Search

Introduction. One of the major changes in the revised (2018) FIGO-staging system is the addition of stage IIIC to the previously used 2009 system. We evaluated the prognostic value of positive pelvic and/or para-aortic lymph nodes in patients with cervical cancer.Methods. A nationwide retrospective cohort study was performed by analyzing data from the Netherlands Cancer Registry. All patients newly diagnosed with stage IB-IVA between 2005 and 2018 were identified. Three-year, 5-year and 15-year overall survival (OS) rates were estimated with the Kaplan-Meier method.Results. Of the included 6082 patients, 1740 patients (29%) had pelvic and/or para-aortic lymph node metas-tases. For patients with FIGO 2009 stage IB-IB1-IIA-IIA1 and stage IB2-IIA2-IIB with pelvic and/or para-aortic lymph node metastases the OS was significantly different (p < 0.001 and p = 0.009), with a 5-year OS of 77% and 67%, compared with 92% and 74% for women without lymph node metastases. For FIGO 2009 stage IIIA-IIIB-IVA with and without lymph node metastases, survival rates are not significantly different (p = 0.064). For FIGO 2018 stage IIIC the 3y-OS, 5y-OS and 15-year OS are 72%, 65% and 59% respectively. Survival rates of IIIC diagnosed based on imaging (IIICr) are significantly impaired compared to stage IIIC diagnosed based on pathology (IIICp) (p < 0.001).Conclusion. Patients with FIGO 2009 stage IB-IIB cervical cancer with pelvic and/or para-aortic lymph node metastases have significantly impaired survival compared to patients without metastases. Survival rates of patients with FIGO 2009 stage IIIA-IVA are not affected by lymph node metastases.(c) 2023 Published by Elsevier Inc.

Simple Summary The treatment for patients with locally advanced cervical cancer generally consists of platinum-based chemotherapy during external beam radiotherapy, followed by brachytherapy. Some medical centers perform adjuvant hysterectomy after chemoradiation therapy, even though the international guideline advises otherwise. Performing adjuvant hysterectomy after chemoradiation therapy is associated with a high complication rate and the percentage residual disease in adjuvant hysterectomy specimen is unknown. Therefore, the aim of our systematic review was to determine the percentage of residual disease in the adjuvant hysterectomy specimen. Furthermore, we want to determine if there is an association between the time of adjuvant hysterectomy and the percentage residual disease in adjuvant hysterectomy specimens. Findings from this research provide insight into potential complications, survival benefits, and an overtreatment rate. Patients need to be well informed before considering an adjuvant hysterectomy. Abstract Objective: To determine the incidence of pathology-proven residual disease in adjuvant hysterectomy specimens in patients with cervical cancer, treated with chemoradiation therapy. Secondly, to assess a possible association for pathology-proven residual disease regarding the time between chemoradiation therapy and adjuvant hysterectomy. Additionally, the survival rate and complication rate were assessed. Methods: PubMed, EMBASE, and the Cochrane database were searched from inception up to 8 March 2021. Results: Of the 4601 screened articles, eleven studies were included. A total of 1205 patients were treated with chemoradiation therapy and adjuvant hysterectomy, ranging from three to twelve weeks after chemoradiation therapy. A total of 411 out of 1205 patients (34%) had pathology-proven residual disease in the adjuvant hysterectomy specimen. There was no association found in the time between chemoradiation therapy and adjuvant hysterectomy. Follow-up ranged from 2.4 to 245 months, during which 270 patients (22%) relapsed, and 298 patients (27%) were deceased. A total of 202 (35%) complications were registered in 578 patients. Conclusion: there is no association found in the time between chemoradiation therapy and residual disease on adjuvant hysterectomy specimens. The survival rates after chemoradiation therapy and adjuvant hysterectomy are suboptimal, while the risk of complications after adjuvant hysterectomy is high.

Objective: Cervical cancer with ≤5 mm depth of invasion and >7 mm horizontal spread is classified FIGO IA instead of FIGO IB in the revised staging system, as horizontal spread is no longer considered. We aimed to determine the incidence of lymph node metastasis (LNM) and, consequently, the necessity of pelvic lymph node assessment. Methods: Patients diagnosed between January 2015 and May 2019 with cervical cancer FIGO (2009) stage IB with ≤5 mm depth of invasion and >7 mm horizontal spread, were identified from the Netherlands Cancer Registry. Associations between disease-characteristics and lymph node metastasis (LNM), and overall survival, were assessed. Results: Of 170 patients, six (3.5%) had LNM: 4/53 (7.6%) with adenocarcinoma and 2/117 (1.7%) with squamous cell carcinoma (p =.077). Four-year overall survival was 98.2%. LNM was observed more often in tumours with LVSI (4/43 patients, 9.3%) than without LVSI (2/117 patients, 1.7%) (p =.045). In adenocarcinoma with 3–5 mm depth of invasion LNM rate was 10% (4/40). None of the following tumours were observed with LNM: squamous cell carcinoma without LVSI (0/74); adenocarcinoma with

Item does not contain fulltext INTRODUCTION: There is currently no standard of care for women with cervical cancer stage IB2 (FIGO 2018, >/=2 cm and

The advances of mechatronic system design and system integration have shown improvements in functionality, performance and energy efficiency in many applications across industries, from autonomous ground vehicles and drones to conveyor belts. This trend has been adopted in some industries more than others. The design of equipment to handle granular or bulk material is commonly based on traditional approaches. Therefore, introducing mechatronic concepts in the design procedure can enable new possibilities, such as sensor integration and data analyses, adaptability and control. The efficiency of bulk material handling equipment in ports, agriculture and food processing is heavily influenced by the operational conditions. Typically, a piece of equipment is designed for defined operational conditions when the maximum performance can be achieved. In this work the concept of adaptability to varying operational conditions is explored by understanding the technologies implemented in other industries and the feasibility to be implemented in the bulk handling equipment design. Sensing technology, actuation and adaptability are systematically presented in this work to support the design process of the next generation of bulk handling equipment. This will pave the way for incorporating the technological trends in the design, such as: sustainability, “smartness”, Internet of Things, Industry 4.0, digital twin and machine learning. Adaptive mechatronic solutions will play a crucial role in generating and implementing innovative sustainable solutions for bulk handling equipment.

Introduction There is currently no standard of care for women with cervical cancer stage IB2 (FIGO 2019, diameter 2–4 cm) who wish to preserve their fertility. Generally, two approaches are offered. Option 1: neoadjuvant platinum-based chemotherapy (NACT) to reduce the tumor size to ≤ 2 cm, followed by Vaginal Radical Trachelectomy (VRT) with Pelvic Lymph Node Dissection (PLND) either before chemotherapy or at the time of VRT. Option 2: Abdominal Radical Trachelectomy (ART) with PLND. Objective To compare rates of fertility, pregnancy, life births as well as recurrence for women with cervical cancer stage IB2 treated with either NACT followed by VRT, or ART. Methods A systematic review was performed using the PubMed database. Articles reporting the search term ‘trachelectomy’ as text word or as Medical Subject Headings (MeSH) were identified. Results Ten studies were identified with a total of 338 patients. After NACT followed by VRT 39% of the women tried to conceive, 70% of these women got pregnant, of which 63% resulted in a life birth. The overall recurrence and death rate were 10% and 2.9% respectively. After ART 40% of the women tried to conceive, 21% of these women got pregnant, which resulted in a life birth rate of 42%. Recurrence and death rate after ART were 6.9%, and 3.4% respectively. Conclusion Women with cervical cancer stage IB2 and a wish to preserve fertility treated with NACT followed by VRT have a significantly higher chance of pregnancy than women treated with ART, with comparative oncological results.

Robots have the potential to support care and independence of older adults. The ENRICHME project is developing an integrated system composed of a robot, sensors and a networking care platform, aiming at assisting older adults with MCI in their home environment. This paper reports findings of the tests performed on a sample of MCI users and their caregivers, with the first version of the ENRICHME system, in a controlled environment.

The main goal of this study was to assess the potential of the mouse thymoma EL-4 cell line in screening for chemical induced immunotoxicity. Therefore, EL-4 cells were exposed to two well-known immunotoxicants, organotin compound tributyltin oxide (TBTO, 0.5 and 1 mu M for 3 or 6 h) and the mycotoxin deoxynivalenol (DON, 0.25, 0.5 and 1 mu M for 3, 6 or 11 h). Previous studies in human Jurkat T cells and mouse thymus in vivo showed that the primary mode of action of TBTO is induction of endoplasmic reticulum (ER) stress, T cell activation and apoptosis. DON induces ribotoxic stress and, similarly to TBTO, induces ER stress, T cell activation and apoptosis. In the present study, the effects of TBTO and DON on EL-4 mRNA expression were assessed by whole genome microarray analysis. The microarray data were then compared to those obtained with mouse thymuses in vivo, mouse thymocytes in vitro, and CTLL-2 cells and human Jurkat cells in vitro exposed to TBTO or DON. Analysis at the level of gene sets revealed that part of the previously detected modes of action of TBTO and DON were not observed in the EL-4 cell line. In EL-4 cells, TBTO induced genes involved in calcium signalling and ER stress but did not induce genes involved in T cell activation and apoptosis. DON induced RNA related processes and ribosome biogenesis. Furthermore, DON downregulated ER stress, T cell activation and apoptosis which is opposite to the mechanism of DON observed in the mouse thymus in vivo and in Jurkat T cells in vitro. Apparently, EL-4 cells lack factors that are necessary to link ribotoxic stress to ER stress. In addition, of the lack of T cell activation response of EL-4 cells to TBTO is likely due to the fact that these cells are in a constitutively activated state already. Based on the results obtained for TBTO and DON, it can be concluded that the EL-4 cell line has limited value for immunotoxicogenomics based screening.

The biocide bis(tri-n-butyltin)oxide (TBTO) causes thymus atrophy in rodents and is toxic to many cell types of which thymocytes are the most sensitive. To obtain insight in the mechanisms of action of TBTO, we exposed primary mouse thymocytes in vitro for 3, Band 11 h to 0.1, 0.5, 1 and 2 mu M TBTO. Subsequently, the cells were subjected to whole-genome gene expression profiling. Biological interpretation of the gene expression data revealed that TBTO affects a wide range of processes. Cell proliferation related genes were downregulated by all treatments except for 3 and 6 h 0.5 mu M TBTO which upregulated these genes. Treatment with TBTO resulted in upregulation of genes involved in endoplasmatic reticulum (ER) stress, NFkB and TNF alpha pathways, and genes involved in DNA damage, p53 signaling and apoptosis. Remarkably, TBTO also increased the expression of genes that are known to be upregulated during T cell activation or during negative selection of thymocytes. The effect of TBTO on expression of genes involved in ER stress and apoptosis was confirmed by qPCR. Induction of the T cell activation response was corroborated by demonstrating that TBTO exposure resulted in translocation of NFAT to the nucleus, which is an essential event for T cell activation.

This paper aims to explore the transnational aspects that have influenced ideological and organizational changes of Islam within Malawi. It is impossible to review these changes from an isolated position, like the national context. In order to truly understand the reasons and elements of change, the national situation of Islamic reformation in Malawi has to be placed within the context of worldwide Islamic reformation. Changes within the transnational arena have affected and influenced financial, social, political, ideological and cultural processes and organization in local situations. This paper presents an analysis of the Muslim community in Malawi beginning from a historical perspective working towards the economical, social and political situation of Muslims in Malawi today. It focuses on the transnational influences that have affected these changes in religious and social identification of a small group of reformist Muslims in Malawi.

The effect of adding steam (at 0·6 and 1·2 bar) and water (1·9% and 64% of the flux of soy grits) in a conventional barrel type conditioner and its effects on protein dispersibility index (PDI), nitrogen solubility in 0·2% KOH and trypsin inhibitor activity (TIA) of commercial soy grits was studied. In addition, conditioned soy grits were subjected to expander treatment at two different screw speeds (2 and 3 rps) and PDI, NSI and TIA were measured. Analysis of variance was used to determine the effects of steam pressure, water addition and screw speed on the mentioned protein quality parameters. In addition, resultant temperature from steam addition was used in an analysis of covariance to determine the effects of temperature as a covariate, water addition and screw speed on protein quality parameters. A significant interaction for steam pressure and water addition was found on all parameters. The highest denaturation or inactivation of the protein was found at the combination incorporating high steam and high water addition. Screw speed during expander treatment did not significantly affect protein quality parameters. It was concluded both from this study and from literature that PDI is a better parameter to evaluate technological treatments when low amounts of motor power are dissipated (

Deoxynivalenol (DON) is a mycotoxin produced by several Fusarium species and is often detected in grains. Because of its high abundance, there has been a large interest in the effects of DON in animals and humans. DON is known to be immunosuppressive at high concentrations and immunostimulatory at low concentrations. The present study aimed to acquire insight into the modes of action of DON. For this, C57Bl6 mice were orally exposed to 5, 10, or 25mg/kg bw DON for 3, 6, or 24h and thymuses were subjected to genome-wide expression microarray analysis. Gene set enrichment analysis (GSEA) demonstrated that DON downregulated genes involved in proliferation, mitochondria, protein synthesis, and ribosomal proteins. Furthermore, GSEA showed a selective downregulation of genes highly expressed at the early precursor thymocytes stage. This indicates that early precursor thymocytes, particularly at the double-positive CD4+CD8+ stage, are more vulnerable to DON than very early or late precursor thymocytes. There was a large overlap of genes upregulated by DON with genes previously reported to be either upregulated during T cell activation or upregulated during negative selection of thymocytes that recognize “self-antigens”. This indicates that DON induces cellular events that also occur after activation of the T cell receptor, for example, release of calcium from the endoplasmatic reticulum. This T cell activation in the thymus then evokes negative selection and depletion of thymocytes, which provides a plausible explanation for the high sensitivity of the thymus for DON exposure. The expression patterns of four genes indicative for some of the processes that were affected after DON treatment were confirmed using real-time PCR. Immunocytological experiments with primary mouse thymocytes demonstrated the translocation of NFAT from the cytoplasm into the nucleus upon exposure top DON, thus providing further evidence for the involvement of T cell activation.

Here, we report the results of proteomic analysis of the mouse thymoma EL4 cell line exposed to bis(tri-n-butylin)oxide (TBTO), an immunotoxic organotin compound. The objective of the work was to examine whether TBTO affects the expression of proteins in this cell line and to compare the differentially expressed proteins with the corresponding mRNA expression data. The identified proteins were quantified using a label-free quantitative method based on counting the observed peptides as an index of protein abundance. The calculation of the ratio of peptides obtained from exposed and control samples allowed us to evaluate the effect of TBTO on protein expression and to compare these results to those obtained in gene expression profiling studies. Correlation of some of the differentially expressed proteins and their corresponding mRNAs was observed. The analysis of the protein ratios revealed that 12 proteins were significantly affected. These proteins included cytoskeleton proteins myosin-9, spectrin beta 2 and plectin 8. The first two proteins were down-regulated 3-fold, whereas the third was up-regulated 2-fold. Ras-related Rab1, a GTP binding protein and T-complex protein-1 subunit alpha, a chaperonin, were decreased 2- and 3.6-fold, respectively. The ribosomal S10 and eukaryotic translation factor (eIf4G1), which are involved in protein synthesis, were down-regulated 2.6- and 3.7-fold, respectively. Also, proteins involved in splicing of pre-mRNA and in transcription, splicing factor arginine/serine-rich 2 and chromodomain-helicase-DNA binding protein 4 (Chd4), were decreased 2.6- and 4.5 times, respectively. Nuclear RNA helicase II was reduced 2.8-fold. Finally, prothymosin-alpha (ProTalpha), an essential protein for cell proliferation, and a protein similar to ProTalpha, (with a molecular weight and a pI (3.54) comparable to that of ProTalpha) were also down-regulated 6-and 8-fold, respectively. We propose that the observed down-regulation of the expression level of ProTalpha in the TBTO-exposed cells could account for the previously reported anti-proliferative effect of TBTO.

Here, we report the results of proteomic analysis of the mouse thymoma EL4 cell line exposed to bis(tri-n-butylin)oxide (TBTO), an immunotoxic organotin compound. The objective of the work was to examine whether TBTO affects the expression of proteins in this cell line and to compare the differentially expressed proteins with the corresponding mRNA expression data. The identified proteins were quantified using a label-free quantitative method based on counting the observed peptides as an index of protein abundance. The calculation of the ratio of peptides obtained from exposed and control samples allowed us to evaluate the effect of TBTO on protein expression and to compare these results to those obtained in gene expression profiling studies. Correlation of some of the differentially expressed proteins and their corresponding mRNAs was observed. The analysis of the protein ratios revealed that 12 proteins were significantly affected. These proteins included cytoskeleton proteins myosin-9, spectrin beta 2 and plectin 8. The first two proteins were down-regulated 3-fold, whereas the third was up-regulated 2-fold. Ras-related Rab1, a GTP binding protein and T-complex protein-1 subunit alpha, a chaperonin, were decreased 2- and 3.6-fold, respectively. The ribosomal S10 and eukaryotic translation factor (eIf4G1), which are involved in protein synthesis, were down-regulated 2.6- and 3.7-fold, respectively. Also, proteins involved in splicing of pre-mRNA and in transcription, splicing factor arginine/serine-rich 2 and chromodomain-helicase-DNA binding protein 4 (Chd4), were decreased 2.6- and 4.5 times, respectively. Nuclear RNA helicase II was reduced 2.8-fold. Finally, prothymosin-alpha (ProTalpha), an essential protein for cell proliferation, and a protein similar to ProTalpha, (with a molecular weight and a pI (3.54) comparable to that of ProTalpha) were also down-regulated 6-and 8-fold, respectively. We propose that the observed down-regulation of the expression level of ProTalpha in the TBTO-exposed cells could account for the previously reported anti-proliferative effect of TBTO.

Outer membranes were prepared from whole cells of various strains of Actinobacillus actinomycetemcomitans and analysed by SDS-polyacrylamide gel (12.5%) electrophoresis (SDS-PAGE). In all strains four common major outer membrane proteins (OMPs) with molecular masses of 30, 34, 36 and 39 kDa could be distinguished. Heating the OMP preparation of strain Y4 at 60, 70, 90 and 100 degrees C produced a band of 30 kDa, which gradually lost its intensity from 70 degrees C onwards concomitantly with the development of two new protein bands of 34 and 36 kDa. Furthermore, the 36 kDa OMP appeared susceptible to proteolysis by trypsin; degraded products apparently produced a new electrophoretic band of 27 kDa. Y4-derived OMP fractions were solubilized with a Triton-SDS mixture to investigate the presence of peptidoglycan-associated proteins. The 39 kDa OMP was found to be peptidoglycan-associated.

The effect of the inoculation dose on the development of antibodies as measured by the indirect fluorescent antibody (IFA) test against E. maxima and E. acervulina was studied in two experiments in each of which six groups of six chickens each were inoculated with varying numbers of oocysts. The IFA titres reached their maximum 2 weeks after inoculation. The response was dose related for both species. This response was more pronounced in the infections with E. acervulina than in those with E. maxima , reflecting a difference in immunogenicity. Reinoculation with E. maxima indicated that the birds were immune and resulted in a rise of the titres. The maximum IFA titres obtained during the primary infection were never reached by reinfection. The titres decreased gradually during the 7 weeks following reinoculation. Reinoculation with E. acervulnia resulted in higher titres than those obtained during the first infection.

Two outbreaks of dropped egg production and production of soft shelled and shell-less eggs are described. The outbreaks were selected from a larger number of flocks with similar problems in the field. The drop in egg production was closely correlated with the appearance of precipitins to adenovirus in the laying birds. Birds were also infected with Mycoplasma synoviae. A number of other infectious causes of production problems could be excluded in these outbreaks. In particular infectious bronchitis was not a factor and, in contrast to experiences following infections with this virus, production recovered nearly completely within 6 to 10 weeks. The observations suggest that in the field infections with adenovirus may cause production problems as serious as those caused by infectious bronchitis virus.

A syndrome of stunting and leg weakness could be reproduced experimentally by inoculation of 1-day-old broilers with homogenised intestines from affected birds. Inoculated birds kept in isolators showed highly impaired growth until 3 weeks p.i. Birds produced mucoid yellowish coloured droppings and at post mortem thin liquid intestinal contents were found. Biochemical examination of blood plasma showed low plasma carotenoid concentrations and an increased alkaline phosphatase (ALP) activity, mainly caused by one isoenzyme, which was most likely of intestinal origin. These findings implicate infectious causal agents with the intestines as the site of primary involvement. Bone abnormalities consisted of rickets-like changes at the age of 3 weeks, whereas a distinct dyschondroplasia was seen at 4 weeks. The syndrome could also be transmitted to uninoculated birds kept in contact with birds inoculated at 1 day of age. Birds inoculated at 7 days of age also showed greatly impaired growth but developed no macroscopical bone disorders. Inoculation at 14 days of age did not result in impaired growth or bone abnormalities. Following inoculation with REO virus, isolated from a field case, no bone abnormalities occurred. However, a shortlived impaired growth, diarrhoea, increased plasma ALP activity and decreased carotenoid concentration were observed. The rapid spread of the disease and the role of REO virus are discussed.