164 research outputs found
The Anatomy of Job Satisfaction and the Role of Contingent Employment Contracts
In this paper I analyse job satisfaction using fixed effect analysis and a multiple equation model. Overall job satisfaction is analysed as an aggregate of satisfaction with several job aspects. I find that overall job satisfaction is mainly determined by satisfaction with job content. All aspect satisfactions are subsequently explained from observed characteristics, with special focus on contingent employment contracts. Satisfaction with job security is the aspect satisfaction with the strongest relation to type of contract. Since this is also the aspect that receives least weight in overall job satisfaction this has little impact on workers' total happiness. More influential is the low satisfaction with job content due to agency work. Overall, temporary agency work leads to the lowest job satisfaction. On-call work and fixed-term work arrangements do not differ from regular work in overall job satisfaction they provide, even though they do lead to highe! r or lower satisfaction with some aspects of the job
Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts
Background:
A subset of human hepatocellular carcinomas (HCC) exhibit mutations of β-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L-sulfoximine (MSO).
Methods:
Immunodeficient mice with subcutaneous xenografts of the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with Crisantaspase and/or MSO, and tumour growth was monitored. At the end of treatment, tumour weight and histology were assessed. Serum and tissue amino acids were determined by HPLC. Gene and protein expression were estimated with RT-PCR and western blot and GS activity with a colorimetric method. mTOR activity was evaluated from the phosphorylation of p70S6K1.
Results:
Crisantaspase and MSO depleted serum glutamine, lowered glutamine in liver and tumour tissue, and inhibited liver GS activity. HepG2 tumour growth was significantly reduced by either Crisantaspase or MSO, and completely suppressed by the combined treatment. The combined treatment was also effective against xenografts of the HC-AFW1 cell line, which is Crisantaspase resistant in vitro.
Conclusions:
The combination of Crisantaspase and MSO reduces glutamine supply to CTNNB1-mutated HCC xenografts and hinders their growth
FoxQ1 Overexpression Influences Poor Prognosis in Non-Small Cell Lung Cancer, Associates with the Phenomenon of EMT
BACKGROUND: We determined the expression of forkhead box Q1 (FoxQ1), E-cadherin (E-cad), Mucin 1 (MUC1), vimentin (VIM) and S100 calcium binding protein A4 (S100A4), all epithelial-mesenchymal transition (EMT) indicator proteins in non-small cell lung cancer (NSCLC) tissue samples. We also investigated the relationship between these five proteins expression and other clinicopathologic factors in NSCLC. Finally, we assessed the potential value of these markers as prognostic indicators of survival in NSCLC's patients. METHODS: Quantitative real-time PCR and immunohistochemistry were used to characterize the expression of the FoxQ1 mRNA and protein in NSCLC. Expression of transcripts and translated products for the other four EMT indicator proteins was assessed by immunohistochemistry in the same clinical NSCLC samples. RESULTS: FoxQ1 mRNA and protein were up-regulated in NSCLC compared with normal tissues (P = 0.015 and P<0.001, respectively). Expression of FoxQ1 in adenocarcinoma was higher than in squamous cell carcinoma (P = 0.005), and high expression of FoxQ1 correlated with loss of E-cad expression (P = 0.012), and anomalous positivity of VIM (P = 0.024) and S100A4 (P = 0.004). Additional survival analysis showed that high expression of FoxQ1 (P = 0.047) and E-cad (P = 0.021) were independent prognostic factors. CONCLUSION: FoxQ1 maybe plays a specific role in the EMT of NSCLC, and could be used as a prognostic factor for NSCLC
What scans we will read: imaging instrumentation trends in clinical oncology
Oncological diseases account for a significant portion of the burden on public healthcare systems with associated
costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific
morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non-
invasively, so as to provide referring oncologists with essential information to support therapy management
decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards
integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/
CT), advanced MRI, optical or ultrasound imaging.
This perspective paper highlights a number of key technological and methodological advances in imaging
instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as
the hardware-based combination of complementary anatomical and molecular imaging. These include novel
detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system
developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing
methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging
in oncology patient management we introduce imaging methods with well-defined clinical applications and
potential for clinical translation. For each modality, we report first on the status quo and point to perceived
technological and methodological advances in a subsequent status go section. Considering the breadth and
dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the
majority of them being imaging experts with a background in physics and engineering, believe imaging methods
will be in a few years from now.
Overall, methodological and technological medical imaging advances are geared towards increased image contrast,
the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall
examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is
complemented by progress in relevant acquisition and image-processing protocols and improved data analysis. To
this end, we should accept diagnostic images as “data”, and – through the wider adoption of advanced analysis,
including machine learning approaches and a “big data” concept – move to the next stage of non-invasive tumor
phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi-
dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and
analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts
with a domain knowledge that will need to go beyond that of plain imaging
Anterolateral Ligament Expert Group consensus paper on the management of internal rotation and instability of the anterior cruciate ligament - deficient knee
Purpose of this paper is to provide an overview of the latest research on the anterolateral ligament (ALL) and present the consensus of the ALL Expert Group on the anatomy, radiographic landmarks, biomechanics, clinical and radiographic diagnosis, lesion classification, surgical technique and clinical outcomes. A consensus on controversial subjects surrounding the ALL and anterolateral knee instability has been established based on the opinion of experts, the latest publications on the subject and an exchange of experiences during the ALL Experts Meeting (November 2015, Lyon, France). The ALL is found deep to the iliotibial band. The femoral origin is just posterior and proximal to the lateral epicondyle; the tibial attachment is 21.6 mm posterior to Gerdy's tubercle and 4-10 mm below the tibial joint line. On a lateral radiographic view the femoral origin is located in the postero-inferior quadrant and the tibial attachment is close to the centre of the proximal tibial plateau. Favourable isometry of an ALL reconstruction is seen when the femoral position is proximal and posterior to the lateral epicondyle, with the ALL being tight upon extension and lax upon flexion. The ALL can be visualised on ultrasound, or on T2-weighted coronal MRI scans with proton density fat-suppressed evaluation. The ALL injury is associated with a Segond fracture, and often occurs in conjunction with acute anterior cruciate ligament (ACL) injury. Recognition and repair of the ALL lesions should be considered to improve the control of rotational stability provided by ACL reconstruction. For high-risk patients, a combined ACL and ALL reconstruction improves rotational control and reduces the rate of re-rupture, without increased postoperative complication rates compared to ACL-only reconstruction. In conclusion this paper provides a contemporary consensus on all studied features of the ALL. The findings warrant future research in order to further test these early observations, with the ultimate goal of improving the long-term outcomes of ACL-injured patients. Level of evidence Level V-Expert opinion
Hepatic stellate cells:central modulators of hepatic carcinogenesis
Hepatocellular carcinoma (HCC) represents the second most common cause of cancer-related death worldwide, and is increasing in incidence. Currently, our therapeutic repertoire for the treatment of HCC is severely limited, and therefore effective new therapies are urgently required. Recently, there has been increasing interest focusing on the cellular and molecular interactions between cancer cells and their microenvironment. HCC represents a unique opportunity to study the relationship between a diseased stroma and promotion of carcinogenesis, as 90 % of HCCs arise in a cirrhotic liver. Hepatic stellate cells (HSC) are the major source of extracellular proteins during fibrogenesis, and may directly, or via secreted products, contribute to tumour initiation and progression. In this review we explore the complex cellular and molecular interplay between HSC biology and hepatocarcinogenesis. We focus on the molecular mechanisms by which HSC modulate HCC growth, immune cell evasion and angiogenesis. This is followed by a discussion of recent progress in the field in understanding the mechanistic crosstalk between HSC and HCC, and the pathways that are potentially amenable to therapeutic intervention. Furthermore, we summarise the exciting recent developments in strategies to target HSC specifically, and novel techniques to deliver pharmaceutical agents directly to HSC, potentially allowing tailored, cell-specific therapy for HCC
Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures
Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo
The Rhinoplasty Health Care Monitor:An Update on the Practical and Clinical Benefits after 10 Years of Prospective Outcome Measurements
The era of value-based health care is characterized by an increasing interest in patient-reported health outcomes. For this purpose we developed the rhinoplasty health care monitor (RHM), a streamlined outcome measurement protocol, including all rhinoplasty patients since 2014. Statistical analyses of patient-reported outcome data are automated and visually presented on a custom web-based dashboard. We describe the clinical and practical benefits of the RHM and discuss how routine prospective outcome measurements have upgraded our care standards. For this prospective study, 979 consecutive patients referred for functional (revision) rhinoplasty from April 2014 to August 2023 were included. Preoperative and 3- and 12-month postoperative scores on the Nasal Obstruction Symptom Evaluation scale (NOSE), Utrecht Questionnaire (UQ), and visual analog scales (VAS) were obtained. Of 979 referred patients, 599 (61.2%) were eligible for rhinoplasty. One year postoperatively, mean NOSE scale sum score improved from 69.1 +/- 22.8 to 23.1 +/- 23.5 (p < 0.001). Functional VAS scores improved from 4.1 +/- 2.8 (left) and 4.1 +/- 2.8 (right) to 7.5 +/- 1.9 (left) and 7.3 +/- 2.0 (right; p < 0.001). Mean UQ sum score improved from 12.0 +/- 6.4 to 6.8 +/- 3.3 and aesthetic VAS score improved from 4.5 +/- 2.5 to 7.4 +/- 1.7 (p < 0.001) 1 year postoperatively. Benefits of the outcome routine were improved patient selection, data-driven expectation management and patient empowerment, and targeted critical appraisals of surgical performance. In conclusion, routine, automated, prospective outcome monitoring provides physicians with a response to the increasing demand for data-driven insights in health outcomes. The limited effort that is needed to gather and monitor outcome data is heavily repaid by valuable insights into aspects of care that can be improved
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