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Journal of Oral Science 2020The purpose of this study was to evaluate the influence of various polishing protocols on the surface roughness of polyetheretherketone (PEEK) and identify an effective...
The purpose of this study was to evaluate the influence of various polishing protocols on the surface roughness of polyetheretherketone (PEEK) and identify an effective polishing method of dental prostheses at the chairside. The PEEK specimens were assigned to seven groups with different protocols: no additional polishing (NT); polishing using a rubber point (C); polishing using "silky shine" (S); polishing using "aqua blue paste" (A); protocol C followed by protocol S (CS); protocol C followed by protocol A (CA); and protocol C followed by protocols S and A (CSA). The surface roughness (Sa and Ra) of the polished surfaces was measured. The surface roughness decreased in the following order of groups: NT, C, S, CS, CSA, CA, and A. In Groups C and S, wide deep pits formed by abrasive grains of SiC paper were observed, whereas only fine linear structures were observed on the surface in other groups. With respect to the polishing protocol of PEEK, clinically acceptable surface roughness was obtained using a soft polishing brush and agent for more than 3 min.
Topics: Benzophenones; Dental Polishing; Ketones; Materials Testing; Polyethylene Glycols; Polymers; Surface Properties
PubMed: 31996521
DOI: 10.2334/josnusd.18-0473 -
Annals of Oncology : Official Journal... Nov 2019Numerous phase I trials testing immune checkpoint inhibitors (CPI)-based combinations are currently being conducted to improve response rates observed with single... (Review)
Review
BACKGROUND
Numerous phase I trials testing immune checkpoint inhibitors (CPI)-based combinations are currently being conducted to improve response rates observed with single agents. However, methodology varies across studies, especially regarding the use of dose escalation.
MATERIALS AND METHODS
A literature search was conducted in Pubmed and major oncology meetings libraries for phase I trials reported between 2011 and 2018, containing at least one CPI [CLTA-4 blocking antibody or a PD(L)1 blocking antibody] plus at least one second agent (e.g. tyrosine kinase inhibitor, chemotherapy). Dose escalation schemes, target doses and recommended phase II doses (RP2D) were captured in our database for each study. Combination RP2D (combo-RP2D) was compared with target dose.
RESULTS
We identified 113 different studies comprising a total of 120 individual cohorts. The backbone was an anti- cytotoxic T-lymphocyte antigen 4 (CTLA-4) in 40 cohorts and an anti-PD(L)1 in 80 cohorts. Dose escalation was used for the CPI in 29 (24%) cohorts [11% for anti-PD(L)1 and 50% for anti-CTLA-4] and for the second agent in 55 cohorts (46%). For 31 s agents (26%), the combo-RP2D was significantly lower than the expected target dose. Failure to reach the target dose was explained by the type of second agent form (e.g. small molecules versus monoclonal antibodies) (P < 0.001) and the choice of trial design for the second agent by investigators.
CONCLUSION
Design of studies investigating new CPI-based combinations must consider the type of second agent. Dose escalation is required for combinations with small molecules but is unnecessary with vaccine/virus/dendritic therapies and monoclonal antibodies.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; CTLA-4 Antigen; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; Humans; Maximum Tolerated Dose; Neoplasms; Programmed Cell Death 1 Receptor; Protein Kinase Inhibitors; Research Design; Treatment Outcome
PubMed: 31435659
DOI: 10.1093/annonc/mdz286 -
Cureus Dec 2020An alliance of established experts on critical care, Front Line COVID-19 Critical Care Alliance (FLCCC), has published two protocols for treatment of COVID-19. The first...
An alliance of established experts on critical care, Front Line COVID-19 Critical Care Alliance (FLCCC), has published two protocols for treatment of COVID-19. The first one, methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+), is intended for hospital and intensive care unit treatment of pulmonary phases of the disease. It is based on affordable, commonly available components: anti-inflammatory corticosteroids (methylprednisolone, "M"), high-dose vitamin C infusion (ascorbic acid, "A"), vitamin B1 (thiamine, "T"), anticoagulant heparin ("H"), antiparasitic agent ivermectin, and supplemental components ("+") including melatonin, vitamin D, elemental zinc, and magnesium. The MATH+ protocol has received scarce attention due to the World Health Organization (WHO) advising against the use of corticosteroids in the beginning of the pandemic. In addition, randomized controlled clinical trials were required as a condition for adoption of the protocol. As the hospital mortality rate of MATH+ treated patients was approximately a quarter of the rate of patients receiving a standard of care, the authors of the protocol considered performing such trials unethical. Other parties have later performed clinical trials with corticosteroids and anticoagulants, which has led to a more widespread adoption of these components. In October 2020, ivermectin was upgraded from an optional component to an essential component of the protocol. According to the authors, ivermectin is considered the first agent effective for both prophylaxis (prevention) of COVID-19 and for treatment of all phases of COVID-19 including outpatient treatment of the early symptomatic phase. Therefore, at the end of October 2020, a separate ivermectin-based I-MASK+ protocol for prophylaxis and early outpatient treatment of COVID-19 was published.
PubMed: 33532161
DOI: 10.7759/cureus.12403 -
Bio-protocol Dec 2021The engineering of poxvirus genomes is fundamental to primary and applied virology research. Indeed, recombinant poxviruses form the basis for many novel vaccines and...
The engineering of poxvirus genomes is fundamental to primary and applied virology research. Indeed, recombinant poxviruses form the basis for many novel vaccines and virotherapies but producing and purifying these viruses can be arduous. In recent years, CRISPR/Cas9 has become the favoured approach for genome manipulation due to its speed and high success rate. However, recent data suggests poxvirus genomes are not repaired well following Cas9 cleavage. As a result, CRISPR/Cas9 is inefficient as an editing tool, but very effective as a programmable selection agent. Here, we describe protocols for the generation and enrichment of recombinant vaccinia viruses using targeted Cas9 as a selection tool. This novel use of Cas9 is a simple addition to current homologous recombination-based methods that are widespread in the field, facilitating implementation in laboratories already working with poxviruses. This is also the first method that allows for isolation of new vaccinia viruses in less than a fortnight, without the need to incorporate a marker gene or manipulation of large poxvirus genomes and reactivation with helper viruses. Whilst this protocol describes applications for laboratory strains of vaccinia virus, it should be readily adaptable to other poxviruses. Graphic abstract: Pipeline for Cas9 selection of recombinant poxviruses.
PubMed: 35087929
DOI: 10.21769/BioProtoc.4270 -
Photodiagnosis and Photodynamic Therapy Jun 2023This study aimed to evaluate, in vitro, the efficacy of photodynamic therapy - PDT using dimethyl methylene blue zinc chloride double salt (DMMB) and red LED light on...
This study aimed to evaluate, in vitro, the efficacy of photodynamic therapy - PDT using dimethyl methylene blue zinc chloride double salt (DMMB) and red LED light on planktonic cultures of Candida albicans. The tests were performed using the ATCC 90,028 strain grown at 37 °C for 24 h, according to a growth curve of C. albicans. The colonies were resuspended in sterile saline adjusted to a concentration of 2 × 10 cells / mL, with three experimental protocols being tested (Protocol 1, 2 and 3) with a fixed concentration of 750 ɳg/mL obtained through the IC, and energy density 20 J/cm. Protocol 1 was carried out using conventional PDT, Protocol 2 was applied double PDT in a single session, and Protocol 3 was applied double PDT in two sessions with a 24 h interval. The results showed logarithmic reductions of 3 (4.252575 ± 0.068526) and 4 logs (2.669533 ± 0.058592) of total fungal load in protocols 3 and 2 respectively in comparison to the Control (6.633547 ± 0.065384). Our results indicated that double application in a single session of PDT was the most effective approach for inhibiting the proliferation of Candida albicans (99.991% inhibition).
Topics: Candida albicans; Photochemotherapy; Photosensitizing Agents; Light; Methylene Blue
PubMed: 36773756
DOI: 10.1016/j.pdpdt.2023.103327 -
Current Protocols Nov 2023Replication timing is significantly correlated with gene expression and chromatin organization, changes dynamically during cell differentiation, and is altered in...
Replication timing is significantly correlated with gene expression and chromatin organization, changes dynamically during cell differentiation, and is altered in diseased states. Genome-wide analysis of replication timing is performed in actively replicating cells by Repli-seq. Current methods for Repli-seq require cells to be fixed in large numbers. This is a barrier for sample types that are sensitive to fixation or are in very limited numbers. In this article, we outline optimized methods to process live cells and intact nuclei for Repli-seq. Our protocol enables the processing of a smaller number of cells per sample and reduces processing time and sample loss while obtaining high-quality data. Further, for samples that tend to form clumps and are difficult to dissociate into a single-cell suspension, we also outline methods for isolation, staining, and processing of nuclei for Repli-seq. The Repli-seq data obtained from live cells and intact nuclei are comparable to those obtained from the standard protocols. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Live cell isolation and staining Alternate Protocol: Nuclei isolation and staining.
Topics: Coloring Agents; Cell Nucleus; DNA Replication Timing; Cell Separation; Genome
PubMed: 38009262
DOI: 10.1002/cpz1.945 -
Veterinary and Comparative Oncology Jun 2022Overall prevalence of severe adverse events (sAE) has been poorly studied in veterinary medicine and peer-reviewed studies mostly focused on a single protocol, making it...
Overall prevalence of severe adverse events (sAE) has been poorly studied in veterinary medicine and peer-reviewed studies mostly focused on a single protocol, making it difficult to have a general overview. The aim of this retrospective study was to assess the frequency and risk factors of sAE secondary to various protocols of chemotherapy in dogs. Medical records of 155 dogs receiving chemotherapy between January 2013 and December 2018 were reviewed. Adverse events (AE) were graded according to Veterinary Comparative Oncology Group-common terminology criteria for AE (VCOG-CTCAE) grading system. Statistical analyses were performed to determine whether demographic, cancer type and chemotherapy protocol were associated with development of sAE and their consequences. AE were reported at least once in 124 (80%) dogs and sAE were observed in 50 (32.3%) dogs. Among them, 23 (14.8%) had gastro-intestinal and 31 (20.0%) had myelotoxic events. sAE led to hospitalisation in 37 (23.9%) dogs, to chemotherapy arrest in 12 (7.7%) dogs and to euthanasia or death in 9 (5.8%) dogs. Haematopoietic tumours were statistically associated with a higher frequency of sAE (p = .004), gastrointestinal sAE (p = .009) and hospitalisation (p = .004). A body weight over 10 kg was associated with less haematological sAE (p < .001). The use of a multi-agent protocol was highlighted as a risk factor for sAE (p = .038) and haematological sAE (p < .001). sAE following chemotherapy and leading to hospitalisation, chemo arrest or death were relatively common. A special attention during chemotherapy follow-up should be given to small dogs and those receiving multi-agent protocol or treated for haematopoietic tumours.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Dog Diseases; Dogs; Hematologic Neoplasms; Neoplasms; Retrospective Studies
PubMed: 34775666
DOI: 10.1111/vco.12782 -
International Journal of Gynecological... Jun 2022Antineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to...
OBJECTIVE
Antineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to such agent. Although desensitization protocols can be used to re-introduce agents after the development of a hypersensitivity reaction, these protocols vary across institutions. Our study evaluated the safety and efficacy of our desensitization protocol.
METHODS
All patients who underwent desensitization to platinum, taxane, liposomal doxorubicin, or trastuzumab between November 2016 and May 2021 after a prior hypersensitivity reaction to the specific agent were included in a retrospective review. The 12-step, outpatient desensitization protocol included pretreatment with a leukotriene receptor antagonist, antihistamines, and corticosteroids, as well as extended infusion times. Successful desensitization was defined as the completion of ≥3 cycles without discontinuation of the agent due to a hypersensitivity reaction.
RESULTS
A total of 186 eligible patients were included. Median age was 59.5 years (range 26-87). 155 (83%) patients were treated with platinum. 55 (30%) patients were treated for colorectal cancer and 52 (28%) for ovarian cancer. 104 (56%) patients completed ≥3 cycles of therapy during desensitization. The median infusion time was 380 min (range 325-360 min). The median number of desensitization cycles was 3, with 694 cycles completed among all patients. A total of 79 (42%) patients had a breakthrough hypersensitivity reaction during desensitization, 4 of whom required epinephrine, and 84 (45%) patients discontinued the agent undergoing desensitization due to progression of disease.
CONCLUSIONS
Our outpatient 12-step, institutional desensitization protocol for antineoplastic therapy proved safe and efficacious, with 56% of patients successfully completing ≥3 cycles and not requiring an inpatient admission.
PubMed: 35675969
DOI: 10.1136/ijgc-2022-003466 -
The Journal of Hospital Infection May 2020Non-tuberculous mycobacteria (NTM) infections in cardiac surgery patients, caused by Mycobacterium chimaera or Mycobacterium abscessus, have been traced to NTM-aerosols...
BACKGROUND
Non-tuberculous mycobacteria (NTM) infections in cardiac surgery patients, caused by Mycobacterium chimaera or Mycobacterium abscessus, have been traced to NTM-aerosols produced by heater-cooler units of cardiopulmonary bypass equipment.
AIM
To develop a protocol to disinfect the water reservoir(s) of heater-coolers to reduce NTM numbers and thereby prevent potential NTM aerosolization; and to devise an approach to disrupt surface biofilms of heater-coolers to reduce reinoculation of the heater-cooler reservoir(s) after disinfection.
METHODS
A laboratory-scale Centers for Disease Control and Prevention bioreactor and a heater-cooler were inoculated with M. chimaera or M. abscessus to measure the ability of different disinfection protocols to reduce NTM colony-forming units in water and biofilm samples and to delay the reappearance of NTM after disinfection.
FINDINGS
The combination of an enzyme detergent cleaning agent and Clorox® were equivalent to Clorox alone in reducing M. chimaera cfu in heater-cooler water reservoir samples. However, reappearance of those bacteria was delayed by 12 weeks by the combination of enzyme detergent cleaning agent and Clorox exposure compared to Clorox disinfection alone.
CONCLUSION
A combination of an enzyme detergent and Clorox was an effective disinfection treatment and significantly delayed the reappearance of M. chimaera in the heater-cooler reservoir.
PubMed: 32422308
DOI: 10.1016/j.jhin.2020.05.005 -
American Journal of Hypertension Jul 2022To compare prevalence of hypertension and stage II hypertension assessed by 2 blood pressure (BP) observation protocols.
Differences in Hypertension and Stage II Hypertension by Demographic and Risk Factors, Obtained by Two Different Protocols in US Adults: National Health and Nutrition Examination Survey, 2017-2018.
BACKGROUND
To compare prevalence of hypertension and stage II hypertension assessed by 2 blood pressure (BP) observation protocols.
METHODS
Participants aged 18 years and older (n = 4,689) in the National Health and Nutrition Examination Survey (NHANES 2017-2018) had their BP measured following 2 protocols: the legacy auscultation protocol (AP) and oscillometric protocol (OP). The order of protocols was randomly assigned. Prevalence estimates for hypertension (BP ≥130/80 mm Hg or use of medication for hypertension) and stage II hypertension (BP ≥140/90 mm Hg) were determined overall, by demographics, and by risk factors for each protocol. Ratios (OP% ÷ AP%) and kappa statistics were calculated.
RESULTS
Age-adjusted hypertension prevalence was 44.5% (95% confidence interval [CI]: 41.1%-48.0%) using OP and 45.1% (95% CI: 41.5%-48.7%) using AP, prevalence ratio = 0.99 (95% CI = 0.94-1.04). Age-adjusted stage II hypertension prevalence was 15.8% (95% CI: 13.6%-18.2%) using AP and 17.1% (95% CI: 14.7%-19.7%) using OP, prevalence ratio = 0.92 (95% CI = 0.81-1.04). For both hypertension and stage II hypertension, the prevalence ratios by demographics and by risk factors all included unity in their 95% CI, except for stage II hypertension in adults 60+ years (ratio: 0.88 [95% CI: 0.78-0.98]). Kappa for agreement between protocols for hypertension and stage II hypertension was 0.75 (95% CI = 0.71-0.79) and 0.67 (95% CI = 0.61-0.72), respectively.
CONCLUSIONS
In adults and for nearly all subcategories there were no significant differences in prevalence of hypertension and stage II hypertension between protocols, indicating that protocol change may not affect the national prevalence estimates of hypertension and stage II hypertension.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Nutrition Surveys; Prevalence; Risk Factors; United States
PubMed: 35333925
DOI: 10.1093/ajh/hpac042