Browsing by Subject "IMPROVES"
Now showing items 1-13 of 13
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(2021)Immune checkpoint inhibitors such as anti-PD-1 have revolutionized the field of oncology over the past decade. Nevertheless, the majority of patients do not benefit from them. Virotherapy is a flexible tool that can be used to stimulate and/or recruit different immune populations. T-cell enabling virotherapy could enhance the efficacy of immune checkpoint inhibitors, even in tumors resistant to these inhibitors. The T-cell potentiating virotherapy used here consisted of adenoviruses engineered to express tumor necrosis factor alpha and interleukin-2 in the tumor microenvironment. To study virus efficacy in checkpoint-inhibitor resistant tumors, we developed an anti-PD-1 resistant melanoma model in vivo. In resistant tumors, adding virotherapy to an anti-PD-1 regimen resulted in increased survival (p=0.0009), when compared to anti-PD-1 monotherapy. Some of the animals receiving virotherapy displayed complete responses, which did not occur in the immune checkpoint-inhibitor monotherapy group. When adenoviruses were delivered into resistant tumors, there were signs of increased CD8 T-cell infiltration and activation, which - together with a reduced presence of M2 macrophages and myeloid-derived suppressor cells - could explain those results. T-cell enabling virotherapy appeared as a valuable tool to counter resistance to immune checkpoint inhibitors. The clinical translation of this approach could increase the number of cancer patients benefiting from immunotherapies.
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(2020)Objective: Inhalation of noble and other gases after cardiac arrest (CA) might improve neurological and cardiac outcomes. This article discusses up-to-date information on this novel therapeutic intervention. Data sources: CENTRAL, MEDLINE, online published abstracts from conference proceedings, clinical trial registry clinicaltrials.gov, and reference lists of relevant papers were systematically searched from January 1960 till March 2019. Study selection: Preclinical and clinical studies, irrespective of their types or described outcomes, were included. Data extraction: Abstract screening, study selection, and data extraction were performed by two independent authors. Due to the paucity of human trials, risk of bias assessment was not performed DATA SYNTHESIS: After screening 281 interventional studies, we included an overall of 27. Only, xenon, helium, hydrogen, and nitric oxide have been or are being studied on humans. Xenon, nitric oxide, and hydrogen show both neuroprotective and cardiotonic features, while argon and hydrogen sulfide seem neuroprotective, but not cardiotonic. Most gases have elicited neurohistological protection in preclinical studies; however, only hydrogen and hydrogen sulfide appeared to preserve CA1 sector of hippocampus, the most vulnerable area in the brain for hypoxia. Conclusion: Inhalation of certain gases after CPR appears promising in mitigating neurological and cardiac damage and may become the next successful neuroprotective and cardiotonic interventions. (C) 2020 Elsevier Inc. All rights reserved.
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(2022)Epidermal growth factor receptor (EGFR) is a validated tumor marker overexpressed in various cancers such as squamous cell carcinoma (SSC) of the head and neck and gliomas. We constructed protein-drug conjugates based on the anti-EGFR Designed Ankyrin Repeat Protein (DARPin) E01, and compared the bivalent DARPin dimer (DD1) and a DARPin-Fc (DFc) to the monomeric DARPin (DM) and the antibody derived scFv425-Fc (scFvFc) in cell culture and a mouse model. The modular conjugation system, which was successfully applied for the preparation of protein-drug and -dye conjugates, uses bio-orthogonal protein-aldehyde generation by the formylglycine-generating enzyme (FGE). The generated carbonyl moiety is addressed by a bifunctional linker with a pyrazolone for a tandem Knoevenagel reaction and an azide for strain-promoted azide-alkyne cycloaddition (SPAAC). The latter reaction with a PEGylated linker containing a dibenzocyclooctyne (DBCO) for SPAAC and monomethyl auristatin E (MMAE) as the toxin provided the stable conjugates DD1-MMAE (drug-antibody ratio, DAR = 2.0) and DFc-MMAE (DAR = 4.0) with sub-nanomolar cytotoxicity against the human squamous carcinoma derived A431 cells. In vivo imaging of Alexa Fluor 647-dye conjugates in A431-xenografted mice bearing subcutaneous tumors as the SCC model revealed unspecific binding of bivalent DARPins to the ubiquitously expressed EGFR. Tumor-targeting was verified 6 h post-injection solely for DD1 and scFvFc. The total of four administrations of 6.5 mg/kg DD1-MMAE or DFc-MMAE twice weekly did not cause any sequela in mice. MMAE conjugates showed no significant anti-tumor efficacy in vivo, but a trend towards increased necrotic areas (p = 0.2213) was observed for the DD1-MMAE (n = 5).
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(2021)Objectives This study investigated the costs of 2-hour multiprofessional in situ hospital trauma team simulation training and its effects on teams’ non-technical skills using the T-NOTECHS instrument.Background Simulation is a feasible and effective teaching and learning method. Calculating the costs of simulated trauma team training in medical emergency situations can yield valuable information for improving its overall cost-effectiveness.Design A prospective cohort study.Setting Trauma resuscitation room in Central Finland Hospital, Finland.Participants 475 medical professionals in 81 consecutive, simulated trauma teams.Primary and secondary outcome measures Team simulation training costs in 2017 and 2018 were analysed in the following two phases: (1) start-up costs and (2) costs of education. Primary outcome measures were training costs per participant and training costs per team. Secondary outcome measures were non-technical skills, which were measured on a 5–25-point scale using the T-NOTECHS instrument.Results The annual mean total costs of trauma team simulation training were €58 000 for 40 training sessions and 238 professionals. Mean cost per participant was €203. Mean cost per team was €1220. The annual costs of simulation training markedly decreased when at least 70–80 teams participated in the training. Mean change in T-NOTECHS score after simulation training was +2.86 points (95% CI 1.97 to 3.75;+14.5%).Conclusions The greater the number of teams trained per year, the lower the costs per trauma team. In this study, we developed an activity-based costing method to calculate the costs of trauma team simulation training to help stakeholders make decisions about whether to initiate or increase existing trauma team simulation training or to obtain these services elsewhere.Data are available upon reasonable request. Technical appendix and statistical code and data set available from the corresponding author at eerika.rosqvist@ksshp.fi.
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(2018)Introduction: Emergency nurses are expected to adopt evidence-based practice (EBP). The aim of this systematic review was to describe educational interventions promoting EBP and their outcomes among emergency nurses, compared with no education, to inform clinicians and researchers about effective educational interventions suitable for use in emergency departments (EDs). Methods: CINAHL, Cochrane, PubMed and Scopus were systematically searched to identify studies published between January 1, 2006 and October 20, 2016 describing educational interventions designed to promote EBP among emergency nurses. 711 studies were identified and screened; 10 were selected for inclusion and quality assessment. The studies were analyzed using deductive content analysis, and the review's results are presented in accordance with the PRISMA guidelines. Results: Ten relevant studies on nine different self-developed educational interventions were identified. Eight studies had highly significant or significant results. Interventions involving face-to-face contact led to significant or highly significant effects on patient benefits and emergency nurses' knowledge, skills, and behavior. Interventions using written self-directed learning material led to significant improvements in nurses' knowledge of EBP. All the descriptions of the interventions were incomplete, and the reported details varied considerably between the studies. Conclusions: There have been few studies on educational interventions to promote EBP among emergency nurses but the available results are promising.
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(2020)Background In bioengineering, growth of microorganisms is limited because of environmental and industrial stresses during fermentation. This study aimed to construct a nisin-producing chassis Lactococcus lactis strain with genome-streamlined, low metabolic burden, and multi-stress tolerance characteristics. Results The Cre-loxP recombination system was applied to reduce the genome and obtain the target chassis strain. A prophage-related fragment (PRF; 19,739 bp) in the L. lactis N8 genome was deleted, and the mutant strain L. lactis N8-1 was chosen for multi-stress tolerance studies. Nisin immunity of L. lactis N8-1 was increased to 6500 IU/mL, which was 44.44% higher than that of the wild-type L. lactis N8 (4500 IU/mL). The survival rates of L. lactis N8-1 treated with lysozyme for 2 h and lactic acid for 1 h were 1000- and 10,000-fold higher than that of the wild-type strain, respectively. At 39 celcius, the L. lactis N8-1 could still maintain its growth, whereas the growth of the wild-type strain dramatically dropped. Scanning electron microscopy showed that the cell wall integrity of L. lactis N8-1 was well maintained after lysozyme treatment. Tandem mass tags labeled quantitative proteomics revealed that 33 and 9 proteins were significantly upregulated and downregulated, respectively, in L. lactis N8-1. These differential proteins were involved in carbohydrate and energy transport/metabolism, biosynthesis of cell wall and cell surface proteins. Conclusions PRF deletion was proven to be an efficient strategy to achieve multi-stress tolerance and nisin immunity in L. lactis, thereby providing a new perspective for industrially obtaining engineered strains with multi-stress tolerance and expanding the application of lactic acid bacteria in biotechnology and synthetic biology. Besides, the importance of PRF, which can confer vital phenotypes to bacteria, was established.
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Gene-hydrogel microenvironment regulates extracellular matrix metabolism balance in nucleus pulposus (2020)Gene therapy provides an ideal potential treatment for intervertebral disk degeneration by delivering synthetic microRNAs (miRNAs) to regulate the gene expression levels. However, it is very challenging to deliver miRNAs directly, which leads to inactivation, low transfection efficiency, and short half‐life. Here, Agomir is loaded in hydrogel to construct a gene‐hydrogel microenvironment for regulating the synthesis/catabolism balance of the tissue extracellular matrix (ECM) to treat degenerative diseases. Agomir is a cholesterol‐, methylation‐, and phosphorothioate‐modified miRNA, which can mimic the function of miRNA to regulate the expression of the target gene. Agomir874 that mimics miRNA874 is synthesized to down regulate the expression of matrix metalloproteinases (MMPs) in nucleus pulposus (NP). At the same time, a polyethylene glycol (PEG) hydrogel is synthesized through Ag‐S coordination of 4‐arm PEG‐SH and silver ion solution, which has injectable, self‐healing, antimicrobial, degradable, and superabsorbent properties and matches perfectly with the mechanism of intervertebral disk. By delivering Agomir‐loaded PEG‐hydrogel to a degenerative intervertebral disk, a gene‐hydrogel microenvironment is constructed in situ, which reduces the expression of MMPs, regulates the synthesis/catabolism balance of ECM in the NP of the intervertebral disk, and improves the tissue microenvironment regeneration.
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(2017)Background: The child-oriented dietary intervention given in the prospective Special Turku Coronary Risk Factor Intervention Project (STRIP) has decreased the intake of saturated fat and lowered serum cholesterol concentration in children from infancy until early adulthood. In this study, we investigated whether the uniquely long-term child-oriented intervention has affected also secondarily parental diet and cardio-metabolic risk factors. Methods: The STRIP study is a longitudinal, randomized infancy-onset atherosclerosis prevention trial continued from the child's age of 8 months to 20 years. The main aim was to modify the child's diet towards reduced intake of saturated fat. Parental dietary intake assessed by a one-day food record and cardio-metabolic risk factors were analysed between the child's ages of 9-19 years. Results: Saturated fat intake of parents in the intervention group was lower [mothers: 12.0 versus 13.9 daily energy (E%), p Conclusions: Child-oriented dietary intervention shifted the dietary fat intakes of parents closer to the recommendations and tended to decrease total and low-density lipoprotein cholesterol in the intervention mothers. Dietary intervention directed to children benefits also parents.
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(2022)Mantle cell lymphoma (MCL) is a rare, often aggressive type of B-cell lymphoma with poor survival and no cure. Cancer and cancer treatment has a negative impact on health-related quality of life (HRQOL) both during active disease and in the long term, and improvement of HRQOL is a crucial objective of cancer therapy in older patients and no curative intent. Baseline HRQOL has in other lymphoma populations been shown to be predictive of outcome. Here, we explored HRQOL, and its association with survival, by the EORTC QLQ-C30 questionnaire, before, during and after chemotherapy in a patient cohort with MCL, treated within the NLG-MCL4 trial, designed to evaluate the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment. Fifty-one patients were enrolled, median age was 71 years (range 62-84), 37 were men (73%). Pre-treatment HRQOL was similar to scores from the reference population with healthy individuals. During treatment, HRQOL deteriorated, but reverted to the same level as the reference population after treatment. There was a correlation between physical function (p = 0.001) and role function (p = 0.006) at baseline and WHO performance status, but not with other clinical or genetic prognostic factors. None of the baseline factors were predictive for treatment related to HRQOL in this cohort. Pre-treatment physical (p = 0.011) and role function (p = 0.032) were independent factors associated with overall survival, and physical function (p = 0.002) was also associated with progression free survival. These findings may possibly be used to design support during treatment and improve rehabilitation. Further investigations are needed for assessment of long-term HRQOL.
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(2018)Purpose: The risk factors for blunt cerebrovascular injuries (BCVIs) are currently under intensive research, yet it is still controversial who should be screened. This study aimed to determine whether craniofacial fractures are associated with BCVI. Patients and Methods: This retrospective cohort study focused on patients with suspected polytrauma after whole-body computed tomographic angiography of the cervical arteries. Patients were reviewed for BCVI and craniofacial fractures. Exclusion criteria were hanging injury, gunshot injury or other penetrating injury to the neck, and a cervical fracture on any level. The outcome variable was BCVI, and the main predictor variable was a craniofacial fracture. A secondary predictor variable was a type of craniofacial fracture classified as a facial fracture, skull fracture, or a combination of facial and skull fracture. Other predictor variables were gender, age, and mechanism of injury In addition, specific craniofacial fractures were analyzed in more detail. The relevance of associations between BCVI and the predictors underwent chi(2) testing. Significance was set at .01. Results: Four hundred twenty-eight patients 13 to 90 years old during a 12-month period were included in the analysis. Craniofacial fractures occurred in 75 (17.5%). BCVI occurred significantly more frequently in those with than in those without a craniofacial fracture (18.6 vs 7.4%; P = .002). Patients with craniofacial fracture had a 4-fold increased risk for BCVI, whereas those 31 to 50 years old had 3.4-fold increased risk. Type of craniofacial fracture, gender, and mechanism of injury were not associated with BCVI. Conclusion: Craniofacial fractures are a serious risk factor for BCVI. This research suggests that in patients with any craniofacial fracture and suspected polytrauma, rigorous imaging of cervical arteries in search of BCVI is essential. (C) 2018 American Association of Oral and Maxillofacial Surgeons
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(2020)Wood is an abundant and sustainable source of emerging food ingredients, namely hemicelluloses that fulfil a number of requirements for functional hydrocolloids. Hemicelluloses, especially spruce galactoglucomannans (GGM) and birch glucuronoxylans (GX), have potential to be used as stabilizers in various foods such as yogurts, beverages, dressings, and desserts. However, in addition to good technological functionality, safety, and low price, the applicability and market potential of new hydrocolloids is determined by their sensory properties. The present study reports, for the first time, the sensory profile of spruce GGM and birch GX in food. Sensory profiles from generic descriptive analysis of GGM- and GX-rich extracts, processed by spray drying or ethanol precipitation, were compared in three types of model food systems: water solutions, yogurt with solutions, and yogurt with emulsions stabilized by GGM or GX. Gum Arabic was included for comparison with a commercial ingredient known to have a mild flavor. The results showed that GGM and GX have a woody flavor, which can be reduced by ethanol precipitation and, in yogurt, masked by other food ingredients.
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(2019)Background To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. Results During TECOS, 616 participants had >= 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. Conclusions In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205
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(2022)The left atrial appendage (LAA) of the adult heart has been shown to contain cardiac and myeloid progenitor cells. The resident myeloid progenitor population expresses an array of pro-regenerative paracrine factors. Cardiac constructs have been shown to inhibit deleterious remodeling of the heart using physical support. Due to these aspects, LAA holds promise as a regenerative transplant. LAAs from adult mT/mG mice were transplanted to the recipient 129X1-SvJ mice simultaneously as myocardial infarction (MI) was performed. A decellularized LAA patch was implanted in the control group. Two weeks after MI, the LAA patch had integrated to the ventricular wall, and migrated cells were seen in the MI area. The cells had two main phenotypes: small F4/80+ cells and large troponin C+ cells. After follow-up at 8 weeks, the LAA patch remained viable, and the functional status of the heart improved. Cardiac echo demonstrated that, after 6 weeks, the mice in the LAA-patch-treated group showed an increasing and statistically significant improvement in cardiac performance when compared to the MI and MI + decellularized patch controls. Physical patch-support (LAA and decellularized LAA patch) had an equal effect on the inhibition of deleterious remodeling, but only the LAA patch inhibited the hypertrophic response. Our study demonstrates that the LAA transplantation has the potential for use as a treatment for myocardial infarction. This method can putatively combine cell therapy (regenerative effect) and physical support (inhibition of deleterious remodeling).
