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Cells May 2020The pleiotropic behavior of mesenchymal stem cells (MSCs) has gained global attention due to their immense potential for immunosuppression and their therapeutic role in... (Review)
Review
The pleiotropic behavior of mesenchymal stem cells (MSCs) has gained global attention due to their immense potential for immunosuppression and their therapeutic role in immune disorders. MSCs migrate towards inflamed microenvironments, produce anti-inflammatory cytokines and conceal themselves from the innate immune system. These signatures are the reason for the uprising in the sciences of cellular therapy in the last decades. Irrespective of their therapeutic role in immune disorders, some factors limit beneficial effects such as inconsistency of cell characteristics, erratic protocols, deviating dosages, and diverse transfusion patterns. Conclusive protocols for cell culture, differentiation, expansion, and cryopreservation of MSCs are of the utmost importance for a better understanding of MSCs in therapeutic applications. In this review, we address the immunomodulatory properties and immunosuppressive actions of MSCs. Also, we sum up the results of the enhancement, utilization, and therapeutic responses of MSCs in treating inflammatory diseases, metabolic disorders and diabetes.
Topics: Adipocytes; Clinical Trials as Topic; Diabetes Mellitus; Humans; Immune Evasion; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 32384763
DOI: 10.3390/cells9051145 -
The International Journal of... 2018To evaluate the accuracy and precision of a digital scanner used to scan four implants positioned according to an immediate loading implant protocol and to assess the...
PURPOSE
To evaluate the accuracy and precision of a digital scanner used to scan four implants positioned according to an immediate loading implant protocol and to assess the accuracy of an aluminum framework fabricated from a digital impression.
MATERIALS AND METHODS
Five master casts reproducing different edentulous maxillae with four tilted implants were used. Four scan bodies were screwed onto the low-profile abutments, and a digital intraoral scanner was used to perform five digital impressions of each master cast. To assess trueness, a metal framework of the best digital impression was produced with computer-aided design/computer-assisted manufacture (CAD/CAM) technology and passive fit was assessed with the Sheffield test. Gaps between the frameworks and the implant analogs were measured with a stereomicroscope. To assess precision, three-dimensional (3D) point cloud processing software was used to measure the deviations between the five digital impressions of each cast by producing a color map. The deviation values were grouped in three classes, and differences were assessed between class 2 (representing lower discrepancies) and the assembled classes 1 and 3 (representing the higher negative and positive discrepancies, respectively).
RESULTS
The frameworks showed a mean gap of < 30 μm (range: 2 to 47 μm). A statistically significant difference was found between the two groups by the 3D point cloud software, with higher frequencies of points in class 2 than in grouped classes 1 and 3 (P < .001).
CONCLUSION
Within the limits of this in vitro study, it appears that a digital impression may represent a reliable method for fabricating full-arch implant frameworks with good passive fit when tilted implants are present.
Topics: Computer-Aided Design; Dental Implants; Dental Impression Materials; Dental Impression Technique; Dental Prosthesis, Implant-Supported; Humans; Jaw, Edentulous; Models, Dental
PubMed: 29518813
DOI: 10.11607/ijp.5535 -
Therapeutic Innovation & Regulatory... Jul 2022Little to no data exist quantifying and benchmarking the magnitude of protocol deviation experience.
BACKGROUND
Little to no data exist quantifying and benchmarking the magnitude of protocol deviation experience.
METHODS
Nearly two-dozen companies provided the Tufts Center for the Study of Drug Development (Tufts CSDD) with data on the design and the performance of 187 protocols.
RESULTS
The results of this working group study show that phase II and III protocols have a mean total of 75 and 119 protocol deviations, respectively, involving nearly one-third of all patients enrolled in each clinical trial. Oncology clinical trials have the highest relative mean number of protocol deviations affecting more than 40% of patients enrolled in each trial. The number of endpoints, the number of procedures per visit, and the number of countries were modestly positively associated with and predictive of, the incidence of deviations per protocol. A strong positive relationship was shown between the number of investigative sites and the number of protocol deviations.
CONCLUSION
The results of this initial study provide useful measures that sponsor companies can use to benchmark their own protocol deviation experience, identify factors most associated with protocol deviations, and determine whether remediation is warranted.
Topics: Benchmarking; Humans
PubMed: 35378712
DOI: 10.1007/s43441-022-00401-4 -
Scientific Reports Jul 2018The traditional quantum secret sharing does not succeed in the presence of rational participants. A rational participant's motivation is to maximize his utility, and...
The traditional quantum secret sharing does not succeed in the presence of rational participants. A rational participant's motivation is to maximize his utility, and will try to get the secret alone. Therefore, in the reconstruction, no rational participant will send his share to others. To tackle with this problem, we propose a rational quantum secret sharing scheme in this paper. We adopt the game theory to analyze the behavior of rational participants and design a protocol to prevent them from deviating from the protocol. As proved, the rational participants can gain their maximal utilities when they perform the protocol faithfully, and the Nash equilibrium of the protocol is achieved. Compared to the traditional quantum secret sharing schemes, our scheme is fairer and more robust in practice.
PubMed: 30042486
DOI: 10.1038/s41598-018-29051-z -
Acta Ophthalmologica Dec 2022To compare retinal function assessed by full-field electroretinography (ffERG) and multifocal electroretinography (mfERG) in diabetes without retinopathy, diabetes with...
OBJECTIVE
To compare retinal function assessed by full-field electroretinography (ffERG) and multifocal electroretinography (mfERG) in diabetes without retinopathy, diabetes with moderate non-proliferative diabetic retinopathy (NPDR) and in the absence of diabetes.
METHODS
Scotopic and photopic ffERG and mfERG was made in non-fasting volunteers, including 26 diabetic participants without retinopathy, 22 diabetic participants with moderate NPDR and 22 participants without diabetes using full International Society for Clinical Electrophysiology of Vision protocols.
RESULTS
Of the ffERG responses, significant deviation (p ≤ 0.05, corrected for multiple sampling and other relevant confounders) from the non-diabetic participants was seen in the diabetic participants only for the OP1-OP3 oscillatory amplitudes and the OP2 implicit time. This finding was independent of whether retinopathy was present or not. For the mfERG, minor amplitude or implicit time deviations were found for a small number of rings (R2, R4 and R5). Receiver of operating characteristic analysis showed that the single most prominent abnormality of the ffERG in diabetes, regardless of whether retinopathy was present or not, was the OP2 implicit time (area under the curve ≥ 0.80).
CONCLUSION
This bi-modal study of electroretinographic characteristics found that the most prominent anomaly associated with diabetes was a prolongation of the implicit time of the OP2 of the scotopic ffERG, while the most prominent added effect of non-proliferative diabetic retinopathy was a further prolongation of the OP2 implicit time. Although the variation in ERG characteristics is far too large for diagnostic purposes, the close association of the oscillatory potentials with the amacrine cells of the retina indicate that their function is particularly sensitive to diabetes.
Topics: Humans; Electroretinography; Diabetic Retinopathy; Diabetes Mellitus, Type 2; Retina
PubMed: 35661609
DOI: 10.1111/aos.15184 -
3 Biotech Mar 2022Maize possesses wide variation in amylose and amylopectin which assumes significance as a part of both food-chain and different industrial applications. Estimation of...
Maize possesses wide variation in amylose and amylopectin which assumes significance as a part of both food-chain and different industrial applications. Estimation of amylose and amylopectin in maize kernels is important for developing suitable hybrids. The existing protocols for estimation of amylose and amylopectin in maize are elaborate and lengthy, and involve high cost. Here, we developed a rapid and cost-effective method for estimation of amylose and amylopectin in maize kernels. 10% toluene and 80% ethanol were used for removal of proteins (~ 10%) and lipids (~ 4%) from maize flour. The over-estimation of amylose was minimized using NaOH with KI to stop free KI to bind with amylopectin. Standards were improved by mixing amylose and amylopectin in different concentrations (0-100%), rather than using amylose or amylopectin alone. Standard curve generated regression equation of = 90.436 + 0.8535 with = 0.9989. Two types of samples viz., (1) protein, amylose and amylopectin (2) amylose and amylopectin, showed that starch fractions were highly comparable to expected values with correlation coefficient () of 0.9998 and mean standard deviation of 0.54. The protocol successfully estimated wide range of amylose (2.79-50.04%) and amylopectin (59.96-97.21%) among diverse maize inbreds including () and () mutants. Present protocol required 75% less time and 92.5% less cost compared to existing protocols. The newly developed method would be highly useful in developing maize hybrids high in amylose or amylopectin. This is the first report of rapid and cost-effective protocol for estimation of starch fractions in maize kernels.
PubMed: 35186659
DOI: 10.1007/s13205-022-03128-z -
Journal of Atrial Fibrillation Dec 2019Manufacturer/federal drug administration (FDA) recommends inpatient initiation of dofetilide with the manufacturer providing an initiation algorithm. The outcomes of...
BACKGROUND
Manufacturer/federal drug administration (FDA) recommends inpatient initiation of dofetilide with the manufacturer providing an initiation algorithm. The outcomes of algorithm deviation have not been reported outside of clinical trials.
OBJECTIVE
We sought to perform a chart review of all the patients admitted for inpatient initiation of dofetilide to report on the incidence of protocol deviations and their implications.
METHODS
We performed a retrospective review of all patients over a 15-month periodwho were initiated on dofetilide for the very first time or reinitiated on dofetilide after a break of three months or more at our institution. We assessed data about patients who were given dofetilide without adherence to the protocol (i.e. protocol deviation).
RESULTS
A total of 189 patients were included in the study with a median age of 66 ± 9 years. Mean baseline QTc interval was 436 ± 32 msec, and 61% (116/189) were in atrial fibrillation (AF) at the time of dofetilide initiation. In 9% (17/189) of patients, the drug was discontinued due to intolerance or inefficacy. Therapy in 49% (93/189) of patients was noted to deviate from manufacturer recommended protocol with deviations more than once in some patients during the same hospitalization. Baseline QTc exceeding 440 msec(>500msec in conduction abnormalities) was the most frequent deviation (25%; 47/189).Ventricular tachyarrhythmia occurred in 4% (7/189) of patients, did not differ between patients, and occurred with and without protocol deviations (5% vs 2%; p = 0.27).
CONCLUSIONS
In our retrospective study, there were frequent deviations from the manufacturer-recommended algorithm guidelines for dofetilideinitation, primarily due to prolonged baseline QTc interval. The impact of these protocol deviations on drug discontinuation was uncertain; however, significant adverse events were higher in the deviation group compared to the group that fully adhered to the protocol. Further multicenter studies are warranted to clarify our findings.
PubMed: 32435348
DOI: 10.4022/jafib.2265 -
CoDAS 2022Verify and compare vocal deviation in quality, vocal symptoms and reflux symptom index in patients with clinical diagnosis of laryngopharyngeal reflux (LPR).
PURPOSE
Verify and compare vocal deviation in quality, vocal symptoms and reflux symptom index in patients with clinical diagnosis of laryngopharyngeal reflux (LPR).
METHODS
100 individuals of both genders participated in this prospective study, aged between 18 and 60 years old, who presented signs of LPR in the nasofibrolaryngological exam. Participants answered the Reflux Symptom Index (RSI) questionnaire to determine the reflux index and the Voice Symptom Scale (VoiSS). Their voices were recorded for the auditory-perceptual assessment. Three speech therapists with voice experience were contacted and the most reliable one was maintained.
RESULTS
100 examined voices, 34 were classified as adapted and 66 as deviated. The predominant vocal quality type was rough and a slight degree of deviation. The average score on VoiSS and RSI of individuals with deviated voice is significantly higher than the adapted voice group on both protocols (p<0.01). The symptom reported with most frequency and intensity, in both analyses, was throat clearing. There were statistically significant differences once analyzed the vocal quality types by pairs: rough-adapted (p=0.0021) and tense-adapted (p=0.0075) on VoiSS, and rough-adapted (p=0.001) on RSI.
CONCLUSION
Individuals with deviated voice reported higher occurrence of LPR related vocal signals and symptoms measured by VoiSS and RSI. The numerous theories about the disease do not make possible a single conclusion on the subject. Further studies are needed in the area to assist the professional in the diagnosis and treatment of the RLF patient.
Topics: Adolescent; Adult; Female; Humans; Laryngopharyngeal Reflux; Male; Middle Aged; Prospective Studies; Surveys and Questionnaires; Voice; Voice Quality; Young Adult
PubMed: 35239772
DOI: 10.1590/2317-1782/20212019065 -
Radiotherapy and Oncology : Journal of... Jan 2022Quality assurance (QA) practices improve the quality level of oncology trials by ensuring that the protocol is followed and the results are valid and reproducible. This... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Quality assurance (QA) practices improve the quality level of oncology trials by ensuring that the protocol is followed and the results are valid and reproducible. This study investigated the utilization of QA among randomized controlled trials that involve radiotherapy (RT).
METHODS AND MATERIALS
We searched ClinicalTrials.gov in February 2020 for all phase III oncology randomized clinical trials (RCTs). These trials were screened for RT-specific RCTs that had published primary trial results. Information regarding QA in each trial was collected from the study publications and trial protocol if available. Two individuals independently performed trial screening and data collection. Pearson's Chi-square tests analyses were used to assess factors that were associated with QA inclusion in RT trials.
RESULTS
Forty-two RCTs with RT as the primary intervention or as a mandatory component of the protocol were analyzed; the earliest was started in 1994 and one trial was still active though not recruiting. Twenty-nine (69%) trials mandated RT quality assurance (RTQA) practices as part of the trial protocol, with 19 (45%) trials requiring institutional credentialing. Twenty-one (50%) trials published protocol deviation outcomes. Clinical trials involving advanced radiation techniques (IMRT, VMAT, SRS, SBRT) did not include more RTQA than trials without these advanced techniques (73% vs. 65%, p = 0.55). Trials that reported protocol deviation outcomes were associated with mandating RTQA in their protocols as compared to trials that did not report these outcomes (100% vs. 38%, p < 0.001).
CONCLUSIONS
There is a lack of RTQA utilization and transparency in RT clinical trials. It is imperative for RT trials to include increased QA for safe, consistent, and high-quality RT planning and delivery.
Topics: Credentialing; Humans; Neoplasms; Quality Assurance, Health Care; Radiation Oncology
PubMed: 34838891
DOI: 10.1016/j.radonc.2021.11.018 -
Journal of the National Cancer Institute Mar 2013Noncompliance with radiotherapy (RT) protocol guidelines has been linked to inferior clinical outcomes. We performed a meta-analysis of cooperative group trials to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Noncompliance with radiotherapy (RT) protocol guidelines has been linked to inferior clinical outcomes. We performed a meta-analysis of cooperative group trials to examine the association between RT quality assurance (QA) deviations and disease control and overall survival (OS).
METHODS
We searched MEDLINE and the Cochrane Central Register of Controlled Trials for multi-institutional trials that reported clinical outcomes in relation to RT QA results. Hazard ratios (HRs) describing the association between RT protocol noncompliance and patient outcomes were extracted directly from the original studies or calculated from survival curves. Inverse variance meta-analyses were performed to assess the association between RT QA deviations and OS. A second meta-analysis tested the association between RT QA deviations and secondary outcomes, including local or locoregional control, event-free survival, and relapse. Random-effects models were used in cases of statistically significant (P < .10) effect heterogeneity. The Egger test was used to detect publication bias. All statistical tests were two-sided.
RESULTS
Eight studies (four pediatric, four adult) met all inclusion criteria and were incorporated into this analysis. The frequency of RT QA deviations ranged from 8% to 71% (median = 32%). In a random-effects model, RT deviations were associated with a statistically significant decrease in OS (HR of death = 1.74, 95% confidence interval [CI] = 1.28 to 2.35; P < .001). A similar effect was seen for secondary outcomes (HR of treatment failure = 1.79, 95% CI = 1.15 to 2.78; P = .009). No evidence of publication bias was detected.
CONCLUSION
In clinical trials, RT protocol deviations are associated with increased risks of treatment failure and overall mortality.
Topics: Clinical Protocols; Clinical Trials as Topic; Disease-Free Survival; Humans; Multicenter Studies as Topic; Neoplasms; Odds Ratio; Patient Compliance; Publication Bias; Quality Assurance, Health Care; Radiotherapy; Selection Bias; Treatment Failure
PubMed: 23468460
DOI: 10.1093/jnci/djt001