We have developed dual sonar equipment and an improved operating method for improving resolution in order to solve the problems of limitations of the optical equipment and the application method of SSS (side scan sonar) in the investigation of damage of underwater structures. We analyzed the influence factors of the resolution of sonar data through the comparison of resolution and data quality in indoor test. Also we confirmed the problems about the overlapping area of the dual sonar. Depth and distance were analyzed as major influencing factors for survey angle. Specimens were scanned while adjusting distance and towfish angle according to depth change in order to verify applicability of the developed dual sonar in the field experiment. Optimal resolution was found to be 3 cm in specimen spacing, and 20 sample data items were extracted. We developed the regression model based on the multiple regression analysis and developed the RealDualSONAR-DAQ tool, the dual sonar optimum operating method program based on proposed correlation equations. We can use the developed tools to get the value of the major influencing factors for dual sonar operation and obtain high quality sonar data to analyze damage of underwater structures.
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Κυριακή 21 Μαΐου 2017
Copy number variation analysis of patients with intellectual disability from North-West Spain
Source:Gene, Volume 626
Author(s): Inés Quintela, Jesús Eirís, Carmen Gómez-Lado, Laura Pérez-Gay, David Dacruz, Raquel Cruz, Manuel Castro-Gago, Luz Míguez, Ángel Carracedo, Francisco Barros
Intellectual disability (ID) is a complex and phenotypically heterogeneous neurodevelopmental disorder characterized by significant deficits in cognitive and adaptive skills, debuting during the developmental period. In the last decade, microarray-based copy number variation (CNV) analysis has been proved as a strategy particularly useful in the discovery of loci and candidate genes associated with these phenotypes and is widely used in the clinics with a diagnostic purpose. In this study, we evaluated the usefulness of two genome-wide high density SNP microarrays -Cytogenetics Whole-Genome 2.7M SNP array (n=126 patients; Group 1) and CytoScan High-Density SNP array (n=447 patients; Group 2)- in the detection of clinically relevant CNVs in a cohort of ID patients from Galicia (NW Spain). In 159 (27.7%) patients, we detected 186 rare exonic chromosomal imbalances, that were grouped into the following classes: Clinically relevant (67/186; 36.0%), of unknown clinical significance (93/186; 50.0%) and benign (26/186; 14.0%). The 67 pathogenic CNVs were identified in 64 patients, which means an overall diagnostic yield of 11.2%. Overall, we confirmed that ID is a genetically heterogeneous condition and emphasized the importance of using genome-wide high density SNP microarrays in the detection of its genetic causes. Additionally, we provided clinical and molecular data of patients with pathogenic or likely pathogenic CNVs and discussed the potential implication in neurodevelopmental disorders of genes located within these variants.
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Why are patients with blood cancers more likely to die without hospice?
BACKGROUND
Although patients with blood cancers have significantly lower rates of hospice use than those with solid malignancies, data explaining this gap in end-of-life care are sparse.
METHODS
In 2015, we conducted a mailed survey of a randomly selected sample of hematologic oncologists in the United States to characterize their perspectives regarding the utility and adequacy of hospice for blood cancer patients, as well as factors that might impact referral patterns. Simultaneous provision of care for patients with solid malignancies was permitted.
RESULTS
We received 349 surveys (response rate, 57.3%). The majority of respondents (68.1%) strongly agreed that hospice care is helpful for patients with hematologic cancers; those with practices including greater numbers of solid tumor patients (at least 25%) were more likely to strongly agree (odds ratio, 2.10; 95% confidence interval, 1.26-3.52). Despite high levels of support for hospice in general, 46.0% felt that home hospice is inadequate for their patients' needs (as compared to inpatient hospice with round-the-clock care). Although more than half of the respondents reported that they would be more likely to refer patients to hospice if red cell and/or platelet transfusions were available, those who considered home hospice inadequate were even more likely to report that they would (67.3% vs 55.3% for red cells [P = .03] and 52.9% vs 39.7% for platelets [P = .02]).
CONCLUSIONS
These data suggest that although hematologic oncologists value hospice, concerns about the adequacy of services for blood cancer patients limit hospice referrals. To increase hospice enrollment for blood cancer patients, interventions tailoring hospice services to their specific needs are warranted. Cancer 2017. © 2017 American Cancer Society.
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Cigarette Filter Ventilation and its Relationship to Increasing Rates of Lung Adenocarcinoma
The 2014 Surgeon General’s Report on smoking and health concluded that changing cigarette designs have caused an increase in lung adenocarcinomas, implicating cigarette filter ventilation that lowers smoking machine tar yields. The Food and Drug Administration (FDA) now has the authority to regulate cigarette design if doing so would improve public health. To support a potential regulatory action, two weight-of-evidence reviews were applied for causally relating filter ventilation to lung adenocarcinoma. Published scientific literature (3284 citations) and internal tobacco company documents contributed to causation analysis evidence blocks and the identification of research gaps. Filter ventilation was adopted in the mid-1960s and was initially equated with making a cigarette safer. Since then, lung adenocarcinoma rates paradoxically increased relative to other lung cancer subtypes. Filter ventilation 1) alters tobacco combustion, increasing smoke toxicants; 2) allows for elasticity of use so that smokers inhale more smoke to maintain their nicotine intake; and 3) causes a false perception of lower health risk from “lighter” smoke. Seemingly not supportive of a causal relationship is that human exposure biomarker studies indicate no reduction in exposure, but these do not measure exposure in the lung or utilize known biomarkers of harm. Altered puffing and inhalation may make smoke available to lung cells prone to adenocarcinomas. The analysis strongly suggests that filter ventilation has contributed to the rise in lung adenocarcinomas among smokers. Thus, the FDA should consider regulating its use, up to and including a ban. Herein, we propose a research agenda to support such an effort.
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MicroRNA-29b Contributes to Collagens Imbalance in Human Osteoarthritic and Dedifferentiated Articular Chondrocytes
Objective. Decreased expression of collagen type II in favour of collagen type I or X is one hallmark of chondrocyte phenotype changes in osteoarthritic (OA) cartilage. MicroRNA- (miR-) 29b was previously shown to target collagens in several tissues. We studied whether it could contribute to collagen imbalance in chondrocytes with an impaired phenotype. Methods. After preliminary microarrays screening, miR-29b levels were measured by RT- quantitative PCR in in vitro models of chondrocyte phenotype changes (IL-1β challenge or serial subculturing) and in chondrocytes from OA and non-OA patients. Potential miR-29b targets identified in silico in 3′-UTRs of collagens mRNAs were tested with luciferase reporter assays. The impact of premiR-29b overexpression in ATDC5 cells was studied on collagen mRNA levels and synthesis (Sirius red staining) during chondrogenesis. Results. MiR-29b level increased significantly in IL-1β-stimulated and weakly in subcultured chondrocytes. A 5.8-fold increase was observed in chondrocytes from OA versus non-OA patients. Reporter assays showed that miR-29b targeted COL2A1 and COL1A2 3′-UTRs although with a variable recovery upon mutation. In ATDC5 cells overexpressing premiR-29b, collagen production was reduced while mRNA levels increased. Conclusions. By acting probably as a posttranscriptional regulator with a different efficacy on COL2A1 and COL1A2 expression, miR-29b can contribute to the collagens imbalance associated with an abnormal chondrocyte phenotype.
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3D Evaluation of Palatal Rugae in Identical Twins
The study of identical twins can point out potential limitations in biometrics and forensic odontology. This case report presents three-dimensional (3D) palatal rugae analysis in monozygotic twins utilizing digital models obtained directly by scanning the maxillary dental arch with the iTero® intraoral digital scanner. The results show that the rugae patterns contain related but not identical features between the pair of identical twins. Dental study models taken on a regular basis for diagnosis and treatment planning in dentistry include the palatal rugae, which could be valuable to forensics in identical twin identification cases.
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Nonparametric Subgroup Identification by PRIM and CART: A Simulation and Application Study
Two nonparametric methods for the identification of subgroups with outstanding outcome values are described and compared to each other in a simulation study and an application to clinical data. The Patient Rule Induction Method (PRIM) searches for box-shaped areas in the given data which exceed a minimal size and average outcome. This is achieved via a combination of iterative peeling and pasting steps, where small fractions of the data are removed or added to the current box. As an alternative, Classification and Regression Trees (CART) prediction models perform sequential binary splits of the data to produce subsets which can be interpreted as subgroups of heterogeneous outcome. PRIM and CART were compared in a simulation study to investigate their strengths and weaknesses under various data settings, taking different performance measures into account. PRIM was shown to be superior in rather complex settings such as those with few observations, a smaller signal-to-noise ratio, and more than one subgroup. CART showed the best performance in simpler situations. A practical application of the two methods was illustrated using a clinical data set. For this application, both methods produced similar results but the higher amount of user involvement of PRIM became apparent. PRIM can be flexibly tuned by the user, whereas CART, although simpler to implement, is rather static.
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Approximation of Functions on a Square by Interpolation Polynomials at Vertices and Few Fourier Coefficients
For a bivariate function on a square, in general, its Fourier coefficients decay slowly, so one cannot reconstruct it by few Fourier coefficients. In this paper we will develop a new approximation scheme to overcome the weakness of Fourier approximation. In detail, we will use Lagrange interpolation and linear interpolation on the boundary of the square to derive a new approximation scheme such that we can use the values of the target function at vertices of the square and few Fourier coefficients to reconstruct the target function with very small error.
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EEG activity as an objective measure of cognitive load during effortful listening: A study on pediatric subjects with bilateral, asymmetric sensorineural hearing loss
Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Pasquale Marsella, Alessandro Scorpecci, Giulia Cartocci, Sara Giannantonio, Anton Giulio Maglione, Isotta Venuti, Ambra Brizi, Fabio Babiloni
ObjectivesDeaf subjects with hearing aids or cochlear implants generally find it challenging to understand speech in noisy environments where a great deal of listening effort and cognitive load are invested. In prelingually deaf children, such difficulties may have detrimental consequences on the learning process and, later in life, on academic performance. Despite the importance of such a topic, currently, there is no validated test for the assessment of cognitive load during audiological tasks. Recently, alpha and theta EEG rhythm variations in the parietal and frontal areas, respectively, have been used as indicators of cognitive load in adult subjects.The aim of the present study was to investigate, by means of EEG, the cognitive load of pediatric subjects affected by asymmetric sensorineural hearing loss as they were engaged in a speech-in-noise identification task.MethodsSeven children (4F and 3M, age range = 8–16 years) affected by asymmetric sensorineural hearing loss (i.e. profound degree on one side, mild-to-severe degree on the other side) and using a hearing aid only in their better ear, were included in the study. All of them underwent EEG recording during a speech-in-noise identification task: the experimental conditions were quiet, binaural noise, noise to the better hearing ear and noise to the poorer hearing ear. The subjects' Speech Recognition Thresholds (SRT) were also measured in each test condition. The primary outcome measures were: frontal EEG Power Spectral Density (PSD) in the theta band and parietal EEG PSD in the alpha band, as assessed before stimulus (word) onset.ResultsNo statistically significant differences were noted among frontal theta power levels in the four test conditions. However, parietal alpha power levels were significantly higher in the “binaural noise” and in the “noise to worse hearing ear” conditions than in the “quiet” and “noise to better hearing ear” conditions (p < 0.001). SRT scores were consistent with task difficulty, but did not correlate with alpha and theta power level variations.ConclusionThis is the first time that EEG has been applied to children with sensorineural hearing loss with the purpose of studying the cognitive load during effortful listening. Significantly higher parietal alpha power levels in two of three noisy conditions, compared to the quiet condition, are consistent with increased cognitive load. Specifically, considering the time window of the analysis (pre-stimulus), parietal alpha power levels may be a measure of cognitive functions such as sustained attention and selective inhibition. In this respect, the significantly lower parietal alpha power levels in the most challenging listening condition (i.e. noise to the better ear) may be attributed to loss of attention and to the subsequent fatigue and “withdrawal” from the task at hand.
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Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Pasquale Marsella, Alessandro Scorpecci, Giulia Cartocci, Sara Giannantonio, Anton Giulio Maglione, Isotta Venuti, Ambra Brizi, Fabio Babiloni
ObjectivesDeaf subjects with hearing aids or cochlear implants generally find it challenging to understand speech in noisy environments where a great deal of listening effort and cognitive load are invested. In prelingually deaf children, such difficulties may have detrimental consequences on the learning process and, later in life, on academic performance. Despite the importance of such a topic, currently, there is no validated test for the assessment of cognitive load during audiological tasks. Recently, alpha and theta EEG rhythm variations in the parietal and frontal areas, respectively, have been used as indicators of cognitive load in adult subjects.The aim of the present study was to investigate, by means of EEG, the cognitive load of pediatric subjects affected by asymmetric sensorineural hearing loss as they were engaged in a speech-in-noise identification task.MethodsSeven children (4F and 3M, age range = 8–16 years) affected by asymmetric sensorineural hearing loss (i.e. profound degree on one side, mild-to-severe degree on the other side) and using a hearing aid only in their better ear, were included in the study. All of them underwent EEG recording during a speech-in-noise identification task: the experimental conditions were quiet, binaural noise, noise to the better hearing ear and noise to the poorer hearing ear. The subjects' Speech Recognition Thresholds (SRT) were also measured in each test condition. The primary outcome measures were: frontal EEG Power Spectral Density (PSD) in the theta band and parietal EEG PSD in the alpha band, as assessed before stimulus (word) onset.ResultsNo statistically significant differences were noted among frontal theta power levels in the four test conditions. However, parietal alpha power levels were significantly higher in the “binaural noise” and in the “noise to worse hearing ear” conditions than in the “quiet” and “noise to better hearing ear” conditions (p < 0.001). SRT scores were consistent with task difficulty, but did not correlate with alpha and theta power level variations.ConclusionThis is the first time that EEG has been applied to children with sensorineural hearing loss with the purpose of studying the cognitive load during effortful listening. Significantly higher parietal alpha power levels in two of three noisy conditions, compared to the quiet condition, are consistent with increased cognitive load. Specifically, considering the time window of the analysis (pre-stimulus), parietal alpha power levels may be a measure of cognitive functions such as sustained attention and selective inhibition. In this respect, the significantly lower parietal alpha power levels in the most challenging listening condition (i.e. noise to the better ear) may be attributed to loss of attention and to the subsequent fatigue and “withdrawal” from the task at hand.
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Salicylate degradation by a cold-adapted Pseudomonas sp.
Abstract
Pseudomonas sp. strain MC1 was characterized as a cold-adapted, naphthalene-degrading bacterium that is able to grow in a broad temperature range of 5–30°C. MC1 harbors a catabolic plasmid, designated pYIC1, which is almost identical to the archetypal NAH7 plasmid from the mesophilic bacterium Pseudomonas putida G7. On pYIC1, the catabolic genes for naphthalene degradation are clustered in two operons: nahAa-Ab-Ac-Ad-B-F-C-Q-E-D encoding the conversion of naphthalene to salicylate, and nahG-T-H-I-N-L-O-M-K-J encoding the conversion of salicylate through meta-cleavage pathway to pyruvate and acetyl CoA. NahH, the bona fide extradiol dioxygenase in MC1 salicylate metabolism, is thermolabile and is a cold-adapted enzyme. The thermal profiles of the NahH enzyme activities expressed in different hosts indicate the presence of a factor(s) or mechanism(s) to protect the thermolabile NahH enzyme (100% aa identity with MC1 counterpart) in G7. Overall, the results reported in the present work suggest that the thermolabile NahH might be a product of the cold-adaptation process of MC1 and thus contribute to the survival and growth ability of MC1 on salicylate and naphthalene in cold environments.
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Specific rebinding of protein imprinted polyethylene glycol grafted calcium alginate hydrogel with different crosslinking degree
Abstract
Bovine serum albumin imprinted polyethylene glycol 600 (PEG600) grafted Calcium alginate (CaA) hydrogel microspheres were prepared and characterized. The adsorption and recognition properties of PEG600 grafted calcium alginate (CaA-g-PEG600) microspheres were evaluated and the results showed that the crosslinking structure of CaA-g-PEG600 microspheres exerted an obvious effect on the adsorption capacity and imprinting properties for bovine serum albumin. The adsorption isotherms and recognition properties indicated that the imprinted modified microspheres had excellent rebinding affinity toward target proteins and the imprinting efficiency varied according to PEG600 grafting degree. The adsorption capacity and the imprinting factor were 5.5 mg g−1 and 3.6, respectively. Adsorption kinetics of CaA-g-PEG600 microspheres in accordance with the molecular weight between crosslinks (Mc) was investigated and the structural influence on protein selective rebinding was discussed. Furthermore, the binary solution separation performance of CaA-g-PEG600 microspheres with different Mc was investigated by selective binding bovine serum albumin from protein mixture solution.
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Title Page/Section Editors
Publication date: July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 7
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Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 7
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Enhancing hair growth in male androgenetic alopecia by a combination of fractional CO 2 laser therapy and hair growth factors
Abstract
Laser therapy and growth factors have been used as alternative treatments for male androgenetic alopecia (MAA). The aim of this study is to determine the efficacy and safety of hair growth factors alone or combined with ablative carbon dioxide (CO2) fractional laser therapy in MAA. Twenty-eight men were enrolled in this randomized half-split study based on a left-head to right-head pattern. Fractional CO2 laser treatment was unilaterally performed; hair growth factors were bilaterally applied. Six sessions with 2-week intervals were performed. Global photographs and dermoscopy assessments were performed at the baseline and 4 months after first treatment. Global photographs underwent blinded review by three independent dermatologists. Scanning electron microscopy was used to compare changes in hair-follicle phase and hair-shaft diameter. Twenty-seven participants completed the 4-month treatment schedule. One patient was lost. Mean hair density increased from 114 ± 27 to 143 ± 25/cm2 (P < 0.001) in the combined group and from 113 ± 24 to 134 ± 19/cm2 in the growth factor group (P < 0.001). The mean change from baseline between two groups was also compared (P = 0.003). Global photographs showed improvement in 93% (25/27) patients in the combined group and 67% (18/27) patients in the growth factor group. Under scanning electron microscopy, hair follicles appeared to transition from telogen to anagen, and hair-shaft diameter increased in five randomly selected patients. Ablative fractional CO2 laser combined with hair growth factors may serve as an alternative treatment for MAA in individuals unwilling/unable to undergo medical or surgical treatment.
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Alone on Mars for 150 Months
-- Read more on ScientificAmerican.com
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05/19/17 PHD comic: 'Upgrade'
| Piled Higher & Deeper by Jorge Cham |
www.phdcomics.com
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title: "Upgrade" - originally published 5/19/2017
For the latest news in PHD Comics, CLICK HERE! |
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newly available online.THE NEW GEOGRAPHY
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newly available online.Japanese Journal of Biofeedback Research
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newly available online.The Library World
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newly available online.PROCEEDINGS OF THE ITE ANNUAL CONVENTION
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The new issue is now available.Aesthetics
Vol.37 No.3
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The new issue is now available.Aesthetics
Vol.40 No.3
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The new issue is now available.Aesthetics
Vol.40 No.4
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The new issue is now available.Aesthetics
Vol.38 No.1
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The new issue is now available.Aesthetics
Vol.38 No.2
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The new issue is now available.NIPPON SUISAN GAKKAISHI
Vol.83 No.3
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The new issue is now available.Shikaigaku
Vol.69 No.3_4
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The new issue is now available.Shikaigaku
Vol.69 No.2
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The new issue is now available.Shikaigaku
Vol.69 No.1
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The new issue is now available.THE NEW GEOGRAPHY
Vol.56 No.2
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The new issue is now available.The Japanese journal of adlescent psychology
Vol.25 No.2
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The new issue is now available.Aesthetics
Vol.37 No.4
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The new issue is now available.Aesthetics
Vol.24 No.3
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The new issue is now available.Aesthetics
Vol.32 No.3
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The new issue is now available.Journal of Synthetic Organic Chemistry, Japan
Vol.75 No.5
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Presence of new mutations in the TP53 gene in patients with low-risk myelodysplastic syndrome: two case reports
Myelodysplastic syndromes are heterogeneous disorders. Patients with myelodysplastic syndrome disease often have ineffective hematopoiesis, cytopenias, blood cell dysplasia in one or more cell types, and are a...
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Hashimoto’s Encephalopathy Presenting with Unusual Behavioural Disturbances in an Adolescent Girl
Hashimoto’s encephalopathy (HE) is a rare autoimmune disorder with neurological and neuropsychiatric manifestations and elevated titres of anti-thyroid antibodies. Here we are reporting a case of HE in a 19-year-old girl who presented with seizure-like episodes, confusion, and behavioural disturbances with catatonic symptoms such as posturing, echopraxia, echolalia, and ambivalence. Patient did not respond to antipsychotics and anticonvulsants. On further investigation, patient was found to have high serum anti-TPO antibodies of about 1261 U/mL with euthyroid status, which supported a suspicion of HE. Our consultant neurologist confirmed the diagnosis and she was started on injection of methylprednisolone 750 mg OD. Since patient started showing clinical improvement, her antipsychotic medications were tapered off. On follow-up, patient has recovered and is functioning well. Since HE is a diagnosis of exclusion, very high anti-TPO antibodies and good response to steroids supported the diagnosis of HE in this patient after excluding other etiological possibilities. This case has been reported because the clinical presentation was predominantly neurobehavioural manifestations which is uncommon with HE.
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Caregiver Burden in Alcohol Dependence Syndrome
Background. Alcoholism is a major threat to the individual as well as the society and the maximum burden of the illness is borne by the family. Aim. The study is aimed at assessing the pattern of burden on the caregivers of alcohol dependent patients and at assessing the relationship between the severity of dependence and the burden on caregivers. Settings and Design. Cross-sectional descriptive study conducted in the Department of Psychiatry, Sri Ramachandra Medical College and Research Institute. Materials and Methods. A cross-sectional assessment was done in 200 patients with alcohol dependence and their caregivers. The severity of dependence and the pattern of burden on caregivers were assessed. Statistical Analysis. The data thus collected was analyzed using SPSS version 20. Results. The study demonstrates that caregivers of alcohol dependent patients reported significant objective burden and subjective burden. Furthermore, the severity of alcohol dependence and the domains of burden such as financial burden, disruption of family interaction, and disruption of family routine activities were positively correlated with high level of significance. Conclusion. The current study has illustrated that all the caregivers experienced significant amount of burden which has to be addressed for better treatment outcome of the patients.
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Antioxidant Treatment Induces Hyperactivation of the HPA Axis by Upregulating ACTH Receptor in the Adrenal and Downregulating Glucocorticoid Receptors in the Pituitary
Glucocorticoid (GC) production is physiologically regulated through a negative feedback loop mediated by the GC, which appears disrupted in several pathological conditions. The inability to perform negative feedback of the hypothalamus-pituitary-adrenal (HPA) axis in several diseases is associated with an overproduction of reactive oxygen species (ROS); however, nothing is known about the effects of ROS on the functionality of the HPA axis during homeostasis. This study analyzed the putative impact of antioxidants on the HPA axis activity and GC-mediated negative feedback upon the HPA cascade. Male Wistar rats were orally treated with N-acetylcysteine (NAC) or vitamin E for 18 consecutive days. NAC-treated rats were then subjected to a daily treatment with dexamethasone, which covered the last 5 days of the antioxidant therapy. We found that NAC and vitamin E induced an increase in plasma corticosterone levels. NAC intensified MC2R and StAR expressions in the adrenal and reduced GR and MR expressions in the pituitary. NAC also prevented the dexamethasone-induced reduction in plasma corticosterone levels. Furthermore, NAC decreased HO-1 and Nrf2 expression in the pituitary. These findings show that antioxidants induce hyperactivity of the HPA axis via upregulation of MC2R expression in the adrenal and downregulation of GR and MR in the pituitary.
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A spiking neural network model of the midbrain superior colliculus that generates saccadic motor commands
Abstract
Single-unit recordings suggest that the midbrain superior colliculus (SC) acts as an optimal controller for saccadic gaze shifts. The SC is proposed to be the site within the visuomotor system where the nonlinear spatial-to-temporal transformation is carried out: the population encodes the intended saccade vector by its location in the motor map (spatial), and its trajectory and velocity by the distribution of firing rates (temporal). The neurons' burst profiles vary systematically with their anatomical positions and intended saccade vectors, to account for the nonlinear main-sequence kinematics of saccades. Yet, the underlying collicular mechanisms that could result in these firing patterns are inaccessible to current neurobiological techniques. Here, we propose a simple spiking neural network model that reproduces the spike trains of saccade-related cells in the intermediate and deep SC layers during saccades. The model assumes that SC neurons have distinct biophysical properties for spike generation that depend on their anatomical position in combination with a center–surround lateral connectivity. Both factors are needed to account for the observed firing patterns. Our model offers a basis for neuronal algorithms for spatiotemporal transformations and bio-inspired optimal controllers.
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Factors Affecting the Periapical Status of Root-Filled Canals: A Cross-Sectional Study at the Undergraduate Level
Objective. The aim was to evaluate the influence of multiple factors on the periapical status of endodontically treated (ET) teeth. Methods. The patients were clinically and radiographically reevaluated after root canal therapy. The quality of the root-filled canals, coronal restorations, intraradicular posts, dental caries, and periodontal parameters were associated with the teeth’s periapical status. Results. The 122 patients provided 154 ET teeth; 97.4% teeth were asymptomatic, and 75.5% had a normal periapical status. The percentage of perfect, satisfactory, and deficient root-filled canals was of the order of 41.6%, 46.1%, and 12.3%, respectively. The percentage of adequate and inadequate coronal restorations was 31.2% and 68.8%, respectively. A total of 14.9% teeth had intraradicular posts, and 29.2% had cavitated carious lesions in the dentin. Gingival bleeding was observed in 31.8% of teeth, and dental biofilm was visible in 58.4%. A total of 11.7% showed pathologic tooth mobility, and 22.1% teeth were diagnosed with periodontal disease. Conclusions. Carious lesions, gingival bleeding, and tooth mobility were significantly associated with the occurrence of periapical lesions in root-filled canals.
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A Modified Lotka–Volterra Model for Diffusion and Substitution of Multigeneration DRAM Processing Technologies
We attempt to develop an effective forecasting model for the diffusion and substitution of multigeneration Dynamic Random Access Memory (DRAM) processing technologies. We consider market share data and propose a modified Lotka–Volterra model, in which an additional constraint on the summation of market share is introduced. The mean absolute error is used to measure the accuracy of our market share predictions. Market share data in DRAM industries from quarter one (Q1) of 2005 to 2013 Q4 is collected to validate the prediction accuracy. Our model significantly outperforms other benchmark forecasting models of both revenue and market share data, including the Bass and Lotka–Volterra models. Compared to prior studies on forecasting the diffusion and substitution of multigeneration technologies, our model has two new perspectives: () allowing undetermined number of multigeneration technologies and inconsecutive adoption of new technologies and () requiring less data for forecasting newborn technologies.
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Exploring the Influence of Attitudes to Walking and Cycling on Commute Mode Choice Using a Hybrid Choice Model
Transport-related problems, such as automobile dependence, traffic congestion, and greenhouse emissions, lead to a great burden on the environment. In developing countries like China, in order to improve the air quality, promoting sustainable travel modes to reduce the automobile usage is gradually recognized as an emerging national concern. Though there are many studies related to the physically active modes (e.g., walking and cycling), the research on the influence of attitudes to active modes on travel behavior is limited, especially in China. To fill up this gap, this paper focuses on examining the impact of attitudes to walking and cycling on commute mode choice. Using the survey data collected in China cities, an integrated discrete choice model and the structural equation model are proposed. By applying the hybrid choice model, not only the role of the latent attitude played in travel mode choice, but also the indirect effects of social factors on travel mode choice are obtained. The comparison indicates that the hybrid choice model outperforms the traditional model. This study is expected to provide a better understanding for urban planners on the influential factors of green travel modes.
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The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens
Galectins are a group of evolutionarily conserved proteins with the ability to bind β-galactosides through characteristic carbohydrate-recognition domains (CRD). Galectin-3 is structurally unique among all galectins as it contains a C-terminal CRD linked to an N-terminal protein-binding domain, being the only chimeric galectin. Galectin-3 participates in many functions, both intra- and extracellularly. Among them, a prominent role for Galectin-3 in inflammation has been recognized. Galectin-3 has also been shown to directly bind to pathogens and to have various effects on the functions of the cells of the innate immune system. Thanks to these two properties, Galectin-3 participates in several ways in the innate immune response against invading pathogens. Galectin-3 has been proposed to function not only as a pattern-recognition receptor (PRR) but also as a danger-associated molecular pattern (DAMP). In this review, we analyze the various roles that have been assigned to Galectin-3, both as a PRR and as a DAMP, in the context of immune responses against pathogenic microorganisms.
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Examining the Benefits and Barriers of Instructional Gardening Programs to Increase Fruit and Vegetable Intake among Preschool-Age Children
Research exists on using instructional gardening programs with school age children as a means of improving dietary quality and for obesity prevention. This article examines the potential use of instructional gardens in childcare settings to improving fruit and vegetable intake in young children. A qualitative study was conducted with childcare providers. Participants () were recruited via e-mails, letters, and follow-up phone calls. Interviews were recorded, transcribed, and coded to identify themes within two areas childcare providers perceptions of children’s fruit and vegetable consumption and components necessary to initiate or improve instructional gardening programs. Themes associated with provider’s perceptions of child fruit and vegetable consumption included benefits of consumption, willingness to try fruits and vegetables, meeting recommendations, and influence of the home and childcare environments on child eating. Benefits, barriers, and resources needed were identified as themes related to starting or improving instructional gardening programs. Benefits to gardening with preschoolers are consistent with those found in school-age populations. While several barriers exist, resources are available to childcare providers to address these barriers. Increased knowledge and awareness of resources are necessary to improve the success of gardening programs in the childcare setting with the goal of improving child diet quality.
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Deep Brain Stimulation: Inducing Self-Estrangement
Abstract
Despite growing evidence that a significant number of patients living with Parkison's disease experience neuropsychiatric changes following Deep Brain Stimulation (DBS) treatment, the phenomenon remains poorly understood and largely unexplored in the literature. To shed new light on this phenomenon, we used qualitative methods grounded in phenomenology to conduct in-depth, semi-structured interviews with 17 patients living with Parkinson's Disease who had undergone DBS. Our study found that patients appear to experience postoperative DBS-induced changes in the form of self-estrangement. Using the insights from patients' subjective perceptions of postoperative self-change provides a potent explanation of potential DBS-induced self-estrangement.
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Home Noninvasive Ventilation to Reduce Readmissions for COPD
The use of long-term noninvasive ventilation (NIV) to benefit patients with severe chronic obstructive pulmonary disease (COPD) has long been controversial. Dating back to the 1960s, clinicians speculated that intermittent respiratory muscle rest afforded by negative pressure ventilators might benefit daytime respiratory muscle performance of patients with severe COPD. However, use of this approach was generally abandoned in the early 1990s when a large randomized clinical trial using a “jacket” negative pressure ventilator nocturnally showed no improvement in exercise endurance or respiratory muscle strength in patients with severe COPD, and acceptance of the device by patients was poor.
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Effect of Home NIV on Outcomes After Acute COPD Exacerbation
This randomized clinical trial compares the effects of home oxygen therapy with vs without home noninvasive ventilation (NIV) on time to readmission or death in patients with persistent hypercapnia after an acute chronic obstructive pulmonary disease (COPD) exacerbation.
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The Case of Reactive Arthritis Secondary to Echinococcus Infestation
Reactive arthritis is an inflammatory joint disease that develops after an infection and it usually occurs following a gastrointestinal or genitourinary system infection and it belongs to the family of arthritis called “spondyloarthritis.” We wanted to represent a rare case of reactive arthritis secondary to Echinococcus infestation. Cyst hydatid disease is common in endemic regions like Turkey. Internal organ involvements, especially liver and lung, are most frequent involvements. Primary bone involvement is rare complication of Echinococcus infestation. In our case, the patient with Echinococcus infection developed right knee arthritis and sacroiliitis. Other reactive and oligoarthritis causes were excluded and diagnosis of reactive arthritis secondary to cyst hydatid infestation was done with the present findings. Cold pack and TENS treatment were applied as symptomatic treatment to the right knee of the patient. Acemetacin was given as medical treatment. On the 5th day of treatment, right knee and ankle arthritis were clinically regressed. In regions where the disease is seen as endemic, such as Turkey, patients with musculoskeletal symptoms should consider the possibility of musculoskeletal involvement due to the hydatid cyst.
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Hypoxia in Obesity and Diabetes: Potential Therapeutic Effects of Hyperoxia and Nitrate
The prevalence of obesity and diabetes is increasing worldwide. Obesity and diabetes are associated with oxidative stress, inflammation, endothelial dysfunction, insulin resistance, and glucose intolerance. Obesity, a chronic hypoxic state that is associated with decreased nitric oxide (NO) bioavailability, is one of the main causes of type 2 diabetes. The hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of several genes of the metabolic pathways including proinflammatory adipokines, endothelial NO synthase (eNOS), and insulin signaling components. It seems that adipose tissue hypoxia and NO-dependent vascular and cellular dysfunctions are responsible for other consequences linked to obesity-related disorders. Although hyperoxia could reverse hypoxic-related disorders, it increases the production of reactive oxygen species (ROS) and decreases the production of NO. Nitrate can restore NO depletion and has antioxidant properties, and recent data support the beneficial effects of nitrate therapy in obesity and diabetes. Although it seems reasonable to combine hyperoxia and nitrate treatments for managing obesity/diabetes, the combined effects have not been investigated yet. This review discusses some aspects of tissue oxygenation and the potential effects of hyperoxia and nitrate interventions on obesity/diabetes management. It can be proposed that concomitant use of hyperoxia and nitrate is justified for managing obesity and diabetes.
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Metronomic chemotherapy: A potent macerator of cancer by inducing angiogenesis suppression and antitumor immune activation
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Eirini Biziota, Leonidas Mavroeidis, Eleftheria Hatzimichael, Periklis Pappas
Metronomic chemotherapy is a low dosing treatment strategy that attracts growing scientific and clinical interest. It refers to dense and uninterrupted administration of low doses of chemotherapeutic agents (without prolonged drug free intervals) over extended periods of time. Cancer chemotherapy is conventionally given in cycles of maximum tolerated doses (MTD) with the aim of inducing maximum cancer cell apoptosis. In contrast, the primary target of metronomic chemotherapy is the tumor's neovasculature. This is relevant to the emerging concept that tumors exist in a complex microenvironment of cancer cells, stromal cells and supporting vessels. In addition to its anti-angiogenetic properties, metronomic chemotherapy halts tumor growth by activating anti-tumor immunity, thus decreasing the acquired resistance to conventional chemotherapy. Herein, we present a review of the literature that provides a scientific basis for the merits of chemotherapy when administered on a metronomic schedule.
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Source:Cancer Letters, Volume 400
Author(s): Eirini Biziota, Leonidas Mavroeidis, Eleftheria Hatzimichael, Periklis Pappas
Metronomic chemotherapy is a low dosing treatment strategy that attracts growing scientific and clinical interest. It refers to dense and uninterrupted administration of low doses of chemotherapeutic agents (without prolonged drug free intervals) over extended periods of time. Cancer chemotherapy is conventionally given in cycles of maximum tolerated doses (MTD) with the aim of inducing maximum cancer cell apoptosis. In contrast, the primary target of metronomic chemotherapy is the tumor's neovasculature. This is relevant to the emerging concept that tumors exist in a complex microenvironment of cancer cells, stromal cells and supporting vessels. In addition to its anti-angiogenetic properties, metronomic chemotherapy halts tumor growth by activating anti-tumor immunity, thus decreasing the acquired resistance to conventional chemotherapy. Herein, we present a review of the literature that provides a scientific basis for the merits of chemotherapy when administered on a metronomic schedule.
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Resistance to metronomic chemotherapy and ways to overcome it
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Maria Riesco-Martinez, Karla Parra, Ronak Saluja, Giulio Francia, Urban Emmenegger
Therapeutic resistance is amongst the major determinants of cancer mortality. Contrary to initial expectations, antivascular therapies are equally prone to inherent or acquired resistance as other cancer treatment modalities. However, studies into resistance to vascular endothelial growth factor pathway inhibitors revealed distinct mechanisms of resistance compared to conventional cytotoxic therapy. While some of these novel mechanisms of resistance also appear to be functional regarding metronomic chemotherapy, herein we summarize available evidence for mechanisms of resistance specifically described in the context of metronomic chemotherapy. Numerous preclinically identified molecular targets and pathways represent promising avenues to overcome resistance and enhance the benefits achieved with metronomic chemotherapy eventually. However, there are considerable challenges to clinically translate the preclinical findings.
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Source:Cancer Letters, Volume 400
Author(s): Maria Riesco-Martinez, Karla Parra, Ronak Saluja, Giulio Francia, Urban Emmenegger
Therapeutic resistance is amongst the major determinants of cancer mortality. Contrary to initial expectations, antivascular therapies are equally prone to inherent or acquired resistance as other cancer treatment modalities. However, studies into resistance to vascular endothelial growth factor pathway inhibitors revealed distinct mechanisms of resistance compared to conventional cytotoxic therapy. While some of these novel mechanisms of resistance also appear to be functional regarding metronomic chemotherapy, herein we summarize available evidence for mechanisms of resistance specifically described in the context of metronomic chemotherapy. Numerous preclinically identified molecular targets and pathways represent promising avenues to overcome resistance and enhance the benefits achieved with metronomic chemotherapy eventually. However, there are considerable challenges to clinically translate the preclinical findings.
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Immunological, anti-angiogenic and clinical effects of intratumoral interleukin 12 electrogene therapy combined with metronomic cyclophosphamide in dogs with spontaneous cancer: A pilot study
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Laetitia Cicchelero, Sofie Denies, Katrien Vanderperren, Emmelie Stock, Leen Van Brantegem, Hilde de Rooster, Niek N. Sanders
The immunological, anti-angiogenic and clinical effects of metronomic cyclophosphamide and 3 consecutive intratumoral interleukin (IL)-12 gene therapy (electrogene therapy (EGT)) treatments were evaluated in 6 dogs with spontaneous cancer. In all dogs, a decrease in peripheral leukocytes 2 days after IL-12 EGT coincided with erythema and swelling of the tumor. In the tumor, a transient increase in IL-12 levels was measured, whereas a continuous increase in interferon γ (IFNγ) and thrombospondin 1 (TSP-1) were determined in contrast to a continuous decrease in vascular endothelial growth factor (VEGF). In the serum, a transient increase in IL-12 and IL-10 levels were noted in contrast to a transient decrease in VEGF and TSP-1. The treatment resulted in a significant anti-angiogenic effect. Although all primary tumors continued to progress in time, this progression was slower than before treatment according to the contrast-enhanced ultrasound data. Besides the encouraging immunostimulatory and anti-angiogenic effects observed in all dogs we also noticed in 4 out of 6 dogs clinically relevant improvements in quality of life and weight. These results hold great promise for combinatorial strategies of IL-12 EGT and metronomic chemotherapy with conventional antitumor (immuno)therapies.
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Source:Cancer Letters, Volume 400
Author(s): Laetitia Cicchelero, Sofie Denies, Katrien Vanderperren, Emmelie Stock, Leen Van Brantegem, Hilde de Rooster, Niek N. Sanders
The immunological, anti-angiogenic and clinical effects of metronomic cyclophosphamide and 3 consecutive intratumoral interleukin (IL)-12 gene therapy (electrogene therapy (EGT)) treatments were evaluated in 6 dogs with spontaneous cancer. In all dogs, a decrease in peripheral leukocytes 2 days after IL-12 EGT coincided with erythema and swelling of the tumor. In the tumor, a transient increase in IL-12 levels was measured, whereas a continuous increase in interferon γ (IFNγ) and thrombospondin 1 (TSP-1) were determined in contrast to a continuous decrease in vascular endothelial growth factor (VEGF). In the serum, a transient increase in IL-12 and IL-10 levels were noted in contrast to a transient decrease in VEGF and TSP-1. The treatment resulted in a significant anti-angiogenic effect. Although all primary tumors continued to progress in time, this progression was slower than before treatment according to the contrast-enhanced ultrasound data. Besides the encouraging immunostimulatory and anti-angiogenic effects observed in all dogs we also noticed in 4 out of 6 dogs clinically relevant improvements in quality of life and weight. These results hold great promise for combinatorial strategies of IL-12 EGT and metronomic chemotherapy with conventional antitumor (immuno)therapies.
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Editorial Board
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
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Source:Cancer Letters, Volume 400
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Safety and efficacy study of metronomic vinorelbine, cyclophosphamide plus capecitabine in metastatic breast cancer: A phase II trial
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Emilia Montagna, Antonella Palazzo, Patrick Maisonneuve, Giuseppe Cancello, Monica Iorfida, Angela Sciandivasci, Angela Esposito, Anna Cardillo, Manuelita Mazza, Elisabetta Munzone, Antonella Lai, Aron Goldhirsch, Marco Colleoni
In a phase II study we assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine, cyclophosphamide capecitabine in patients with metastatic breast cancer, either as first-line (naïve group) or second-line or greater therapy (pre-treated group). Eligible patients had histologically or cytologically proven, hormone-receptor positive metastatic breast cancer. The primary end point was median time to progression (TTP). A total of 43 patients in the naïve group and 65 in the pre-treated group were enrolled. The median TTP was 25.1 months in the naïve group and 11.2 months in the pre-treated group. The most frequently reported grade 2 treatment-related adverse events were leukopenia and hand and foot syndrome. Metronomic combination of cyclophosphamide, capecitabine and vinorelbine showed significant activity and good tolerability in patients hormonal receptor positive, metastatic breast cancer patients.
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Source:Cancer Letters, Volume 400
Author(s): Emilia Montagna, Antonella Palazzo, Patrick Maisonneuve, Giuseppe Cancello, Monica Iorfida, Angela Sciandivasci, Angela Esposito, Anna Cardillo, Manuelita Mazza, Elisabetta Munzone, Antonella Lai, Aron Goldhirsch, Marco Colleoni
In a phase II study we assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine, cyclophosphamide capecitabine in patients with metastatic breast cancer, either as first-line (naïve group) or second-line or greater therapy (pre-treated group). Eligible patients had histologically or cytologically proven, hormone-receptor positive metastatic breast cancer. The primary end point was median time to progression (TTP). A total of 43 patients in the naïve group and 65 in the pre-treated group were enrolled. The median TTP was 25.1 months in the naïve group and 11.2 months in the pre-treated group. The most frequently reported grade 2 treatment-related adverse events were leukopenia and hand and foot syndrome. Metronomic combination of cyclophosphamide, capecitabine and vinorelbine showed significant activity and good tolerability in patients hormonal receptor positive, metastatic breast cancer patients.
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Metronomic S-1 dosing and thymidylate synthase silencing have synergistic antitumor efficacy in a colorectal cancer xenograft model
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Amr S. Abu Lila, Naoto Moriyoshi, Masakazu Fukushima, Cheng-Long Huang, Hiromi Wada, Tatsuhiro Ishida
Metronomic chemotherapy is currently considered an emerging therapeutic option in clinical oncology. S-1, an oral formulation of Tegafur (TF), a prodrug of 5-fluorouracil (5-FU), is designed to improve the antitumor activity of 5-FU in tandem with reducing its toxicity. Clinically, metronomic S-1 dosing has been approved for the standard first- and second-line treatment of metastatic or advanced stage of colorectal (CRC). However, expression of intratumor thymidylate synthase (TS), a significant gene in cellular proliferation, is associated with poor outcome to 5-FU-based chemotherapeutic regimens. In this study, therefore, we examined the effect of a combination of TS silencing by an RNA interfering molecule, chemically synthesized short hairpin RNA against TS (shTS), and 5-FU on the growth of human colorectal cancer cell (DLD-1) both in vitro and in vivo. The combined treatment of both shTS with 5-FU substantially inhibited cell proliferation in vitro. For in vivo treatments, the combined treatment of metronomic S-1 dosing with intravenously injected polyethylene glycol (PEG)-coated shTS-lipoplex significantly suppressed tumor growth, compared to a single treatment of either S-1 or PEG-coated shTS-lipoplex. In addition, the combined treatment increased the proportion of apoptotic cells in the DLD-1 tumor tissue. Our results suggest that metronomic S-1 dosing combined with TS silencing might represent an emerging therapeutic strategy for the treatment of patients with advanced CRC.
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Source:Cancer Letters, Volume 400
Author(s): Amr S. Abu Lila, Naoto Moriyoshi, Masakazu Fukushima, Cheng-Long Huang, Hiromi Wada, Tatsuhiro Ishida
Metronomic chemotherapy is currently considered an emerging therapeutic option in clinical oncology. S-1, an oral formulation of Tegafur (TF), a prodrug of 5-fluorouracil (5-FU), is designed to improve the antitumor activity of 5-FU in tandem with reducing its toxicity. Clinically, metronomic S-1 dosing has been approved for the standard first- and second-line treatment of metastatic or advanced stage of colorectal (CRC). However, expression of intratumor thymidylate synthase (TS), a significant gene in cellular proliferation, is associated with poor outcome to 5-FU-based chemotherapeutic regimens. In this study, therefore, we examined the effect of a combination of TS silencing by an RNA interfering molecule, chemically synthesized short hairpin RNA against TS (shTS), and 5-FU on the growth of human colorectal cancer cell (DLD-1) both in vitro and in vivo. The combined treatment of both shTS with 5-FU substantially inhibited cell proliferation in vitro. For in vivo treatments, the combined treatment of metronomic S-1 dosing with intravenously injected polyethylene glycol (PEG)-coated shTS-lipoplex significantly suppressed tumor growth, compared to a single treatment of either S-1 or PEG-coated shTS-lipoplex. In addition, the combined treatment increased the proportion of apoptotic cells in the DLD-1 tumor tissue. Our results suggest that metronomic S-1 dosing combined with TS silencing might represent an emerging therapeutic strategy for the treatment of patients with advanced CRC.
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Metronomics in the neoadjuvant and adjuvant treatment of breast cancer
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Elisabetta Munzone, Marco Colleoni
The concept of metronomic chemotherapy (MC) has evolved from a descriptive preclinical phenomenon encompassing inhibition of angiogenesis to a clinically validated treatment concept involving multiple potential mechanisms of action. Clinicians are progressively more incline to consider MC as a component of mainstream medical oncology practice in advanced breast cancer. However, more recently MC has been tested even in the adjuvant/neoadjuvant setting, taking the opportunity to obtain tumor specimens and blood samples, in order to identify tumor-specific or patient-specific biomarkers for personalizing treatments. In addition, the antiangiogenic and pro-immune nature of metronomic chemotherapy made triple negative breast cancer (TNBC) a good candidate for exploring low-dose maintenance treatment in the adjuvant setting or in combination with immunomodulatory drugs. The potential development of MC in breast cancer pass through the research to identify biomarkers and individual tumor characteristics that can better address the use of this treatment strategy in the future. Finally, the subjective attitude of patients represents one of the major factors that influence the choice and acceptance of a therapeutic program. Personal preference and considerations about quality of life should guide the treatment choice eventually prioritizing the use of MC. Nevertheless, more robust data from randomized phase III trials are needed in the future, in order to make clinicians more confident in using metronomic strategies.
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Source:Cancer Letters, Volume 400
Author(s): Elisabetta Munzone, Marco Colleoni
The concept of metronomic chemotherapy (MC) has evolved from a descriptive preclinical phenomenon encompassing inhibition of angiogenesis to a clinically validated treatment concept involving multiple potential mechanisms of action. Clinicians are progressively more incline to consider MC as a component of mainstream medical oncology practice in advanced breast cancer. However, more recently MC has been tested even in the adjuvant/neoadjuvant setting, taking the opportunity to obtain tumor specimens and blood samples, in order to identify tumor-specific or patient-specific biomarkers for personalizing treatments. In addition, the antiangiogenic and pro-immune nature of metronomic chemotherapy made triple negative breast cancer (TNBC) a good candidate for exploring low-dose maintenance treatment in the adjuvant setting or in combination with immunomodulatory drugs. The potential development of MC in breast cancer pass through the research to identify biomarkers and individual tumor characteristics that can better address the use of this treatment strategy in the future. Finally, the subjective attitude of patients represents one of the major factors that influence the choice and acceptance of a therapeutic program. Personal preference and considerations about quality of life should guide the treatment choice eventually prioritizing the use of MC. Nevertheless, more robust data from randomized phase III trials are needed in the future, in order to make clinicians more confident in using metronomic strategies.
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The potential clinical promise of ‘multimodality’ metronomic chemotherapy revealed by preclinical studies of metastatic disease
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Robert S. Kerbel, Yuval Shaked
We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse models of cancer involving treatment of advanced metastatic disease. Historically, mouse cancer therapy models have been dominated by treating established primary tumors or early stage low volume microscopic disease. Treatment of primary tumors is also almost always the case when using genetically engineered mouse models (GEMMs) of cancer or patient-derived xenografts (PDXs). Studies using such models, and others including transplanted cell lines, often yield highly encouraging results which are seldom recapitulated in the clinic, especially when assessed in randomized phase III clinical trials. While there are likely many different reasons for this discrepancy, one is likely the failure to recapitulate treatment of advanced visceral metastatic disease in mice. With this gap in mind, we have developed a number of models of metastatic human tumor xenografts (and more recently, of mouse tumors in syngeneic immunocompetent mice). A pattern of response we have observed with various targeted agents, e.g. VEGF pathway targeting antiangiogenic drugs or trastuzumab, is effective when treating primary tumors in contrast to a complete or severely reduced lack of such efficacy when treating advanced metastatic disease. Interestingly, an exception to this pattern has been observed using various continuous low-dose metronomic chemotherapy regimens, where counterintuitively, superior responses are observed in the metastatic setting, as well as superiority or equivalence of metronomic chemotherapy over standard maximum tolerated dose (MTD) chemotherapy, with lesser toxicity. The basis for these encouraging results may be related to the multiple mechanisms responsible for the anti-tumor effects and longer duration of metronomic chemotherapy regimens made possible by lesser toxicity. These include antiangiogenesis, stimulation of the immune system, stromal cell targeting in tumors, and possibly direct tumor cell targeting, including targeting cancer stem cells (CSCs). In addition, metronomic chemotherapy regimens minimize or even eliminate the problem of chemotherapy-induced host responses that may actually secondarily promote tumor growth and malignancy after causing an initial and beneficial anti-tumor response. We suggest that future preclinical studies of metronomic chemotherapy should be concentrated in the following areas: i) further comparative assessment of anti-tumor efficacy in primary vs metastatic treatment settings; ii) rigorous comparative assessment of conventional MTD chemotherapy vs metronomic chemotherapy using the same agent; iii) assessment of potential predictive biomarkers for metronomic chemotherapy, and methods to determine optimal biologic dose and schedule; and iv) a further detailed assessment of the potential of different chemotherapy drugs administered using MTD or metronomic regimens on stimulating or suppressing components of the innate or adaptive immune systems.
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Source:Cancer Letters, Volume 400
Author(s): Robert S. Kerbel, Yuval Shaked
We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse models of cancer involving treatment of advanced metastatic disease. Historically, mouse cancer therapy models have been dominated by treating established primary tumors or early stage low volume microscopic disease. Treatment of primary tumors is also almost always the case when using genetically engineered mouse models (GEMMs) of cancer or patient-derived xenografts (PDXs). Studies using such models, and others including transplanted cell lines, often yield highly encouraging results which are seldom recapitulated in the clinic, especially when assessed in randomized phase III clinical trials. While there are likely many different reasons for this discrepancy, one is likely the failure to recapitulate treatment of advanced visceral metastatic disease in mice. With this gap in mind, we have developed a number of models of metastatic human tumor xenografts (and more recently, of mouse tumors in syngeneic immunocompetent mice). A pattern of response we have observed with various targeted agents, e.g. VEGF pathway targeting antiangiogenic drugs or trastuzumab, is effective when treating primary tumors in contrast to a complete or severely reduced lack of such efficacy when treating advanced metastatic disease. Interestingly, an exception to this pattern has been observed using various continuous low-dose metronomic chemotherapy regimens, where counterintuitively, superior responses are observed in the metastatic setting, as well as superiority or equivalence of metronomic chemotherapy over standard maximum tolerated dose (MTD) chemotherapy, with lesser toxicity. The basis for these encouraging results may be related to the multiple mechanisms responsible for the anti-tumor effects and longer duration of metronomic chemotherapy regimens made possible by lesser toxicity. These include antiangiogenesis, stimulation of the immune system, stromal cell targeting in tumors, and possibly direct tumor cell targeting, including targeting cancer stem cells (CSCs). In addition, metronomic chemotherapy regimens minimize or even eliminate the problem of chemotherapy-induced host responses that may actually secondarily promote tumor growth and malignancy after causing an initial and beneficial anti-tumor response. We suggest that future preclinical studies of metronomic chemotherapy should be concentrated in the following areas: i) further comparative assessment of anti-tumor efficacy in primary vs metastatic treatment settings; ii) rigorous comparative assessment of conventional MTD chemotherapy vs metronomic chemotherapy using the same agent; iii) assessment of potential predictive biomarkers for metronomic chemotherapy, and methods to determine optimal biologic dose and schedule; and iv) a further detailed assessment of the potential of different chemotherapy drugs administered using MTD or metronomic regimens on stimulating or suppressing components of the innate or adaptive immune systems.
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Naturally occurring anti-cancer agents targeting EZH2
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Fahimeh Shahabipour, Michele Caraglia, Muhammed Majeed, Giuseppe Derosa, Pamela Maffioli, Amirhossein Sahebkar
Natural products are considered as promising tools for the prevention and treatment of cancer. The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase unit of polycomb repressor complexes such as PRC2 complex that has oncogenic roles through interference with growth and metastatic potential. Several agents targeting EZH2 has been discovered but they often induce side effects in clinical trials. Recently, EZH2 has emerged as a potential target of natural products with documented anti-cancer effects and this discloses a new scenario for the development of EZH2 inhibitory strategies with agents with low cytotoxic detrimental effects. In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators. Mechanisms like inhibition of histone H3K4, H3K27 and H3K36 trimethylation, down-regulation of matrix metalloproteinase expression, competitive binding to the S-adenosylmethionine binding site of EZH2 and modulation of tumor-suppressive microRNAs have been demonstrated to mediate the EZH2-inhibitory activity of the mentioned natural products. This review summarizes the pathways that are regulated by various natural products resulting in the suppression of EZH2, and provides a plausible molecular mechanism for the putative anti-cancer effects of these compounds.
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Source:Cancer Letters, Volume 400
Author(s): Fahimeh Shahabipour, Michele Caraglia, Muhammed Majeed, Giuseppe Derosa, Pamela Maffioli, Amirhossein Sahebkar
Natural products are considered as promising tools for the prevention and treatment of cancer. The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase unit of polycomb repressor complexes such as PRC2 complex that has oncogenic roles through interference with growth and metastatic potential. Several agents targeting EZH2 has been discovered but they often induce side effects in clinical trials. Recently, EZH2 has emerged as a potential target of natural products with documented anti-cancer effects and this discloses a new scenario for the development of EZH2 inhibitory strategies with agents with low cytotoxic detrimental effects. In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators. Mechanisms like inhibition of histone H3K4, H3K27 and H3K36 trimethylation, down-regulation of matrix metalloproteinase expression, competitive binding to the S-adenosylmethionine binding site of EZH2 and modulation of tumor-suppressive microRNAs have been demonstrated to mediate the EZH2-inhibitory activity of the mentioned natural products. This review summarizes the pathways that are regulated by various natural products resulting in the suppression of EZH2, and provides a plausible molecular mechanism for the putative anti-cancer effects of these compounds.
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Featuring the Guest Editors
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): M.N.V. Ravi Kumar, Anil K. Sood
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Source:Cancer Letters, Volume 400
Author(s): M.N.V. Ravi Kumar, Anil K. Sood
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Metronomic chemotherapy in head and neck cancer
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Francesca De Felice, Ilaria Benevento, Angela Musella, Daniela Musio, Vincenzo Tombolini
Head neck cancer (HNC) is generally treated with a multimodality approach. Loco-regional-distant control is often worst, due to the advantage stage disease at diagnosis and the optimal treatment option remains an unresolved issue. Metronomic chemotherapy (MCHT) is an emerging therapeutic option in clinical oncology and it may prove useful in HNC patients.
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Source:Cancer Letters, Volume 400
Author(s): Francesca De Felice, Ilaria Benevento, Angela Musella, Daniela Musio, Vincenzo Tombolini
Head neck cancer (HNC) is generally treated with a multimodality approach. Loco-regional-distant control is often worst, due to the advantage stage disease at diagnosis and the optimal treatment option remains an unresolved issue. Metronomic chemotherapy (MCHT) is an emerging therapeutic option in clinical oncology and it may prove useful in HNC patients.
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Metronomic chemotherapy and nanocarrier platforms
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Amr S. Abu Lila, Tatsuhiro Ishida
The therapeutic concept of administering chemotherapeutic agents continuously at lower doses, relative to the maximum tolerated dose (MTD) without drug-free breaks over extended periods –known as “metronomic chemotherapy”– is a promising approach for anti-angiogenic cancer therapy. In comparison with MTD chemotherapy regimens, metronomic chemotherapy has demonstrated reduced toxicity. However, as a monotherapy, metronomic chemotherapy has failed to provide convincing results in clinical trials. Therapeutic approaches including combining the anti-angiogenic “metronomic” therapy with conventional radio-/chemo-therapy and/or targeted delivery of chemotherapeutic agents to tumor tissues via their encapsulation with nanocarrier-based platforms have proven to potentiate the overall therapeutic outcomes. In this review, therefore, we focused on the mutual contribution made by nanoscale drug delivery platforms to the therapeutic efficacy of metronomic-based chemotherapy. In addition, the influence that the dosing schedule has on the overall therapeutic efficacy of metronomic chemotherapy is discussed.
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Source:Cancer Letters, Volume 400
Author(s): Amr S. Abu Lila, Tatsuhiro Ishida
The therapeutic concept of administering chemotherapeutic agents continuously at lower doses, relative to the maximum tolerated dose (MTD) without drug-free breaks over extended periods –known as “metronomic chemotherapy”– is a promising approach for anti-angiogenic cancer therapy. In comparison with MTD chemotherapy regimens, metronomic chemotherapy has demonstrated reduced toxicity. However, as a monotherapy, metronomic chemotherapy has failed to provide convincing results in clinical trials. Therapeutic approaches including combining the anti-angiogenic “metronomic” therapy with conventional radio-/chemo-therapy and/or targeted delivery of chemotherapeutic agents to tumor tissues via their encapsulation with nanocarrier-based platforms have proven to potentiate the overall therapeutic outcomes. In this review, therefore, we focused on the mutual contribution made by nanoscale drug delivery platforms to the therapeutic efficacy of metronomic-based chemotherapy. In addition, the influence that the dosing schedule has on the overall therapeutic efficacy of metronomic chemotherapy is discussed.
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Metronomic chemotherapy for advanced breast cancer patients
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Marina Elena Cazzaniga, Maria Rita Dionisio, Francesca Riva
Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. This schedule seems to have not only a direct cytotoxicity on cancer cells but also an effect on the tumor microenvironment by inhibiting tumor angiogenesis and modulating immune response.Metronomic chemotherapy was widely investigated in patients with breast cancer. The results of these studies showed that this strategy is not only effective but has a low toxicity profile too, proposing as a promising strategy for breast cancer patients. In this review we summarize the results of Phase II and III studies evaluating metronomic therapy in metastatic breast cancer.
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Source:Cancer Letters, Volume 400
Author(s): Marina Elena Cazzaniga, Maria Rita Dionisio, Francesca Riva
Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. This schedule seems to have not only a direct cytotoxicity on cancer cells but also an effect on the tumor microenvironment by inhibiting tumor angiogenesis and modulating immune response.Metronomic chemotherapy was widely investigated in patients with breast cancer. The results of these studies showed that this strategy is not only effective but has a low toxicity profile too, proposing as a promising strategy for breast cancer patients. In this review we summarize the results of Phase II and III studies evaluating metronomic therapy in metastatic breast cancer.
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Potential role of metronomic chemotherapy in the treatment of esophageal and gastroesophageal cancer
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Vanita Noronha, Vijay M. Patil, Amit Joshi, Anuradha Chougule, Shripad Banavali, Kumar Prabhash
Patients with esophagogastric cancer have poor prognoses in spite of the best available therapies. Patients are debilitated and may not tolerate, or may progress, on standard cytotoxic chemotherapy regimens. Metronomic chemotherapy is an attractive treatment option due to its very low reported toxicity, modest efficacy, low cost and ease of administration. Capecitabine is the most common drug used in metronomic scheduling; other drugs include cyclophosphamide and paclitaxel. Dosing of capecitabine can range from 1000 mg orally daily for 4 weeks on and 1 week off to a continuous dosing schedule of 1500 mg orally daily. Reported toxicities, including neutropenia, mucositis and hand-foot syndrome, occur in <10% of patients. As there is a lack of well-conducted, randomized clinical trials evaluating the role of metronomic chemotherapy in esophagogastric cancer, it cannot be recommended as the standard of care; however, it can be considered to be a therapeutic option, especially in elderly patients with relapsed disease for whom other therapeutic options are limited.
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Source:Cancer Letters, Volume 400
Author(s): Vanita Noronha, Vijay M. Patil, Amit Joshi, Anuradha Chougule, Shripad Banavali, Kumar Prabhash
Patients with esophagogastric cancer have poor prognoses in spite of the best available therapies. Patients are debilitated and may not tolerate, or may progress, on standard cytotoxic chemotherapy regimens. Metronomic chemotherapy is an attractive treatment option due to its very low reported toxicity, modest efficacy, low cost and ease of administration. Capecitabine is the most common drug used in metronomic scheduling; other drugs include cyclophosphamide and paclitaxel. Dosing of capecitabine can range from 1000 mg orally daily for 4 weeks on and 1 week off to a continuous dosing schedule of 1500 mg orally daily. Reported toxicities, including neutropenia, mucositis and hand-foot syndrome, occur in <10% of patients. As there is a lack of well-conducted, randomized clinical trials evaluating the role of metronomic chemotherapy in esophagogastric cancer, it cannot be recommended as the standard of care; however, it can be considered to be a therapeutic option, especially in elderly patients with relapsed disease for whom other therapeutic options are limited.
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Metronomic chemotherapy and immunotherapy in cancer treatment
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Yu-Li Chen, Ming-Cheng Chang, Wen-Fang Cheng
Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.
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Source:Cancer Letters, Volume 400
Author(s): Yu-Li Chen, Ming-Cheng Chang, Wen-Fang Cheng
Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.
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ATP-binding cassette transporters in tumor endothelial cells and resistance to metronomic chemotherapy
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): Kyoko Hida, Hiroshi Kikuchi, Nako Maishi, Yasuhiro Hida
Drug resistance is a major problem in anticancer therapy. ATP-binding cassette (ABC) transporters have a role in the multidrug resistance. A new regimen of chemotherapy has been proposed, called “metronomic chemotherapy”. Metronomic chemotherapy is the frequent, regular administration of drug doses designed to maintain low, but active, concentrations of chemotherapeutic drugs over prolonged periods of time, without causing serious toxicities. Metronomic chemotherapy regimens were developed to optimize the antitumor efficacy of agents that target the tumor vasculature instead of tumor cells, and to reduce toxicity of antineoplastic drugs [1]. Nevertheless, recent studies revealed that ABC transporters are expressed at a higher level in the endothelium in the tumor. To avoid resistance to metronomic anti-angiogenic chemotherapy, ABC transporter inhibition of tumor endothelial cells may be a promising strategy. In this mini-review, we discuss the possible mechanism of resistance to metronomic chemotherapy from the viewpoint of tumor endothelial cell biology, focusing on ABC transporters.
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Source:Cancer Letters, Volume 400
Author(s): Kyoko Hida, Hiroshi Kikuchi, Nako Maishi, Yasuhiro Hida
Drug resistance is a major problem in anticancer therapy. ATP-binding cassette (ABC) transporters have a role in the multidrug resistance. A new regimen of chemotherapy has been proposed, called “metronomic chemotherapy”. Metronomic chemotherapy is the frequent, regular administration of drug doses designed to maintain low, but active, concentrations of chemotherapeutic drugs over prolonged periods of time, without causing serious toxicities. Metronomic chemotherapy regimens were developed to optimize the antitumor efficacy of agents that target the tumor vasculature instead of tumor cells, and to reduce toxicity of antineoplastic drugs [1]. Nevertheless, recent studies revealed that ABC transporters are expressed at a higher level in the endothelium in the tumor. To avoid resistance to metronomic anti-angiogenic chemotherapy, ABC transporter inhibition of tumor endothelial cells may be a promising strategy. In this mini-review, we discuss the possible mechanism of resistance to metronomic chemotherapy from the viewpoint of tumor endothelial cell biology, focusing on ABC transporters.
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Metronomic chemotherapy in metastatic colorectal cancer
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): In Sook Woo, Yun Hwa Jung
Overall survival and quality of life of patients with metastatic colorectal cancer (mCRC) have improved due to the development of standard systemic treatment. However, many patients are still suffering from the eventual progression of cancer, treatment-related toxicities, and the economic burden of new drugs. Salvage or maintenance therapy, which consistently controls or stabilizes tumor progression without debilitating quality of life, is required. Recently, metronomic capecitabine maintenance therapy after disease control using conventional chemotherapy with maximal tolerated doses has demonstrated beneficial results in a phase III trial. Metronomic chemotherapy has been known to control tumors through antiangiogenesis and immunomodulation as well as a direct effect on tumor-initiating cells. It has the characteristics of being minimally toxic, inexpensive, and durable for maintaining disease stabilization. Therefore, patients with mCRC, who tend to be elderly and frail and have been previously treated, might be suitable for metronomic therapeutic strategies. Furthermore, antiangiogenic therapy has been an important component in treating mCRC, but the schedules and doses of metronomic chemotherapy have not yet been established. Here we review translational and clinical research on metronomic chemotherapy in colorectal cancer (CRC).
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Source:Cancer Letters, Volume 400
Author(s): In Sook Woo, Yun Hwa Jung
Overall survival and quality of life of patients with metastatic colorectal cancer (mCRC) have improved due to the development of standard systemic treatment. However, many patients are still suffering from the eventual progression of cancer, treatment-related toxicities, and the economic burden of new drugs. Salvage or maintenance therapy, which consistently controls or stabilizes tumor progression without debilitating quality of life, is required. Recently, metronomic capecitabine maintenance therapy after disease control using conventional chemotherapy with maximal tolerated doses has demonstrated beneficial results in a phase III trial. Metronomic chemotherapy has been known to control tumors through antiangiogenesis and immunomodulation as well as a direct effect on tumor-initiating cells. It has the characteristics of being minimally toxic, inexpensive, and durable for maintaining disease stabilization. Therefore, patients with mCRC, who tend to be elderly and frail and have been previously treated, might be suitable for metronomic therapeutic strategies. Furthermore, antiangiogenic therapy has been an important component in treating mCRC, but the schedules and doses of metronomic chemotherapy have not yet been established. Here we review translational and clinical research on metronomic chemotherapy in colorectal cancer (CRC).
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Editorial – Metronomic chemotherapy
Publication date: 1 August 2017
Source:Cancer Letters, Volume 400
Author(s): M.N.V. Ravi Kumar, Anil K. Sood
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Source:Cancer Letters, Volume 400
Author(s): M.N.V. Ravi Kumar, Anil K. Sood
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Incidence of Mycotoxins in Local and Branded Samples of Chocolates Marketed in Pakistan
The present overview was intended to evaluate the degree of total aflatoxins and ochratoxin A contamination in different samples of bitter, dark, milk, and white chocolates marketed in Pakistan. For that exploration, two hundred () samples of chocolates, 100 branded and 100 local, were analyzed for mycotoxins profile by HPLC-FLD. The outcomes firmly sustained that the majority of the samples were contaminated with aflatoxins and ochratoxin A. The incidence of total aflatoxins and ochratoxin A in branded samples was 83% and 90%, whereas the local samples showed 91% and 97% contamination, respectively. The highest amount of total aflatoxins was found in branded dark chocolates, that is, 2.27 μg/kg, and maximum ochratoxin A level was detected white chocolates (2.06 μg/kg). On average, the local white chocolates and dark chocolates faced the highest level of total aflatoxins (3.35 μg/kg) and ochratoxin A (3.48 μg/kg), respectively. The local samples of chocolates were more contaminated with mycotoxins as compared to branded ones accredited to the lack of quality control and quality assurance during the manufacturing as well as packing processes. In recent years, consumption of chocolate is rapidly increasing especially by young generation, so monitoring of mycotoxin occurrence in them is a matter of great concern and more studies are required to comprehend the production of mycotoxins in these products.
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Gastrodia elata Blume Rhizome Aqueous Extract Improves Arterial Thrombosis, Dyslipidemia, and Insulin Response in Testosterone-Deficient Rats
Testosterone deficiency deteriorates glucose and lipid metabolism with reducing muscle mass. We investigated whether the consumption of water extracts of Gastrodia elata Blume rhizome (GEB) rich in gastrodin would reduce the symptoms of testosterone deficiency and improve blood flow in orchidectomized (ORX) rats. ORX rats were given high-fat diets supplemented with either 1% cellulose (ORX-control), 0.3% GEB (GEB-L), or 1% GEB (GEB-H) for 8 weeks. Sham-operated rats were fed the same diet as OVX-control rats (normal-control). ORX-control rats had reduced serum testosterone levels by one-fifth, compared to normal-control rats. ORX-control rats exhibited decreased lean body mass, attenuated blood flow, and impaired cholesterol metabolism and glucose control due to decreased insulin secretory response. GEB increased serum insulin levels dose-dependently and GEB-H mostly enhanced dyslipidemia in ORX rats. GEB completely normalized arterial thrombosis time and blood flow in ORX rats. Interestingly, ORX-control rats showed attenuated hepatic insulin signaling but greater AMPK and CREB activities, which reduced triglyceride accumulation, compared to normal-control. GEB-H improved hepatic insulin signaling but maintained the AMPK and CREB activities in ORX rats. In conclusions, GEB ameliorated the impairment of cholesterol and glucose metabolism and blood flow in ORX rats. GEB may be a potential preventive measure for reducing the risk of cardiovascular diseases associated with testosterone deficiency.
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Lower Extremity Peripheral Arterial Disease Is an Independent Predictor of Coronary Heart Disease and Stroke Risks in Patients with Type 2 Diabetes Mellitus in China
We aimed to determine the relationship between lower extremity peripheral arterial disease (PAD), 10-year coronary heart disease (CHD), and stroke risks in patients with type 2 diabetes (T2DM) using the UKPDS risk engine. We enrolled 1178 hospitalized T2DM patients. The patients were divided into a lower extremity PAD group (ankle-brachial or >1.4; 88 patients, 7.5%) and a non-PAD group (ankle-brachial and ≤1.4; 1090 patients, 92.5%). Age; duration of diabetes; systolic blood pressure; the hypertension rate; the use of hypertension drugs, ACEI /ARB, and statins; CHD risk; fatal CHD risk; stroke risk; and fatal stroke risk were significantly higher in the PAD group than in the non-PAD group ( for all). Logistic stepwise regression analysis indicated that ABI was an independent predictor of 10-year CHD and stroke risks in T2DM patients. Compared with those in the T2DM non-PAD group, the odds ratios (ORs) for CHD and stroke risk were 3.6 (95% confidence interval (CI), 2.2–6.0; ) and 6.9 (95% CI, 4.0–11.8; ) in those with lower extremity PAD, respectively. In conclusion, lower extremity PAD increased coronary heart disease and stroke risks in T2DM.
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Gender Disparity in the Relationship between Prevalence of Thyroid Nodules and Metabolic Syndrome Components: The SHDC-CDPC Community-Based Study
The study is aimed to investigate the pathogenesis underlying the increased prevalence of thyroid nodule (TN) in different levels of metabolic syndrome (MetS) components and analyze the relationships between TN and MetS components. A total of 6,798 subjects, including 2201 patients with TN, were enrolled in this study. Anthropometric, biochemical, thyroid ultrasonographic, and other metabolic parameters were all measured. There was obviously sexual difference in the prevalence of TN (males 26.0%, females 38.5%, resp.). The prevalence of TN in hyperuricemia (45.7% versus 37.4%, P = 0.001), NAFLD (41.2% versus 36.4%, P
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Predictors and Delays Associated with the Need for Advanced Techniques for Intravenous Access
Source:The Journal of Emergency Medicine
Author(s): Michael D. Witting, Siamak Moayedi, Latoya A. Brown, Ammar Ismail
BackgroundThe need for advanced techniques for intravenous access (ATIVA) can lead to delays in care and contribute to emergency department (ED) crowding.ObjectiveIn this article, we estimate the delay and predictors associated with the need for ATIVA.MethodsIn this case-control study, we collected data from ED cases requiring ATIVA and control patients in whom i.v. access was gained by traditional inspection and palpation. We included two control groups—a random retrospective sample and a prospective limited convenience sample. We collected time and acuity data from all groups and data on predictor variables from cases and prospective controls. We analyzed time data using quartile regression and predictor variable data using contingency table analysis and logistic regression.ResultsWe collected data from 116 cases (91 of which had time interval data), 98 retrospective controls, and 144 prospective controls. The median time from triage to i.v. line establishment was 199 min for cases vs. 64 min for prospective controls and 81 min for retrospective controls. The need for ATIVA was associated with a 1.1-greater quartile time interval (95% confidence interval [CI] 0.8–1.3). Two variables—i.v. drug use (IVDU; odds ratio 3.7; 95% CI 1.8–7.3) and prior need for ATIVA (odds ratio 5.2; 95% CI 2.7–9.8)—were associated with a need for ATIVA; obesity, renal failure, and diabetes were not.ConclusionsThe need for ATIVA increases median time to i.v. line placement by 118 to 135 min compared with traditional inspection and palpation. IVDU and prior need for an advanced technique are associated with a need for ATIVA.
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A Constellation of Rare Findings in a Case of Goldenhar Syndrome
An 18-month-old child presented with right macrostomia, bilateral preauricular skin tags, bilateral CTEV, squint in bilateral eyes, thoracic vertebral anomalies, right sided aortic arch, and associated left pulmonary agenesis. The patient did not have any associated respiratory symptoms. Ipsilateral pulmonary agenesis is considered as a rare association with Goldenhar syndrome and a case of contralateral pulmonary aplasia has been described as an even rarer association.
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Effects of Diatomite and SBS on Freeze-Thaw Resistance of Crumb Rubber Modified Asphalt Mixture
Asphalt mixture is susceptible to moisture damage under the effect of freeze-thaw (F-T) cycles. In this paper, crumb rubber (CR) was used to modify stone mastic asphalt (SMA) and the effects of diatomite and styrene butadiene styrene (SBS) on antifreezing performances of crumb rubber modified SMA (CRSMA) were investigated. Regression analysis and modified grey model (MGM) were used to construct the prediction models for properties of modified mixtures. CRSMA, CR and diatomite modified SMA (CRDSMA), and CR and SBS modified SMA (CRSSMA) were prepared in laboratory, respectively. Process of F-T cycles was designed. Air void, indirect tensile strength (ITS), and indirect tensile stiffness modulus (ITSM) were measured to evaluate the antifreezing performances of CRSMA, CRDSMA, and CRSSMA. Results indicate that air voids increase with the increasing of F-T cycles. ITS and ITSM all decrease with the increasing of F-T cycles. The addition of diatomite and SBS can reduce the air void and improve the ITS and ITSM of CRSMA. CRSSMA presents the lowest air void, highest tensile strength, and largest stiffness modulus, which reveals that CRSSMA has the best F-T resistance among three different kinds of mixtures. Moreover, MGM (1, 2) models present more favorable accuracy in prediction of air void and ITS compared with regression ones.
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Treatment of Cervical Artery Dissection: Antithrombotics, Thrombolysis, and Endovascular Therapy
Cervical artery dissection (CAD) is an important cause of stroke for young patients, accounting for 5–22% of strokes in patients
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Effects of Radix Astragali and Its Split Components on Gene Expression Profiles Related to Water Metabolism in Rats with the Dampness Stagnancy due to Spleen Deficiency Syndrome
Radix Astragali (RA) with slight sweet and warm property is a significant “qi tonifying” herb; it is indicated for the syndrome of dampness stagnancy due to spleen deficiency (DSSD). The purpose of this research was to explore effects of RA and its split components on gene expression profiles related to water metabolism in rats with the DSSD syndrome for identifying components representing property and flavor of RA. The results indicated that RA and its split components, especially polysaccharides component, significantly increased the body weight and the urine volume and decreased the water load index of model rats. Our data also indicated differentially expressed genes (DEGs) related to water metabolism involved secretion, ion transport, water homeostasis, regulation of body fluid levels, and water channel activity; the expression of AQP1, AQP3, AQP4, AQP5, AQP6, and AQP8 was improved; calcium, cAMP, MAPK, PPAR, AMPK, and PI3K-Akt signaling pathway may be related to water metabolism. In general, results indicate that RA and its split components could promote water metabolism in rats with the DSSD syndrome via regulating the expression of AQPs, which reflected sweet-warm properties of RA. Effects of the polysaccharides component are better than others.
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Malignant Transformation of Mature Cystic Teratoma Diagnosed after a 10-Year Interval
A 67-year-old uniparous woman had undergone surgery for acute perforated gastric ulcer 10 years prior to the current presentation. Although abdominal computed tomography (CT) performed at that point had revealed a mature cystic teratoma measuring 6 cm in diameter in the right ovary, it was left untreated. She visited the department of surgery at our hospital with chief complaints of appetite loss, nausea, and vomiting that had persisted for the prior two weeks. She was admitted with a diagnosis of ileus attributed to an abdominal incisional hernia. CT performed on admission revealed a tumor measuring 21 cm in diameter with mural nodules in the right ovary. Thus, surgery was performed under suspicion of malignant transformation of the previously detected ovarian mature cystic teratoma. While neither lymphadenopathy nor distant metastasis was detected by imaging studies, bilateral adnexectomy and repair of the abdominal incisional hernia were performed. Cytology of ascites was negative. The postoperative pathological diagnosis was squamous cell carcinoma arising from teratoma, and the postoperative clinical diagnosis was stage IA ovarian cancer. It was assumed that the mature cystic teratoma which had been detected in the right ovary 10 years earlier had undergone malignant transformation.
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An Observational Cohort Study on Delayed-Onset Infections after Mandibular Third-Molar Extractions
Objectives. The purpose of the present study was to investigate the occurrence and clinical features of delayed-onset infections after mandibular third-molar extractions. Method and Materials. An observational cohort study was conducted on 179 patients undergoing mandibular third-molar extraction between January 2013 and December 2015, for a total of 217 extractions. Data were recorded at the time of extraction , on suture removal seven days later , and 30 days after the extraction, when patients were contacted and asked about their healing process . The statistical analysis was performed with nonparametric tests. A value lower than 0.05 was considered statistically significant. Results. Eight delayed-onset infections were recorded, amounting to 3.7% of all extractions. The median time elapsing from the extraction to the delayed-onset infection was 35 days (IQR 28–40; min 24–max 49). Younger age and longer surgical procedures seemed to be more often associated with this complication. Conclusion. Delayed-onset infections after third-molar extractions are relatively rare postoperative complications characterized by a swelling, usually with a purulent discharge. Patients should be informed of this possibility, which might develop even several weeks after the extraction.
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The Protective Effect of N-Acetylcysteine on Ionizing Radiation Induced Ovarian Failure and Loss of Ovarian Reserve in Female Mouse
Ionizing radiation may cause irreversible ovarian failure, which, therefore, calls for an effective radioprotective reagent. The aim of the present study was to evaluate the potential radioprotective effect of N-acetylcysteine (NAC) on ionizing radiation induced ovarian failure and loss of ovarian reserve in mice. Kun-Ming mice were either exposed to X-irradiation (4 Gy), once, and/or treated with NAC (300 mg/kg), once daily for 7 days before X-irradiation. We examined the serum circulating hormone levels and the development of ovarian follicles as well as apoptosis, cell proliferation, and oxidative stress 24 hours after X-irradiation. In addition, morphological observations on the endometrial luminal epithelium and the fertility assessment were performed. We found that NAC successfully restored the ovarian and uterine function, enhanced the embryo implantation, improved the follicle development, and altered the abnormal hormone levels through reducing the oxidative stress and apoptosis level in granulosa cells while promoting the proliferation of granulosa cells. In conclusion, the radioprotective effect of NAC on mice ovary from X-irradiation was assessed, and our results suggested that NAC can be a potential radioprotector which is capable of preventing the ovarian failure occurrence and restoring the ovarian reserve.
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Detailed Distribution of Corneal Epithelial Thickness and Correlated Characteristics Measured with SD-OCT in Myopic Eyes
Purpose. To investigate the detailed distribution of corneal epithelial thickness in single sectors and its correlated characteristics in myopic eyes. Methods. SD-OCT was used to measure the corneal epithelial thickness distribution profile. Differences of corneal epithelial thickness between different parameters and some correlations of characteristics were calculated. Results. The thickest and thinnest part of epithelium were found at the nasal-inferior sector () and at the superior side (), respectively. Subjects in the low and moderate myopia groups have thicker epithelial thickness than those in the high myopia group (). Epithelial thickness was 1.39 μm thicker in male subjects than in female subjects (). There was a slight negative correlation between corneal epithelial thickness and age (, ). Weak positive correlations were found between corneal epithelial thickness and corneal thickness (, ). No correlations were found between corneal epithelial thickness, astigmatism axis, corneal front curvature, and IOP. Conclusions. The epithelial thickness is not evenly distributed across the cornea. The thickest location of the corneal epithelium is at the nasal-inferior sector. People with high myopia tend to have thinner corneal epithelium than low–moderate myopic patients. The corneal epithelial thickness is likely to be affected by some parameters, such as age, gender, and corneal thickness.
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Proximal Tibial Epiphysis Fracture in a 13-Year-Old Male Athlete
Fractures of the proximal epiphysis of the tibia are rare, representing 0.5 to 3.0% of all epiphyseal injuries. These injuries can damage the popliteal vessels and their bifurcation, affecting the blood supply of the lower limb, as well as the nerves below the knee. Epiphyseal growth arrest is also a potential complication, leading to various angular deformities. We present a case of a 13-year-old male athlete with a posteriorly displaced Salter-Harris type II fracture of the proximal epiphysis of the left tibia who was treated conservatively with closed reduction and cast immobilization.
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FTO Gene Associates and Interacts with Obesity Risk, Physical Activity, Energy Intake, and Time Spent Sitting: Pilot Study in a Nigerian Population
Fat mass and obesity-associated (FTO) gene influences obesity but studies have shown that environmental/lifestyle variables like physical activity (PA), time spent sitting (TSS), and energy intake might mediate the effect. However, this is poorly understood in Nigeria due to scarce studies. We demystified association and interaction between FTO rs9939609, obesity, PA, TSS, and energy intake in Nigeria. FTO gene variant was genotyped by restriction fragment length polymorphism and gene sequencing analysis in 103 people with obesity and 98 controls. Anthropometrics and environmental variables were measured using standard procedures. Significant associations were found between FTO rs9939609 with obesity and environmental/lifestyle variables before and after adjusting for age. Carriers of allele A have significantly higher odds of being overweight/obese using BMI [0.191 (0.102–0.361), ] but this was attenuated by PA (); odds of being overweight reduced from 0.625 (0.181–2.159) to 0.082 (0.009–0.736) for low and high PA, respectively. Mediation analysis of total indirect effect also confirmed this by showing a simultaneous mediating role of total PA, energy intake, and TSS in the relationship between FTO and BMI (unstandardized-coefficient = 1.68; 95% CI: 1.26–2.22). This study shows a relationship between FTO and obesity phenotype and environmental/lifestyle factors might be an important modulator/mediator in the association.
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Extraction Method of Driver’s Mental Component Based on Empirical Mode Decomposition and Approximate Entropy Statistic Characteristic in Vehicle Running State
In the driver fatigue monitoring technology, the essence is to capture and analyze the driver behavior information, such as eyes, face, heart, and EEG activity during driving. However, ECG and EEG monitoring are limited by the installation electrodes and are not commercially available. The most common fatigue detection method is the analysis of driver behavior, that is, to determine whether the driver is tired by recording and analyzing the behavior characteristics of steering wheel and brake. The driver usually adjusts his or her actions based on the observed road conditions. Obviously the road path information is directly contained in the vehicle driving state; if you want to judge the driver’s driving behavior by vehicle driving status information, the first task is to remove the road information from the vehicle driving state data. Therefore, this paper proposes an effective intrinsic mode function selection method for the approximate entropy of empirical mode decomposition considering the characteristics of the frequency distribution of road and vehicle information and the unsteady and nonlinear characteristics of the driver closed-loop driving system in vehicle driving state data. The objective is to extract the effective component of the driving behavior information and to weaken the road information component. Finally the effectiveness of the proposed method is verified by simulating driving experiments.
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Enhanced Decision Support Systems in Intensive Care Unit Based on Intuitionistic Fuzzy Sets
In areas of medical diagnosis and decision-making, several uncertainty and ambiguity shrouded situations are most often imposed. In this regard, one may well assume that intuitionistic fuzzy sets (IFS) should stand as a potent technique useful for demystifying associated with the real healthcare decision-making situations. To this end, we are developing a prototype model helpful for detecting the patients risk degree in Intensive Care Unit (ICU). Based on the intuitionistic fuzzy sets, dubbed Medical Intuitionistic Fuzzy Expert Decision Support System (MIFEDSS), the shown work has its origins in the Modified Early Warning Score (MEWS) standard. It is worth noting that the proposed prototype effectiveness validation is associated through a real case study test at the Polyclinic ESSALEMA cited in Sfax, Tunisia. This paper does actually provide some practical initial results concerning the system as carried out in real life situations. Indeed, the proposed system turns out to prove that the MIFEDSS does actually display an imposing capability for an established handily ICU related uncertainty issues. The performance of the prototypes is compared with the MEWS standard which exposed that the IFS application appears to perform highly better in deferring accuracy than the expert MEWS score with higher degrees of sensitivity and specificity being recorded.
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Dark Signals in the Choroidal Vasculature on Optical Coherence Tomography Angiography: An Artefact or Not?
Optical coherence tomography angiography (OCTA) based on mathematical processing of sequentially acquired structural OCT images has been applied widely in both retinal and choroidal research and may have advantages over traditional angiography. Images obtained by OCTA are rendered under the assumption that the only moving entity in the retina is blood flow. Optical phenomena and image processing algorithms may create imaging artefacts. Therefore, OCTA images require careful interpretation. This review discusses the dark signals seen in the choroidal vasculature on OCTA using multiple factor analysis. For accurate and comprehensive interpretation of the choroidal vasculature, we recommend simultaneous consideration of the laser light penetration depth and masking effect of retinal pigment epithelium, the orientation of vessels in relation to the scanning lasers and blood flow, the range of regional detectable velocity of blood flow, atrophic tissues in the periphery, and absorption of superior vessels on the scanning laser.
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Challenging a Misnomer? The Role of Inflammatory Pathways in Inflammatory Breast Cancer
Inflammatory breast cancer is a rare, yet highly aggressive form of breast cancer, which accounts for less than 5% of all locally advanced presentations. The clinical presentation of inflammatory breast cancer often differs significantly from that of noninflammatory breast cancer; however, immunohistochemistry reveals few, if any, distinguishing features. The more aggressive triple-negative and HER2-positive breast cancer subtypes are overrepresented in inflammatory breast cancer compared with noninflammatory breast cancer, with a poorer prognosis in response to conventional therapies. Despite its name, there remains some controversy regarding the role of inflammation in inflammatory breast cancer. This review summarises the current molecular evidence suggesting that inflammatory signaling pathways are upregulated in this disease, including NF-κB activation and excessive IL-6 production among others, which may provide an avenue for novel therapeutics. The role of the tumor microenvironment, through tumor-associated macrophages, infiltrating lymphocytes, and cancer stem cells is also discussed, suggesting that these tumor extrinsic factors may help account for the differences in behavior between inflammatory breast cancer and noninflammatory breast cancer. While there are various novel treatment strategies already underway in clinical trials, the need for further development of preclinical models of this rare but aggressive disease is paramount.
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Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis
The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.
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Investigation of the Characteristic Properties of Glacial Acetic Acid-Catalyzed Carbon Xerogels and Their Electrochemical Performance for Use as Electrode Materials in Electrical Double-Layer Capacitors
Glacial acetic acid was used as a catalyst in the preparation process of carbon xerogels from the condensation of resorcinol and formaldehyde for shortening significantly the gelation time. The effect of the resorcinol/catalyst ratio over a large range of 2 to 500, the solvent exchange manner with acetone, and the pyrolysis temperature of 700 to 1000°C on the characteristic properties of the carbon xerogels were investigated. A resorcinol/catalyst ratio of 2 and a pyrolysis temperature at 800°C were found to be the optimal condition for the preparation of carbon xerogels with a well-balanced porosity between micro- and mesopores, high surface area (577.62 m2g−1), and large pore volume (0.97 cm3g−1), which are appropriate for use as electrode materials in an electrical double-layer capacitor. The carbon xerogel electrodes that were prepared under these optimal conditions exhibited a good electrochemical performance with the highest specific capacitance of 169 Fg−1 in 6 M KOH electrolyte at a scan rate of 5 mVs−1 from cyclic voltammetry.
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Ipsilateral Rupture of Quadriceps Tendon with Distal Tibia Fracture: A Case Report and Review of the Literature
Traumatic rupture of the quadriceps tendon by itself is not an uncommon clinical condition. However, its association with concurrent ipsilateral closed distal tibia oblique fracture is exceedingly rare with only one previously reported case in English literature. The dual diagnosis of this atypical combination of injury may be masked by pain and immobilization of the more obvious fracture and may be missed, unless the treating physician maintains a high index of suspicion. Suprapatellar knee pain with or without a palpable gap in the quadriceps tendon and inability to straight leg raise in the setting of a distal tibia fracture should raise concern, but if initial treatment employs a long-leg splint the knee symptoms may be muted. In this report, we describe this unusual combination of injury in a 67-year-old male patient who sustained a trivial twisting injury to the leg. The aim of this report is to raise awareness and emphasize the importance of thorough and repeated clinical examinations in the presence of distracting injuries. Despite the complexity of the problem, standard techniques for quadriceps tendon repair using transpatellar bone tunnels following locked intramedullary rodding of the tibia fracture may lead to optimal outcomes.
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IJMS, Vol. 18, Pages 1104: Dual-Component Gelatinous Peptide/Reactive Oligomer Formulations as Conduit Material and Luminal Filler for Peripheral Nerve Regeneration
Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR.
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