Search

Mesocosms allow the simulation of environmentally relevant conditions and can be used to establish more realistic scenarios of organism exposure to nanoparticles. An indoor mesocosm experiment simulating an aquatic stream ecosystem was conducted to assess the toxicokinetics and bioaccumulation of silver sulfide nanoparticles (Ag 2 S NPs) and AgNO 3 in the freshwater invertebrates Girardia tigrina, Physa acuta and Chironomus riparius, and determine if previous single-species tests can predict bioaccumulation in the mesocosm. Water was daily spiked at 10 μg Ag L -1 . Ag concentrations in water and sediment reached values of 13.4 μg Ag L -1 and 0.30 μg Ag g -1 in the Ag 2 S NP exposure, and 12.8 μg Ag L -1 and 0.20 μg Ag g -1 in the AgNO 3 . Silver was bioaccumulated by the species from both treatments, but with approximately 1.5, 3 and 11 times higher body Ag concentrations in AgNO 3 compared to Ag 2 S NP exposures in snails, chironomids and planarians, respectively. In the Ag 2 S NP exposures, the observed uptake was probably of the particulate form. This demonstrates that this more environmentally relevant Ag nanoform may be bioavailable for uptake by benthic organisms. Interspecies interactions likely occurred, namely predation (planarians fed on chironomids and snails), which somehow influenced Ag uptake/bioaccumulation, possibly by altering organisms´ foraging behaviour. Higher Ag uptake rate constants were determined for AgNO 3 (0.64, 80.4 and 1.12 L water g -1 organism day -1 ) than for Ag 2 S NPs (0.05, 2.65 and 0.32 L water g -1 organism day -1 ) for planarians, snails and chironomids, respectively. Biomagnification under environmentally realistic exposure seemed to be low, although it was likely to occur in the food chain P. acuta to G. tigrina exposed to AgNO 3 . Single-species tests generally could not reliably predict Ag bioaccumulation in the more complex mesocosm scenario. This study provides methodologies/data to better understand exposure, toxicokinetics and bioaccumulation of Ag in complex systems, reinforcing the need to use mesocosm studies to improve the risk assessment of environmental contaminants, specifically NPs, in aquatic environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The fate of engineered nanomaterials in ecosystems is unclear. An aquatic stream mesocosm explored the fate and bioaccumulation of silver sulfide nanoparticles (Ag 2 S NPs) compared to silver nitrate (AgNO 3 ). The aims were to determine the total Ag in water, sediment and biota, and to evaluate the bioavailable fractions of silver in the sediment using a serial extraction method. The total Ag in the water column from a nominal daily dose of 10 μg L -1 of Ag for the AgNO 3 or Ag 2 S NP treatments reached a plateau of around 13 and 12 μg L -1 , respectively, by the end of the study. Similarly, the sediment of both Ag-treatments reached ~380 μg Ag kg -1 , and with most of it being acid-extractable/labile. The biota accumulated 4-59 μg Ag g -1 dw, depending on the type of Ag-treatment and organism. The oligochaete worm, Lumbriculus variegatus, accumulated Ag from the Ag 2 S exposure over time, which was similar to the AgNO 3 treatment by the end of the experiment. The planarian, Girardia tigrina, and the chironomid larva, Chironomus riparius, showed much higher Ag concentrations than the oligochaete worms; and with a clearer time-dependent statistically significant Ag accumulation relative to the untreated controls. For the pulmonate snail, Physa acuta, bioaccumulation of Ag from AgNO 3 and Ag 2 S NP exposures was observed, but was lower from the nano treatment. The AgNO 3 exposure caused appreciable Ag accumulation in the water flea, Daphnia magna, but accumulation was higher in the Ag 2 S NP treatment (reaching 59 μg g -1 dw). In the rainbow trout, Oncorhynchus mykiss, AgNO 3 , but not Ag 2 S NPs, caused total Ag concentrations to increase in the tissues. Overall, the study showed transfer of total Ag from the water column to the sediment, and Ag bioaccumulation in the biota, with Ag from Ag 2 S NP exposure generally being less bioavailable than that from AgNO 3 ., Competing Interests: Declaration of competing interest The authors have no known financial or other conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Angioimmunoblastic T-cell lymphoma (AITL) is a unique subtype of peripheral T-cell lymphoma (PTCL) with distinct clinicopathologic features and poor prognosis. We performed a subset analysis of 282 patients with AITL enrolled between 2006 and 2018 in the international prospective T-cell Project (NCT01142674). The primary and secondary end points were 5-year overall survival (OS) and progression-free survival (PFS), respectively. We analyzed the prognostic impact of clinical covariates and progression of disease within 24 months (POD24) and developed a novel prognostic score. The median age was 64 years, and 90% of patients had advanced-stage disease. Eighty-one percent received anthracycline-based regimens, and 13% underwent consolidative autologous stem cell transplant (ASCT) in first complete remission (CR1). Five-year OS and PFS estimates were 44% and 32%, respectively, with improved outcomes for patients who underwent ASCT in CR1. In multivariate analysis, age ≥60 years, Eastern Cooperative Oncology Group performance status >2, elevated C-reactive protein, and elevated β2 microglobulin were associated with inferior outcomes. A novel prognostic score (AITL score) combining these factors defined low-, intermediate-, and high-risk subgroups with 5-year OS estimates of 63%, 54%, and 21%, respectively, with greater discriminant power than established prognostic indices. Finally, POD24 was a powerful prognostic factor with 5-year OS of 63% for patients without POD24 compared with only 6% for patients with POD24 (P < .0001). These data will require validation in a prospective cohort of homogeneously treated patients. Optimal treatment of AITL continues to be an unmet need, and novel therapeutic approaches are required., (© 2021 by The American Society of Hematology.)

Gestational diabetes (GDM) is a common metabolic complication of pregnancy that is generally asymptomatic in its clinical course, although it is potentially associated with a wide range of both maternal and foetal complications. The population prevalence of GDM varies widely, depending on the clinical diagnostic criteria, ethnicity, demographics and background prevalence of type 2 diabetes. Climate variability and environmental temperature have recently come to the forefront as potential direct or indirect determinants of human health. The association between GDM and environmental temperature is complex, and studies have often reported conflicting findings. Epidemiologic studies have shown a direct relation between rising environmental temperature and the risk of both GDM and impaired beta cell function. Seasonal trends in the prevalence of GDM have been reported in several populations, with a higher prevalence in summer months. Multiple mechanisms have been proposed to explain the GDM-temperature correlation. A growing body of evidence supports a link between temperature, energy expenditure and adipose tissue metabolism. Brown adipose tissue thermogenesis, induced by cold temperatures, improves insulin sensitivity. Further biological explanations for the GDM-temperature correlation lie in potential association with low vitamin D levels, which varies according to sunshine exposure. Observational studies are also complicated by lifestyle factors, such as diet and physical activity, that could exhibit seasonal variation. In this review article, we provide a systematic overview of available epidemiological evidence linking environmental temperature and gestational diabetes. Furthermore, the physiological mechanisms that give biological plausibility to association between GDM and temperature are explored. As future climate patterns could drive global changes in GDM prevalence, this knowledge has important implications for both clinicians and researchers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Updates on the latest diagnostic methods and features of MODY (Maturity Onset Diabetes of the Young) and promotion of education and awareness on the subject are discussed., Method: Previous recommendations were identified using PubMed and using combinations of terms including "MODY" "monogenic diabetes" "mature onset diabetes" "MODY case review". The diabetesgenes.org website and the US Monogenic Diabetes Registry (University of Colorado) were directly referenced. The remaining referenced papers were taken from peer-reviewed journals. The initial literature search occurred in January 2017 and the final search occurred in September 2018., Results: A diagnosis of MODY has implications for treatment, quality of life, management in pregnancy and research. The threshold for referral and testing varies among different ethnic groups, and depends on body mass index, family history of diabetes and associated syndromes. Novel causative genetic variations are still being discovered however testing is currently limited by low referral rates. Educational material is currently being promoted in the UK in an effort to raise awareness., Conclusions: The benefits and implications of life altering treatment such as termination of insulin administration are significant but little can be done without appropriate identification and referral., (Copyright © 2019 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Publishing scholarly work is a requisite in academia. Identifying a suitable journal for a particular paper can be difficult. Authors need to initially establish whether they want to publish in a subscription-based or an open access journal, which requires a clear understanding of the pros and cons of both options as well as issues relating to copyright licences. Establishing specific journal selection criteria ranging from whether to publish in a general or a specialised journal to the publication frequency of the journal is essential. A number of web-based tools are available that can facilitate this selection process., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Once an author/s submits a manuscript to a journal, editorial and review processes are initiated which will determine acceptance or rejection of a manuscript. Understanding the editor's perspective and role enables authors to appreciate the factors that can ensure that the submitted manuscript meets the editor's expectations. This increases the chances that the manuscript passes the initial scrutiny and is forwarded for peer review. The reviewers' comments and recommendations make or break the manuscript and will take the form of comments for the authors as well as confidential recommendations to the Editor. Rejection should not lead to dejection. Authors need to digest the reasons for rejection, review comments and suggestions and incorporate them into the revised manuscript prior to identifying another journal for possible submission. If the manuscript is accepted with minor or major revisions, the authors need to make sure all comments and recommendations are dealt with. Once the manuscript satisfies the editor's and reviewers' expectations, it is on its way to publication., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Critical appraisal of research involves a systematic process which assesses the question/s posed, study design and execution, statistical evaluation, interpretation of the results, and appropriateness of the conclusions. It necessitates identification of conflicts of interest, analyses the strengths and weaknesses of the study and ultimately the validity, reliability and relevance of the reported findings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There are now over a thousand nano-containing products on the market and the antibacterial properties of some nanomaterials has created interest in their use as cleaning agents, biocides and disinfectants. Engineered nanomaterials (ENMs) are being released into the environment and this raises concerns about their effects on microbes in the receiving ecosystems. This study evaluated the bacterial toxicity of a wide range of nanomaterials with different surface coatings on Escherichia coli K-12 MG1655. The minimum inhibitory concentration (MIC) assay, which quantifies the threshold for growth inhibition in suspensions of bacteria, was used to rank the toxicity of silver (Ag), cupric oxide (CuO), cadmium telluride (CdTe) quantum dots, titanium dioxide (TiO 2 ), nanodiamonds and multi-walled carbon nanotubes (MWCNTs). Bacteria were exposed for 12 h at 37 °C to a dilution series of the test suspensions in 96-well plates. The precision and accuracy of the method was good with coefficients of variation < 10%. In terms of the measured MIC values, the toxicity order of the ENMs was as follows: CdTe quantum dots ammonium-coated, 6 mg L -1 > Ag nanoparticles, 12 mg L -1 > CdTe quantum dots carboxylate-coated, 25 mg L -1 > CdTe quantum dots polyethylene glycol-coated, 100 mg L -1 . The MIC values were above the highest test concentration used (100 mg L -1 ) for CuO, TiO 2 , nanodiamonds and MWCNTs, indicating low toxicity. The MIC assay can be a useful tool for the initial steps of ENMs hazard assessment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This paper aims to define and discuss the various forms and degrees of plagiarism. The potential consequences of this particular form of scientific misconduct will be highlighted. The overarching principles in ensuring adherence to research and work ethics are reviewed and the necessity for honesty, objectivity, integrity, respect for intellectual property, confidentiality as well as responsible publication emphasised. The "Publish or Perish" mantra has led to an increasing need for an understanding of the responsibilities related to authorship, acknowledgments and what these encompass. Whilst there is undoubtedly an obligation to disseminate knowledge through publication, the pitfalls that lie therein particularly when dealing with the media, potential interference from funding bodies and the impact of other conflicts of interest will be reviewed. Aspects of interaction with colleagues such as appropriate mentoring, non-discrimination, adherence to standards regarding safety of colleagues and students, in addition to the societal and legal responsibility of researchers will be discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Triage is a key principle in the effective management at a major incident. There are at least three different triage systems in use worldwide and previous attempts to validate them, have revealed limited sensitivity. Within a civilian adult population, there has been no work to develop an improved system., Methods: A retrospective database review of the UK Joint Theatre Trauma Registry was performed for all adult patients (>18years) presenting to a deployed Military Treatment Facility between 2006 and 2013. Patients were defined as Priority One if they had received one or more life-saving interventions from a previously defined list. Using first recorded hospital physiological data (HR/RR/GCS), binary logistic regression models were used to derive optimum physiological ranges to predict need for life-saving intervention. This allowed for the derivation of the Modified Physiological Triage Tool-MPTT (GCS≥14, HR≥100, 12

Introduction: Triage is a key principle in the effective management of major incidents. The process currently relies on algorithms assigning patients to specific triage categories; there is, however, little guidance as to what these categories represent. Previously, these algorithms were validated against injury severity scores, but it is accepted now that the need for life-saving intervention is a more important outcome. However, the definition of a life-saving intervention is unclear. The aim of this study was to define what constitutes a life-saving intervention, in order to facilitate the definition of an adult priority one patient during the definitive care phase of a major incident., Methods: We conducted a modified Delphi study, using a panel of subject matter experts drawn from the United Kingdom and Republic of South Africa with a background in Emergency Care or Major Incident Management. The study was conducted using an online survey tool, over three rounds between July and December 2013. A four point Likert scale was used to seek consensus for 50 possible interventions, with a consensus level set at 70%., Results: 24 participants completed all three rounds of the Delphi, with 32 life-saving interventions reaching consensus., Conclusions: This study provides a consensus definition of what constitutes a life-saving intervention in the context of an adult, priority one patient during the definitive care phase of a major incident. The definition will contribute to further research into major incident triage, specifically in terms of validation of an adult major incident triage tool., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Major Incidents (MI) occur frequently and their unpredictable nature makes prospective research difficult and largely unethical. A key step in MI management is triage; the identification of the critically injured. Within a MI environment this is commonly performed using simple physiological ‘tools’, such as the Triage Sieve (TS). However the most commonly used tools appear to lack an evidence base. In a previous study, the authors used a military population to compare the performance of the TS to the Military Sieve (MS) at predicting need for Life-Saving Intervention (LSI). The MS differs only with the addition of a measurement of consciousness. The outcome from this study was that the MS outperformed the TS, but could be further improved with small changes to its physiological parameters, the Modified Military Sieve (MMS)., Materials and Methods: Physiological data and interventions performed within the Emergency Department (ED) and Operating Theatre were prospectively collected for consecutive adult trauma patients (>18years) presenting to the ED at Camp Bastion, Afghanistan between March and September 2011. All patients receiving a LSI were considered Gold Standard Priority One. Patients were triaged using the TS, MS, MMS, START (ST) and Careflight (CF) triage tools. Sensitivities and specificities were estimated with 95% confidence intervals and differences were checked for statistical significance using a McNemar test with Bonferroni correction., Results: 482 patients presented to the ED during the study period, sufficient data was recorded for 335 (71%) with 199 (59%) P1s. The MMS (sensitivity 68.3%, specificity 79.4%) showed an absolute increase in sensitivity over existing tools ranging from 5.0% (MS) to 23.6% (CF). There was a statistically significant difference (P = 0.0005) between the MMS and MS., Discussion: A key limitation to this study, is the use of a military cohort to validate the MMS, a tool which itself was developed using military data. The mechanism of injury also is unlikely to translate fully to the civilian population., Conclusions: Within a military population, the MMS outperforms existing MI triage tools. Before it is recommended as a replacement to the existing TS in UK civilian practice, it needs to be tested in a civilian environment.

Introduction: A key challenge at a major incident is to quickly identify those casualties most urgently needing treatment in order to survive - triage. The UK Triage Sieve (TS) advocated by the Major Incident Medical Management (MIMMS) Course categorises casualties by ability to walk, respiratory rate (RR) and heart rate (HR) or capillary refill time. The military version (MS) includes assessment of consciousness. We tested whether the MS better predicts need for life-saving intervention in a military trauma population. Ideal HR, RR and Glasgow Coma Score (GCS) thresholds were calculated., Methods: A gold standard Priority 1 casualty was defined using resource-based criteria. Pre-hospital data from a military trauma database allowed calculation of triage category, which was compared with this standard, and presented as 2×2 tables. Sensitivity and specificity of each physiological parameter was calculated over a range of values to identify the ideal cut-offs., Results: A gold standard could be ascribed in 1657 cases. In 1213 both the MS and TS could ascribe a category. MS was significantly more sensitive than TS (59% vs 53%, p<0.001) with similar specificity (89 vs 88%). Varying the limits for each parameter allowed some improvements in sensitivity (70-80%) but specificity dropped rapidly., Discussion: Previous studies support the inclusion of GCS assessment for blunt as well as penetrating trauma. Optimising the physiological cut-offs increased sensitivity in this sample to only 71% - a Sieve based purely on physiological parameters may not be capable of an acceptable level of sensitivity., Conclusions: The MS is more sensitive than the TS. Major incident planners utilising the Sieve should consider adopting the military version as their first line triage tool. If validated, altering the HR and RR thresholds may further improve the tool., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate whether risk scores used to classify patients with primary myelofibrosis and JAK-2 V617F mutation status can predict clinical outcome., Methods: A review of clinical and laboratory data from 74 patients with primary myelofibrosis diagnosed between 1992 and 2011. The IPSS and Lille scores were calculated for risk stratification and correlated with overall survival., Results: A V617F JAK2 mutation was detected in 32 cases (47%), with no significant correlation with overall survival. The patients were classified according to the scores: Lille - low, 53 (73.%); intermediate, 13 (18%); and high, 5 (7%); and IPSS- low, 15 (26%); intermediate-1, 23 (32%); intermediate-2, 19 (26%); and high, 15 (31%). Those patients presenting a higher risk according to the IPSS (high and intermediate-2) had a significantly shorter overall survival relative to the low risk groups (intermediate-1 and low) (p = 0.02)., Conclusions: These results emphasize the importance of the IPSS prognostic score for risk assessment in predicting the clinical outcome of primary myelofibrosis patients.

The objective of this case report is to present a rare association of a mucosa-associated lymphoid tissue lymphoma masquerading as Graves' orbitopathy in a patient with autoimmune hyperthyroidism, without evidence of Graves' ophthalmopathy. A 66-year-old male patient had pain and swelling of the right eye. Evaluation of serum thyroid hormone revealed low thyrotropin, elevated free thyroxin and antithyroperoxidase antibody levels, confirming the diagnosis of Graves' disease. Computed tomographic scan showed intraorbital muscle asymmetry. Biopsy demonstrated a low-grade, B-cell type non-Hodgkin's lymphoma of the mucosa-associated lymphoid tissue. Treatment included radiotherapy and chemotherapy, with regression of the orbital lesion and medical treatment with methimazole and (131)I. Detailed orbital evaluation should be considered in all patients who present any atypical signs and symptoms of the eyes, to prevent missing important and progressive diagnoses.

Non-Hodgkin lymphomas (NHLs) of the oral cavity and oropharynx constitute 13% of all primary extranodal NHLs. Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) in the palatine tonsil is rare, corresponding to 6% of the NHLs of the Waldeyer ring. Some cases of MALT lymphoma can present prominent plasma cell differentiation, and less commonly, monoclonal gammopathy. The differential diagnosis of these cases from other NHLs with plasmacytic differentiation or plasma cell neoplasms is very difficult. In this article, we describe a rare case of MALT lymphoma in a 34-year-old man presenting as a swelling of the palatine tonsil. The tumor mass was diagnosed as MALT lymphoma with prominent plasma cell differentiation. Systemic evaluation was noncontributory. This is the first report of MALT lymphoma showing extensive plasmacytic differentiation of the palatine tonsil, and reinforces a possible relationship between extramedullary plasmacytoma and MALT lymphoma., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aim: To evaluate the prognostic importance of MGMT and PTEN concerning their correlation with other prognostic factors evaluated by immunohistochemistry (IHC) and the molecular phenotype of breast cancers., Methods: IHC for estrogen and progesterone receptors, HER2, Ki67, p53, p63, e-cadherin, EGFR, CK5, CK14, MGMT and PTEN was performed on 200 breast tumors. Basal-like and luminal breast carcinomas were defined by the IHC evaluation of these markers. Fluorescent in situ hybridization (FISH) was performed for PTEN and HER2 analysis using the Vysis PTEN and HER2 DNA probe kits (Abbott™). RT-PCR was performed to evaluate gene expressions of MGMT and PTEN in frozen tissue of 59/200 cases., Results: 147/200 cases were triple-negative (73.5%), 47/147 were basal-like carcinomas (31.9%). 53 cases (26.5%) were luminal-like type A or B. 56 (93.3%) and 46 samples (76.6%) expressed lower levels of MGMT and PTEN mRNA, respectively, compared with normal breast (p<0.001). There was a positive correlation between the IHC results and the RT-PCR values for MGMT and PTEN. Tumors with homozygotic deletion of PTEN expressed little or no mRNA or protein. Positive p53, high Ki67, and basal-like tumors expressed significant lower MGMT and PTEN., Conclusions: We hypothesize that MGMT and PTEN expressions have prognostic significance in breast cancer. Also, based on their predictive value of response to therapy, evaluating MGMT and PTEN and learning to interpret their patterns of immunoexpression will undoubtedly lead to a greater understanding of breast cancer and its treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Chronic myeloproliferative diseases without the Philadelphia chromosome marker (Ph-), although first described 60 years ago, only became the subject of interest after the turn of the millennium. In 2001, the World Health Organization (WHO) defined the classification of this group of diseases and in 2008 they were renamed myeloproliferative neoplasms based on morphological, cytogenetic and molecular features. In 2005, the identification of a recurrent molecular abnormality characterized by a gain of function with a mutation in the gene encoding Janus kinase 2 (JAK2) paved the way for greater knowledge of the pathophysiology of myeloproliferative neoplasms. The JAK2 mutation is found in 90-98% of polycythemia vera and in about 50% essential thrombocytosis and primary myelofibrosis. In addition to the JAK2 mutation, other mutations involving TET2 (ten-eleven translocation), LNK (a membrane-bound adaptor protein); IDH1/2 (isocitrate dehydrogenase 1/2 enzyme); ASXL1 (additional sex combs-like 1) genes were found in myeloproliferative neoplasms thus showing the importance of identifying molecular genetic alterations to confirm diagnosis, guide treatment and improve our understanding of the biology of these diseases. Currently, polycythemia vera, essential thrombocytosis, myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia and mastocytosis are included in this group of myeloproliferative neoplasms, but are considered different situations with individualized diagnostic methods and treatment. This review updates pathogenic aspects, molecular genetic alterations, the fundamental criteria for diagnosis and the best approach for each of these entities.

Objectives: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3(+) lymphocyte infiltration in differentiated thyroid carcinoma cells., Methods: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues., Results: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3(+) lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis., Conclusions: We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness.

Objectives: The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis., Methods: We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10 ± 68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism., Results: Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74% of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto's thyroiditis who had received a lower 131I cumulative dose and did not present lymph node metastases., Conclusions: We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients, and this autoimmunity may favor a better prognosis for these patients.

The purpose was to determine the immunophenotype of canine lymphomas (CLs) classified according to the WHO nomenclature for domestic animals, and to relate these findings to the immunoexpression of p53 protein. Lymphomas were immunophenotyped with antibodies to CD79a, CD3, and p53 protein, suitable for paraffin wax-embedded tissue sections. Of 55 cases, 40 (72.7%) were of the B-cell phenotype, 12 (21.8%) of the T-cell phenotype, and three (5.4%) were non-B-non-T lymphomas. Of the 40 B-cell lymphomas, 31 were of the large B-cell type, six were lymphoplasmacytic, one lymphocytic, one follicular (grade II) and one unclassified low-grade. One of the peripheral T-cell lymphomas was morphologically consistent with anaplastic large cell lymphoma. Immunolabelling for p53 occurred in 24 B-cell and seven T-cell lymphomas. Lymphomas with high grade histology showed a significantly increased frequency of p53 positivity (P = 0.01). Positivity for p53 (more than 10% positive cells) tended to be associated with the T-cell phenotype (P = 0.06). Mean patient age was significantly higher in p53-positive cases (P = 0.02). These data are comparable with findings in human lymphomas.

The bacteria involved in tonsil disease have been well studied, but we cannot say the same for the viruses. The method to detect virus make this approach difficult to study. Epstein-Barr Virus (EBV) infection usually occurs in early childhood and can persist in palatine and pharyngeal tonsil lymphocytes. EBV has been closely associated with the undifferentiated form of nasopharyngeal carcinoma (NPC) in its effect. Nevertheless, the presence of EBV in non-neoplastic lymphoid tissue of the nasopharynx and tonsil has rarely been investigated. Our objective was to study the frequency of EBV in tonsils and adenoids and to define the correlation between EBV and adenoid hyperplasia. In this study, we looked for EBV in adenoid and tonsil tissue of 165 patients (2 and 15 years old ) by in situ hybridization (ISH) for EBER 1/2 RNA. Resection of the adenoids was done for relief of upper respiratory tract obstruction, and the tonsils were resected because of recurrent tonsillitis and/or hyperplasia with upper airway obstruction. We divided the adenoid samples in two groups: one group 12-24 months old (average 18 months old) and the second group, 25 months to 15 years old. Tonsils were obtained from 85 patients, 3-13 years old (mean age 5.6 years) who underwent surgery due to recurrent tonsillitis or hyperplasia. EBV was demonstrated in lymphoid cells of 11 (34.3%) out of 32 adenoids for the first group and 36 (72%) out of 48 children of the second group. EBV was found in the respiratory epithelial cells of adenoid in one case. Children under 24 months of age can be infected by EBV, and this virus might be responsible for obstructive hyperplasia. Tonsils are less affected by EBV than the adenoids, suggesting that the EBV is more attracted to the adenoid tissue than the tonsillar tissue., (Copyright © 2003 Elsevier B.V. All rights reserved.)

The purpose of the present work was to characterize the effect of musk xylene (MX) and musk ketone (MK) treatment on rat hepatic cytochrome P450 enzymes. Male F344 rats were dosed orally with MX (10, 50 or 200 mg/kg) or MK (20, 100 or 200 mg/kg) for 7 days, after which CYP1A, 2B and 3A enzyme activities and protein levels were determined. MX treatment resulted in a two- to four-fold increase in the activity of CYP1A, 2B and 3A enzymes. For CYP1A and 3A, these changes were consistent with small increases in immunoreactive proteins. However, for CYP2B, despite only a three-fold increase in enzyme activity, protein levels were increased nearly 50-fold relative to control. This induction occurred by transcriptional activation of the CYP2B1 gene as evidenced by increased steady state CYP2B1 mRNA levels. In contrast to MX, MK treatment increased CYP2B activity, protein and mRNA levels. However MK treatment also increased CYP1A enzyme activity nearly 30-fold higher than control rats, a profile that was markedly different from MX, and very different from its effects in mice (Stuard, S.B., Caudill, D., Lehman-Mc-Keeman, L.D., 1997. Characterization of the effects of musk ketone on mouse cytochrome P450 enzymes. Fund. Appl. Toxicol. 40, 264-271). These results indicate that in rats, MX is an inducer of CYP2B enzymes, but these enzymes are not functionally active. In contrast, MK also induces CYP2B enzymes, with no concurrent inactivation. MK also exhibits a unique pattern of cytochrome P450 induction by increasing both CYP1A and CYP2B in rats.