scholarly journals Genetic Deletion of Polo-Like Kinase 2 Induces a Pro-Fibrotic Pulmonary Phenotype

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 617
Author(s):  
Theresa A. Kant ◽  
Manja Newe ◽  
Luise Winter ◽  
Maximilian Hoffmann ◽  
Susanne Kämmerer ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Histological Analysis ◽  
Early Stage ◽  
Future Research ◽  
Wall Thickening ◽  
Alveolar Wall ◽  
Myofibroblast Phenotype ◽  
Genetic Deletion ◽  
Healthy Lung Tissue ◽  
Healthy Lung

Pulmonary fibrosis is the chronic-progressive replacement of healthy lung tissue by extracellular matrix, leading to the destruction of the alveolar architecture and ultimately death. Due to limited pathophysiological knowledge, causal therapies are still missing and consequently the prognosis is poor. Thus, there is an urgent clinical need for models to derive effective therapies. Polo-like kinase 2 (PLK2) is an emerging regulator of fibroblast function and fibrosis. We found a significant downregulation of PLK2 in four different entities of human pulmonary fibrosis. Therefore, we characterized the pulmonary phenotype of PLK2 knockout (KO) mice. Isolated pulmonary PLK2 KO fibroblasts displayed a pronounced myofibroblast phenotype reflected by increased expression of αSMA, reduced proliferation rates and enhanced ERK1/2 and SMAD2/3 phosphorylation. In PLK2 KO, the expression of the fibrotic cytokines osteopontin and IL18 was elevated compared to controls. Histological analysis of PLK2 KO lungs revealed early stage remodeling in terms of alveolar wall thickening, increased alveolar collagen deposition and myofibroblast foci. Our results prompt further investigation of PLK2 function in pulmonary fibrosis and suggest that the PLK2 KO model displays a genetic predisposition towards pulmonary fibrosis, which could be leveraged in future research on this topic.

Paraquat-induced pulmonary fibrosis starts at an early stage of inflammation in rats

Immunotherapy ◽  
2012 ◽  
Vol 4 (12) ◽  
pp. 1809-1815 ◽  
Author(s):  
Hui Xie ◽  
Ruilan Wang ◽  
Xue Tang ◽  
Ying Xiong ◽  
Rong Xu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Early Stage

scholarly journals Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 7797
Author(s):  
Joseph A. M. J. L. Janssen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Insulin Secretion ◽  
Early Stage ◽  
Insulin Clearance ◽  
Future Research ◽  
Age Related ◽  
Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

scholarly journals Efficacy of early antifibrotic treatment for idiopathic pulmonary fibrosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keishi Sugino ◽  
Hirotaka Ono ◽  
Natsumi Watanabe ◽  
Masahiro Ando ◽  
Eiyasu Tsuboi ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
Vital Capacity ◽  
Early Stage ◽  
Japanese Patients ◽  
Oxygen Desaturation ◽  
Stage I ◽  
Relative Decline ◽  
Antifibrotic Drugs

Abstract Background Although antifibrotic drugs, including nintedanib and pirfenidone, slow the progression of idiopathic pulmonary fibrosis (IPF), there is little data about the timing of start of antifibrotic treatment in real-world clinical practice. The present study aimed to clarify the efficacy of nintedanib and pirfenidone in patients with early-stage IPF. Methods We compared survival and disease progression between patients with IPF with Japanese Respiratory Society (JRS) disease severity system stage I with and without oxygen desaturation on the 6-min walk test (6MWT) and increased the gender–age–physiology (GAP) staging. We examined the efficacy of antifibrotic drugs in patients with early-stage IPF. Results The severity of stage I IPF (n = 179) according to the JRS criteria consisted of the following GAP staging criteria: stage I, 111 cases; stage II, 58 cases; stage III, 10 cases. The duration from the initial visit to disease progression and survival time was significantly shorter in JRS stage I patients with oxygen desaturation on the 6MWT or with increased GAP staging (unfavorable group) compared with patients without those factors. In the unfavorable group, the relative decline in percentage predicted forced vital capacity (%FVC) over 6 months was significantly lower in patients undergoing antifibrotic treatment compared with non-treated patients. Conclusion Antifibrotic drugs have a beneficial effect on the decline in %FVC in Japanese patients with early-stage IPF who have oxygen desaturation on the 6MWT or increased GAP staging.

scholarly journals Mobile three-dimensional visualisation technologies for clinician-led fall prevention assessments

2017 ◽  
Vol 25 (3) ◽  
pp. 788-810 ◽  
Author(s):  
Julian Hamm ◽  
Arthur G Money ◽  
Anita Atwal ◽  
Gheorghita Ghinea
Keyword(s):  
Early Stage ◽  
Three Dimensional ◽  
Occupational Therapists ◽  
Structured Interview ◽  
Future Research ◽  
Dimensional Measurement ◽  
Fall Risk Factors ◽  
System Usability Scale ◽  
Process Guidance ◽  
Three Dimensional Measurement

The assistive equipment provision process is routinely carried out with patients to mitigate fall risk factors via the fitment of assistive equipment within the home. However, currently, over 50% of assistive equipment is abandoned by the patients due to poor fit between the patient and the assistive equipment. This paper explores clinician perceptions of an early stage three-dimensional measurement aid prototype, which provides enhanced assistive equipment provision process guidance to clinicians. Ten occupational therapists trialled the three-dimensional measurement aid prototype application; think-aloud and semi-structured interview data was collected. Usability was measured with the System Usability Scale. Participants scored three-dimensional measurement aid prototype as ‘excellent’ and agreed strongly with items relating to the usability and learnability of the application. The qualitative analysis identified opportunities for improving existing practice, including, improved interpretation/recording measurements; enhanced collaborative practice within the assistive equipment provision process. Future research is needed to determine the clinical utility of this application compared with two-dimensional counterpart paper-based guidance leaflets.

scholarly journals Development and Formative Evaluation of a Low-Fidelity Equine Castration Model for Veterinary Education

2021 ◽  
Vol 8 ◽  
Author(s):  
M. Katie Sheats ◽  
Megan J. Burke ◽  
James B. Robertson ◽  
Katherine E. Fiebrandt ◽  
Callie A. Fogle
Keyword(s):  
Student Performance ◽  
Student Attitudes ◽  
Formative Evaluation ◽  
Performance Metrics ◽  
Early Stage ◽  
Future Research ◽  
Student Survey ◽  
Significant Difference ◽  
Veterinary Faculty ◽  
Fidelity Model

Entrustable Professional Activities (EPAs) are units of activity that early-stage professionals perform in the workplace that necessitate simultaneous integration of multiple competencies. EPA #6 requires students to perform a common surgical procedure on a stable patient, including pre-operative and post-operative management. Castration is one of the most common surgeries performed by equine primary care practitioners and is considered an “entry-level competency” for veterinary graduates entering equine private practice, however, to our knowledge there are no equine castration models available for veterinary student education. Therefore, we developed an inexpensive, low-fidelity model of equine field castration and evaluated it using a mixed-methods approach. Two different groups of students, with or without model experience, completed surveys before and after live horse castration. Students who used the model also completed model specific surveys. Videos of the students completing the model were evaluated by at least two different equine veterinary faculty using a 15-point rubric, and inter-rater reliability of the rubric was determined. After completing the model, students reflected on strengths and weaknesses of their performance. From our student survey results, we determined that student attitudes toward the model were mostly positive. Interestingly, there were several student attitudes toward the model that became significantly more favorable after live horse castration. Prior to live horse castration, there was no significant difference in confidence in model vs. no-model groups. Following live horse castration, students who used the model had higher confidence in procedure preparation and hand-ties than students who did not use the model, but they had lower scores for confidence during patient recovery. When reflecting on model castration, students most commonly cited preparation and surgical description as strengths, and ligature placement and hand-ties as weaknesses. Experts provided several suggestions to improve the model, including incorporation of emasculators and the need for better model stabilization. Our findings suggest that both students and veterinary educators feel that this low-fidelity model has educational value. Rubric performance metrics were favorable, but additional steps are needed to improve grading consistency among educators. Future research will determine whether student performance on the model is predictive of competence score during live-horse castration.

scholarly journals A Soft Voting Ensemble-Based Model for the Early Prediction of Idiopathic Pulmonary Fibrosis (IPF) Disease Severity in Lungs Disease Patients

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1092
Author(s):  
Sikandar Ali ◽  
Ali Hussain ◽  
Satyabrata Aich ◽  
Moo Suk Park ◽  
Man Pyo Chung ◽  
...  
Keyword(s):  
Machine Learning ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Lung Diseases ◽  
Early Stage ◽  
Confusion Matrix ◽  
Machine Learning Techniques ◽  
Training Dataset ◽  
Proposed Model

Idiopathic pulmonary fibrosis, which is one of the lung diseases, is quite rare but fatal in nature. The disease is progressive, and detection of severity takes a long time as well as being quite tedious. With the advent of intelligent machine learning techniques, and also the effectiveness of these techniques, it was possible to detect many lung diseases. So, in this paper, we have proposed a model that could be able to detect the severity of IPF at the early stage so that fatal situations can be controlled. For the development of this model, we used the IPF dataset of the Korean interstitial lung disease cohort data. First, we preprocessed the data while applying different preprocessing techniques and selected 26 highly relevant features from a total of 502 features for 2424 subjects. Second, we split the data into 80% training and 20% testing sets and applied oversampling on the training dataset. Third, we trained three state-of-the-art machine learning models and combined the results to develop a new soft voting ensemble-based model for the prediction of severity of IPF disease in patients with this chronic lung disease. Hyperparameter tuning was also performed to get the optimal performance of the model. Fourth, the performance of the proposed model was evaluated by calculating the accuracy, AUC, confusion matrix, precision, recall, and F1-score. Lastly, our proposed soft voting ensemble-based model achieved the accuracy of 0.7100, precision 0.6400, recall 0.7100, and F1-scores 0.6600. This proposed model will help the doctors, IPF patients, and physicians to diagnose the severity of the IPF disease in its early stages and assist them to take proactive measures to overcome this disease by enabling the doctors to take necessary decisions pertaining to the treatment of IPF disease.

scholarly journals Developing a tool to assess technical skills in talented youth table tennis players—a multi-method approach combining professional and scientific literature and coaches’ perspectives

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Irene R. Faber ◽  
Till Koopmann ◽  
Dirk Büsch ◽  
Jörg Schorer
Keyword(s):  
Scientific Literature ◽  
Early Stage ◽  
Technical Skills ◽  
Measurement Properties ◽  
Future Research ◽  
Single Element ◽  
Table Tennis ◽  
Professional Literature ◽  
Tennis Players ◽  
New Instrument

Abstract Background The assessment of technical skills as part of a multidimensional approach for talent identification and development in sports seems promising, especially in a technique-based sport like table tennis. However, current instruments mostly focus on a single element of technical skills, mainly use quantitative outcomes, and/or are not developed for talent purposes. Practice would benefit from a new instrument using a more ecologically valid approach. Thus, the purpose of this study was to identify the essential elements of technical skills in young table tennis players and to establish a first tool while using a multi-methods study design including an archive search for professional literature, a systematic search for scientific literature, as well as ten in-depth interviews with expert coaches. Results This approach taken ensured empirical findings to be combined with knowledge and experiences from the practical field and detailed explications by high-level expert coaches. Results for the literature searches yielded 23 professional and 21 scientific articles while data saturation was reached through all ten interviews. The triangulation process resulted in two general (i.e., individuality, interconnection between elements) and five specific (i.e., bat grip, ready position, footwork/body positioning, service, stroke) elements of technical skills in young table tennis players. In addition, criteria for both flawed and excellent executions were identified for each of the five specific elements. Finally, these results were used to create an observation sheet usable for an assessment during competition. Conclusions This study revealed the crucial elements of technical skills that should be taken into account when assessing sport-specific technical skills of youth table tennis players (8–12 years). Moreover, it provided concise descriptions of what is considered to be flawed or excellent executions of technical skills. Based on these findings, a first observation sheet, the Oldenburg observation sheet for Table Tennis Technique (O3T), was created to be used for the assessment of the current technical skill level within a competitive context at the early stage of a table tennis player’s career. Future research should focus on its measurement properties and its value within a multidimensional assessment for talent purposes.

scholarly journals Endogenous Hydrogen Sulfide Is an Important Factor in Maintaining Arterial Oxygen Saturation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Huang ◽  
Gang Wang ◽  
Zhan Zhou ◽  
Zhengshan Tang ◽  
Ningning Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Wall Thickening ◽  
Alveolar Wall ◽  
Leukocyte Infiltration ◽  
Wild Type ◽  
Interstitial Edema ◽  
And Oxidative Stress

The gasotransmitter H2S is involved in various physiological and pathophysiological processes. The aim of this study was to investigate the physiological functions of H2S in the lungs. In the model of mouse with genetic deficiency in a H2S natural synthesis enzyme cystathionine-γ-lyase (CSE), we found that arterial oxygen saturation (SaO2) was decreased compared with wild type mice. Hypoxyprobe test showed that mild hypoxia occurred in the tissues of heart, lungs and kidneys in Cse-/- mice. H2S donor GYY4137 treatment increased SaO2 and ameliorated hypoxia state in cardiac and renal tissues. Further, we revealed that lung blood perfusion and airway responsiveness were not linked to reduced SaO2 level. Lung injury was found in Cse-/- mice as evidenced by alveolar wall thickening, diffuse interstitial edema and leukocyte infiltration in pulmonary tissues. IL-8, IL-1β, and TNF-α levels were markedly increased and oxidative stress levels were also significantly higher with increased levels of the pro-oxidative biomarker, MDA, decreased levels of the anti-oxidative biomarkers, T-AOC and GSH/GSSG, and reduced superoxide dismutase (SOD) activity in lung tissues of Cse-/- mice compared with those of wild type mice. GYY4137 treatment ameliorated lung injury and suppressed inflammatory state and oxidative stress in lung tissues of Cse-/- mice. A decrease in SaO2 was found in normal mice under hypoxia. These mice displayed lung injury as evidenced by alveolar wall thickening, interstitial edema and leukocyte infiltration. Increased levels of inflammatory cytokines and oxidative stress were also found in lung tissues of the mice with hypoxia insult. GYY4137 treatment increased SaO2 and ameliorated lung injury, inflammation and oxidative stress. Our data indicate that endogenous H2S is an important factor in maintaining normal SaO2 by preventing oxidative stress and inflammation in the lungs.

scholarly journals Incorporating biomarkers in ecological risk assessment of chemical contaminants of soils

2007 ◽  
Vol 26 (2) ◽  
pp. 120-137
Author(s):  
A. J. Reinecke ◽  
S. A. Reinecke ◽  
M. S. Maboeta ◽  
J. P. Odendaal ◽  
R. Snyman
Keyword(s):  
Risk Assessment ◽  
South African ◽  
Field Experiments ◽  
Early Stage ◽  
Population Level ◽  
Diagnostic Tools ◽  
Future Research ◽  
Chemical Contaminants ◽  
Toxic Response ◽  
Future Research Directions

Soil is an important but complex natural resource which is increasingly used as sink for chemicals. The monitoring of soil quality and the assessment of risks posed by contaminants have become crucial. This study deals with the potential use of biomarkers in the monitoring of soils and the assessment of risk resulting from contamination. Apart from an overview of the existing literature on biomarkers, the results of various of our field experiments in South African soils are discussed. Biomarkers may have potential in the assessment of risk because they can indicate at an early stage that exposure has taken place and that a toxic response has been initiated. It is therefore expected that early biomarkers will play an increasing role as diagnostic tools for determining exposure to chemicals and the resulting effects. They may have predictive value that can assist in the prevention or minimising of risks. The aim of this study was to investigate the possibilities of using our results on biomarker responses of soil dwelling organisms to predict changes at higher organisational levels (which may have ecological implications). Our recent experimental results on the evaluation of various biomarkers in both the laboratory and the field are interpreted and placed in perspective within the broader framework of response biology. The aim was further to contribute to the development and application of biomarkers in regulatory risk assessment schemes of soils. This critical review of our own and recent literature on biomarkers in ecotoxicology leads to the conclusion that biomarkers can, under certain conditions, be useful tools in risk assessment. Clear relationships between contamination loads in soil organisms and certain biomarker responses were determined in woodlice, earthworms and terrestrial snails. Clear correlations were also established in field experiments between biomarker responses and changes at the population level. This indicated that, in spite of the fact that direct mechanistic links are still not clarified, biomarkers may have the potential to provide early indications of forthcoming changes at higher organisational levels. Ways are proposed in which biomarkers could be used in the future in risk assessment schemes of soils and future research directions are suggested. 

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