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1.
Cell ; 170(2): 298-311.e20, 2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28708998

RESUMO

The yeast Hsp70 chaperone Ssb interacts with ribosomes and nascent polypeptides to assist protein folding. To reveal its working principle, we determined the nascent chain-binding pattern of Ssb at near-residue resolution by in vivo selective ribosome profiling. Ssb associates broadly with cytosolic, nuclear, and hitherto unknown substrate classes of mitochondrial and endoplasmic reticulum (ER) nascent proteins, supporting its general chaperone function. Ssb engages most substrates by multiple binding-release cycles to a degenerate sequence enriched in positively charged and aromatic amino acids. Timely association with this motif upon emergence at the ribosomal tunnel exit requires ribosome-associated complex (RAC) but not nascent polypeptide-associated complex (NAC). Ribosome footprint densities along orfs reveal faster translation at times of Ssb binding, mainly imposed by biases in mRNA secondary structure, codon usage, and Ssb action. Ssb thus employs substrate-tailored dynamic nascent chain associations to coordinate co-translational protein folding, facilitate accelerated translation, and support membrane targeting of organellar proteins.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Dobramento de Proteína , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Adenosina Trifosfatases/química , Motivos de Aminoácidos , Proteínas de Choque Térmico HSP70/química , Modelos Moleculares , Biossíntese de Proteínas , Ribossomos/metabolismo , Saccharomyces cerevisiae/citologia , Proteínas de Saccharomyces cerevisiae/química
2.
Ann Surg Oncol ; 31(4): 2461-2469, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38142255

RESUMO

BACKROUND: Real-world, long-term survival outcomes of neoadjuvant, docetaxel-based therapy for esophageal and junctional adenocarcinoma are lacking. This study describes the long-term survival outcomes of patients with esophageal and junctional adenocarcinoma treated with neoadjuvant docetaxel-based chemotherapy and en bloc transthoracic esophagectomy. METHODS: A retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada, was performed. From January 2007 to December 2021, all patients with locally advanced (cT3 and/or N1) esophageal/Siewert I/II adenocarcinoma treated with neoadjuvant DCFx3 (Docetaxel/Cisplatin/5FU) or FLOTx4 (5FU/Leucovorin/Oxaliplatin/Docetaxel) and transthoracic en bloc esophagectomy were identified. Postoperative, pathological, and survival outcomes were compared. RESULTS: Overall, 236 of 420 patients met the inclusion criteria. Tumor location was esophageal/Siewert I/Siewert II (118/33/85), most were cT3-4 (93.6%) and cN+ (61.0%). DCF and FLOT were used in 127 of 236 (53.8%) and 109 of 236 (46.2%). All neoadjuvant cycles were completed in 87.3% with no difference between the regimens. Operative procedures included Ivor Lewis (81.8%), left thoraco-abdominal esophagectomy (10.6%) and McKeown (7.6%) with an R0 resection in 95.3% and pathological complete response in 9.7% (DCF 12.6%/FLOT 6.4%, p = 0.111). The median lymph node yield was 32 (range 4-79), and 60.6% were ypN+. Median follow-up was longer for the DCF group (74.8 months 95% confidence interval [CI] 4-173 vs. 37.8 months 95% CI 2-119, p <0.001. Overall survival was similar between the groups (FLOT 97.3 months, 78.6-115.8 vs. DCF 92.9, 9.2-106.5, p = 0.420). CONCLUSIONS: Neoadjuvant DCF and FLOT followed by transthoracic en bloc resection are both highly effective regimens for locally advanced esophageal adenocarcinoma with equivalent survival outcomes despite high disease load.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Humanos , Docetaxel , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Esofagectomia/métodos , Estadiamento de Neoplasias , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Fluoruracila , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino
3.
Environ Res ; 241: 117522, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37967707

RESUMO

Cancer patients face a significant clinical and socio-economic burden due to increased incidence, mortality, and poor survival. Factors like late diagnosis, recurrence, drug resistance, severe side effects, and poor bioavailability limit the scope of current therapies. There is a need for novel, cost-effective, and safe diagnostic methods, therapeutics to overcome recurrence and drug resistance, and drug delivery vehicles with enhanced bioavailability and less off-site toxicity. Advanced nanomaterial-based research is aiding cancer biologists by providing solutions for issues like hypoxia, tumor microenvironment, low stability, poor penetration, target non-specificity, and rapid drug clearance. Currently, nanozymes and carbon-dots are attractive due to their low cost, high catalytic activity, biocompatibility, and lower toxicity. Nanozymes and carbon-dots are increasingly used in imaging, biosensing, diagnosis, and targeted cancer therapy. Integrating these materials with advanced diagnostic tools like CT scans and MRIs can aid in clinical decision-making and enhance the effectiveness of chemotherapy, photothermal, photodynamic, and sonodynamic therapies, with minimal invasion and reduced collateral effects.


Assuntos
Nanoestruturas , Neoplasias , Humanos , Carbono , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Microambiente Tumoral
4.
Paediatr Anaesth ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38887922

RESUMO

The treatment of pediatric patients with diabetes is frequently orchestrated within a multidisciplinary framework at tertiary, specialized institutions. In situations where emergent surgery is indicated or when a procedure is scheduled in a facility devoid of an endocrinology service, the onus of managing perioperative glycemic levels may rest with the attending anesthesiologist. The objective of this review is to furnish a comprehensive examination of the anesthetic considerations and perioperative governance of pediatric patients with diabetes. Furthermore, this paper delineates a streamlined protocol for perioperative glycemic control, tailored to both major and minor surgical interventions.

5.
Subst Use Misuse ; 59(9): 1303-1312, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38664196

RESUMO

BACKGROUND: With increases in cannabis use and potency, there is a need to improve our understanding of the impact of use on cognitive function. Previous research indicates long-term cannabis use may have a negative effect on executive function. Few studies have examined persistence of it in protracted abstinence, and there is limited evidence of predictors of worse cognitive function in current and former users. In this study, we aim to evaluate the associations between cannabis use status (current, former, and never use) and self-report cognition. Further, we investigate if cannabis use characteristics predict self-report cognitive function. METHODS: Cross-sectional cannabis use data from the National Epidemiological Survey on Alcohol and Related Conditions-III (NESARC-III), a national survey (N = 36,309) conducted in the USA between 2012 and 2013 were used alongside the Executive Function Index scales. The data were analyzed by using Ordinary Least Squares regression. RESULTS: Current (N = 3,681, Female = 37.7%) and former users (N = 7,448, Female = 45.4%) reported poorer cognition than never users (N = 24,956, Female = 56.6%). Self-reported cognition of former users was in-between that of current and never users. Several cannabis use characteristics were associated with self-reported cognition in current and former users. CONCLUSION: While prospective studies are required to confirm, findings suggest cannabis use is linked to worse cognition. There may be some limited recovery of cognition in former users and some cannabis use characteristics predict impairment. These findings add to our understanding of the cognitive impact of cannabis use. As worse cognitive function may impact relapse, findings have implications for personalization of cannabis use disorder treatment.


Assuntos
Cognição , Autorrelato , Humanos , Masculino , Feminino , Adulto , Estados Unidos/epidemiologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Função Executiva , Uso da Maconha/epidemiologia , Uso da Maconha/psicologia , Abuso de Maconha/epidemiologia , Abuso de Maconha/psicologia , Fumar Maconha/epidemiologia , Fumar Maconha/psicologia
6.
BMC Oral Health ; 24(1): 65, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200506

RESUMO

BACKGROUND: In dentistry, there is a growing preference for computer-aided design and computer-aided manufacturing (CAD/CAM) systems over traditional laboratory procedures. However, there is not much literature comparing various CAD/CAM materials. Thus, this study aimed to assess and compare the color stability and hardness of gingival and tooth colored milled and 3D-printed acrylic resins. MATERIALS AND METHODS: Four types of CAD/CAM materials were prepared: 3D-printed pink shade (PP), milled polymenthymethacrylate (PMMA) pink shade (MP), 3D-printed tooth shade (PT) and milled PMMA tooth shade (MT) (n = 6). For hardness, disc shaped samples of 15 mm × 2 mm and for color stability, bar shaped samples of 65mmx10mmx2.5 mm were prepared and polished. Vickers hardness test was performed in a microhardness tester. Color stability test was done by immersing in coffee solution and coca cola for 7 days. Day 0 and day 7 measurements were recorded using a digital spectrophotometer and the change in color was calculated. For statistical analysis, one-way ANOVA and Tukey's post hoc tests were done. RESULTS: For color stability, milled PMMA was superior to 3D-printed resin samples. Milled pink and tooth shade samples had similar color stability, whereas 3D-printed tooth shade samples were more color stable as compared to pink shade 3D-printed samples. For hardness, milled tooth shade PMMA was the most superior one, followed by 3D-printed tooth shade, whereas pink shade milled PMMA and 3D-printed resin samples had similar hardness values and were inferior to the tooth shade CAD/CAM materials. CONCLUSION: Color stability of milled PMMA is superior to that of 3D-printed resins. Hardness of tooth shade milled and 3D-printed resins is more than that of pink shade milled and 3D-printed resins.


Assuntos
Polimetil Metacrilato , Projetos de Pesquisa , Humanos , Gengiva , Desenho Assistido por Computador , Materiais Dentários , Prótese Total
7.
BMC Oral Health ; 24(1): 248, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368396

RESUMO

INTRODUCTION: The prevalence of adults with partially dental arches is expected to be more than imagined and patients requiring replacement of missing teeth are slowly increasing in number too. Removable partial dentures are known to provide for substantial replacement for the missing teeth with also added advantages when compared to fixed or implant prosthesis, mainly in elderly patients. Denture base material performance and durability are greatly influenced by wettability and water contact angle. In the case of dentures; adequate moisture distribution is necessary to ensure excellent wettability which has an influence on comfort and oral health. The purpose of conducting this study was to find out whether the advancements made using PEEK (Polyether ether ketone) would prove to be more beneficial than the current upgrades in the current material spectrum. MATERIALS AND METHODS: This study was performed under in vitro conditions. All the fabrication and processing was done only by one operator. The materials used were divided into three groups each comprising 20 samples. Group A was modified polymethylmethacrylate (Bredent Polyan), Group B was polyoxymethylene acetal resin (Biodentaplast) and Group C was PEEK. An Ossila Goniometer was used to measure the contact angle. The three types of liquids used for the testing included distilled water, natural saliva and mouth wetting solution (Wet Mouth Liquid, ICPA India). Human saliva was collected from an individual with no medical conditions and normal salivary secretion. RESULTS: The data was analyzed using One-way ANOVA test and a pairwise comparison using the Post Hoc Tukey's Honest Significant Difference. Table 1 consists of the mean water contact angles of the denture base materials and mean contact angles of various denture base materials. In saliva, mouth wetting solution and distilled water, the highest mean and least mean contact angle was seen in Polyan and Biodentaplast respectively. A signicant difference was seen between PEEK and Polyan and Biodentaplast and Polyan on further comparison. CONCLUSION: From the resources and the materials at our disposal, it could be concluded that Polyan, Biodentaplast and PEEK and could be used as viable options in cast partial denture framework.


Assuntos
Resinas Acrílicas , Benzofenonas , Polímeros , Polimetil Metacrilato , Bases de Dentadura , Prótese Parcial , Cetonas , Teste de Materiais , Metacrilatos , Polietilenoglicóis , Água , Molhabilidade
8.
BMC Oral Health ; 24(1): 379, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519932

RESUMO

INTRODUCTION: Over the years, implant therapy has been a commonly used treatment option for individuals who are partially or totally edentulous, with a long-term success rate of over 90%. With significant advancements in biomaterials and technology, implant dentistry can now conduct prosthetic rehabilitations in the majority of patients catering to all types of needs. However, in order to meet the demands of a patient base that is always growing, new trends in implantology are emerging in recent years that are focused on minimally invasive surgery and financial sustainability. In certain clinical scenarios, connecting teeth and implants to support fixed partial prosthesis (FPPs) may be a predictable and workable course of treatment. MATERIALS AND METHODS: 22 patients were selected for this study who had tooth and implant supported prosthesis placed as a final restoration. Out of these 22 patients; 12 were male and 10 were female patients. Implants were placed following proper protocol and if grafting procedures were required they were carried out. A second stage surgical procedure was carried out and delayed loading protocols were followed. The statistical analysis was done using the IBM SPSS 24.0, Chicago, USA. The survival of the implants and teeth were measured by the Kaplan Meier survival scale. Bone loss was assessed at baseline(upon loading), 12 months and 24 months. RESULTS: The implant survival rate was measured at 6 months, 12 months, 18 months and 24 months. At 24 months, one implant showed failure, so the survival rate of the implants were 95.4%. Bone loss of 1 mm was seen around one implant at 12 months. Bone loss of 1 and 2 mm was present around two implants and one implant respectively at 24 months. CONCLUSION: From the results of this study, we can conclude that tooth implant supported prosthesis show very good survival when used in rehabilitation cases.


Assuntos
Perda do Osso Alveolar , Implantes Dentários , Carga Imediata em Implante Dentário , Humanos , Masculino , Feminino , Implantes Dentários/efeitos adversos , Seguimentos , Implantação Dentária Endóssea/métodos , Implantação Dentária , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Resultado do Tratamento , Planejamento de Prótese Dentária , Perda do Osso Alveolar/etiologia
9.
BMC Bioinformatics ; 24(1): 462, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062391

RESUMO

BACKGROUND: Synonymous mutations, which change the DNA sequence but not the encoded protein sequence, can affect protein structure and function, mRNA maturation, and mRNA half-lives. The possibility that synonymous mutations might be enriched in cancer has been explored in several recent studies. However, none of these studies control for all three types of mutational heterogeneity (patient, histology, and gene) that are known to affect the accurate identification of non-synonymous cancer-associated genes. Our goal is to adopt the current standard for non-synonymous mutations in an investigation of synonymous mutations. RESULTS: Here, we create an algorithm, MutSigCVsyn, an adaptation of MutSigCV, to identify cancer-associated genes that are enriched for synonymous mutations based on a non-coding background model that takes into account the mutational heterogeneity across these levels. Using MutSigCVsyn, we first analyzed 2572 cancer whole-genome samples from the Pan-cancer Analysis of Whole Genomes (PCAWG) to identify non-synonymous cancer drivers as a quality control. Indicative of the algorithm accuracy we find that 58.6% of these candidate genes were also found in Cancer Census Gene (CGC) list, and 66.2% were found within the PCAWG cancer driver list. We then applied it to identify 30 putative cancer-associated genes that are enriched for synonymous mutations within the same samples. One of the promising gene candidates is the B cell lymphoma 2 (BCL-2) gene. BCL-2 regulates apoptosis by antagonizing the action of proapoptotic BCL-2 family member proteins. The synonymous mutations in BCL2 are enriched in its anti-apoptotic domain and likely play a role in cancer cell proliferation. CONCLUSION: Our study introduces MutSigCVsyn, an algorithm that accounts for mutational heterogeneity at patient, histology, and gene levels, to identify cancer-associated genes that are enriched for synonymous mutations using whole genome sequencing data. We identified 30 putative candidate genes that will benefit from future experimental studies on the role of synonymous mutations in cancer biology.


Assuntos
Neoplasias , Mutação Silenciosa , Humanos , Genoma Humano , Mutação , Neoplasias/patologia , RNA Mensageiro , Proteínas Proto-Oncogênicas c-bcl-2 , Análise Mutacional de DNA
10.
Dis Esophagus ; 36(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37448141

RESUMO

The outcomes of different treatment modalities for patients aged 80 and above with locally advanced and resectable esophageal carcinoma are not well described. The aim of this study was to explore survival and perioperative outcomes among this specific group of patients. A retrospective, cohort analysis was performed on a prospectively maintained esophageal cancer database from the McGill regional upper gastroinestinal cancer network. Between 2010 and 2020, all patients ≥80 years with cT2-4a, Nany, M0 esophageal carcinoma were identified and stratified according to the treatment modality: Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT); definitive CRT (dCRT); upfront surgery; palliative CT/RT; or best supportive care (BSC). Of the 162 patients identified, 79 were included in this study. The median age was 83 years (80-97), most were cT3 (73%), cN- (56%), and had adenocarcinoma (62%). Treatment included: nCT/nCRT (16/79, 20%); surgery alone (19/79, 24%); dCRT (12/29, 15%); palliative RT/CT (27/79, 34%); and BSC (5/79, 6%). Neoadjuvant treatment was completed in 10/16 (63%). Of the 35/79 who underwent surgery, major complications occurred in 13/35 (37%) and 90-day mortality in 3/35 (9%). Overall survival (OS) for the cohort at 1- and 3-years was 58% and 19%. Among patients treated with nCT/nCRT, this was 94% and 46% respectively. Curative intent treatment (nCT/nCRT/upfront surgery/dCRT) had significantly increased 1- and 3- year OS compared with non-curative treatment (76%/31% vs. 34%/3.3%). Multimodal standard of care treatment is feasible and safe in select octo/nonagenarians, and may be associated with improved OS. Age alone should not bias against treatment with curative intent.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Idoso de 80 Anos ou mais , Humanos , Estudos Retrospectivos , Nonagenários , Esofagectomia , Neoplasias Esofágicas/cirurgia , Terapia Neoadjuvante , Quimiorradioterapia , Adenocarcinoma/cirurgia
11.
BMC Bioinformatics ; 22(1): 156, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765913

RESUMO

BACKGROUND: Translation is a fundamental process in gene expression. Ribosome profiling is a method that enables the study of transcriptome-wide translation. A fundamental, technical challenge in analyzing Ribo-Seq data is identifying the A-site location on ribosome-protected mRNA fragments. Identification of the A-site is essential as it is at this location on the ribosome where a codon is translated into an amino acid. Incorrect assignment of a read to the A-site can lead to lower signal-to-noise ratio and loss of correlations necessary to understand the molecular factors influencing translation. Therefore, an easy-to-use and accurate analysis tool is needed to accurately identify the A-site locations. RESULTS: We present RiboA, a web application that identifies the most accurate A-site location on a ribosome-protected mRNA fragment and generates the A-site read density profiles. It uses an Integer Programming method that reflects the biological fact that the A-site of actively translating ribosomes is generally located between the second codon and stop codon of a transcript, and utilizes a wide range of mRNA fragment sizes in and around the coding sequence (CDS). The web application is containerized with Docker, and it can be easily ported across platforms. CONCLUSIONS: The Integer Programming method that RiboA utilizes is the most accurate in identifying the A-site on Ribo-Seq mRNA fragments compared to other methods. RiboA makes it easier for the community to use this method via a user-friendly and portable web application. In addition, RiboA supports reproducible analyses by tracking all the input datasets and parameters, and it provides enhanced visualization to facilitate scientific exploration. RiboA is available as a web service at https://a-site.vmhost.psu.edu/ . The code is publicly available at https://github.com/obrien-lab/aip_web_docker under the MIT license.


Assuntos
Biossíntese de Proteínas , Ribossomos , Códon de Terminação , Fases de Leitura Aberta , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribossomos/genética , Ribossomos/metabolismo
12.
J Am Chem Soc ; 142(13): 6103-6110, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32138505

RESUMO

The ejection of nascent proteins out of the ribosome exit tunnel, after their covalent bond to transfer-RNA has been broken, has not been experimentally studied due to challenges in sample preparation. Here, we investigate this process using a combination of multiscale modeling, ribosome profiling, and gene ontology analyses. Simulating the ejection of a representative set of 122 E. coli proteins we find a greater than 1000-fold variation in ejection times. Nascent proteins enriched in negatively charged residues near their C-terminus eject the fastest, while nascent chains enriched in positively charged residues tend to eject much more slowly. More work is required to pull slowly ejecting proteins out of the exit tunnel than quickly ejecting proteins, according to all-atom simulations. An energetic decomposition reveals, for slowly ejecting proteins, that this is due to the strong attractive electrostatic interactions between the nascent chain and the negatively charged ribosomal-RNA lining the exit tunnel, and for quickly ejecting proteins, it is due to their repulsive electrostatic interactions with the exit tunnel. Ribosome profiling data from E. coli reveals that the presence of slowly ejecting sequences correlates with ribosomes spending more time at stop codons, indicating that the ejection process might delay ribosome recycling. Proteins that have the highest positive charge density at their C-terminus are overwhelmingly ribosomal proteins, suggesting the possibility that this sequence feature may aid in the cotranslational assembly of ribosomes by delaying the release of nascent ribosomal proteins into the cytosol. Thus, nascent chain ejection times from the ribosome can vary greatly between proteins due to differential electrostatic interactions, can influence ribosome recycling, and could be particularly relevant to the synthesis and cotranslational behavior of some proteins.


Assuntos
Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Ribossomos/metabolismo , Modelos Moleculares , Biossíntese de Proteínas , Eletricidade Estática
13.
Chem Res Toxicol ; 33(10): 2668-2674, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-32894672

RESUMO

Inflammation is an immune response to protect against various types of infections. When unchecked, acute inflammation can be life-threatening, as seen with the current coronavirus pandemic. Strong oxidants, such as peroxynitrite produced by immune cells, are major mediators of the inflammation-associated pathogenesis. Cellular thiols play important roles in mitigating inflammation-associated macromolecular damage including DNA. Herein, we have demonstrated a role of glutathione (GSH) and other thiols in neutralizing the effect of peroxynitrite-mediated DNA damage through stable GSH-DNA adduct formation. Our observation supports the use of thiol supplements as a potential therapeutic strategy against severe COVID-19 cases and a Phase II (NCT04374461) open-label clinical trial launched in early May 2020 by the Memorial Sloan Kettering Cancer Center.


Assuntos
Adutos de DNA/efeitos dos fármacos , DNA/efeitos dos fármacos , Glutationa/farmacologia , Inflamação/fisiopatologia , Ácido Peroxinitroso/efeitos adversos , Doença Aguda , Animais , Betacoronavirus , COVID-19 , Bovinos , Infecções por Coronavirus/tratamento farmacológico , DNA/química , Adutos de DNA/química , Dano ao DNA , Glutationa/química , Células HEK293 , Humanos , Mutagênicos/química , Mutagênicos/farmacologia , Pandemias , Ácido Peroxinitroso/química , Pneumonia Viral/tratamento farmacológico , SARS-CoV-2 , Salmonella typhimurium/genética
14.
PLoS Comput Biol ; 15(5): e1007070, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31120880

RESUMO

Analysis methods based on simulations and optimization have been previously developed to estimate relative translation rates from next-generation sequencing data. Translation involves molecules and chemical reactions, hence bioinformatics methods consistent with the laws of chemistry and physics are more likely to produce accurate results. Here, we derive simple equations based on chemical kinetic principles to measure the translation-initiation rate, transcriptome-wide elongation rate, and individual codon translation rates from ribosome profiling experiments. Our methods reproduce the known rates from ribosome profiles generated from detailed simulations of translation. By applying our methods to data from S. cerevisiae and mouse embryonic stem cells, we find that the extracted rates reproduce expected correlations with various molecular properties, and we also find that mouse embryonic stem cells have a global translation speed of 5.2 AA/s, in agreement with previous reports that used other approaches. Our analysis further reveals that a codon can exhibit up to 26-fold variability in its translation rate depending upon its context within a transcript. This broad distribution means that the average translation rate of a codon is not representative of the rate at which most instances of that codon are translated, and it suggests that translational regulation might be used by cells to a greater degree than previously thought.


Assuntos
Elongação Traducional da Cadeia Peptídica , Iniciação Traducional da Cadeia Peptídica , Animais , Códon/genética , Códon/metabolismo , Biologia Computacional , Simulação por Computador , Cinética , Camundongos , Modelos Biológicos , Células-Tronco Embrionárias Murinas/metabolismo , Conformação de Ácido Nucleico , Capuzes de RNA/química , Capuzes de RNA/genética , Capuzes de RNA/metabolismo , RNA Fúngico/química , RNA Fúngico/genética , RNA Fúngico/metabolismo , Ribossomos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Transcriptoma
16.
Cureus ; 16(8): e67614, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39310437

RESUMO

INTRODUCTION:  Interim restorations are essential in restorative dentistry, serving as temporary solutions until permanent restorations can be placed. Polymethyl methacrylate (PMMA) is a promising solution for customizing teeth for removable dentures to match the exact requirements of patients. The color stability of these restorations is critical for patient satisfaction. PMMA is a widely used material for interim restorations due to its favorable properties. The study compares the color stability of PMMA interim restorations polished using traditional pumice versus Algishine, a novel polishing agent derived from pulverized old alginate impressions. MATERIALS AND METHODS:  The 3-D design software Geomagic Design X (3D Systems, Rock Hill, CA) created a standard tessellation language file of 2-cm radius circles. Sixty PMMA samples were milled and divided into two groups of 30 each. Group A samples were polished using pumice, while group B samples were polished with Algishine. Baseline color measurements were taken using a spectrophotometer (VITA Easyshade V, VITA Zahnfabrik, Bad Säckingen, Germany). The samples were then subjected to staining with coffee, tea, and red wine solutions for 30 days, simulating oral conditions. Post-staining color measurements were taken, and color changes (ΔE) were calculated at the seven-day (t1) and one-month (t2) mark. The Shapiro-Wilk test assessed normality, followed by a two-way ANOVA test to compare color change values at different time points. RESULTS:  At t1 (seven days), there were no significant differences between groups A and B in the coffee and tea staining groups. However, significant differences were observed in red wine staining, with group B exhibiting lower ΔE values (0.14 ± 0.067) compared to group A (0.38 ± 0.076) (p < 0.01). At t2 (30 days), significant differences were noted in all staining groups. Group B consistently showed lower ΔE values: coffee (0.125 ± 0.084 vs. 0.236 ± 0.015, p < 0.01), tea (0.254 ± 0.087 vs. 0.391 ± 0.015, p < 0.01), and red wine (1.174 ± 0.045 vs. 1.309 ± 0.074, p < 0.01), indicating superior resistance to staining compared to group A. DISCUSSION:  The results suggest that Algishine is more effective than pumice in maintaining the color stability of PMMA interim restorations. The novel polishing agent derived from old alginate impressions enhances esthetic longevity and provides an eco-friendly solution for recycling dental material waste. CONCLUSION:  Algishine performs superiorly in preserving the color of PMMA interim restorations against common staining agents. Its application can potentially improve patient satisfaction and contribute to sustainable dental practices.

17.
Cureus ; 16(6): e63290, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39070325

RESUMO

INTRODUCTION: Conventionally fabricated denture base resins have been used for over 150 years. Newer denture base resins can provide a superior fit and may be customized to the patient's characteristics, but the literature on their cleansibility remains limited. The oral cavity can be a hub for thousands of microflora. The maintenance of complete dentures by edentulous patients depends not only on the maintenance of the patient but also on the material used, biofilm adherence, and polishability. MATERIALS AND METHODS: Cuboid specimens of 10 × 5 × 2 mm were designed using the Meshmixer version 3.5 software (Meshmixer, Australia). The standard tessellation (STL) file was imported and sent for printing (NextDent, Netherlands) (Group 1), milling in polymethyl methacrylate (PMMA) (Ivotion, Ivoclar, Schaan, Liechtenstein) (Group 2), and wax milling (Upcera, China), followed by flasking, counter flasking, and packing using heat-cured acrylic resin (DPI, India) (Group 3). The obtained specimens were polished using pumice and sterilized using a UV sterilization unit. The specimens were then immersed in a suspension of candida broth. After three days of biofilm formation, a colony count was performed and noted as colony-forming units per milliliter (CFU/mL). Specimens were treated using Secure denture cleansing tablets (Ghent, New York), table salt (iodized table salt, Tata, India), Clinsodent (ICPA, Mumbai, India), and Polident denture cleansing powder (Polident, Ontario, Canada). A colony count was done after treatment, and the data were tabulated. Statistical analysis was done using SPSS software to compare the efficiency of denture cleansers in all three groups, and statistical significance was set at 0.05. The Kolmogorov-Smirnov test was done to confirm the normality of the data, followed by a one-way analysis of variance (ANOVA) test to compare the efficiency of denture cleansers on the removal of candida colonies. RESULTS: Milled denture base resins showed a significantly lower colony count when compared to printed and conventionally fabricated denture base resins. The denture cleansers showed high efficacy in all groups, with the most significant being Secure, which showed a mean difference ranging from 8.114 to 9.887 CFU/mL, followed by Clinsodent, showing a mean of 6.699-9.863 CFU/mL, followed closely by Polident, showing 4.964-7.114 CFU/mL, followed by table salt, being 5.254-8.920 CFU/mL. The 95% confidence interval confirmed statistical significance. CONCLUSION: The highest candida colony count was demonstrated by the conventional, followed by rapid prototyping, and was least with milled denture base resins. Following treatment with denture cleansers, Secure demonstrated almost complete eradication of colonies, making it the most effective option. Salt exhibited the lowest efficiency, followed closely by Polident and Clinsodent, and the most effective was Secure denture cleanser.

18.
Cureus ; 16(6): e62080, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38989398

RESUMO

Introduction The main reason veneered zirconia restorations fail is due to porcelain veneer chipping. This chipping usually starts from wear marks on the chewing surface. As a result, small cracks under the contact area can grow into larger ones across the veneer layer. The veneer ceramic layer is more vulnerable to fractures because it has lower toughness and slightly lower stiffness compared to the base framework material. Thus, even when there's significant chipping, the main framework material usually stays protected with a thin layer of veneer ceramic on top. The aim of this in vitro study is to compare the edge strength of Monolithic Zirconia Crowns with that of Indirect Composite Layered Zirconia Crowns without aging. Materials and methods This research involved creating 12 hand-layered all-ceramic crowns and 12 indirect composite layered zirconia crowns. The sample size was determined using a G*Power calculation (Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany). The zirconia frameworks (Upcera HT White; UPCERA Dental America Inc., Cerritos, CA, US) were milled and sintered following the manufacturer's instructions. For the all-ceramic group, veneering porcelain (e.max Ceram; Ivoclar Vivadent, Schaan, Liechtenstein) was hand-applied. In contrast, the indirect composite group utilized Ceramage (Shofu, Kyoto, Japan). An Instron 4501 universal testing machine (Instron Corp., Canton, MA, USA) was employed for the edge chipping tests, and a Vickers indenter (Shanghai Toyo Diamond Tools Co., LTD, Shanghai, China) was used to apply the load. The mean value for edge chipping was analyzed using an unpaired t-test with IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, NY, USA). The normality of the data was confirmed, and statistical significance was set at 0.05. Results Monolithic Zirconia Crowns (Group 1) require significantly more force (mean: 405 N) to induce an edge chip compared to Indirect Composite Layered Zirconia Crowns (Group 2) (mean: 300 N). The 95% confidence interval (83.43261 N to 109.90072 N) confirms the statistical significance of this difference. Conclusion In conclusion, when evaluating restorative materials based on both esthetic and functional criteria, monolithic zirconia stands out due to its combination of strength, esthetic potential, biocompatibility, and versatility.

19.
Cureus ; 16(8): e68073, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39347209

RESUMO

BACKGROUND: Indirect restorations are a staple restorative option in dentistry due to their versatility, exceptional aesthetics, and desirable strength and longevity. Metal ceramics and all ceramics are the material of choice for permanent restorations but come with certain disadvantages, such as chipping, fracture, and wear of the antagonist tooth or restoration. Polymethylmethacrylate (PMMA) and indirect composite resins are commonly used materials due to their favourable properties for temporary restorations, but lately, they have been chosen as the restorative material of choice for implant-supported full-mouth rehabilitations. This study aimed to evaluate and compare the colour stability and surface roughness of PMMA and indirect composite resins under both ageing and non-ageing conditions. This would greatly help a clinician in choosing materials depending on the clinical scenarios. AIM: This study aims to evaluate the colour stability and surface roughness of PMMA and indirect composite resins with and without ageing. METHODS: Specimens of PMMA and indirect composite resins were fabricated and subjected to an ageing process involving thermocycling in the TW-C4.4 (Tae-Won Tech, Incheon, Korea) and immersion in a staining solution. Colour stability was assessed using a spectrophotometer (SpectraMagic NX, RM2002QC, Konica Minolta Corp., Ramsey, Japan), and surface roughness was measured using a stylus profilometer (Mituyoto, Mituyoto Corporation, Kawasaki, Japan). Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 24 (Released 2016; IBM Corp., Armonk, New York) to determine significant differences between materials and ageing effects. RESULTS: PMMA exhibited significantly higher colour changes and increased surface roughness post-ageing compared to indirect composite resins. The findings underscored PMMA's susceptibility to discolouration and surface degradation under thermal stress conditions. CONCLUSION: PMMA demonstrates inferior colour stability and increased surface roughness following thermocycling compared to indirect composite materials, suggesting careful consideration in material selection for provisional restorations. Further research should explore additional ageing processes and materials to enhance understanding and improve clinical outcomes.

20.
Cureus ; 16(6): e61633, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38966468

RESUMO

Introduction The evolution of computer-aided design/computer-aided manufacturing (CAD/CAM) systems has heightened the significance of digital models in dentistry, particularly for fabricating prostheses like inlays, crowns, and bridges. While digital dentistry offers enhanced speed and precision, the initial investment in intraoral scanners may pose a barrier for some clinicians. Extraoral or lab scanners, however, offer a viable alternative, reducing laboratory time and providing accurate prostheses fit, though challenges such as reflective surfaces and availability of scanning sprays persist, impacting scanning quality and operator technique. Optical scanning using laboratory scanners is a routine practice in today's age of digital dentistry. Often these require powder opacification to record fine details. There are numbered studies on the accuracy of scanning sprays. Materials and methods Ten casts, poured with type 4 dental stone (Elite Rock, Zhermack, Italy) with single implants, were used for the purpose of this study. Each cast was scanned by two different operators, using both mediums. It was scanned using an extraoral scanner (E4, 3Shape, Copenhagen, Denmark). Operator A used easy scan (Alphadent, Korea), followed by zirconia dust (Upcera, Guangdong, China), whereas operator B used zirconia dust first. Digital models within each group were superimposed individually to measure precision. Results Easy scan operator 1 and zirconia dust operator 1 differ by 0.16000 (p = 0.0802). In scenario 2, easy scan operator 2 and zirconia dust operator 2 differ by 0.21900 (p = 0.0212) . Operator type significantly affects performance, emphasizing the need to account for operator variability in relevant contexts. The trueness values obtained for zirconia dust and easy scan among both operators were statistically insignificant.  Conclusion Zirconia dust can be reliably used for extraoral scanning of abutments in place of optical scanning sprays.

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