scholarly journals Establishment and Characterisation of Heterotopic Patient-Derived Xenografts for Glioblastoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 871 ◽  
Author(s):  
Sarah Meneceur ◽  
Annett Linge ◽  
Matthias Meinhardt ◽  
Sandra Hering ◽  
Steffen Löck ◽  
...  

Glioblastoma is an aggressive brain tumour with a patient median survival of approximately 14 months. The development of innovative treatment strategies to increase the life span and quality of life of patients is hence essential. This requires the use of appropriate glioblastoma models for preclinical testing, which faithfully reflect human cancers. The aim of this study was to establish glioblastoma patient-derived xenografts (PDXs) by heterotopic transplantation of tumour pieces in the axillae of NMRI nude mice. Ten out of 22 patients’ samples gave rise to tumours in mice. Their human origin was confirmed by microsatellite analyses, though minor changes were observed. The glioblastoma nature of the PDXs was corroborated by pathological evaluation. Latency times spanned from 48.5 to 370.5 days in the first generation. Growth curve analyses revealed an increase in the growth rate with increasing passages. The methylation status of the MGMT promoter in the primary material was maintained in the PDXs. However, a trend towards a more methylated pattern could be found. A correlation was observed between the take in mice and the proportion of Sox2+ cells (r = 0.49, p = 0.016) and nestin+ cells (r = 0.55, p = 0.007). Our results show that many PDXs maintain key features of the patients’ samples they derive from. They could thus be used as preclinical models to test new therapies and biomarkers.

Author(s):  
Falaq Naz ◽  
Yasir Hasan Siddique

: Neurodegenerative diseases including Alzheimer’s, Parkinson’s and Huntington disease are have serious concern due to its effect on the quality of life of affected persons. Neurodegenerative diseases have some limitations for both diagnostic as well as at treatment level. Introducing nanotechnology, for the treatment of these diseases may contribute significantly in solving the problem. There are several treatment strategies for the neurodegenerative diseases, but their limitations are the entry into the due to the presence of the blood-brain barrier (BBB). The present review highlights the application of nanotechnology during last 20 years for the treatment of neurodegenerative diseases.


2020 ◽  
Author(s):  
Almira Osmanovic Thunström ◽  
Iris Sarajlic Vuković ◽  
Lilas Ali ◽  
Tomas Larson ◽  
Steinn Steingrimsson

BACKGROUND Immersive virtual reality (VR) games are increasingly becoming part of everyday life. Several studies support immersive VR technology as a treatment method for mental health problems. There is however minimal research into the feasibility, prevalence, and quality of commercially available VR games on commercial platforms as tools for treatment or add on to treatment of mental health problems. OBJECTIVE The aim of this study was to explore the prevalence, feasibility and quality of commercially available games related to psychotherapy on a commercially available platform. METHODS We performed a search for keywords related to diagnosis and treatment strategies of mental health problems. The search was performed during March 27th on STEAM (VR content and gaming platform). A usability scale was used as a tool to look at the interaction and usability of the games, the VR-UI-UX-8. The tool contains 8 statements about usability scored 0-10, 0 indicating “Not at all” and 10 indicating “very much so”. The score ranges from 0-80 with a higher score indicating worse usability. RESULTS In total, 516 hits were found, 371 unique games. After the games were reviewed, 83 games passed the inclusion criteria, were purchased and played. Majority of the games which were excluded were either not connected to mental health, contained violence, adult content or were in other ways irrelevant or inappropriate. The mean score for the games on the VR-UI-UX-8 was 16.5 (standard deviation 15.8) with a range from 0-68. Most relevant and feasible games were found in the search words meditation, mindfulness, and LSD. CONCLUSIONS Commercial platforms hold great potential for VR games with psychotherapeutic components. The platforms are only at the beginning of the development towards serious games, e-learning and psychotherapeutic treatments. Currently the quality and usability for clinical and at home applicability are scarce, but hold great potential.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
T. Dolev ◽  
S. Zubedat ◽  
Z. Brand ◽  
B. Bloch ◽  
E. Mader ◽  
...  

AbstractLack of established knowledge and treatment strategies, and change in work environment, may altogether critically affect the mental health and functioning of physicians treating COVID-19 patients. Thus, we examined whether treating COVID-19 patients affect the physicians’ mental health differently compared with physicians treating non-COVID-19 patients. In this cohort study, an association was blindly computed between physiologically measured anxiety and attention vigilance (collected from 1 May 2014 to 31 May 31 2016) and self-reports of anxiety, mental health aspects, and sleep quality (collected from 20 April to 30 June 2020, and analyzed from 1 July to 1 September 2020), of 91 physicians treating COVID-19 or non-COVID-19 patients. As a priori hypothesized, physicians treating COVID-19 patients showed a relative elevation in both physiological measures of anxiety (95% CI: 2317.69–2453.44 versus 1982.32–2068.46; P < 0.001) and attention vigilance (95% CI: 29.85–34.97 versus 22.84–26.61; P < 0.001), compared with their colleagues treating non-COVID-19 patients. At least 3 months into the pandemic, physicians treating COVID-19 patients reported high anxiety and low quality of sleep. Machine learning showed clustering to the COVID-19 and non-COVID-19 subgroups with a high correlation mainly between physiological and self-reported anxiety, and between physiologically measured anxiety and sleep duration. To conclude, the pattern of attention vigilance, heightened anxiety, and reduced sleep quality findings point the need for mental intervention aimed at those physicians susceptible to develop post-traumatic stress symptoms, owing to the consequences of fighting at the forefront of the COVID-19 pandemic.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wenxiao Jia ◽  
Qianqian Gao ◽  
Min Wang ◽  
Ji Li ◽  
Wang Jing ◽  
...  

Abstract Background The exact rate and relevant risk factors of radiation pneumonitis (RP) for non-small-cell cancer (NSCLC) patients treated with the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and thoracic radiotherapy have not been reported. Thus, this study aimed to investigate the rate and risk factors of RP for EGFR-positive NSCLC patients simultaneously treated with first-generation EGFR-TKI and TRT. Patients and methods We retrospectively evaluated NSCLC patients simultaneously treated with first-generation EGFR-TKI and thoracic radiotherapy between January 2012 and December 2019 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed via computed tomography and was classified according to the Common Terminology Criteria for Adverse Events v5.0. The risk factors of RP were identified using uni- and multivariate analyses. Results Of the 67 patients included, 44.78% (30/67) developed grade ≥ 2 RP. Grade ≥ 2 RP occurred within a median of 3.48 (range 1.07–13.6) months. The EGFR-TKI icotinib, ipsilateral lung V30 > 34%, and overlap time of > 20 days between EGFR-TKI and thoracic radiotherapy were identified to be independent predictive factors of grade ≥ 2 RP. Conclusions Grade ≥ 2 RP is highly frequent in NSCLC patients simultaneous treated with first-generation EGFR-TKI and thoracic radiotherapy. Icotinib, ipsilateral lung V30 ≤ 34%, and overlap time of ≤ 20 days for EGFR-TKI and thoracic radiotherapy will be helpful to lower the risk of RP in these patients. The addition of thoracic radiotherapy should be cautious, and the treatment strategies can be optimized to reduce the rate of RP for patients treat with simultaneous EGFR-TKI and thoracic radiotherapy.


2021 ◽  
Vol 8 ◽  
pp. 237437352110073
Author(s):  
Richard M Elias ◽  
Karen M Fischer ◽  
Mustaqeem A Siddiqui ◽  
Trevor Coons ◽  
Cindy A Meyerhofer ◽  
...  

Previous studies show that patient complaints can identify gaps in quality of care, but it is difficult to identify trends without categorization. We conducted a review of complaints relating to admissions on hospital internal medicine (HIM) services over a 26-month period. Data were collected on person characteristics and key features of the complaint. The complaints were also categorized into a previously published taxonomy. Seventy-six unsolicited complaints were identified, (3.5 per 1000 hospital admissions). Complaints were more likely on resident services. The mean duration between encounter and complaint was 18 days, and it took an average of 12 days to resolve the complaint. Most patients (59%) had a complaint in the Relationship domain. Thirty-nine percent of complaints mentioned a specific clinician. When a clinician was mentioned, complaints regarding communication and humaneness predominated (68%). The results indicate that the efforts to reduce patient complaints in HIM should focus on the Relationships domain.


2021 ◽  
pp. 239698732110141
Author(s):  
H Bart van der Worp ◽  
Jeannette Hofmeijer ◽  
Eric Jüttler ◽  
Avtar Lal ◽  
Patrik Michel ◽  
...  

Space-occupying brain oedema is a potentially life-threatening complication in the first days after large hemispheric or cerebellar infarction. Several treatment strategies for this complication are available, but the size and quality of the scientific evidence on which these strategies are based vary considerably. The aim of this Guideline document is to assist physicians in their management decisions when treating patients with space-occupying hemispheric or cerebellar infarction. These Guidelines were developed based on the European Stroke Organisation (ESO) standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. A working group identified 13 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. An expert consensus statement was provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high-quality evidence to recommend surgical decompression to reduce the risk of death and to increase the chance of a favourable outcome in adult patients aged up to and including 60 years with space-occupying hemispheric infarction who can be treated within 48 hours of stroke onset, and low-quality evidence to support this treatment in older patients. There is continued uncertainty about the benefit and risks of surgical decompression in patients with space-occupying hemispheric infarction if this is done after the first 48 hours. There is also continued uncertainty about the selection of patients with space-occupying cerebellar infarction for surgical decompression or drainage of cerebrospinal fluid. These Guidelines further provide details on the management of specific subgroups of patients with space-occupying hemispheric infarction, on the value of monitoring of intracranial pressure, and on the benefits and risks of medical treatment options. We encourage new high-quality studies assessing the risks and benefits of different treatment strategies for patients with space-occupying brain infarction.


2021 ◽  
Vol 6 (2) ◽  
pp. 91
Author(s):  
Pier Francesco Indelli ◽  
Stefano Ghirardelli ◽  
Ferdinando Iannotti ◽  
Alessia Maria Indelli ◽  
Gennaro Pipino

Background: Periprosthetic joint infection (PJI) represents a devastating consequence of total joint arthroplasty (TJA) because of its high morbidity and its high impact on patient quality of life. The lack of standardized preventive and treatment strategies is a major challenge for arthroplasty surgeons. The purpose of this article was to explore the potential and future uses of nanotechnology as a tool for the prevention and treatment of PJI. Methods: Multiple review articles from the PubMed, Scopus and Google Scholar databases were reviewed in order to establish the current efficacy of nanotechnology in PJI preventive or therapeutic scenarios. Results: As a prevention tool, anti-biofilm implants equipped with nanoparticles (silver, silk fibroin, poly nanofibers, nanophase selenium) have shown promising antibacterial functionality. As a therapeutic tool, drug-loaded nanomolecules have been created and a wide variety of carrier materials (chitosan, titanium, calcium phosphate) have shown precise drug targeting and efficient control of drug release. Other nanotechnology-based antibiotic carriers (lipid nanoparticles, silica, clay nanotubes), when added to common bone cements, enhanced prolonged drug delivery, making this technology promising for the creation of antibiotic-added cement joint spacers. Conclusion: Although still in its infancy, nanotechnology has the potential to revolutionize prevention and treatment protocols of PJI. Nevertheless, extensive basic science and clinical research will be needed to investigate the potential toxicities of nanoparticles.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Michelle Murphy ◽  
Julian G. Mercer

A substantial proportion of noncommunicable disease originates in habitual overconsumption of calories, which can lead to weight gain and obesity and attendant comorbidities. At the other end of the spectrum, the consequences of undernutrition in early life and at different stages of adult life can also have major impact on wellbeing and quality of life. To help address some of these issues, greater understanding is required of interactions with food and contemporary diets throughout the life course and at a number of different levels: physiological, metabolic, psychological, and emotional. Here we review the current literature on the effects of dietary manipulation on anxiety-like behaviour. This evidence, assembled from study of preclinical models of diet challenge from gestation to adult life, supports a role for diet in the important connections between psychology, physiology, and behaviour. Analogous processes in the human population in our current obesogenic environment are likely to contribute to individual and societal challenges in this area.


2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Kazunori Omote ◽  
Frederik H. Verbrugge ◽  
Barry A. Borlaug

Approximately half of all patients with heart failure (HF) have a preserved ejection fraction, and the prevalence is growing rapidly given the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. Functional capacity and quality of life are severely impaired in heart failure with preserved ejection fraction (HFpEF), and morbidity and mortality are high. In striking contrast to HF with reduced ejection fraction, there are few effective treatments currently identified for HFpEF, and these are limited to decongestion by diuretics, promotion of a healthy active lifestyle, and management of comorbidities. Improved phenotyping of subgroups within the overall HFpEF population might enhance individualization of treatment. This review focuses on the current understanding of the pathophysiologic mechanisms underlying HFpEF and treatment strategies for this complex syndrome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2021 ◽  
Vol 79 (9) ◽  
pp. 799-807
Author(s):  
Sehnaz Basaran ◽  
Halil İbrahim Tas

ABSTRACT Background: Investigating predictive factors of reduced quality of life (QOL) of patients and their association with focal epilepsy can improve management and treatment strategies. Objective: This study aimed to investigate the relationship between affective temperaments, depression, anxiety, disease characteristics, and QOL and to explore the predictors of QOL in patients with temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). Methods: A total of 50 patients with TLE, 51 patients with ETLE, and 70 controls were enrolled. Affective temperaments were evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A). QOL was assessed by the Short-Form Health Survey (SF-36). Beck Depression Inventory and Beck Anxiety Inventory were used to explore depression and anxiety severity, respectively. Results: Compared with the controls, patients with TLE and ETLE had significantly higher scores on all TEMPS-A scales, except on hyperthymic temperament. All the SF-36 subscale scores were lower in the TLE and ETLE groups. Linear regression analysis revealed that depressive symptoms, anxiety, depressive and irritable temperament, and seizure frequency were significant predictors of QOL in TLE. Patients with ETLE with temperamental disturbances, depressive symptoms, and polytherapy had a poorer QOL. Conclusions: Affective temperaments, psychiatric disorders, and clinical factors may predict impaired QOL in patients with TLE and ETLE. Further studies are needed to identify predictors of QOL in various epilepsy subtypes.


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