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Lab on a Chip Feb 2023Cold atmospheric plasma treatment promises a targeted cancer therapy due to its selectivity and specificity in killing tumor cells. However, the current plasma exposure...
Cold atmospheric plasma treatment promises a targeted cancer therapy due to its selectivity and specificity in killing tumor cells. However, the current plasma exposure devices produce diverse and coupled reactive species, impeding the investigation of the underlying plasma-anticancer mechanisms. Also, the limited mono-sample and mono-dosage treatment modality result in tedious and manual experimental tasks. Here, we propose a cold atmospheric plasma chip producing targeted species, delivering multiple dosages, and treating multiple cell lines in a single treatment. Three modules are integrated into the chip. The environment control module and multi-inlet gas-feed module coordinately ignite component-tunable and uniformly distributed plasma. The multi-sample holding module enables multiplex treatment: multi-sample and -dosage treatment with single radiation. By exposing the HepG2 cell line to nitrogen-feed plasmas, we prove the crucial role of nitrogen-based species in inhibiting cell growth and stimulating apoptosis. By loading four-type cell lines on our chip, we can identify the most vulnerable cell line for plasma oncotherapy. Simultaneously, three-level treatment dosages are imposed on the cells with single radiation to optimize the applicable treatment dosage for plasma oncotherapy. Our chip will broaden the design principles of plasma exposure devices, potentially help clarify plasma-induced anticancer mechanisms, and guide the clinical application of plasma-based oncotherapy.
Topics: Plasma Gases; Apoptosis; Cell Line; Treatment Outcome; Nitrogen
PubMed: 36644992
DOI: 10.1039/d2lc00951j -
The Journal of Pain May 2024Opioid use and dosage following knee arthroplasty (KA) has not been reported for subgroups with persistent moderate pain versus rapidly improving mild pain, externally... (Randomized Controlled Trial)
Randomized Controlled Trial
Perioperative Opioid Use and Dosage Trajectories Vary Depending on Pain Outcome Classification and Bodily Pain in Patients who Catastrophize About Their Pain: A Secondary Analysis of a Randomized Trial in Knee Arthroplasty.
Opioid use and dosage following knee arthroplasty (KA) has not been reported for subgroups with persistent moderate pain versus rapidly improving mild pain, externally validated from prior work. We determined if opioid use and dosage varied for persons classified into these externally validated subgroups. A secondary purpose determined if bodily pain scores are associated with the outcome subgroup. This was a secondary analysis of a prospective no-effect randomized clinical trial conducted on 384 participants with pain catastrophizing and scheduled for KA. Data were collected preoperatively and at 2-, 6-, and 12-month following surgery. Two-piece latent class growth curve analyses applied previously validated pain outcomes to determine subgroup outcome trajectories for the proportion of opioid users and oral morphine equivalent (OME) dosages. Substantial trajectory separation was found for opioid use and OME. Specifically, the average OME dosage for the persistent moderate pain subgroup was more than double that for the other outcome subgroup. The average preoperative opioid daily OME dosage for 170 patients reporting opioid use was 24.94 (95% [confidence interval] CI = 20.52, 29.38). Bodily pain was consistently higher for the persistent moderate pain subgroup compared to the other subgroup. Outcome subgroups in patients with pain catastrophizing demonstrated substantial differences in opioid use and dosage and were predicted by high pain catastrophizing, more bodily pain, and changes in bodily pain over time. The persistent moderate pain subgroup is at greater risk of opioid use and greater opioid dosages and should be targeted for preoperative screening and interventions to reduce opioid use and potential opioid misuse. PERSPECTIVE: More frequent and higher opioid dosage following KA was found for the persistent moderate pain subgroup compared to the other subgroup. Patients with persistent pain had worse catastrophizing, contralateral and ipsilateral lower extremity pain, low back pain, and whole body pain compared to the rapidly improving mild pain subgroup.
Topics: Humans; Arthroplasty, Replacement, Knee; Analgesics, Opioid; Catastrophization; Male; Female; Pain, Postoperative; Middle Aged; Aged; Pain Measurement; Prospective Studies
PubMed: 38007035
DOI: 10.1016/j.jpain.2023.11.017 -
Journal of Drugs in Dermatology : JDD Sep 2015More than ever, male patients are seeking cosmetic procedures for a variety of reasons including but not limited to: a less aged appearance, social, or work related... (Review)
Review
More than ever, male patients are seeking cosmetic procedures for a variety of reasons including but not limited to: a less aged appearance, social, or work related issues. Injectable neurotoxins and fillers are appealing to the male patient for their safety, rapid results, and minimal downtime. However, methods applied to the female patient do not always translate to the male patient. In this article, we review the anatomical, biological, and behavioral differences in men. We also provide an in-depth discussion of the techniques and dosages that are used in men, emphasizing the distinctions between the sexes. While once overlooked, this gender is becoming an important demographic in cosmetic dermatology.
Topics: Cosmetic Techniques; Dermal Fillers; Face; Facial Bones; Facial Muscles; Female; Humans; Injections; Male; Neurotoxins; Sex Factors; Skin Aging
PubMed: 26355626
DOI: No ID Found -
Molecular Biology and Evolution Sep 2015Polyploidy provides evolutionary and morphological novelties in many plants and some animals. However, the role of genome dosage and composition in gene expression...
Polyploidy provides evolutionary and morphological novelties in many plants and some animals. However, the role of genome dosage and composition in gene expression changes remains poorly understood. Here, we generated a series of resynthesized Arabidopsis tetraploids that contain 0-4 copies of Arabidopsis thaliana and Arabidopsis arenosa genomes and investigated ploidy and hybridity effects on gene expression. Allelic expression can be defined as dosage dependent (expression levels correlate with genome dosages) or otherwise as dosage independent. Here, we show that many dosage-dependent genes contribute to cell cycle, photosynthesis, and metabolism, whereas dosage-independent genes are enriched in biotic and abiotic stress responses. Interestingly, dosage-dependent genes tend to be preserved in ancient biochemical pathways present in both plant and nonplant species, whereas many dosage-independent genes belong to plant-specific pathways. This is confirmed by an independent analysis using Arabidopsis phylostratigraphic map. For A. thaliana loci, the dosage-dependent alleles are devoid of TEs and tend to correlate with H3K9ac, H3K4me3, and CG methylation, whereas the majority of dosage-independent alleles are enriched with TEs and correspond to H3K27me1, H3K27me3, and CHG (H = A, T, or C) methylation. Furthermore, there is a parent-of-origin effect on nonadditively expressed genes in the reciprocal allotetraploids especially when A. arenosa is used as the pollen donor, leading to metabolic and morphological changes. Thus, ploidy, epigenetic modifications, and cytoplasmic-nuclear interactions shape gene expression diversity in polyploids. Dosage-dependent expression can maintain growth and developmental stability, whereas dosage-independent expression can facilitate functional divergence between homeologs (subfunctionalization and/or neofunctionalization) during polyploid evolution.
Topics: Alleles; Arabidopsis; Arabidopsis Proteins; Base Sequence; Epigenesis, Genetic; Evolution, Molecular; Gene Dosage; Gene Expression; Gene Expression Regulation, Plant; Gene Ontology; Genome, Plant; Histones; Polyploidy; Protein Processing, Post-Translational
PubMed: 25976351
DOI: 10.1093/molbev/msv116 -
Nurse Education in Practice Jan 2018Medication errors are common and may jeopardize the patient safety. As paediatric dosages are calculated based on the child's age and weight, risk of error in dosage...
Medication errors are common and may jeopardize the patient safety. As paediatric dosages are calculated based on the child's age and weight, risk of error in dosage calculations is increasing. In paediatric patients, overdose drug prescribed regardless of the child's weight, age and clinical picture may lead to excessive toxicity and mortalities while low doses may delay the treatment. This study was carried out to evaluate the knowledge of nursing students about paediatric dosage calculations. This research, which is of retrospective type, covers a population consisting of all the 3rd grade students at the bachelor's degree in May, 2015 (148 students). Drug dose calculation questions in exam papers including 3 open ended questions on dosage calculation problems, addressing 5 variables were distributed to the students and their responses were evaluated by the researchers. In the evaluation of the data, figures and percentage distribution were calculated and Spearman correlation analysis was applied. Exam question on the dosage calculation based on child's age, which is the most common method in paediatrics, and which ensures right dosages and drug dilution was answered correctly by 87.1% of the students while 9.5% answered it wrong and 3.4% left it blank. 69.6% of the students was successful in finding the safe dose range, and 79.1% in finding the right ratio/proportion. 65.5% of the answers with regard to Ml/dzy calculation were correct. Moreover, student's four operation skills were assessed and 68.2% of the students were determined to have found the correct answer. When the relation among the questions on medication was examined, a significant relation (correlation) was determined between them. It is seen that in dosage calculations, the students failed mostly in calculating ml/dzy (decimal). This result means that as dosage calculations are based on decimal values, calculations may be ten times erroneous when the decimal point is placed wrongly. Moreover, it is also seen that students lack maths knowledge in respect of four operations and calculating safe dose range. Relations among the medications suggest that a student wrongly calculating a dosage may also make other errors. Additional courses, exercises or utilisation of different teaching techniques may be suggested to eliminate the deficiencies in terms of basic maths knowledge, problem solving skills and correct dosage calculation of the students.
Topics: Child; Drug Dosage Calculations; Education, Nursing, Baccalaureate; Educational Measurement; Health Knowledge, Attitudes, Practice; Humans; Mathematics; Medication Errors; Nursing Education Research; Patient Safety; Pediatrics; Retrospective Studies; Students, Nursing
PubMed: 28942096
DOI: 10.1016/j.nepr.2017.09.013 -
Journal of the American Pharmacists... 2019To provide guidance for safe and appropriate vitamin and mineral supplementation regimens for patients who use vitamins marketed for ocular use concurrently with... (Review)
Review
OBJECTIVES
To provide guidance for safe and appropriate vitamin and mineral supplementation regimens for patients who use vitamins marketed for ocular use concurrently with general-purpose multivitamin (MVI) supplementation.
DATA SOURCES
Primary and tertiary evidence was compiled from secondary literature reference databases.
STUDY SELECTION
Dosage exposure with the use of supplements marketed for the prevention of ocular disease, including those recommended by the Age-Related Eye Disease Studies (AREDS), when used in combination with conventional MVI/nutrient products was determined. An analysis of the data was performed to suggest appropriate supplement recommendations.
DATA EXTRACTION
Combined dosages for single and duplicate ingredients found in ocular supplements and select MVI/nutrient supplements were compared with U.S. Food and Drug Administration--recommended daily value intake levels and the National Academy of Medicine recommendations on vitamin and nutrient tolerable upper intake levels (TUILs).
RESULTS
With the exception of copper, all studied product components that conformed to AREDS guidelines for vitamin and nutrient levels far exceeded U.S. Food and Drug Administration--recommended daily value intake level limits. Furthermore, vitamin A and zinc exceeded the National Academies of Medicine TUIL when a multivitamin product was combined with an ocular-specific vitamin or nutrient that conformed with AREDS-recommended dosage levels. Several products marketed specifically for ocular use failed to provide AREDS-recommended vitamin or nutrient levels even when combined with MVI products.
CONCLUSION
With the exception of vitamin A and zinc, the addition of typical multivitamin preparations to AREDS-recommended vitamin and nutrient regimens do not result in vitamin and mineral dosages that exceed TUIL as outlined by the National Academy of Medicine. However, combined AREDS and MVI regimens can create a substantial vitamin or mineral burden that is not appropriate for all older adult populations, particularly those with comorbidities, contributing to susceptibility of component toxicity.
Topics: Humans; Dietary Supplements; Drug Combinations; Drug Dosage Calculations; Eye; Eye Diseases; Macular Degeneration; Minerals; Nutrients; Risk Factors; Vitamins
PubMed: 30948238
DOI: 10.1016/j.japh.2019.01.013 -
Journal of Oral & Maxillofacial Research 2018The objective of the present systematic review was to test the hypothesis of no difference in facial swelling, pain and trismus after surgical removal of mandibular... (Review)
Review
OBJECTIVES
The objective of the present systematic review was to test the hypothesis of no difference in facial swelling, pain and trismus after surgical removal of mandibular third molar with different dosages of corticosteroids and administration routes.
MATERIAL AND METHODS
A MEDLINE (PubMed), Embase database and Cochrane Library search in combination with a hand-search of relevant journals was conducted by including randomized controlled trials published in English until 1 December 2017.
RESULTS
Seven studies fulfilled the inclusion criteria. Considerable variation in the included studies prevented meta-analysis from being performed. Preoperative submucosal injection of corticosteroids significantly diminishes facial swelling, pain and trismus compared with placebo. However, different dosages of corticosteroid and administration routes reveal contrary results indicating that administration of a higher dosage of corticosteroids do not necessarily cause a further decrease in facial swelling, pain and trismus.
CONCLUSIONS
Consequently, the optimal dosage of corticosteroids and administration route for diminishing postsurgical morbidity and improve quality of life after surgical removal of mandibular third molar is presently unknown. Therefore, further well-designed randomized clinical trials including a standardised protocol, patient-reported outcome measures and three-dimensional analysis of facial swelling is needed.
PubMed: 30116513
DOI: 10.5037/jomr.2018.9201 -
Pharmaceutics Oct 2021Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication...
Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger-Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.
PubMed: 34684010
DOI: 10.3390/pharmaceutics13101717 -
Briefings in Bioinformatics Nov 2023Large-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However,...
Large-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However, whether large-size multi-ancestry or small-size population-specific reference panels are the optimal choices for under-represented populations continues to be debated. We imputed genotypes of East Asian (180k Japanese) subjects using the Trans-Omics for Precision Medicine reference panel and found that the standard imputation quality metric (Rsq) overestimated dosage r2 (squared correlation between imputed dosage and true genotype) particularly in marginal-quality bins. Variance component analysis of Rsq revealed that the increased imputed-genotype certainty (dosages closer to 0, 1 or 2) caused upward bias, indicating some systemic bias in the imputation. Through systematic simulations using different template switching rates (θ value) in the hidden Markov model, we revealed that the lower θ value increased the imputed-genotype certainty and Rsq; however, dosage r2 was insensitive to the θ value, thereby causing a deviation. In simulated reference panels with different sizes and ancestral diversities, the θ value estimates from Minimac decreased with the size of a single ancestry and increased with the ancestral diversity. Thus, Rsq could be deviated from dosage r2 for a subpopulation in the multi-ancestry panel, and the deviation represents different imputed-dosage distributions. Finally, despite the impact of the θ value, distant ancestries in the reference panel contributed only a few additional variants passing a predefined Rsq threshold. We conclude that the θ value substantially impacts the imputed dosage and the imputation quality metric value.
Topics: Humans; Genome-Wide Association Study; Gene Frequency; Polymorphism, Single Nucleotide; Genotype
PubMed: 38221906
DOI: 10.1093/bib/bbad509 -
Frontiers in Nutrition 2023There is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized...
Association of folic acid dosage with circulating unmetabolized folic acid in Chinese adults with H-type hypertension: a multicenter, double-blind, randomized controlled trial.
BACKGROUND
There is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized clinical trial has been conducted to examine the FA-UMFA dose-response relationship.
OBJECTIVE
This study aimed to investigate the FA-UMFA dose-response relationship in Chinese adults with hypertension and elevated homocysteine (H-type hypertension), a population with clear clinical indication for FA treatment.
METHODS
The data for this study were derived from a randomized, double-blind, multicenter clinical trial of 8 FA dosages on efficacy of homocysteine (Hcy) lowering. The parent trial had three 3 stages: screening period (2-10 days), run-in period (0-2 weeks, baseline visit), and double-blind treatment period (8 weeks) with follow-up visits at the end of the 2nd, 4th, 6th, and 8th weeks of treatment. Participants were randomly assigned to 8 treatment groups corresponding to FA dosages of 0, 0.4, 0.6, 0.8, 1.2, 1.6, 2.0 mg to 2.4 mg.
RESULTS
This study included 1,567 Chinese adults aged ≥45 years with H-type hypertension. There was a positive but non-linear association between FA supplementation and UMFA levels in the dosage range of 0 mg to 2.4 mg. In the regression analysis, the coefficients for the linear and quadratic terms of FA dosage were both statistically significant ( < 0.001). Notably, the slope for UMFA was greater for FA dosages >0.8 mg (ß = 11.21, 95% CI: 8.97, 13.45) compared to FA dosages ≤0.8 mg (ß = 2.94, 95% CI: 2.59, 3.29). Furthermore, FA dosages higher than 0.8 mg did not confer additional benefits in terms of increasing 5-methyl tetrahydrofolic acid (5-MTHF, active form of folate) or reducing homocysteine (Hcy).
CONCLUSION
In Chinese adults with H-type hypertension, this study showed a positive, non-linear, dosage-response relationship between FA supplementation ranging from 0 to 2.4 mg and circulating UMFA levels. It revealed that 0.8 mg FA is an optimal dosage in terms of balancing efficacy (increasing 5-MTHF and lowering Hcy) while minimizing undesirable elevation of UMFA.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1, identifier NCT03472508.
PubMed: 37781132
DOI: 10.3389/fnut.2023.1191610