ABSTRACT
A single-institution observational study with 43 newly diagnosed diffuse gliomas defined the isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation status and evaluated the prognostic relevance of the methylation status of the epigenetic marker O6-methylguanine-DNA methyltransferase (MGMT). Younger patients (<50 years) with surgically resected glioma and temozolomide (TMZ) adjuvant chemotherapy were associated with better prognosis, consistent with other studies. The methylation status depends on the chosen method and the cut-off value determination. Methylation-specific PCR (MSP) established the methylation status for 36 glioma patients (19 (52.8%) positively methylated and 17 (47.2%) unmethylated) without relevancy for the overall survival (OS) (p = 0.33). On the other side, real-time methylation-specific PCR (qMSP) revealed 23 tumor samples (54%) that were positively methylated without association with OS (p = 0.15). A combined MSP analysis, which included the homogenous cohort of 24 patients (>50 years with surgical resection and IDH1/2-wildtype diffuse glioma), distinguished 10 (41.6%) methylated samples from 14 (58.4%) unmethylated samples. Finally, significant correlation between OS and methylation status was noticed (p ≈ 0.05). The OS of the hypermethylated group was 9.6 ± 1.77 months, whereas the OS of the unmethylated group was 5.43 ± 1.04 months. Our study recognized the MGMT promoter methylation status as a positive prognostic factor within the described homogenous cohort, although further verification in a larger population of diffuse gliomas is required.
Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Humans , Brain Neoplasms/pathology , DNA Methylation , Glioma/pathology , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Promoter Regions, Genetic , Temozolomide/therapeutic use , O(6)-Methylguanine-DNA Methyltransferase/genetics , Glioblastoma/genetics , Tumor Suppressor Proteins/geneticsABSTRACT
Recent advances in computing algorithms and hardware have rekindled interest in developing high-accuracy, low-cost surrogate models for simulating physical systems. The idea is to replace expensive numerical integration of complex coupled partial differential equations at fine time scales performed on supercomputers, with machine-learned surrogates that efficiently and accurately forecast future system states using data sampled from the underlying system. One particularly popular technique being explored within the weather and climate modelling community is the echo state network (ESN), an attractive alternative to other well-known deep learning architectures. Using the classical Lorenz 63 system, and the three tier multi-scale Lorenz 96 system (Thornes T, Duben P, Palmer T. 2017 Q. J. R. Meteorol. Soc. 143, 897-908. (doi:10.1002/qj.2974)) as benchmarks, we realize that previously studied state-of-the-art ESNs operate in two distinct regimes, corresponding to low and high spectral radius (LSR/HSR) for the sparse, randomly generated, reservoir recurrence matrix. Using knowledge of the mathematical structure of the Lorenz systems along with systematic ablation and hyperparameter sensitivity analyses, we show that state-of-the-art LSR-ESNs reduce to a polynomial regression model which we call Domain-Driven Regularized Regression (D2R2). Interestingly, D2R2 is a generalization of the well-known SINDy algorithm (Brunton SL, Proctor JL, Kutz JN. 2016 Proc. Natl Acad. Sci. USA 113, 3932-3937. (doi:10.1073/pnas.1517384113)). We also show experimentally that LSR-ESNs (Chattopadhyay A, Hassanzadeh P, Subramanian D. 2019 (http://arxiv.org/abs/1906.08829)) outperform HSR ESNs (Pathak J, Hunt B, Girvan M, Lu Z, Ott E. 2018 Phys. Rev. Lett. 120, 024102. (doi:10.1103/PhysRevLett.120.024102)) while D2R2 dominates both approaches. A significant goal in constructing surrogates is to cope with barriers to scaling in weather prediction and simulation of dynamical systems that are imposed by time and energy consumption in supercomputers. Inexact computing has emerged as a novel approach to helping with scaling. In this paper, we evaluate the performance of three models (LSR-ESN, HSR-ESN and D2R2) by varying the precision or word size of the computation as our inexactness-controlling parameter. For precisions of 64, 32 and 16 bits, we show that, surprisingly, the least expensive D2R2 method yields the most robust results and the greatest savings compared to ESNs. Specifically, D2R2 achieves 68 × in computational savings, with an additional 2 × if precision reductions are also employed, outperforming ESN variants by a large margin. This article is part of the theme issue 'Machine learning for weather and climate modelling'.
ABSTRACT
Traditional static publication formats make visualization, exploration, and sharing of massive phylogenetic trees difficult. A phylogenetic study often involves hundreds of taxa, and the resulting tree has to be split across multiple journal pages, or be shrunk onto one, which jeopardizes legibility. Furthermore, additional data layers, such as species-specific information or time calibrations are often displayed in separate figures, making the entire picture difficult for readers to grasp. Web-based technologies, such as the Data Driven Document (D3) JavaScript library, were created to overcome such challenges by allowing interactive displays of complex data sets. The new phylogeny.IO web server (https://phylogeny.io) overcomes this issue by allowing users to easily import, annotate, and share interactive phylogenetic trees. It allows a range of static (e.g. such as shapes and colors) and dynamic (e.g. pop-up text and images) annotations. Annotated trees can be saved on the server for subsequent modification or they may be shared as IFrame HTML objects, easily embeddable in any web page. The principal goal of phylogeny.IO is not to produce publication-ready figures, but rather to provide a simple and intuitive annotation interface that allows easy and rapid sharing of figures in blogs, lecture notes, press releases, etc.
Subject(s)
Computer Graphics , Databases, Factual , Internet , Phylogeny , User-Computer Interface , Datasets as Topic , Species SpecificityABSTRACT
The present article investigates the chemical composition of volatiles of essential oil (EO) and headspace (HS) fraction, as well as biological activities of EO obtained from needles with twigs of Pseudotsuga menziesii var. menziesii cultivated in Serbia. The major class of compounds was monoterpene hydrocarbons with α-terpinolene, sabinene and ß-pinene (EO), and sabinene, α-terpinolene and ß-pinene (HS) as the dominant volatiles. Tested EO exhibited mostly low antimicrobial potential against investigated strains (ATCC and respiratory isolates), where MICs ranged 1.25-20.00â mg/mL. Nevertheless, based on presented results, where antimicrobial testing was done for the first time on human respiratory system isolates, there is a potential of this EO to be used as an adjuvant in the treatment of human respiratory infections, especially those caused by Pseudomonas aeruginosa or Candida albicans strains. Regarding toxicological evaluation, EO showed moderate toxicity in Artemia salina toxicity bioassay (LC50 =347.41, after 24â h) as well as week toxicity against Drosophila melanogaster with the ability only to moderately delay larval and pupal development.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Oils, Volatile/pharmacology , Plant Extracts/pharmacology , Pseudotsuga/chemistry , Volatile Organic Compounds/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Artemia/drug effects , Candida albicans/drug effects , Drosophila melanogaster/drug effects , Humans , Microbial Sensitivity Tests , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Shoots/chemistry , Pseudomonas aeruginosa/drug effects , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/isolation & purificationABSTRACT
Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an MGMT promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. Materials and methods: A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for MGMT promoter methylation and correlated with clinical data. Results: MGMT methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). MGMT promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of MGMT promoter methylation did not correlate with patients' gender (p = 0.409), age (p = 0.536), and OS (p = 0.394). Treatment with TMZ significantly prolonged the median survival of a patient (from 5 to 15 months; p < 0.001). Conclusions: Due to a small cohort of primary GBM patients, our study is not sufficient for definitive conclusions regarding the prognostic value of MGMT methylation for the Serbian population. Our preliminary data suggest a lack of association between MGMT promoter methylation and overall survival and a significant correlation of TMZ treatment with overall survival. Further population-based studies are needed to assess the prognostic value of the MGMT promoter methylation status for patients with primary glioblastoma.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Biomarkers, Tumor/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , DNA Methylation , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Glioblastoma/drug therapy , Glioblastoma/mortality , Temozolomide/therapeutic use , Tumor Suppressor Proteins/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/administration & dosage , Brain Neoplasms/radiotherapy , Cohort Studies , Female , Glioblastoma/radiotherapy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Serbia , Survival Analysis , Temozolomide/administration & dosageABSTRACT
The chemical composition and biological activities of the essential oils obtained from Serbian Artemisia species (A. alba, A. absinthium, A. annua, A. vulgaris, and A. scoparia) were analysed. The essential oil was obtained by merging several samples (same plant species, different localities) and the chemical composition was compared with pre-merging results. In the merged A. scoparia sample four components were not found in any pre-merging sample and one of those is present in the highest percentage (capillin 35.7%). The least toxic essential oil in Artemia salina test was A. annua, followed by A. alba (both showing medium toxicity), while A. absinthium, A. vulgaris, and A. scoparia showed strong toxicity. All tested samples showed activity against Drosophila melanogaster larvae in descending order ΣAS > ΣAN > ΣAV > ΣAB > ΣAA. The essential oil of A. scoparia has exceptional larvicidal activity (in concentrations of 2% and 1% causes complete mortality).
ABSTRACT
OBJECTIVES: To verify the protective effect of plant extracts associated with fluoride against dental erosion of dentine, in the presence and absence of a salivary pellicle. METHODS: Dentine specimens (n = 270) were randomly distributed into 9 experimental groups (n = 30/group): GT (green tea extract); BE (blueberry extract); GSE (grape seed extract); NaF (sodium fluoride); GT+NaF (green tea extract and NaF); BE+NaF (blueberry extract and NaF); GSE+NaF (grape seed extract and NaF); negative control (deionized water); and a positive control (commercialized mouthrinse containing stannous and fluoride). Each group was further divided into two subgroups (n = 15), according to the presence (P) or absence (NP) of salivary pellicle. The specimens were submitted to 10 cycles: 30 min incubation in human saliva (P) or only in humid chamber (NP), 2 min immersion in experimental solutions, 60 min of incubation in saliva (P) or not (NP), and 1 min erosive challenge. Dentine surface loss (dSL-10 and dSL-total), amount of degraded collagen (dColl) and total calcium release (CaR) were evaluated. Data were analyzed with Kruskal-Wallis, Dunn's and Mann-Whitney U tests (p>0.05). RESULTS: Overall, the negative control presented the highest values of dSL, dColl and CaR, and the plant extracts showed different degrees of dentine protection. For the subgroup NP, GSE showed the best protection of the extracts, and the presence of fluoride generally further improved the protection for all extracts. For the subgroup P, only BE provided protection, while the presence of fluoride had no impact on dSL and dColl, but lowered CaR. The protection of the positive control was more evident on CaR than on dColl. CONCLUSION: We can conclude that the plant extracts showed a protective effect against dentine erosion, regardless of the presence of salivary pellicle, and that the fluoride seems to improve their protection.
Subject(s)
Grape Seed Extract , Tooth Erosion , Humans , Dental Pellicle , Dentin , Fluorides/pharmacology , Grape Seed Extract/pharmacology , Sodium Fluoride/pharmacology , Tea , Tooth Erosion/prevention & controlABSTRACT
Comparative analysis of the conventional methylation-specific PCR (MSP) vs. the quantitative MSP (qMSP) assessment of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in 34 snap-frozen (SF) glioma samples was performed. The accuracy of the semi-quantitative MSP was compared with the corresponding qMSP semi-quantitative values using two semi-quantitative cut-off values (0-unmethylated and 1-weakly methylated) to discriminate methylated from unmethylated samples. In the case of the cut-off value 0, MSP test showed 80.0% sensitivity and 78.9% specificity compared to the reference qMSP analysis. However, when using the cut-off value 1, the diagnostic accuracy of the MSP test was significantly higher (85.7% sensitivity, 85.2% specificity). Fleiss' Kappa statistical analyses indicated moderate agreement (Fleiss' Kappa Coefficient = 0.509; 70.59% agreement) between MSP and qMSP semi-quantitative measurements of MGMT promoter methylation in glioma patients, justifying the conventional MSP use in diagnostics and confirming its high reliability. Further, we aimed to compare the validity of SF and formalin-fixed paraffin-embedded (FFPE) glioma samples for MGMT testing. Statistical analyses indicated moderate overall agreement of FFPE glioma samples and SF MSP semi-quantitative measurements (Fleiss' Kappa Coefficient = 0.516/0.509; 70.0% agreement) and emphasized their low reliability in the assessment of highly methylated MGMT promoter samples.
ABSTRACT
The oil extracted from hemp seeds has significant nutritional and biological properties due to the unique composition of polyunsaturated fatty acids and various antioxidant compounds. The potential of this oil for the prevention of oxidative stress and for the treatment of oxidative-stress-induced ailments is of increasing interest. Most studies of hemp seed oil were conducted in-vitro, meaning we lack information about effects and activity in vivo. In the present study, we evaluated the hypothesis that hemp seed oil at different concentrations improves the oxidative state of D. melanogaster, under non-stress as well as hydrogen-peroxide-induced stress. We analyzed the effects of hemp seed oil on oxidative stress markers and on the life cycle of D.melanogaster under non-stress and hydrogen-peroxide-induced stress conditions. D.melanogaster larvae were exposed to hemp seed oil concentrations ranging from 12.5 to 125 µL/mL. The results revealed that under non-stress conditions, oil concentrations up to 62.5 µL/mL did not induce negative effects on the life cycle of D. melanogaster and maintained the redox status of the larval cells at similar levels to the control level. Under oxidative stress conditions, biochemical parameters were significantly affected and only two oil concentrations, 18.7 and 31.2 µL/mL, provided protection against hydrogen peroxide stress effects. A higher oil concentration (125 µL/mL) exerted negative effects on the oxidative status and increased larval mortality. The tested oil was characterized chemically by NMR, transesterification, and silylation, followed by GC-MS analyses, and was shown to contain polyunsaturated fatty acid triglycerides and low levels of tocopherols. The high levels of linoleic and linolenic acids in the oil are suggested to be responsible for the observed in vivo antioxidant effects. Taken together, the results show that hemp seed oil is effective for reducing oxidative stress at the cellular level, thus supporting the hypothesis. The obtained results point to the potential of hemp seed oil for the prevention and treatment of conditions caused by the action of reactive oxygen species.
ABSTRACT
The aim of our research was to assess if the pain and discomfort following each quarterly onabotulinumtoxinA (BTA) injection given to prevent daily headaches/migraines is circadian time-dependent so as to determine the best administration time for least discomfort and minimal follow-up pain. A total of 61 diurnally active patients with a medical history of chronic migraine headaches and undergoing preventative BTA injection therapy for the first time were enrolled in the study. Patients were randomly assigned to morning or afternoon clinics, but had the ability to choose within the assigned clinic the injection time that best fits their schedule. 155 units of BTA was administered by following the standardized PREEMPT injection protocol. Patients reported the typical time of sleep onset and wakeup time for the week prior to injections. Patients then self-reported three levels of pain in the head and neck area: prior to BTA injections, immediately after, and 24 h after BTA injections. This was carried out by marking the pain level on 100 mm visual analog pain scale. Descriptive summaries were frequencies and percentages for categorical data and medians and quartiles for continuous variables. Demographic variables of gender, race, and age were tested using Chi-Square. Groups of morning versus afternoon patients were compared using the non-parametric Wilcoxson's Rank Sum Tests and student T tests. All analysis was done in SAS for Windows Version 9.4. 38 (62%) patients were injected during morning clinic and 23 (38%) during afternoon clinic. There was no difference in gender, race, and age variables between morning and afternoon patients. 67% of the patients experienced increased pain following the initial injection. Higher pain score was more frequent following morning than afternoon injections (78% vs. 50%, p = .021). The 24 h post-injection pain level was also significantly higher in patients injected in the morning than afternoon (64% vs. 28%, p = .024). Performing BTA injections for migraine prevention during the morning was associated with significantly more treatment-related discomfort, both immediately and 24 h after injection. Scheduling diurnal active patients with stable circadian sleep/wake routine for afternoon BTA injections appears beneficial for decreasing treatment-related discomfort and potentially increase compliance to therapy.
Subject(s)
Botulinum Toxins, Type A , Migraine Disorders , Circadian Rhythm , Humans , Migraine Disorders/drug therapy , Migraine Disorders/prevention & control , Pain/drug therapy , Pain/prevention & control , SleepABSTRACT
Drosophila is among the most commonly used models for toxicity assessment of different types of nanoparticles. This study aims to examine the effects of a constant exposure to the low concentration of human food grade titanium dioxide nanoparticles (TiO2 E171) on Drosophila melanogaster wing morphology over multiple generations. Subsequently, the Geometric Morphometrics Analysis was employed to examine possible changes in the wing shape and size of the treated flies. The treatment resulted in the diminishment but not a disruption in the sexual dimorphism in wings. Consequently, the female flies were clearly separated from the male flies by the differences in wing morphology as in the control group. A splitting by generations was overly similar within the control and the treatment, but it was slightly more pronounced in the treatment. However, the observed generational differences seemed mostly random between generations, irrespective of the treatment. Specifically, the treated groups displayed slightly higher splitting by generations in females than in males. Regardless of the generation, the results show a clear splitting by the differences in the wing shape between the treated flies and the flies from control. The mean value of centroid size, which refers to the wing size, of both female and male wings was smaller in the treatment when compared to the control. The overall effect of TiO2 was to induce significant difference in Drosophila wing morphology but it did not alter the general wing morphology pattern. Therefore, the change in the wings occurred only within the normally allowed wing variation.
Subject(s)
Drosophila melanogaster/physiology , Nanoparticles/toxicity , Titanium/toxicity , Wings, Animal/drug effects , Animals , Drosophila , Drosophila melanogaster/drug effects , Female , Food , Humans , Male , Sex Characteristics , Wings, Animal/anatomy & histologyABSTRACT
The gut is a first point of contact with ingested xenobiotics, where chemicals are metabolized directly by the host or microbiota. Atrazine is a widely used pesticide, but the role of the microbiome metabolism of this xenobiotic and the impact on host responses is unclear. We exposed successive generations of the wasp Nasonia vitripennis to subtoxic levels of atrazine and observed changes in the structure and function of the gut microbiome that conveyed atrazine resistance. This microbiome-mediated resistance was maternally inherited and increased over successive generations, while also heightening the rate of host genome selection. The rare gut bacteria Serratia marcescens and Pseudomonas protegens contributed to atrazine metabolism. Both of these bacteria contain genes that are linked to atrazine degradation and were sufficient to confer resistance in experimental wasp populations. Thus, pesticide exposure causes functional, inherited changes in the microbiome that should be considered when assessing xenobiotic exposure and as potential countermeasures to toxicity.
Subject(s)
Gastrointestinal Microbiome , Pesticides/toxicity , Wasps/microbiology , Animals , Atrazine/metabolism , Atrazine/toxicity , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/metabolism , Directed Molecular Evolution , Drug Resistance/genetics , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/genetics , Genes, Bacterial , Maternal Inheritance , Metagenomics , Pesticides/metabolism , Pseudomonas/genetics , Pseudomonas/isolation & purification , Pseudomonas/metabolism , Serratia marcescens/genetics , Serratia marcescens/isolation & purification , Serratia marcescens/metabolism , Wasps/drug effects , Xenobiotics/metabolism , Xenobiotics/toxicityABSTRACT
BACKGROUND: All objects put into a child's mouth could be hazardous in terms of trauma and toxic substance exposure. The aims of this study were to evaluate morphological characteristics of the primary teeth bite marks inflicted on various materials and to assess material wear using experimental model. METHODS: Bite marks were analyzed on five materials: rubber, plastic, foil, wood, and silicone. In order to mimic children mouthing behavior an experimental setup has been designed using primary teeth placed in dentures and children's equipment specimens. RESULTS: Deciduous teeth make visible and recognizable traces when using physiological forces on all investigated materials. The most significant material loss was revealed in silicone samples, but it has been observed in all material groups, while mouthing with incisors using higher mastication forces were identified as significant predictors for material wear. There were no significant differences between type, species, and morphological-morphometric characteristics of the bite marks which are made by incisors, canines, and molars. CONCLUSIONS: In the range of physiological bite forces, deciduous teeth lead to wear of material from which toys are made while the analysis of bite marks in children equipment could give some information regarding the risk of trauma and exposure.
Subject(s)
Bite Force , Bites, Human , Dental Impression Technique , Forensic Dentistry/methods , Risk Assessment/methods , Safety Management/methods , Tooth, Deciduous , Child , Child, Preschool , Female , Humans , MaleABSTRACT
BACKGROUND: Anxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general population, and the comorbid presence of anxiety disorders is known to have an impact on the diabetes outcome and the quality of life. However, the information on the type of anxiety disorder and its prevalence in persons with T2DM is limited. AIMS: To assess the prevalence and correlates of anxiety disorder in people with type 2 diabetes in different countries. METHODS: People aged 18-65 years with diabetes and treated in outpatient settings were recruited in 15 countries and underwent a psychiatric interview with the Mini-International Neuropsychiatric Interview. Demographic and medical record data were collected. RESULTS: A total of 3170 people with type 2 diabetes (56.2% women; with mean (SD) duration of diabetes 10.01 (7.0) years) participated. The overall prevalence of anxiety disorders in type 2 diabetic persons was 18%; however, 2.8% of the study population had more than one type of anxiety disorder. The most prevalent anxiety disorders were generalised anxiety disorder (8.1%) and panic disorder (5.1%). Female gender, presence of diabetic complications, longer duration of diabetes and poorer glycaemic control (HbA1c levels) were significantly associated with comorbid anxiety disorder. A higher prevalence of anxiety disorders was observed in Ukraine, Saudi Arabia and Argentina with a lower prevalence in Bangladesh and India. CONCLUSIONS: Our international study shows that people with type 2 diabetes have a high prevalence of anxiety disorders, especially women, those with diabetic complications, those with a longer duration of diabetes and poorer glycaemic control. Early identification and appropriate timely care of psychiatric problems of people with type 2 diabetes is warranted.
Subject(s)
Delusions/epidemiology , Hallucinations/epidemiology , Psychotic Disorders/epidemiology , Female , Humans , MaleABSTRACT
In this study, fruit flies (Drosophila melanogaster) were exposed to an estimated daily human E171 consumption concentration for 20 generations. Exposure to E171 resulted in: a change in normal developmental and reproductive dynamics, reduced fecundity after repetitive breeding, increased genotoxicity, the appearance of aberrant phenotypes and morphologic changes to the adult fat body. Marks of adaptive evolution and directional selection were also exhibited. The larval stages were at a higher risk of sustaining damage from E171 as they had a slower elimination rate of TiO2 compared to the adults. This is particularly worrisome, since among the human population, children tend to consume higher daily concentrations of E171 than do adults. The genotoxic effect of E171 was statistically higher in each subsequent generation compared to the previous one. Aberrant phenotypes were likely caused by developmental defects induced by E171, and were not mutations, since the phenotypic features were not transferred to any progeny even after 5 generations of consecutive crossbreeding. Therefore, exposure to E171 during the early developmental period carries a higher risk of toxicity. The fact that the daily human consumption concentration of E171 interferes with and influences fruit fly physiological, ontogenetic, genotoxic, and adaptive processes certainly raises safety concerns.
Subject(s)
Drosophila melanogaster/growth & development , Food Additives/adverse effects , Titanium/adverse effects , Adaptation, Physiological/drug effects , Animals , Child , Child Development/drug effects , Disease Models, Animal , Drosophila melanogaster/drug effects , Drosophila melanogaster/genetics , Fat Body/drug effects , Female , Fertility/drug effects , Humans , Male , Mutagenicity TestsABSTRACT
BACKGROUND: The prognostic significance of lymph node metastases (LNM) in follicle cell-derived differentiated thyroid carcinoma (DTC) is still controversial. The management of cervical lymph nodes varies from "berry picking" to modified radical neck dissection (MRND). The incidence of LNM in papillary thyroid carcinoma varies from 27% to 80%. The importance of sentinel lymph node (SLN) biopsy for decisions about the surgical management of lymph nodes in DTC has been the subject of several previous studies. PATIENTS AND METHODS: In 40 patients with DTC methylene blue dye was applied peritumorally. Both SLN and non-SLN in the lower third of the jugulo-carotid chain were dissected prior to total thyroidectomy and routine dissection of the central neck compartment and examined by frozen-section and standard histology. MRND was performed in 9 cases of LNM in the lateral neck compartment. RESULTS: The SLN identification rate was 92.5%. Metastases in SLNs were revealed by frozen-section histology in 7 cases, leading to immediate MRND. The findings were confirmed on standard HE examination. In 2 false-negative cases SLN metastases were revealed on standard histology and MRND was performed 1 week later. The specificity of the method was 100%, sensitivity 77.7%, negative predictive value 94%, positive predictive value 100%, with overall accuracy of 95%. CONCLUSION: Our results seem to imply that SLN biopsy in the jugulo-carotid chain using methylene blue dye mapping may be a feasible and valuable method for estimating lymph node status in the lateral neck compartment. It may be helpful in the detection of true-positive but nonpalpable lymph nodes, and in such cases may support the decision to perform MRND in patients with DTC.
Subject(s)
Neck Dissection , Sentinel Lymph Node Biopsy , Thyroid Neoplasms/pathology , Adenocarcinoma, Follicular/pathology , Adenocarcinoma, Follicular/surgery , Adenocarcinoma, Papillary/pathology , Adenocarcinoma, Papillary/surgery , Adenoma, Oxyphilic/pathology , Adenoma, Oxyphilic/surgery , Adult , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Thyroid Neoplasms/surgery , ThyroidectomyABSTRACT
Postoperative pain is the most important factor od so called "tumor-promotive effect of surgery" i.e. of endocrine-metabolic changes having the consequence drop in immune, antiinfective and antitumor defense. Due to presence of organic involutive changes, old people (= 65 years), often have serious side effects during application of usual analgetics. Since hypertonic glucose (33%) given i.v. or per os, works analgesically in small children there is assumption that it can be used in treatment of postoperative pain in old oncology patients. We tested the hypothesis that postoperative pain in old oncology patients can be treated with i.v. application of 50% of glucose solution. 37 oncology patients over 65 years, 26 females and 11 males, operated for breast cancer and soft tissue cancer, were investigated. Average age of the patients was 72 +/- 4 years. 50% Glucose solution was given in two boluses of 20 ml each: the first bolus was given to all patients at the end of anesthesia, and the other bolus was given individually after appearance of post-operative pain. Pain intensity (in coefficients of the visual analogue scale VAK = 1-100) and its characteristics were tested by oral testing of operated patients; after weakening from anesthesia, after the first appearance of the pain and 15 minutes after giving of the second glucose bolus. None patient had pain weakening from anesthesia. All tested patients experienced pain during the first 70 minutes and it could be categorized as very strong pain (= 82 VAK). The pain was decreased with another glucose bolus by approximately (= 56% VAK) so it was classifies in category of bearable pains (= 36 VAK). In 9 patients (24.3%) the pain had neuropathic component (filing of "burning") which could not be eliminated by hypertonic glucose, but only with application of tramadol. Activation of the central cholinergic transmission is the most significant mechanism of analgesic glucose effect, but, probably there is another one: facilitation of entrance of formerly given analgesics in the brain cells. As energetic substrate, entering all organism cells, glucose could make easier intracell breakthrough of any other analgesic drug, of the peripheral or central action, and final antipain effect could be potential or additional one. It was concluded that 40 ml of 50% glucose solution given in two identical boluses, has good analgesic effect in treatment of postoperative pain in old oncology patient: the pain was not completely eliminated, but it was significantly decreased and became tolerable. Hypertonic glucose neither eliminates, nor decreases neuropathic component of the pain, so, when the pain appears the therapy should be supplemented with other drugs, which may completely eliminate all pain components.