RESUMO
BACKGROUND: Extracellular vesicles (EVs) are membrane-enclosed structures containing lipids, proteins, and RNAs that play a crucial role in cell-to-cell communication. However, the precise mechanism through which circulating EVs disrupt hepatic glucose homeostasis in gestational diabetes mellitus (GDM) remains unclear. RESULTS: Circulating EVs isolated from human plasma were co-cultured with mammalian liver cells to investigate the potential induction of hepatic insulin resistance by GDM-EVs using glucose output assays, Seahorse assays, metabolomics, fluxomics, qRT-PCR, bioinformatics analyses, and luciferase assays. Our findings demonstrated that hepatocytes exposed to GDM-EVs exhibited increased gluconeogenesis, attenuated energy metabolism, and upregulated oxidative stress. Particularly noteworthy was the discovery of miR-1299 as the predominant miRNA in GDM-EVs, which directly targeting the 3'-untranslated regions (UTR) of STAT3. Our experiments involving loss- and gain-of-function revealed that miR-1299 inhibits the insulin signaling pathway by regulating the STAT3/FAM3A axis, resulting in increased insulin resistance through the modulation of mitochondrial function and oxidative stress in hepatocytes. Moreover, experiments conducted in vivo on mice inoculated with GDM-EVs confirmed the development of glucose intolerance, insulin resistance, and downregulation of STAT3 and FAM3A. CONCLUSIONS: These results provide insights into the role of miR-1299 derived from circulating GDM-EVs in the progression of insulin resistance in hepatic cells via the STAT3/FAM3A axis and downstream metabolic reprogramming.
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Diabetes Gestacional , Vesículas Extracelulares , Glucose , Hepatócitos , Homeostase , Resistência à Insulina , Fígado , MicroRNAs , Fator de Transcrição STAT3 , Animais , Feminino , Humanos , Camundongos , Gravidez , Regiões 3' não Traduzidas , Diabetes Gestacional/metabolismo , Diabetes Gestacional/genética , Vesículas Extracelulares/metabolismo , Glucose/metabolismo , Células Hep G2 , Hepatócitos/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/genética , Estresse Oxidativo , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genéticaRESUMO
STATEMENT OF PROBLEM: Denture stomatitis can pose serious health risks, especially to older people. Chemical denture cleaning agents must be effective, yet not adversely affect the longevity of removable dentures. Ready-to-use (RTU) neutral pH electrolyzed oxidizing water (EOW) is an effective biocide against Candida albicans biofilms on denture resins, but the effects of daily disinfection with EOW on the physical and mechanical properties of resins have not been established. PURPOSE: The purpose of this in vitro study was to investigate the effects of simulated long-term exposure to RTU EOW on the color, surface characteristics, and flexural strength of denture base resins. MATERIAL AND METHODS: Heat-polymerized (HP), 3D printed (3D) and computer-aided design and computer-aided manufacture (CAD-CAM)-milled (CC) denture resin specimens (square: 20×20×3.3 mm; beam: 64×10×3.3 mm) were immersed in tap water (TW), RTU EOW (Neutral Anolyte ANK; Envirolyte; EOW), or a commercial denture cleaning tablet solution (Polident 3-Minute; Glaxo SmithKline; PD), mimicking a 5-minute once daily disinfection routine performed up to 3.0 years. Color and surface roughness were recorded (n=3, squares), and changes in color (∆E00) and surface roughness (∆Ra) were calculated. Flexural strength (n=12, beams) and surface hardness (n=18, beams) were measured with a universal testing machine. The fractured surfaces of specimens were examined by scanning electron microscopy and energy dispersive spectroscopy. Data were assessed by performing the Shapiro-Wilk or D'Agostino and Pearson normality tests. Two-way ANOVA or the Kruskal-Wallis test with a post hoc Tukey HSD or Dunn multiple comparisons (α=.05) was used for statistical analyses. RESULTS: No significant changes were found in either color or surface roughness for HP, 3D, and CC resins after 1.5-year and 3.0-year immersion in any of the agents (P>.05). The surface hardness of 3D resins reduced by 14% with TW and by 23% with EOW and PD at 3.0 years. The flexural strengths of all 3 resins were unaffected by 3.0-year immersion (P>.05). CONCLUSIONS: Simulated long-term immersion disinfection with RTU neutral pH EOW did not adversely affect the physical and mechanical properties of HP or CC denture resins.
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Bases de Dentadura , Higienizadores de Dentadura , Propriedades de Superfície , Água , Água/química , Concentração de Íons de Hidrogênio , Higienizadores de Dentadura/química , Teste de Materiais , Resistência à Flexão , Humanos , Materiais Dentários/química , Desenho Assistido por Computador , Técnicas In Vitro , Eletrólise , Resinas Acrílicas/química , Cor , Boratos , SulfatosRESUMO
Currently used wound dressings are ineffective. Hence, there is a need to develop introduce a high-performance medicament with multiple functions including rapid hemostasis and excellent antibacterial activity to meet the growing worldwide demand for wound healing products. Here, inspired by the strong adhesion of mussels and the enzyme-mimicking activity of nanometallic biomaterials, the authors developed an injectable hydrogel to overcome multiple limitations of current wound dressings. The hydrogel is synthesized via esterification reaction between poly(vinyl alcohol) (PVA) and 3,4-dihydroxyphenylalanine (DOPA), followed by catechol-metal coordination between Cu2+ and the catechol groups of DOPA to form a PVA-DOPA-Cu (PDPC) hydrogel. The PDPC hydrogel possesses excellent tissue adhesive, antioxidative, photothermal, antibacterial, and hemostatic properties. The hydrogel rapidly and efficiently stopped bleeding under different traumatic conditions, including otherwise-lethal liver injury, high-pressure carotid artery rupture, and even fatal cardiac penetration injuries in animal models. Furthermore, it is demonstrated that the PDPC hydrogel affected high-performance wound repair and tissue regeneration by accelerating re-epithelialization, promoting collagen deposition, regulating inflammation, and contributing to vascularization. The results show that PDPC hydrogel is a promising candidate for rapid hemorrhage control and efficient wound healing in multiple clinical applications.
Assuntos
Hemostáticos , Animais , Hemostáticos/farmacologia , Antioxidantes/farmacologia , Hidrogéis , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Catecóis , HemostasiaRESUMO
The aim of the study was to investigate the microbial colonization (by Candida species, anaerobic and facultative anaerobic bacteria) of maxillary obturators used for the restoration of maxillary defects, including during radiotherapy.Retrospective cohort study.Fifteen patients requiring a maxillary obturator prosthesis had swabs of their obturators and adjacent tissues taken at different stages of their treatment over a period of 8 years.Identification of microbial species from the swabs was carried out using randomly amplified polymorphic DNA polymerase chain reaction (RAPD PCR) analysis, checkerboard DNA-DNA hybridization, CHROMagar Candida chromogenic agar, and DNA sequencing.Candida species were detected in all patients and all patients developed mucositis and candidiasis during radiotherapy which was associated with an increase in colonization of surfaces with Candida spp., particularly C albicans. Microbial colonization increased during radiotherapy and as an obturator aged, and decreased following a reline, delivery of a new prosthesis, or antifungal treatment during radiotherapy.Microbial colonization of maxillary obturators was related to the stage of treatment, age of the obturator material, radiotherapy and antifungal medications, and antifungal treatment may be recommended if C albicans colonization of palatal tissues is greater than 105 colony-forming units per cm2 following the first week of radiotherapy.
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Antifúngicos , Prostodontia , Idoso , Humanos , Candida/genética , Obturadores Palatinos , Técnica de Amplificação ao Acaso de DNA Polimórfico , Estudos RetrospectivosRESUMO
OBJECTIVES: The objective of this scoping review was to map evidence of electrolysed oxidising water (EOW) as a biocide for dental applications of relevance to older people and identify research gaps. BACKGROUND: EOW is an emerging, "green," and cost-effective biocide. There are no reviews on the landscape of EOW research as either an antiseptic or disinfectant in dental healthcare or its suitability for the oral healthcare of older people. MATERIALS AND METHODS: The review follows the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. Database searches (Google Scholar, PubMed, Web of Science, Ovid, Scopus and Science Direct) were undertaken using MESH terms and Boolean operators with no date restrictions, to identify full-text, original reports published in English-language peer-reviewed journals. RESULTS: The search yielded 114 papers that met the inclusion/exclusion criteria. Dental applications of EOW include its use as an endodontic irrigant (39%); mouth rinse/surgical irrigant (21%); disinfectant for dental unit water lines (19%) and dental biomaterials (17%); and for antimicrobial efficacy, effects on oral tissues and on dental material properties. Most studies (83%) evaluated a single EOW formulation (acidic, moderately acidic or neutral) that was either generated at 'point-of-use' (POU; 72%), bottled ('ready-to-use', RTU; 24%) or from unspecified (3%) sources. Six reports evaluated storage-related parameters and 25 evaluated clinical applications; 89 were in vitro studies and one investigated the cost-effectiveness of POU EOW. CONCLUSIONS: Neutral-pH, EOW is effective as an antimicrobial agent without deleterious effects on oral tissues. However, research on the impact of storage conditions, anti-Candida biofilm efficacy and mechanism of action against yeasts, long-term effects on denture materials and cost-effectiveness is required to establish the suitability of EOW as a multipurpose biocide for dental healthcare, including infection-control requirements relating to older people.
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Anti-Infecciosos Locais , Anti-Infecciosos , Desinfetantes , Humanos , Idoso , Desinfetantes/uso terapêutico , Água , Atenção à SaúdeRESUMO
Overexpression of ATP-binding cassette (ABC) transporters is a major cause of drug resistance in fungal pathogens. Milbemycins, enniatin B, beauvericin, and FK506 are promising leads for broad-spectrum fungal multidrug efflux pump inhibitors. The characterization of naturally generated inhibitor-resistant mutants is a powerful tool to elucidate structure-activity relationships in ABC transporters. We isolated 20 Saccharomyces cerevisiae mutants overexpressing Candida albicans ABC pump Cdr1 variants resistant to fluconazole efflux inhibition by milbemycin α25 (8 mutants), enniatin B (8), or beauvericin (4). The 20 mutations were in just 9 residues at the centers of transmembrane segment 1 (TMS1) (6 mutations), TMS4 (4), TMS5 (4), TMS8 (1), and TMS11 (2) and in A713P (3), a previously reported FK506-resistant "hot spot 1" mutation in extracellular loop 3. Six Cdr1-G521S/C/V/R (TMS1) variants were resistant to all four inhibitors, four Cdr1-M639I (TMS4) variants were resistant to milbemycin α25 and enniatin B, and two Cdr1-V668I/D (TMS5) variants were resistant to enniatin B and beauvericin. The eight milbemycin α25-resistant mutants were altered in four amino acids as follows: G521R, M639I, A713P, and T1355N (TMS11). These four Cdr1 variants responded differently to various types of inhibitors, and each exhibited altered substrate specificity and kinetic properties. The data infer an entry gate function for Cdr1-G521 and a role for Cdr1-A713 in the constitutively high Cdr1 ATPase activity. Cdr1-M639I and -T1355N possibly cause inhibitor resistance by altering TMS contacts near the substrate/inhibitor-binding pocket. Models for the interactions of substrates and different types of inhibitors with Cdr1 at various stages of the transport cycle are presented.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Candida albicans , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Candida albicans/genética , Candida albicans/metabolismo , Farmacorresistência Fúngica/genética , Fluconazol/metabolismo , Fluconazol/farmacologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Especificidade por SubstratoRESUMO
Survival outcomes of patients with histiocytic neoplasms are poor, with no standard-of-care treatments available for these malignancies. Recent characterization of the genomic landscape of various histiocytic neoplasms have shown a predominance of activating driver mutations within the MAPK/ERK pathway (ie, BRAF, MEK, KRAS, MAPK, and NRAS). Subsequently, successful treatment of these malignancies with BRAF and MEK inhibitors has been reported. This report presents the first patient with histiocytic sarcoma harboring a somatic KRAS Q61H mutation who was subsequently treated to a near complete response with the MEK inhibitor trametinib. Due to patient preference, lack of standard of care treatments, and associated morbidity from head and neck dissection, initial disease reduction provided by trametinib therapy allowed for a less morbid resection. This case report highlights the utility of up-front next-generation sequencing and the efficacy of MEK inhibition in patients with histiocytic sarcoma harboring activating KRAS mutations.
Assuntos
Sarcoma Histiocítico , Humanos , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas B-raf/genética , Inibidores de Proteínas Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , MutaçãoRESUMO
INTRODUCTION: Early detection of coronavirus disease 2019 (COVID-19) is paramount for controlling the progression and spread of the disease. Currently, nasopharyngeal swabbing (NPS) is the standard method for collecting specimens. Saliva was recently proposed as an easy and safe option with many authorities adopting the methodology despite the limited evidence of efficacy. OBJECTIVES: The aim of this review was to systematically evaluate the current literature on the use of saliva test for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and carry out a meta-analysis to determine its diagnostic accuracy. MATERIALS AND METHODS: Prospective studies were searched for in electronic databases, complemented by hand-searching relevant journals. The risk of bias and applicability were assessed using the revised Quality Assessment of Studies of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analyses and meta-regression modeling were performed to calculate the diagnostic accuracy and examine sources of heterogeneity. RESULTS: A total of 16 studies were included with 2928 paired samples. The overall meta-analysis showed a high sensitivity and specificity for saliva test at 0.88 (95% CI 0.82-0.92) and 0.92 (95% CI 0.75-0.98), respectively. The diagnostic odds ratio was calculated at 87 (95% CI 19-395) and area under the curve was calculated as 0.92 (95% CI 0.90-0.94) suggesting very good performance of the saliva tests in detecting SARS-CoV-2. CONCLUSION: Saliva testing has a very good discriminative and diagnostic ability to detect of SARS-CoV-2. Additional large and well-designed prospective studies are needed to further validate the diagnostic accuracy and determine a safe sample collection method prior to its recommendation for mass application. CLINICAL RELEVANCE: Saliva demonstrated high sensitivity and specificity. The use of saliva will allow for self-collection of specimens and specimen collection in outpatient and community clinics.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Saliva , Estudos Prospectivos , Manejo de Espécimes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Many modifications to fixed orthodontic appliances have been introduced to manage biofilm formation. The aim of this review was to investigate elastomeric ligation in comparison with stainless steel ligation and self-ligation with regard to microbiological and clinical indicators of biofilm formation in patients wearing multi-bracketed fixed orthodontic appliances. METHODS: The MEDLINE and the EMBASE databases were searched up to February 2021 and supplemented by additional manual searches of bibliographies. Parallel-group and split-mouth randomized controlled trials (RCTs) comparing different ligation methods were identified. The Cochrane Risk of Bias-2 tool was applied to assess the quality of evidence. RESULTS: A total of 11 RCTs were included in this review. Nine RCTs compared self-ligation and elastomeric ligation; two compared elastomeric ligation and stainless steel ligation. The included studies had either some concerns or were at a high risk of bias. Qualitative assessment of the studies identified that there were no significant differences in biofilm formation between elastomeric ligation and self-ligation, but that stainless steel ligation was less susceptible to biofilm formation than elastomeric ligation. CONCLUSIONS: There were no significant differences between self-ligation and elastomeric ligation for biofilm formation in patients wearing multi-bracketed fixed orthodontic appliances. Stainless steel ligation may accumulate less biofilm than elastomeric ligation; however, the clinical significance of the difference could not be evaluated. Further high-quality studies are required in order to determine which ligation method is better for managing biofilm formation in patients wearing multi-bracketed fixed orthodontic appliances.
Assuntos
Braquetes Ortodônticos , Biofilmes , Humanos , Aço InoxidávelRESUMO
OBJECTIVES: To investigate the prevalence of halitosis in young adults. METHODS: Young adults (n = 372; mean age = 21.0 ± 2.6 years old, range = 18-30 years) in Dunedin, New Zealand, were recruited into the cross sectional study after providing informed consent. The prevalence of halitosis was determined using both objective measurements (parts per billion [ppb] volatile sulphur compounds [VSCs] in the exhaled air) and subjective measurements (self-reported halitosis questionnaire, tongue coating index, and organoleptic assessment). RESULTS: Volatile sulphur compounds measurements indicated that the prevalence of halitosis (values ≥140 ppb) was 31.2%; 25.6% of participants self-reported halitosis. The organoleptic assessment revealed that 14.3% of the participants had a score of ≥2. A positive correlation was found between the VSC measurements and organoleptic assessment (p < 0.05). No significant relationship was found between self-reported halitosis and either organoleptic assessment or VSC measurements. Self-reported dry mouth, smoking, oral hygiene index, DMFT index, and tongue coating score were significantly associated with the organoleptic assessment (p < 0.05). The self-reported dry mouth, mouth breathing and tongue coating score were significantly associated with the VSC scores (p < 0.05). CONCLUSION: Halitosis, as represented by VSC, was found in 31.2% of the participants. VSC scores and organoleptic assessment were positively correlated. There was no significant relationship between self-reported halitosis and either organoleptic assessment or VSC measurements.
Assuntos
Halitose , Xerostomia , Adulto Jovem , Humanos , Adolescente , Adulto , Halitose/diagnóstico , Halitose/epidemiologia , Prevalência , Estudos Transversais , Nova Zelândia/epidemiologia , Língua , Compostos de EnxofreRESUMO
The aim of the study was to compare the response of calvarial and femoral osteoblasts cultured in a 3D hydrogel environment to cyclic compressive mechanical loading. Human foetal femoral and calvarial osteoblasts were encapsulated in a semi-synthetic thiol-modified hyaluronan gelatin polyethylene glycol diacrylate (PEGDA) cross-linked HyStemC hydrogel. Constructs were subjected to a cyclic compressive strain of 33.4 kPa force every second for 5 s every hour for 6 h per day using FlexCell BioPress culture plates and compared to non-compressed constructs. Cell viability, mineralisation, and morphological changes were observed over 21 days. BMP2, ALP, COL1A1, COL2A1, and OCN gene expression levels were quantified. Encapsulated osteoblast numbers increased and formed hydroxyapatite over a 21-day period. Cell viability decreased under a cyclical strain when compared to cells under no strain. Femoral osteoblasts under strain expressed increased levels of BMP2 (53.9-fold) and COL1A1 (5.1-fold) mRNA compared to no strain constructs. Surprisingly, no BMP2 mRNA was detected in calvarial osteoblasts. Osteoblasts derived from endochondral (femoral) and intra-membranous (calvarial) processes behaved differently in 3D-constructs. We therefore recommend that site-specific osteoblasts be used for future bone engineering and bone replacement materials and further research undertaken to elucidate how site-specific osteoblasts respond to cyclic compressive loads.
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Fêmur , Osteoblastos , Durapatita , Expressão Gênica , Humanos , Estresse MecânicoRESUMO
OBJECTIVES: To examine the relationship between masticatory muscle activity (MMA), self-reported oral behaviours (OBs) and overall physical activity (PA) in adult women. MATERIALS AND METHODS: MMA and PA were assessed by a wearable electromyography (EMG) device and accelerometer respectively, worn over 2 non-consecutive days by 53 women (mean age 27.5 ± 6.4 years). Following the second recording day, self-reported OBs were assessed. MMA was assessed by the number, amplitude and duration of masseter contraction episodes. Masseter muscle EMG outcome measures were number of contraction episodes per hour (CEs/h) and the relative contraction time (RCT%). PA was assessed by time accumulated in moderate to vigorous physical activity (MVPA) and 10-min bouts of MVPA per hour. Data were analysed using mixed model analysis. RESULTS: MMA in free-living conditions consisted mostly of low-amplitude (<10% maximum voluntary clenching) and short-duration (<10 s) contraction episodes. Masseter CEs/h were not associated with self-reported levels of OB. Masseter CEs/h were positively associated with time accumulated in MVPA (F = 9.9; p = 0.002) and negatively associated with 10-min bouts of MVPA/h (F = 15.8; p <0.001). RCT% was not significantly associated with either. CONCLUSIONS: Objectively assessed MMA is not associated with self-reported OB in free-moving adult females. Moderate to vigorous exercise and physical inactivity are accompanied with an increase in the number of masseter muscle contractions and thus possibly tooth clenching activity. CLINICAL RELEVANCE: OB can be influenced by the type and extent of PA. Subjective assessment of MMA by questionnaire and/or interviews may be invalid.
Assuntos
Bruxismo , Músculo Masseter , Adulto , Exercício Físico , Feminino , Humanos , Músculos da Mastigação , Autorrelato , Adulto JovemRESUMO
BACKGROUND: Maxillofacial prosthetics includes restoration of maxillary defects resulting from resection of palate and nasosinus neoplasms with obturator prostheses which may be colonized by microorganisms and function as a reservoir of infection. Patients with neoplasms commonly also require radiotherapy that can result in changes in saliva quality and quantity and changes in the oral microbial flora. The altered flora, in individuals immunocompromised from cancer therapy, increases their risk of prosthesis-related infections. OBJECTIVES: In this review article, we explore microbial biofilms, their main components, mechanisms of microbial adhesion, and stages of biofilm development. We also discuss the different materials that are used for manufacturing maxillary obturators, their characteristic features, and how these can affect microbial adhesion. Furthermore, we shed some light on the factors that affect microbial adhesion to the surface of maxillary obturators including tissue proteins, protein adsorption, and the acquired enamel pellicle. CONCLUSIONS: The conclusions drawn from this literature review are that it is imperative to minimize the risk of local and systemic infections in immunocompromised patients with cancer having maxillary defects. It is also important to determine the role of saliva in microbial adhesion to obturator materials as well as develop materials that have a longer life span with surface characteristics that promote less microbial adhesion than current materials.
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Implantes Dentários , Neoplasias Maxilares , Biofilmes , Humanos , Maxila , Obturadores PalatinosRESUMO
The 23-membered-ring macrolide tacrolimus, a commonly used immunosuppressant, also known as FK506, is a broad-spectrum inhibitor and an efflux pump substrate of pleiotropic drug resistance (PDR) ATP-binding cassette (ABC) transporters. Little, however, is known about the molecular mechanism by which FK506 inhibits PDR transporter drug efflux. Thus, to obtain further insights we searched for FK506-resistant mutants of Saccharomyces cerevisiae cells overexpressing either the endogenous multidrug efflux pump Pdr5 or its Candida albicans orthologue, Cdr1. A simple but powerful screen gave 69 FK506-resistant mutants with, between them, 72 mutations in either Pdr5 or Cdr1. Twenty mutations were in just three Pdr5/Cdr1 equivalent amino acid positions, T550/T540 and T552/S542 of extracellular loop 1 (EL1) and A723/A713 of EL3. Sixty of the 72 mutations were either in the ELs or the extracellular halves of individual transmembrane spans (TMSs), while 11 mutations were found near the center of individual TMSs, mostly in predicted TMS-TMS contact points, and only two mutations were in the cytosolic nucleotide-binding domains of Pdr5. We propose that FK506 inhibits Pdr5 and Cdr1 drug efflux by slowing transporter opening and/or substrate release, and that FK506 resistance of Pdr5/Cdr1 drug efflux is achieved by modifying critical intramolecular contact points that, when mutated, enable the cotransport of FK506 with other pump substrates. This may also explain why the 35 Cdr1 mutations that caused FK506 insensitivity of fluconazole efflux differed from the 13 Cdr1 mutations that caused FK506 insensitivity of cycloheximide efflux.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Antifúngicos/farmacologia , Candida albicans/genética , Proteínas Fúngicas/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Tacrolimo/farmacologia , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/genética , Candida albicans/efeitos dos fármacos , Depsipeptídeos/farmacologia , Farmacorresistência Fúngica/genética , Saccharomyces cerevisiae/efeitos dos fármacosRESUMO
Human genome and exome sequencing are powerful research tools that can generate secondary findings beyond the scope of the research. Most secondary genomic findings are of low importance, but some (for a current estimate of 1%-3% of individuals) confer high risk of a serious disease that could be mitigated by timely medical intervention. The impact and scope of secondary findings in genome and exome sequencing will only increase in the future. There is considerable agreement that high-impact findings should be returned to participants, but many researchers performing genomic research studies do not have the background, skills, or resources to identify, verify, interpret, and return such variants. Here, we introduce a proposal for the formation of a secondary-genomic-findings service (SGFS) that would support researchers by enabling the return of clinically actionable sequencing results to research participants in a standardized manner. We describe a proposed structure for such a centralized service and evaluate the advantages and challenges of the approach. We suggest that such a service would be of greater benefit to all parties involved than present practice, which is highly variable. We encourage research centers to consider the adoption of a centralized SGFS.
Assuntos
Genoma Humano , Genômica/métodos , Achados Incidentais , Predisposição Genética para Doença , Humanos , Análise de SequênciaRESUMO
OBJECTIVES: To test a smartphone-assisted wireless device for assessing electromyographic (EMG) activity of the masseter muscle in freely moving individuals undertaking routine activities. MATERIALS AND METHODS: EMG activity was detected unilaterally from the masseter muscle in 12 volunteers using surface electrodes connected to both a smartphone-assisted wireless EMG device and a fixed-wired EMG equipment (reference standard). After performing a series of standardized tasks in the laboratory, participants wore the wireless device for 8 h while performing their normal routine. RESULTS: The wireless device reliably detected masseter muscle contraction episodes under both laboratory and natural environment conditions. The intraclass correlation coefficients for the muscle contraction episode amplitude and duration detected by the wireless and the wired equipment ranged from 0.94-1.00 to 0.82-1.00, respectively. Most masseter contraction episodes during normal routine were of low amplitude (< 10% MVC) and short duration (< 10 s), with no significant differences between sexes or facial side. CONCLUSIONS: Within the limitations of the study, smartphone-assisted monitoring of the jaw muscles represents a promising tool to investigate oral behavior patterns in free moving individuals. CLINICAL RELEVANCE: Smartphone-assisted monitoring of masticatory muscle activity may enable possible associations between excessive muscle activity, bruxism, dysfunction, and pain to be investigated, and managed via biofeedback.
Assuntos
Bruxismo , Eletromiografia , Músculos da Mastigação , Smartphone , Eletromiografia/métodos , Voluntários Saudáveis , Humanos , Músculo Masseter , Músculos da Mastigação/fisiologia , Contração MuscularRESUMO
BACKGROUND: This study evaluated the efficacy of four methods in removing Candida albicans from the acrylic base material used to fabricate removable orthodontic appliances. METHODS: Heat-processed bars of orthodontic acrylic were incubated in a suspension of C. albicans for 2 h at 37 °C. Samples were allocated into five groups (five bars per group) according to the cleaning method: (1) manual brushing using a toothbrush; (2) soaking in a commercial denture cleaning solution; (3) soaking in a commercial mouthwash solution; (4) using an ultrasonic cleaner; and (5) soaking in distilled water as a negative control. Yeast remaining attached to the bars after cleaning were removed by vortexing in growth medium and plated on Sabouraud dextrose agar. The reduction in yeast colony count after cleaning was calculated and expressed as the number of colony forming units per acrylic bar (CFU/bar). The experiment was carried out three times. RESULTS: All four cleaning methods resulted in a significant decrease in viable yeast cells associated with the acrylic bars compared to the control group. The mean percentage reduction in viable yeast cells affected by the cleaning methods was: brushing 89.9%; chlorhexidine 95.8%; ultrasonic cleaning 99.9%; and denture tablet 100%. CONCLUSIONS: All four methods evaluated in this study were effective, to some extent, in removing C. albicans from orthodontic acrylic samples. The most effective, and readily available, cleaning method was the use of commercial denture sterilizing tablets.
Assuntos
Resinas Acrílicas/química , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Bases de Dentadura/microbiologia , Higienizadores de Dentadura/farmacologia , Prótese Total/microbiologia , Higiene Bucal/métodos , Escovação Dentária/métodos , Contagem de Colônia Microbiana , Higienizadores de Dentadura/química , Desinfecção/métodos , Humanos , Água/químicaRESUMO
PURPOSE/OBJECTIVES: Overall non-melanoma head and neck skin cancer has a good prognosis; however, rarely patients have an aggressive variant which results in orbital invasion via perineural spread or direct extension. Despite these consequences, there are limited published studies defining this clinical entity. The main objectives of the current study are to describe orbital invasion patterns of non-melanoma head and neck skin cancers and their impact on survival. METHODS: Retrospective case series from a tertiary-care, academic institution performed between 2004 and 2014. Demographic and tumour characteristics are reported as well as patterns of orbital invasion, types of treatments received, and survival outcomes. RESULTS: There were 17 consecutive patients with non-melanoma skin cancer and orbital invasion who met inclusion criteria. Average age at orbital invasion diagnosis was 70.8 years old. 76% were male. Mean follow-up time was 28.5 months. Of these patients, 71% had squamous cell carcinoma and 29% had basal cell carcinoma. Brow (41%) was the most common primary sub-site followed by cheek (23%) and temple (12%). 76% of patients had a history of prior treatment. The lateral orbital wall (41%) was the most common site of invasion, followed by the medial orbital wall (29%) and antero-superior invasion (23%). Age, histology, and location of orbital invasion were associated with disease-specific and overall survival. CONCLUSION: Orbital invasion for non-melanoma head and neck skin cancers creates a treatment dilemma and the patterns of invasion are described. In addition, the location of orbital invasion is associated with survival outcomes.
Assuntos
Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Orbitárias/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/mortalidade , Carcinoma de Células Escamosas/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Orbitárias/mortalidade , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
Head and neck cancer surgery is often a complex multi-step procedure that includes major resections, vascularised tissue reconstruction, and extensive neck dissection. The upper aerodigestive tract mucosal lining is often disrupted during surgery, which requires the management of a clean-contaminated field and the need to reconstruct the mucosal lining. With bacterial contamination, surgical site infections (SSI) are a serious complication that can result in delayed wound healing, wound breakdown, fistula formation, and compromised tissue reconstruction. Methods to reduce SSI in patients with head and neck cancer have been intensely researched, yielding evolving and varied practice patterns. In this Review, we outline the data supporting perioperative antibiotic prophylaxis for clean-contaminated surgeries, which suggest that clindamycin is an inadequate prophylactic antibiotic therapy in the reduction of SSI, and that prolonged antibiotic courses have no established benefit. For salvage laryngectomy after radiotherapy with or without chemotherapy, reconstruction with vascularised tissue reduces the frequency and severity of pharyngocutaneous fistula formation. These evidence-based recommendations have been shown to reduce the chance of SSI after head and neck surgery.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Neoplasias de Cabeça e Pescoço/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Infecção da Ferida Cirúrgica/prevenção & controle , Clindamicina/uso terapêutico , Humanos , Procedimentos de Cirurgia Plástica , Fatores de RiscoRESUMO
Yeast, in particular Candida albicans, are the principal fungal cause of denture stomatitis, and can also be present as a commensal in many individuals. Few studies, however, have examined oral retention of yeast strains over time. We analyzed the yeast present in saliva samples and from the dentures of 10 individuals colonized with yeast but with no signs of stomatitis, before new complete maxillary dentures were fitted and also at 1, 3, and 6 months after denture replacement. Yeast species were presumptively identified on selective agar plates and were present in nine individuals before denture replacement and in six at the 6-month time point. C. albicans was detected in seven individuals pre-replacement, and in three by 6 months post-replacement. Sixty-two isolates (up to five from each C. albicans-positive sample) were analyzed by multilocus sequence typing (MLST) (33 from saliva and 29 from dentures). Six MLST allele profiles were identified that were common to several individuals. These profiles included three previously reported diploid sequence types (DSTs) and three novel DSTs. Two of the novel DSTs were closely related variants of a previously reported DST, and both showed loss of heterozygosity polymorphisms within one of the seven MLST gene sequences. For three individuals, at least one DST that was present before denture replacement was still detected in either saliva or on dentures at subsequent sampling times. Our results indicate that denture replacement reduces but does not remove, colonising yeast and confirm previous observations of C. albicans strain microevolution.