stimuli. Here, we used a large-scale silicon probe recording system to examine the visual response properties of SC cells of head-fixed and alert male mice. We found cells with diverse response properties including: (1) orientation/direction-selective (OS/DS) cells with a firing rate that is suppressed by drifting sinusoidal gratings (negative OS/DS cells); (2) suppressed-by-contrast cells; (3) cells with complex-like spatial summation nonlinearity; and (4) cells with Y-like spatial summation nonlinearity. We also found specific response properties that are enriched in different depths of the SC. The sSC is enriched with cells with small RFs, high evoked firing rates (FRs), and sustained temporal responses, whereas the dSC is enriched with the negative OS/DS cells and with cells with large RFs, low evoked FRs, and transient temporal responses. Locomotion modulates the activity of the SC cells both additively and multiplicatively and changes the preferred spatial frequency of some SC cells. These results provide the first description of the negative OS/DS cells and demonstrate that the SC segregates cells with different response properties and that the behavioral state of a mouse affects SC activity.
SIGNIFICANCE STATEMENT The superior colliculus (SC) receives visual input from the retina in its superficial layers (sSC) and induces eye/head-orientating movements and innate defensive responses in its deeper layers (dSC). Despite their importance, very little is known about the visual response properties of dSC neurons. Using high-density electrode recordings and novel model-based analysis, we found several novel visual response properties of the SC cells, including encoding of a cell's preferred orientation or direction by suppression of the firing rate. The sSC and the dSC are enriched with cells with different visual response properties. Locomotion modulates the cells in the SC. These findings contribute to our understanding of how the SC processes visual inputs, a critical step in comprehending visually guided behaviors.
http://ift.tt/2x5TiRa
Romantic Matches Are Hard to Predict Before People Meet
Dating websites often claim attraction between two people can be predicted from the right combination of traits and preferences, but a new study casts doubt on that assertion. The findings are published in the journal Psychological Science, a journal of the Association for Psychological Science.
The study, which used speed dating data, found that a computer-based algorithm could predict who is desirable and how much someone would desire others — who's hot and who's not — but it could not unravel the mystery of unique desire for a specific person.
"Attraction for a particular person may be difficult or impossible to predict before two people have actually met," said Samantha Joel, a University of Utah psychology professor and lead author. "A relationship is more than the sum of its parts. There is a shared experience that happens when you meet someone that can't be predicted beforehand."
Co-authors on the paper are Paul W. Eastwick of the University of California, Davis, and Eli J. Finkel of the Kellogg School of Management at Northwestern University.
The researchers used data from two samples of speed daters, who filled out questionnaires about more than 100 traits and preferences and then met in a series of four-minute dates. Afterward, the participants rated their interactions, indicating level of interest in and sexual attraction to each person they met.
Joel and her colleagues used a cutting-edge machine learning algorithm to test whether it was possible to predict unique romantic desire based on participants' questionnaire responses and before the individuals met.
The answer was no. They found it was possible to predict the overall tendency for someone to like and to be liked by others — but not which two particular people were a match.
"We found we cannot anticipate how much individuals will uniquely desire each other in a speed-dating context with any meaningful level of accuracy," Joel said. "I thought that out of more than 100 predictors, we would be able to predict at least some portion of the variance. I didn't expect we would find zero."
It would be great if people were able to circumvent the hassle and heartache of the dating process by entering information into a computer and having it produce the perfect soul mate, Joel said.
"We tried to do it and we couldn't do it," Joel said. "Dating can be hard and anxiety provoking and there's a market there for a short cut. What if you didn't have to kiss all the frogs? What if you could skip to the part where you click with someone? But our data suggests that, at least with the tools we currently have available, there isn't an easy fix for finding love."
While online dating sites provide a valuable service by narrowing the field and identifying potential romantic prospects, "they don't let you bypass the process of having to physically meet someone to find out how you feel about them," Joel said.
The bottom line is relationship science still has a long way to go to decipher romantic attraction and what makes two particular people click, said co-author Eastwick.
"It may be that we never figure it out, that it is a property we can never get at because it is simply not predictable," Eastwick said. "Romantic desire may well be more like an earthquake, involving a dynamic and chaos-like process, than a chemical reaction involving the right combination of traits and preferences."
This research was supported by a postdoctoral fellowship from the Social Sciences and Humanities Research Council of Canada (to S. Joel).
All data and materials (including R syntax for all analyses) have been made publicly available via the UK Data Service and the Open Science Framework. The complete Open Practices Disclosure for this article is available online . This article has received badges for Open Data and Open Materials.
http://ift.tt/2x5q9FN
Cancer-related risk factors and incidence of major cancers by race, gender and region; analysis of the NIH-AARP diet and health study
Abstract
Background
Racial disparities in the incidence of major cancers may be attributed to differences in the prevalence of established, modifiable risk factors such as obesity, smoking, physical activity and diet.
Methods
Data from a prospective cohort of 566,398 adults aged 50–71 years, 19,677 African-American and 450,623 Whites, was analyzed. Baseline data on cancer-related risk factors such as smoking, alcohol, physical activity and dietary patterns were used to create an individual adherence score. Differences in adherence by race, gender and geographic region were assessed using descriptive statistics, and Cox proportional hazards models were used to determine the association between adherence and cancer incidence.
Results
Only 1.5% of study participants were adherent to all five cancer-related risk factor guidelines, with marked race-, gender- and regional differences in adherence overall. Compared with participants who were fully adherent to all five cancer risk factor criteria, those adherent to one or less had a 76% increased risk of any cancer incidence (HR: 1.76, 95% CI: 1.70 – 1.82), 38% increased risk of breast cancer (HR: 1.38, 95% CI: 1.25 – 1.52), and doubled the risk of colorectal cancer (HR: 2.06, 95% CI: 1.84 – 2.29). However, risk of prostate cancer was lower among participants adherent to one or less compared with those who were fully adherent (HR: 0.79, 95% CI: 0.75 – 0.85). The proportion of cancer incident cases attributable to low adherence was higher among African-Americans compared with Whites for all cancers (21% vs. 19%), and highest for colorectal cancer (25%) regardless of race.
Conclusion
Racial differences in the proportion of cancer incidence attributable to low adherence suggests unique opportunities for targeted cancer prevention strategies that may help eliminate racial disparities in cancer burden among older US adults.
http://ift.tt/2wiXNY1
Chemoradiotherapy versus surgery followed by postoperative radiotherapy in tonsil cancer: Korean Radiation Oncology Group (KROG) study
Abstract
Background
Treatment of tonsil cancer, a subset of oropahryngeal cancer, varies between surgery and radiotherapy. Well-designed studies in tonsil cancer have been rare and it is still controversial which treatment is optimal. This study aimed to assess the outcome and failure patterns in tonsil cancer patients treated with either approaches.
Methods
We retrospectively reviewed medical records of 586 patients with tonsil cancer, treated between 1998 and 2010 at 16 hospitals in Korea. Two hundred and one patients received radiotherapy and chemotherapy (CRT), while 385 patients received surgery followed by radiotherapy and/or chemotherapy (SRT). Compared with the SRT group, patients receiving CRT were older, with more advanced T stage and received higher radiotherapy dose given by intensity modulation techniques. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and clinicopathologic factors were analyzed.
Results
At follow-up, the 5-year OS, DFS, LRRFS and DMFS rates in the CRT group were 82, 78, 89, and 94%, respectively, and in the SRT group were 81, 73, 87, and 89%, respectively. Old age, current smoking, poor performance status, advanced T stage, nodal involvement, and induction chemotherapy were associated with poor OS. Induction chemotherapy had a negative prognostic impact on OS in both treatment groups (p = 0.001 and p = 0.033 in the CRT and SRT groups, respectively).
Conclusions
In our multicenter, retrospective study of tonsil cancer patients, the combined use of radiotherapy and chemotherapy resulted in comparable oncologic outcome to surgery followed by postoperative radiotherapy, despite higher-risk patients having been treated with the definitive radiotherapy. Induction chemotherapy approaches combined with either surgery or definitive radiotherapy were associated with unfavorable outcomes.
http://ift.tt/2xyBFr6
Self-reported sexual health: Breast cancer survivors compared to women from the general population – an observational study
Abstract
Background
Cancer survivorship is of increasing importance in post-treatment care. Sexual health (SH) and femininity can be crucial issues for women surviving cancer. We aimed to determine a more complete understanding of the contribution that a breast cancer (BC) diagnosis and its treatment exert on patients' follow-up SH. For this purpose, self-reported levels and predictors of SH in breast cancer survivors (BCS) were compared with those of women with no previous or current BC (WNBC).
Methods
BCS and WNBC underwent a comprehensive, cross-sectional patient-reported outcome (PRO) assessment. Validated PRO instruments were used to measure SH, body image, anxiety and depression and menopausal symptoms. Assessments were performed within the routine clinical setting.
Instruments used were the Sexual Interest and Desire Inventory - Female, Sexual Activity Questionnaire, Body Image Scale, Hospital Anxiety and Depression Scale and the Menopause-Specific Quality of Life Questionnaire.
Results
One hundred five BCS (average time since diagnosis of 3 years) and 97 WNBC with a mean age of 49 years completed the assessment. SH was significantly worse in BCS compared to WNBC (p = 0.005; BCS SIDI-F mean = 24.9 vs. WNBC mean = 29.8). 68.8% of BCS and 58.8% of WNBC met criteria of a hypo-active sexual desire disorder. Higher depressive symptoms, higher age and lower partnership satisfaction were predictive for poorer SH in BCS.
Conclusion
SH problems are apparent in BCS and differ significantly from those seen in the general population. Consequently, BC survivorship care should include interventions to ameliorate sexual dysfunction and provide help with depressive symptoms and partnership problems, which are associated with poor BCS SH.
http://ift.tt/2wiXwnN
Innovative dressing and securement of tunneled central venous access devices in pediatrics: a pilot randomized controlled trial
Abstract
Background
Central venous access device (CVAD) associated complications are a preventable source of patient harm, frequently resulting in morbidity and delays to vital treatment. Dressing and securement products are used to prevent infectious and mechanical complications, however current complication rates suggest customary practices are inadequate. The aim of this study was to evaluate the feasibility of launching a full-scale randomized controlled efficacy trial of innovative dressing and securement products for pediatric tunneled CVAD to prevent complication and failure.
Methods
An external, pilot, four-group randomized controlled trial of standard care (bordered polyurethane dressing and suture), in comparison to integrated securement-dressing, suture-less securement device, and tissue adhesive was undertaken across two large, tertiary referral pediatric hospitals in Australia. Forty-eight pediatric participants with newly inserted tunneled CVADs were consecutively recruited. The primary outcome of study feasibility was established by elements of eligibility, recruitment, attrition, protocol adherence, missing data, parent and healthcare staff satisfaction and acceptability, and effect size estimates for CVAD failure (cessation of function prior to completion of treatment) and complication (associated bloodstream infection, thrombosis, breakage, dislodgement or occlusion). Dressing integrity, product costs and site complications were also examined.
Results
Protocol feasibility was established. CVAD failure was: 17% (2/12) integrated securement-dressing; 8% (1/13) suture-less securement device; 0% tissue adhesive (0/12); and, 0% standard care (0/11). CVAD complications were: 15% (2/13) suture-less securement device (CVAD associated bloodstream infection, and occlusion and partial dislodgement); 8% (1/12) integrated securement-dressing (partial dislodgement); 0% tissue adhesive (0/12); and, 0% standard care (0/11). One CVAD-associated bloodstream infection occurred, within the suture-less securement device group. Overall satisfaction was highest in the integrated securement-dressing (mean 8.5/10; standard deviation 1.2). Improved dressing integrity was evident in the intervention arms, with the integrated securement-dressing associated with prolonged time to first dressing change (mean days 3.5).
Conclusions
Improving the security and dressing integrity of tunneled CVADs is likely to improve outcomes for pediatric patients. Further research is necessary to identify novel, effective CVAD securement to reduce complications, and provide reliable vascular access for children.
Trial registration
ACTRN12614000280606; prospectively registered on 17/03/2014.
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Retrospective study on timing of resection of hepatocellular adenoma
Background
Hepatocellular adenoma (HCA) is a benign liver tumour that may be complicated by bleeding or malignant transformation. Present guidelines advise cessation of oral contraceptives and surgical resection if the lesion is still larger than 5 cm at 6 months after diagnosis. The aim of this study was to evaluate whether this 6-month interval is sufficient to expect regression of a large HCA to 5 cm or smaller.
Methods
This retrospective cohort study included all patients with an HCA larger than 5 cm diagnosed between 1999 and 2015 with follow-up of at least 6 months. Medical records were reviewed for patient characteristics, clinical presentation, lesion characteristics, management and complications. Differences in characteristics were assessed between patients kept under surveillance and those who underwent treatment for an HCA larger than 5 cm.
Results
Some 194 patients were included, of whom 192 were women. Eighty-six patients were kept under surveillance and 108 underwent HCA treatment. Patients in the surveillance group had a significantly higher BMI (P = 0·029), smaller baseline HCA diameter (P < 0·001), more centrally located lesions (P < 0·001) and were more likely to have multiple lesions (P = 0·001) than those in the treatment group. There were no significant differences in sex, age at diagnosis, symptoms, complication rates and HCA subtype distribution. Time-to-event analysis in patients managed conservatively and those still undergoing treatment more than 6 months after diagnosis showed that 69 of 118 HCAs (58·5 per cent) regressed to 5 cm or smaller after a median of 104 (95 per cent c.i. 80–128) weeks. Larger HCAs took longer to regress (P < 0·001). No complications were documented during follow-up.
Conclusion
This study suggests that a 6-month cut-off point for assessment of regression of HCA larger than 5 cm to no more than 5 cm is too early. As no complications were documented during follow-up, the cut-off point in women with typical, non-β-catenin-activated HCA could be prolonged to 12 months, irrespective of baseline diameter.
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Membrane-Associated Effects of Glucocorticoid on BACE1 Upregulation and A{beta} Generation: Involvement of Lipid Raft-Mediated CREB Activation
Glucocorticoid has been widely accepted to induce Alzheimer's disease, but the nongenomic effect of glucocorticoid on amyloid β (Aβ) generation has yet to be studied. Here, we investigated the effect of the nongenomic pathway induced by glucocorticoid on amyloid precursor protein processing enzymes as well as Aβ production using male ICR mice and human neuroblastoma SK-N-MC cells. Mice groups exposed to restraint stress or intracerebroventricular injection of Aβ showed impaired cognition, decreased intracellular glucocorticoid receptor (GR) level, but elevated level of membrane GR (mGR). In this respect, we identified the mGR-dependent pathway evoked by glucocorticoid using impermeable cortisol conjugated to BSA (cortisol-BSA) on SK-N-MC cells. Cortisol-BSA augmented the expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), the level of C-terminal fragment β of amyloid precursor protein (C99) and Aβ production, which were maintained even after blocking intracellular GR. We also found that cortisol-BSA enhanced the interaction between mGR and Gαs, which colocalized in the lipid raft. The subsequently activated CREB by cortisol-BSA bound to the CRE site of the BACE1 promoter increasing its expression, which was downregulated by inhibiting CBP. Consistently, blocking CBP attenuated cognitive impairment and Aβ production induced by corticosterone treatment or intracerebroventricular injection of Aβ more efficiently than inhibiting intracellular GR in mice. In conclusion, glucocorticoid couples mGR with Gαs and triggers cAMP-PKA-CREB axis dependent on the lipid raft to stimulate BACE1 upregulation and Aβ generation.
SIGNIFICANCE STATEMENT Patients with Alzheimer's disease (AD) have been growing sharply and stress is considered as the major environment factor of AD. Glucocorticoid is the primarily responsive factor to stress and is widely known to induce AD. However, most AD patients usually have impaired genomic pathway of glucocorticoid due to intracellular glucocorticoid receptor deficiency. In this respect, the genomic mechanism of glucocorticoid faces difficulties in explaining the consistent amyloid β (Aβ) production. Therefore, it is necessary to investigate the novel pathway of glucocorticoid on Aβ generation to find a more selective therapeutic approach to AD patients. In this study, we revealed the importance of nongenomic pathway induced by glucocorticoid where membrane glucocorticoid receptor plays an important role in Aβ formation.
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Selective Phosphorylation of AMPA Receptor Contributes to the Network of Long-Term Potentiation in the Anterior Cingulate Cortex
Phosphorylation of AMPA receptor GluA1 plays important roles in synaptic potentiation. Most previous studies have been performed in the hippocampus, while the roles of GluA1 phosphorylation in the cortex remain unknown. Here we investigated the involvement of the phosphorylation of GluA1 in the LTP in the anterior cingulate cortex (ACC) using mice with a GluA1 knock-in mutation at the PKA phosphorylation site serine 845 (s845A) or CaMKII/PKC phosphorylation site serine 831 (s831A). The network LTP, which is constructed by multiple recordings of LTP at different locations within the ACC, was also investigated. We found that the expression of LTP and network LTP was significantly impaired in the s845A mice, but not in the s831A mice. By contrast, basal synaptic transmission and NMDA receptor-mediated responses were not affected. Furthermore, to uncover potential information under the current acquired data, a new method for reconstruction and better visualization of the signals was developed to observe the spatial localizations and dynamic temporal changes of fEPSP signals and multiple LTP responses within the ACC circuit. Our results provide strong evidence that PKA phosphorylation of the GluA1 is important for the network LTP expression in the ACC.
SIGNIFICANCE STATEMENT Previous studies have shown that PKA and PKC phosphorylation of AMPA receptor GluA1 plays critical roles in LTP in the hippocampus, while the roles of GluA1 phosphorylation in the cortex remain unknown. In the present study, by combining a 64-channel multielectrode system and a novel analysis and visualization method, we observed the accurate spatial localization and dynamic temporal changes of network fEPSP signals and LTP responses within the ACC circuit and found that PKA phosphorylation, but not PKC phosphorylation, of the GluA1 is required for LTP in the ACC.
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Low-Resolution Vision—at the Hub of Eye Evolution
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Yuneec International announces availability of Yuneec H520 Commercial UAV
The H520 Incorporates Multiple Interchangeable Payload Options, DataPilot™ Mission Planning Software and All-New YES! Commercial Service Program
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HeartRescue expands effort to reduce sudden cardiac arrest deaths
By EMS1 Staff MINNEAPOLIS — Three more states joined a project dedicated to increasing sudden cardiac arrest survival rates. The HeartRescue Project is a collaborative forum that lets partners share strategies to improve survival rates for sudden cardiac arrest victims. Recently, Maine, New Hampshire and Vermont joined the organization, bringing the total number of states to 15. "While every ...
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Table of Contents
Publication date: September 2017
Source:The Spine Journal, Volume 17, Issue 9
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Table of Contents
Publication date: September 2017
Source:The Spine Journal, Volume 17, Issue 9
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Editorial Board
Publication date: September 2017
Source:The Spine Journal, Volume 17, Issue 9
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Meetings Calendar
Publication date: September 2017
Source:The Spine Journal, Volume 17, Issue 9
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Moisture content of root canal dentine affects detection of microcracks using micro-computed tomography
Abstract
Aim
To evaluate the effect of moisture content in root canal dentine on detection of microcracks using micro-computed tomography.
Methodology
Ten roots with and without craze lines or cracks (each n = 5) were selected and scanned six times with different moisture conditions of root dentine using a micro-CT scanner at a high resolution of 10.5 μm. Scanning conditions were as follows: 1. after 30 d wet storage, 2. after 2 h dry time, 3. after 48 h wet storage, 4. after 24 h dry time, 5. after 48 h wet storage, 6. after 2 h dry time. From each scan, cross-sectional images were obtained at intervals of 1 mm (total n = 708) and evaluated for the presence of dentinal microcracks twice by 5 calibrated blinded observers. Statistical analysis was performed by nonparametric analysis of variance for longitudinal data (P < 0.05).
Results
Intra-rater percentage agreement ranged between 92% and 98%, whereas inter-rater percentage agreement was 81% and 83%, respectively. No significant differences between all wet groups as well as between both groups with 2 h dry time were detected (P > 0.05). Almost no cracks were observed after wet storage with a significant increase of cracks after 2 h dry time (P < 0.001). Significantly more microcracks were identified after 24 h than after 2 h dry time (P < 0.004).
Conclusions
Moisture content of dentine influenced detection of microcracks when evaluated using micro-CT. Scanning should be performed on dried specimens to allow reliable identification of dentinal defects. Formation of new cracks during dry periods up to 24 h was disproved.
This article is protected by copyright. All rights reserved.
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The effect of dental bleaching on pulpal tissue response in a diabetic animal model: A study of immunoregulatory cytokines
Abstract
Aim
To evaluate the influence of dental bleaching in immunoregulatory cytokines production (IL-6, TNF-α, and IL-17) in the pulp tissue of normoglycaemic and diabetic rats.
Methodology
Twenty-eight rats were divided in normoglycaemic and diabetic rats (n = 14). Diabetes mellitus (DM) was induced with a single dose of alloxan diluted in citrate buffer via intramuscular injection. After DM confirmation, all rats were sedated and dental bleaching was performed using 35% hydrogen peroxide in the right maxillary molars for 30 minutes. Left molars were used as controls. Bleaching resulted in 4 hemimaxillae groups: normoglycaemic (N), N-bleached (NBle), diabetic (D), and D-bleached (DBle). After 2 and 30 days, rats were euthanized and hemimaxillae processed for analysis by haematoxylin-eosin and immunohistochemistry. Results within and between animals were submitted to Wilcoxon signed-rank and Mann-Whitney tests (P < 0.05).
Results
At 2 days, the NBle group had mild, and the DBle had severe inflammatory infiltration in the pulpal tissue (P < 0.05). TNF-α and IL-6 cytokines were associated with increased immunolabelling in the bleached groups compared to nonbleached (P < 0.05). However, IL-17 had increased immunolabelling in the NBle compared to the N and DBle group (P < 0.05). At 30 days, reactionary dentine was observed in the coronal pulp of all bleached teeth and no inflammation was present (P > 0.05). TNF-α cytokines had increased immunolabelling in the DBle group compared to the D group (P < 0.05). However, for IL-6 and IL-17, no difference was observed in this period (P > 0.05).
Conclusions
Dental bleaching increased IL-6 and TNF-α in the pulp tissue regardless of Diabetes mellitus; however, diabetic rats had higher TNF-α levels for longer periods. Dental bleaching influenced the increase of IL-17 in the early periods in normoglycaemic rats.
This article is protected by copyright. All rights reserved.
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Assessment of alternative emergency treatments for symptomatic irreversible pulpitis: a randomized clinical trial
Abstract
Aim
To evaluate three emergency procedures for their ability to alleviate clinical symptoms associated with symptomatic teeth having signs of (at least) partial irreversible pulpitis.
Methodology
Sixty-six maxillary and mandibular molars were randomly assigned to a total pulpectomy group (TP; n=22), partial pulpectomy group (PP; n=22), or pulpotomy group (P; n=22). Procedure durations were recorded. Patients answered a questionnaire on daily analgesic requirements and about clinical symptoms (pain intensity, chewing sensitivity, and thermal sensitivity) after the anaesthetic effect had disappeared (Day 0) and on Days 1, 3, and 7 post-treatment.
Results
The total pulpectomy group was associated with the longest procedures (median, 24 min), followed by the partial pulpectomy and pulpotomy groups (P < 0.001 for all). In all three groups, pain intensity, thermal sensitivity, and chewing sensitivity decreased significantly from the preoperative time point to Day 7 (P < 0.001 for all). The total pulpectomy group reported greater reductions in pain intensity than the pulpotomy group between Days 0 and 7, Days 1 and 3, Days 1 and 7 (P < 0.001 for all). No other intergroup differences were noted regarding reductions in pain intensity, and none were observed with respect to changes in prevalence of thermal sensitivity and chewing sensitivity. There were also no significant intergroup differences regarding the analgesic requirements throughout the 7 days.
Conclusion
As emergency treatments for teeth having signs of irreversible pulpitis, pulpotomy, partial pulpectomy and total pulpectomy were comparable with respect to relieving clinical symptoms. Pulpotomy may be preferred because it requires significantly less time and is a simple technique that relieves symptoms quickly and effectively.
This article is protected by copyright. All rights reserved.
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M2 macrophages coexist with a Th1-driven profile in periapical cysts
Abstract
Aim
To evaluate the participation of both Th1 and Th2 responses in periapical cysts by assessing the presence of M2 macrophages, as well as acute IL-1 β, TNF-α and IL-6 cytokines.
Methodology
Twenty-four cases of periapical cysts were selected. Immuno-expressions of IL-1 β, IL-6, TNF-α and CD163 were analyzed in the cystic capsules in both superficial and deeper regions. Data were analyzed with paired Wilcoxon test and Spearman correlation coefficient (P ≤ .05).
Results
There was a higher expression of IL-1β, IL-6, TNF-α and M2 macrophages in the superficial region (P < 0.001) of cystic capsules. All acute cytokines had significant positive correlations among them regardless of the cystic capsule region. Regarding CD163, positive correlations occurred only with TNF-α (P = 0.007; r = 0.537) and IL-6 (P = 0.018; r = 0.478) in the superficial regions of the cystic capsule.
Conclusions
M2 macrophages participated actively in the inflammatory response of periapical cysts and correlated with the expression of certain acute Th1 related cytokines. This illustrates the coexistence of an acute and chronic Th2-driven immune response in these lesions. Although M2 macrophages favour the healing process, their presence is not sufficient for periapical cyst regression, once an acute active response has occurred due to an infectious stimuli.
This article is protected by copyright. All rights reserved.
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Up-regulation of lncRNA CASC9 promotes esophageal squamous cell carcinoma growth by negatively regulating PDCD4 expression through EZH2
Abstract
Background
Abnormal expression of numerous long non-coding RNAs (lncRNAs) has been reported in esophageal squamous cell carcinoma (ESCC) recently, but the great majority of their roles and mechanisms remain largely unclear. We aim to identify the critical ESCC-associated lncRNAs and elucidate the functions and mechanisms in detail.
Methods
Microarrays were used to analyze the differentially expressed lncRNAs in ESCC tissues. qRT-PCR was used to verify the result of microarrays. The effects of the most up-regulated lncRNA, cancer susceptibility candidate 9(CASC9), on cell growth, proliferation and cell cycle were investigated by in vivo and in vitro assays. Microarrays and recovery tests were used to discover the regulatory targets of CASC9. RNA FISH and subcellular fractionation assays were used to detect the subcellular location of CASC9. Finally, the mechanism of CASC9 regulating PDCD4 was explored by RIP, RNA-protein pull down and ChIP assays.
Results
ESCC tissue microarrays showed that CASC9 was the most up-regulated lncRNA. qRT-PCR analysis indicated that CASC9 expression was positively associated with tumor size and TNM stage, and predicted poor overall survival of ESCC patients. Knockdown of CASC9 inhibited ESCC cell growth in vitro and tumorigenesis in nude mice. Furthermore interfering CASC9 decreased cell proliferation and blocked cell cycle G1/S transition. CASC9-associated microarrays indicated that PDCD4 might be the target of CASC9. Consistent with this, PDCD4 expression was negatively associated with CASC9 expression in ESCC tissues and predicted good prognosis. Manipulating CASC9 expression in ESCC cells altered both PDCD4 mRNA and protein levels and cell cycle arrest caused by CASC9 knockdown could be rescued by suppressing PDCD4 expression. CASC9 located both in the nucleus and cytoplasm. Mechanistically, enhancer of zeste homolog2 (EZH2) could bind to both CASC9 and PDCD4 promoter region. Interfering CASC9 reduced the enrichment of EZH2 and H3K27me3 in the PDCD4 promoter region.
Conclusions
Our study firstly demonstrates that lncRNA CASC9 functions as an oncogene by negatively regulating PDCD4 expression through recruiting EZH2 and subsequently altering H3K27me3 level. Our study implicates lncRNA CASC9 as a valuable biomarker for ESCC diagnosis and prognosis.
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The biology of Hepatocellular carcinoma: implications for genomic and immune therapies
Abstract
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is a leading cause of cancer-related death worldwide. It is highly refractory to most systemic therapies. Recently, significant progress has been made in uncovering genomic alterations in HCC, including potentially targetable aberrations. The most common molecular anomalies in this malignancy are mutations in the TERT promoter, TP53, CTNNB1, AXIN1, ARID1A, CDKN2A and CCND1 genes. PTEN loss at the protein level is also frequent. Genomic portfolios stratify by risk factors as follows: (i) CTNNB1 with alcoholic cirrhosis; and (ii) TP53 with hepatitis B virus-induced cirrhosis. Activating mutations in CTNNB1 and inactivating mutations in AXIN1 both activate WNT signaling. Alterations in this pathway, as well as in TP53 and the cell cycle machinery, and in the PI3K/Akt/mTor axis (the latter activated in the presence of PTEN loss), as well as aberrant angiogenesis and epigenetic anomalies, appear to be major events in HCC. Many of these abnormalities may be pharmacologically tractable. Immunotherapy with checkpoint inhibitors is also emerging as an important treatment option. Indeed, 82% of patients express PD-L1 (immunohistochemistry) and response rates to anti-PD-1 treatment are about 19%, and include about 5% complete remissions as well as durable benefit in some patients. Biomarker-matched trials are still limited in this disease, and many of the genomic alterations in HCC remain challenging to target. Future studies may require combination regimens that include both immunotherapies and molecularly matched targeted treatments.
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CRCHD Hosts Career Development and Scientific Workshop
CRCHD recently hosted a Career Development and Scientific Workshop to support investigators interested in applying for Continuing Umbrella of Research Experiences (CURE) and cancer health disparities translational research funding opportunities.
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Pulmonary tumor embolism secondary to soft tissue and bone sarcomas: a case report and literature review
Abstract
Background
Tumor embolisms (TE) are an underappreciated source of pulmonary embolisms in sarcoma. Most evidence in the literature is limited to case reports and none have described the presence of TE secondary to myxofibrosarcoma. We report the first case of myxofibrosarcoma TE and perform a review of the literature for TE secondary to bone and soft tissue sarcomas (STS).
Case presentation
A 36-year-old female presented with debilitating pain of the right upper extremity secondary to a recurrent soft tissue sarcoma. She had distant metastasis to the lung. An MRI revealed a 25-cm shoulder mass involving the proximal arm muscles with encasement of the axillary artery, vein, and brachial plexus. A palliative forequarter amputation was performed and tumor thrombus was evident within the axillary artery and vein. Postoperatively, she developed an acute onset of dyspnea and hypoxia. A computed tomography scan revealed a pulmonary saddle embolism. A bilateral lower extremity venous duplex was negative. She became hemodynamically unstable despite resuscitation and was placed on vasopressor support. A transthoracic echocardiogram revealed elevated pulmonary artery pressure, tricuspid regurgitation, right heart dilation, and reduced right heart systolic function consistent with acute cor pulmonale. The patient did not want to pursue a median sternotomy with pulmonary artery embolectomy and expired from cardiopulmonary arrest within 24 h of the operation. The final pathology revealed a 25 × 16 × 13 cm high-grade myxofibrosarcoma with invasion into the bone, skin, and neurovascular bundle as well as evidence of tumor thrombus.
Conclusion
TE is a rare but deadly cause of pulmonary embolism in sarcoma. A high index of suspicion is necessary in individuals who present with respiratory-related symptoms, especially dyspnea. Diagnostic confirmation with a computed tomography scan of the chest and echocardiogram should be rapid. Unlike venous thromboembolism, pulmonary embolectomy remains the preferred therapeutic approach.
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Gefitinib-loaded DSPE-PEG2000 nanomicelles with CD133 aptamers target lung cancer stem cells
Abstract
Background
Lung cancer stem cells (CSCs) are considered to be the seed of lung cancer, and CD133 is a marker of lung CSCs. Here, we developed gefitinib-loaded poly(ethylene glycol) 2000-distearoylphosphatidylethanolamine nanomicelles with CD133 aptamers (M-Gef-CD133) to eliminate CD133+ lung CSCs.
Methods
M-Gef-CD133 was prepared using a lipid-film-based approach. The targeting and activity of M-Gef-CD133 towards lung CSCs were evaluated.
Results
M-Gef-CD133 were small (25 nm) and showed enhanced cytotoxic effect towards CD133+ lung CSCs compared with non-targeted M-Gef and gefitinib. Notably, M-Gef-CD133 could significantly reduce tumor sphere formation and the percentage of CD133+ lung CSCs, indicating that it possesses selective toxicity against CD133+ lung CSCs.
Conclusions
The interaction of CD133 aptamers and CD133 shows promise in the delivery of gefitinib to CD133+ lung CSCs, and M-Gef-CD133 represents a promising treatment to target lung CSCs.
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Development and validation of a severity scoring system for Zellweger spectrum disorders
Abstract
The lack of a validated severity scoring system for individuals with Zellweger spectrum disorders (ZSD) hampers optimal patient care and reliable research. Here, we describe the development of such severity score and its validation in a large, well characterized cohort of ZSD individuals. We developed a severity scoring system based on the 14 organs that typically can be affected in ZSD. A standardized and validated method was used to classify additional care needs in individuals with neurodevelopmental disabilities (Capacity Profile [CAP]). Thirty ZSD patients of varying ages were scored by the severity score and the CAP. The median score was 9 (range 6–19) with a median scoring age of 16.0 years (range 2–36 years). The ZSD severity score was significantly correlated with all 5 domains of the CAP, most significantly with the sensory domain (r = 0.8971, p = <0.0001). No correlation was found between age and severity score. Multiple peroxisomal biochemical parameters were significantly correlated with the severity score. The presently reported severity score for ZSD is a suitable tool to assess phenotypic severity in a ZSD patient at any age. This severity score can be used for objective phenotype descriptions, genotype-phenotype correlation studies, the identification of prognostic features in ZSD patients and for classification and stratification of patients in clinical trials.
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Biallelic mutations in DYNC2LI1 are a rare cause of Ellis-van Creveld syndrome
Abstract
Ellis van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutations in the EVC, EVC2 and WDR35 genes. A proportion of cases with clinical diagnosis of EvC, however, do not carry mutations in these genes. To identify the genetic cause of EvC in a cohort of mutation-negative patients, exome sequencing was undertaken in a family with three affected members, and mutation scanning of a panel of clinically and functionally relevant genes was performed in 24 additional subjects with features fitting/overlapping EvC. Compound heterozygosity for the c.2T>C (p.Met1?) and c.662C>T (p.Thr221Ile) variants in DYNC2LI1, which encodes a component of the intraflagellar transport-related dynein-2 complex previously found mutated in other short-rib thoracic dysplasias, was identified in the three affected members of the first family. Targeted resequencing detected compound heterozygosity for the same missense variant and a frameshift change (p.Val141*) in two siblings with EvC from a second family, while a newborn with a more severe phenotype carried two DYNC2LI1 truncating variants. Our findings indicate that DYNC2LI1 mutations are associated with a wider clinical spectrum than previously appreciated, including EvC, with the severity of the phenotype likely depending on the extent of defective DYNC2LI1 function.
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Say-Barber-Biesecker-Young-Simpson syndrome and Genitopatellar syndrome: lumping or splitting?
Abstract
The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) and Genitopatellar syndrome (GTPTS) are two rare but clinically well-described diseases caused by de novo heterozygous sequence variants in the KAT6B gene. Both phenotypes are characterized by significant global developmental delay/intellectual disability, hypotonia, genital abnormalities, and patellar hypoplasia/agenesis. In addition, congenital heart defects, dental abnormalities, hearing loss, and thyroid anomalies are common to both phenotypes. This broad clinical overlap led some Authors to propose the concept of KAT6B spectrum disorders. On the other hand, some clinical features could help to differentiate the two disorders. Furthermore, it is possible to establish a genotype-phenotype correlation when considering the position of the sequence variant along the gene, supporting the notion of the two disorders as really distinct entities.
SBBYSS and GTPTS are two rare but clinically well-described diseases. Some Authors propose to unify them under a single denomination (KAT6B-related disorders) because they have many clinical features in common and are caused by sequence variants in the same gene. We believe that from a clinical point of view the facial phenotype of the patients with SBBYSS is striking enough to consider it appropriate to still maintain a distinction.
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Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells
Abstract
Background
Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients' sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients' sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena.
Methods
We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients' sera or cancer patients' sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts' membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes.
Results
Cells treated with exosomes isolated from cancer patients' sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits.
Conclusion
These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes.
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Divergent trends in lung cancer incidence by gender, age and histological type in Estonia: a nationwide population-based study
Abstract
Background
Lung cancer (LC) is the leading cause of cancer deaths in men and the second most frequent cause of cancer deaths in women in Estonia. The study aimed to analyze time trends in LC incidence and mortality in Estonia over the 30-year period, which included major social, economic and health care transition. The results are discussed in the context of changes in tobacco control and smoking prevalence. Long-term predictions of incidence and mortality are provided.
Methods
Data for calculating the incidence and mortality rates in 1985–2014 were obtained from the nationwide population-based Estonian Cancer Registry and the Causes of Death Registry. Joinpoint regression was used to analyze trends and estimate annual percentage change (APC) with 95% confidence interval (CI). Nordpred model was used to project future incidence and mortality trends for 2015–2034.
Results
Incidence peaked among men in 1991 and decreased thereafter (APC: -1.5, 95% CI: -1.8; −1.3). A decline was seen for all age groups, except age ≥ 75 years, and for all histological types, except adenocarcinoma and large cell carcinoma. Incidence among women increased overall (APC: 1.6, 95% CI: 1.1; 2.0) and in all age groups and histological types, except small cell carcinoma. Age-standardized incidence rate (world) per 100,000 was 54.2 in men and 12.9 in women in 2014. Changes in mortality closely followed those in incidence. According to our predictions, the age-standardized incidence and mortality rates will continue to decrease in men and reach a plateau in women.
Conclusions
The study revealed divergent LC trends by gender, age and histological type, which were generally consistent with main international findings. Growing public awareness and stricter tobacco control have stimulated overall favorable changes in men, but not yet in women. Large increase in incidence was observed for adenocarcinoma, which in men showed a trend opposite to the overall decline. LC will remain a serious public health issue in Estonia due to a high number of cases during the next decades, related to aging population, and previous and current smoking patterns. National tobacco control policy in Estonia should prioritize preventing smoking initiation and promoting smoking cessation, particularly among women.
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VEGFR2 regulates endothelial differentiation of colon cancer cells
Abstract
Background
Recent studies suggested that cancer stem-like cells contribute to tumor vasculogenesis by differentiating into endothelial cells. However, such process is governed by still undefined mechanism.
Methods
At varying differentiation levels, three representative colon cancer cells were cultured in endothelial-inducing conditioned medium: human colon cancer cells HCT116 (HCT116) (poorly differentiated), SW480 (moderately differentiated), and HT29 (well differentiated). We tested for expression of endothelial markers (cluster of differentiation (CD) 31, CD34, and vascular endothelial (VE)-cadherin and their ability to form tube-like structures in 3D culture. We also observed VEGF secretion and expressions of endothelial markers and VEGFRs in HCT116 cells under hypoxia to simulate physiological conditions. In in vitro and in xenotransplantation experiments, VE growth factor receptor 2 (VEGFR2) antagonist SKLB1002 was used to test effect of VEGFR2 in endothelial differentiation of HCT116 cells. Expression levels of VEGFR2 and VE-cadherin were assessed by immunohistochemistry of human colon cancer tissues to evaluate clinicopathological significance of VEGFR2.
Results
After culturing in endothelial-inducing conditioned medium, poorly differentiated HCT116 cells expressed endothelial markers and formed tube-like structure in vitro. HCT116 cells secreted more endogenous VEGF and expressed higher VEGFR2 under hypoxia. SKLB1002 impaired endothelial differentiation in vitro and xenotransplantation experiments, suggesting a VEGFR2-dependent mechanism. Increased expression of VEGFR2 correlated with differentiation, metastasis/recurrence, and poor prognosis in 203 human colon cancer samples. Positive correlation was observed between VEGFR2 and VE-cadherin expression.
Conclusions
VEGFR2 regulates endothelial differentiation of colon cancer cell and may be potential platform for anti-angiogenesis cancer therapy.
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Novel three-dimensional bone ‘mapping’ software can help assess progression of osseous metastases from routine CT
Abstract
Imaging of bone metastasis response to therapy is a research priority. Stradwin is a new software-tool, with demonstrated sub-voxel accuracy in assessing cortical bone properties from routine CT. We applied this technology to the context of osseous metastases, with particular focus on disease progression using prostate cancer as a model. 3D–rendered 'bone-maps' were produced for 20 men with advanced prostate cancer, including a sub-cohort of 9 who had undergone serial scans. Correlation between baseline interpretation and assessments of progression between modalities was assessed. Bone-maps took significantly less time to interpret than CT bone windows (P < 0.001). Initial bone-mapping, without adjustment, demonstrated sensitivity and specificity for suspicious areas on CT of 70.7% and 73.1% respectively. Evaluating disease over time, concordance between bone-maps and current practice using RECIST outcomes was 100%.
This study demonstrates the feasibility and potential use of this free post-processing software in the serial assessment of osseous metastases.
http://ift.tt/2vsjgPh
CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer
Abstract
The ability of some tumors to exclude effector T cells represents a major challenge to immunotherapy. T cell exclusion is particularly evident in pancreatic ductal adenocarcinoma (PDAC), a disease where blockade of the immune checkpoint molecule CTLA-4 has not produced significant clinical activity. In PDAC, effector T cells are often scarce within tumor tissue and confined to peritumoral lymph nodes and lymphoid aggregates. We hypothesized that CTLA-4 blockade, despite a lack of clinical efficacy seen thus far in PDAC, might still alter T cell immunobiology, which would have therapeutic implications. Using clinically relevant genetic models of PDAC, we found that regulatory T cells (Tregs), which constitutively express CTLA-4, accumulate early during tumor development but are largely confined to peritumoral lymph nodes during disease progression. Tregs were observed to regulate CD4+, but not CD8+, T cell infiltration into tumors through a CTLA-4/CD80 dependent mechanism. Disrupting CTLA-4 interaction with CD80 was sufficient to induce CD4 T cell infiltration into tumors. These data have important implications for T cell immunotherapy in PDAC and demonstrate a novel role for CTLA-4/CD80 interactions in regulating T cell exclusion. In addition, our findings suggest distinct mechanisms govern CD4+ and CD8+ T cell infiltration in PDAC.
http://ift.tt/2iJ1sJA
Harvey victims use social media when 911 fails
"We called 911 and it rang and rang and rang and rang," a Houston resident said
http://ift.tt/2vs8f0c
The Role of BAFF System Molecules in Host Response to Pathogens [Reviews]
SUMMARY
The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the "BAFF system molecules." BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development.
http://ift.tt/2x5sZuo
Protocol for a mixed studies systematic review on the implementation of the recovery approach in adult mental health services
Introduction
Recovery is integral to mental health planning in G-8 countries including Canada. A recovery-oriented approach to care aims to promote personal empowerment, illness self-management and a life beyond services for people with serious mental illness (SMI), while reducing the financial burden associated with mental illness. Although there is a growing body of literature on recovery, no synthesis of research on the implementation of recovery into mental health services exists.
ObjectivesThe objective is to conduct a mixed studies systematic review on the operationalisation of recovery into mental health services for adults with SMI. It will inform the transformation of Canadian services to a recovery orientation, but may be applicable to other countries.
Methods and analysisSeven databases including PubMed, Ovid Medline, Ovid Embase, Ovid PsycInfo, CINAHL, the Cochrane Library and Scopus will be searched for peer-reviewed empirical studies published from 1998 to December 2016. Systematic reviews and studies using quantitative, qualitative and mixed methodologies will be included. Secondary searches will be conducted in reference lists of all selected full text articles. Handsearches will also be performed in the tables of contents of three recovery-focused journals for the last 5 years. International experts in the field will be contacted for comments and advice. Data extraction will include identification and methodological synthesis of each study; definition of recovery; information on recovery implementation; facilitators and barriers and study outcomes. A quality assessment will be conducted on each study. The data will be synthesised and a stepwise thematic analysis performed.
Ethics and disseminationEthics approval is not required for this knowledge synthesis. Findings will be disseminated through knowledge translation activities including: (1) a 1-day symposium; (2) presentations in national and international conferences and to local stakeholders; (3) publications in peer-reviewed journals; (4) posts on the organisational websites.
http://ift.tt/2x4Y7u1
Prevalence and associated factors of diabetic retinopathy in Beijing, China: a cross-sectional study
Objectives
The study aimed to determine the exact risk factors for diabetic retinopathy (DR) in the Chinese population using a cohort of 17 985 individuals from Beijing, China.
DesignCross-sectional study.
SettingA hospital.
Participants17 985 individuals from Beijing, China.
Primary and secondary outcome measuresThis was a cross-sectional study of permanent residents from the Changping area (Beijing, China) recruited from July 2010 to March 2011 and from March 2014 to February 2015 during a routine health examination at the Tongren Hospital of Beijing. Eye examinations were conducted by experienced ophthalmologists. Medical history, height, weight, body mass index (BMI) and blood pressure were recorded. Routine laboratory examinations were performed.
ResultsThe prevalence of DR was 1.5% in the general study population and 8.1% among individuals with diabetes. Compared with the non-DR group, individuals in the DR group in the diabetes population had longer disease duration, higher systolic blood pressure (SBP), fasting plasma glucose (FPG) and uric acid (UA) (in men) and lower UA (in women) (all p<0.05). The multivariate analysis showed that disease duration (p<0.001), BMI (p=0.046), SBP (p=0.012), creatinine clearance rate (CCR) (p=0.014), UA (p=0.018) and FPG (p<0.001) were independently associated with DR in patients with diabetes.
ConclusionThe prevalence of DR was 8.1% among patients with diabetes. Disease duration, BMI, SBP, CCR, UA and FPG were independently associated with DR.
http://ift.tt/2x4sMYw
Intersectoral approaches and integrated services in achieving the right to health for refugees upon resettlement: a scoping review protocol
Introduction
Global insecurity and climate change are exacerbating the need for improved management of refugee resettlement services. International standards hold states responsible for the protection of the right of non-citizens to an adequate standard of physical and mental health while recognising the importance of social determinants of health. However, programmes to protect refugees' right to health often lack coordination and monitoring. This paper describes the protocol for a scoping review to explore barriers and facilitators to the integration of health services for refugees; the content, process and actors involved in protecting refugee health; and the extent to which intersectoral approaches are leveraged to protect refugees' right to health on resettlement, especially for vulnerable groups such as women and children.
Methods and analysisPeer-reviewed (through four databases including MEDLINE, Web of Science, Global Health and PsycINFO) and grey literature were searched to identify programmes and interventions designed to promote refugee health in receiving countries. Two reviewers will screen articles and abstract data. Two frameworks for integration and intersectoral action will be applied to understand how and why certain approaches work while others do not and to identify the actors involved in achieving success at different levels of integration as defined by these frameworks.
Ethics and disseminationFindings from the scoping review will be shared in relevant conferences and meetings. A brief will be created with lessons learnt from successful programmes to inform decision making in design of refugee programmes and services. Ethical approval is not required as human subjects are not involved.
Trial registration numberRegistered on Open Science Framework at https://osf.io/gt9ck/.
http://ift.tt/2vEncbQ
Correction: Do cognitive interventions improve general cognition in dementia? a meta-analysis and meta-regression
Huntley JD, Gould RL, Liu K, et al. Do cognitive interventions improve general cognition in dementia? A meta-analysis and meta-regression. BMJ Open 2015;5:e005247. doi: 10.1136/bmjopen-2014-005247
There is an error in the reporting of the CIs in the abstract compared with those reported in the results section and figures 2 and 3 of the paper.
In the Abstract, the sentence,
'Significant positive effect sizes (Hedges' g) were found for CS with the mini-mental state examination (MMSE) (g=0.51, 95% CI 0.29 to 0.69; p<0.001) compared to non-active controls and (g=0.35, 95% CI 0.06 to 0.65; p=0.019) compared to active controls.'
should read:
'Significant positive effect sizes (Hedges' g) were found for CS with the mini-mental state examination (MMSE) (g=0.51, 95% CI 0.35 to 0.66; p<0.001) compared to non-active controls and (g=0.35, 95% CI 0.06 to 0.64; p=0.019) compared to active controls.'
http://ift.tt/2x4XhO8
Prevalence and Risk Factors of Asthma, Rhinitis, and Eczema and Their Multimorbidity among Young Adults in Kuwait: A Cross-Sectional Study
Objective. To estimate the prevalence of allergic diseases and allergic multimorbidity (coexistence) among young adults in Kuwait and to examine associations between risk factors with allergic diseases and allergic multimorbidity. Methods. A cross-sectional study was conducted by enrolling 1,154 students, aged 18–26 years, attending Kuwait University. Participants self-completed a questionnaire on symptoms and clinical history of allergic diseases. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated by applying Poisson regression with robust variance estimation. Results. The prevalence of current asthma, rhinitis, and eczema was estimated to be 11.9% (135/1135), 20.4% (232/1138), and 9.2% (105/1143), respectively. The coexistence of "asthma and rhinitis" (5.1%, 57/1125) was the most frequent allergic multimorbidity. Both maternal history (PR = 3.97, 95% CI: 2.32–6.80) and paternal history (PR = 1.72, 95% CI: 1.10–2.68) of allergy were independently associated with having two or more coexisting allergic diseases. The joint effect of having both maternal and paternal history of allergy was associated with 8.16 times (95% CI: 4.19–15.90) higher risk of allergic multimorbidity. Conclusion. Allergic diseases and allergic multimorbidity are common among young adults in Kuwait and their burden mirrors that of westernized countries. Parental history of allergy is a strong predisposing factor for allergic multimorbidity.
http://ift.tt/2x4l2Wi
Late-onset Pompe disease in a 54 year-old sportsmaan with an episode of syncope: a case report
Pompe disease is an extra-rare metabolic storage disease with deficiency of acid-alpha-glucosidase (GAA) enzyme activity, which leads to the pathologic accumulation of glycogen in target tissues (skeletal muscles, heart, brain). Clinical features and severity vary by the age of onset, rate of extent of organ involvement. In the late-onset Pompe disease (LOPD) form, essential cardiomyopathy seems to be uncommon. Muscles weakness and respiratory failure are the main symptoms of adult patient with Pompe disease. In presented case LOPD coupled with patient's regular sporting activity and healthy diet, which may explain the low intensity of the symptoms and the slow progress of the disease, lack of skeletal muscles weakness and lack of brain manifestation. Myocardial storage deposits are the only abnormalities found.
L'articolo Late-onset Pompe disease in a 54 year-old sportsmaan with an episode of syncope: a case report sembra essere il primo su European Review.
http://ift.tt/2whYh0k
The study on the effect of hyperglycaemia on offspring fatty tissue metabolism during pregnancy
OBJECTIVE: In this study, we adopted maternal diabetes model on rats, which induced by streptozotocin to explore the metabolism changes of rat adipose tissue during the neonatal period.
MATERIALS AND METHODS: The female rats were induced as diabetes models by streptozotocin (STZ), and mated with the normal male rats when they entered into adulthood. The chosen male offspring rats were executed at week 12 and the epididymis and subcutaneous fat pad were obtained. Then the adipose cells were extracted and the foundation level and absorbing of insulin induced 2-deoxyglucose (2DG) were assessed.
RESULTS: Compared with normal control group, the body weight, fat pad weight of the epididymis and diameter of lipid cells for maternal diabetes offspring rats all increased. Lipid cells of epididymis and the intake of glucose induced by insulin increased. At the same time, glucose was oxidized to CO2 and increased lipid. However, there was no change in the capacity of in vitro lipid decomposition. Also, GLUT4, insulin receptor (IRβ), acetyl coenzyme A (ACC), etc. increased in fat pad of maternal offspring of diabetes.
CONCLUSIONS: Maternal diabetes had effect on fat metabolism of offspring; lipid storage capacity increased but the ability of lipid decomposition had no change.
L'articolo The study on the effect of hyperglycaemia on offspring fatty tissue metabolism during pregnancy sembra essere il primo su European Review.
http://ift.tt/2vDBUzI
Comparison of the outcomes between thoracoscopic and laparoscopic esophagectomy via retrosternal and prevertebral lifting paths by the same surgeon
Abstract
Background
The objective of the study is to explore the effects of retrosternal and prevertebral lifting paths of the tubular stomach on postoperative complications of patients undergoing cervical anastomosis in thoracoscopic and laparoscopic esophagectomy.
Methods
Sixty-three patients were retrospectively analyzed. The patients received thoracoscopic and laparoscopic esophagectomy by the same surgeon. According to the path by which the stomach was lifted upward, the patients were divided into two groups: the retrosternal path group (32 patients) and the prevertebral path group (31 patients). Operative indications and complications of postoperative patients in these two groups were observed.
Results
There was no statistically significant difference in the time duration of surgery, amount of bleeding, number of dissected lymph node, and postoperative hospitalization time between the retrosternal and prevertebral lifting paths (P > 0.05). Furthermore, the two groups did not show significant difference in the incidence rate of postoperative anastomosis fistula complications (P = 0.702). Instead, the amount of postoperative gastric drainage and the incidence rates of the pulmonary infection were significantly lower in the retrosternal path group than in the prevertebral path group, respectively (P = 0.001, P = 0.012, respectively).
Conclusion
The esophagogastrostomic cervical anastomoses performed via the retrosternal and prevertebral paths are both feasible methods of digestive tract reconstruction. The amount of postoperative gastric drainage volume and the pulmonary infection incidence rate in the retrosternal path group were lower than those in the prevertebral path group. Therefore, gastroesophageal anastomosis via the retrosternal lifting path may be preferably considered for thoracoscopic and laparoscopic surgery for esophageal carcinoma patients.
http://ift.tt/2vrUy1m
Esophagogastric junction cancer successfully treated by laparoscopic proximal gastrectomy and lower esophagectomy with intrathoracic double-flap technique: A case report
Abstract
A 66-year-old man was referred to our hospital for treatment of esophagogastric junction cancer. He was diagnosed as cT2N0M0, and the esophageal invasion was found to be 1 cm from the esophagogastric junction. He underwent laparoscopy-assisted proximal gastrectomy and lower esophagectomy with esophagogastrostomy using the intrathoracic double-flap technique through the transhiatal approach. The operative time was 662 min (suturing time was 198 min), and blood loss was 200 mL. The operative time was much longer for this procedure than for esophagogastrostomy with the conventional (intra-abdominal) double-flap technique. The postoperative course was uneventful. No abnormal gastroesophageal reflux, esophageal motility, or lower esophageal sphincter (LES) pressure was demonstrated 3 months after the operation. Laparoscopic proximal gastrectomy and lower esophagectomy with esophagogastrostomy using the double-flap technique through the transhiatal approach is safe and feasible. It may be recommended for patients with esophagogastric junction cancer with esophageal invasion of about 1 cm.
http://ift.tt/2vEldnJ
Latif’s point: A new point for Veress needle insertion for pneumoperitoneum in difficult laparoscopy
Abstract
Introduction
Creating pneumoperitoneum is the most challenging step during laparoscopy. The periumbilical area is the classic site for Veress needle insertion. We adopted a new access point for peritoneal insufflation.
Methods
We introduced a new point for Veress needle insertion to create pneumoperitoneum during difficult laparoscopic procedures. The needle is placed between the xiphoid process and the right costal margin, and it then proceeds toward the patient's right axilla. We collected data to compare using this new method of peritoneal insufflation with using Palmer's point for pneumoperitoneum.
Results
Since 2013, we have used this new technique in 570 patients (first group) and Palmer's point in 459 patients (second group). Among these patients, 196 patients (20%) had had previous abdominal operations, 98 patients (10%) had irreducible ventral hernia, and 735 patients (70%) were morbidly obese. The two groups were comparable in terms of patient characteristics. The mean time to create pneumoperitoneum in the first group was 0.8 ± 0.002 min compared to 1.08 ± 0.007 min in the second group (P ≤ 0.5). The mean number of punctures was 1.57 ± 1.02 in the first group compared to 2.9 ± 1.5 in the second group (P≤ 0.5); in the first group, 97% were successful on the first attempt entry, whereas this figure was 91% in second group. In the first group, the liver was punctured in 13 patients without any further complications; no other viscera were punctured. In the second group, gastric puncture occurred in 5 cases, transverse colon in 2 cases, and omental injury in 12 cases.
Conclusion
This new access point may represent a safe, fast, and easy way to create pneumoperitoneum, as well as a promising alternative to Palmer's point in patients who are not candidates for classic midline entry.
http://ift.tt/2x4uLvW
Life-threatening hemorrhage from the corona mortis after laparoscopic inguinal hernia repair: Report of a case
Abstract
Along with the increased use of other laparoscopic procedures, laparoscopic inguinal hernia repair has become widely used because of its minimally invasive nature. Here, we report a case of 66-year-old man who underwent transabdominal preperitoneal laparoscopic hernioplasty and developed hemorrhagic shock on postoperative day 1. CT showed postoperative venous hemorrhage from the retropubic space. Successful hemostasis of the massive hemorrhage was achieved laparoscopically. The origin of the hemorrhage was assumed to be the corona mortis vein, which was slightly injured during the operation. Despite the rarity of this complication, surgeons must be aware of the need to carefully dissect and fix the mesh in the retropubic space to avoid injuring the corona mortis. Laparoscopic hemostasis may be an effective alternative to the open approach.
http://ift.tt/2vEvO25
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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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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
