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Antibody incompatible transplantation (AIT) may be an only option for highly sensitized patients. Severe form of early antibody mediated rejection (AMR) adversely affects graft survival after AIT. The aim of this study was to identify individuals at risk of AMR. We analyzed 213 living donor AITs performed at our center. Among 120 ABOi, 58 HLAi and 35 DSA + FCXM-negative cases, the rates of early AMR were 6%, 31%, and 9%, respectively (p < 0.001). On multivariate analysis for graft loss, early AMR had a HR of 3.28 (p < 0.001). The HLAi group had worse death-censored graft survival (p = 0.003). In the HLAi group, Patients with aggressive variant AMR (AAMR) had greater percentage of C3d complement fixing DSA, higher baseline class I and total DSA MFI levels and B-cell FCXM RMF. C1q and C3d complement fixing DSA and strong positivity of baseline B- or T-cell FXCM as predictors of AAMR had 100% sensitivity. Early AMR is of significant clinical concern in AIT as it results in poor graft survival and is not well described in literature. An aggressive variant is characterized by massive rise in DSA levels at rejection. Baseline DSA, C1q, and C3d and baseline FCXM values can be used to risk-stratify candidates for AIT.
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Rejeição de Enxerto , Sobrevivência de Enxerto , Isoanticorpos , Transplante de Rim , Doadores Vivos , Humanos , Rejeição de Enxerto/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Sobrevivência de Enxerto/imunologia , Isoanticorpos/imunologia , Isoanticorpos/sangue , Complemento C1q/imunologia , Estudos Retrospectivos , Complemento C3d/imunologia , Idoso , Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Antígenos HLA/imunologia , Análise MultivariadaRESUMO
Exhaustive efforts have been dedicated to uncovering genomic aberrations linked to cancer susceptibility. Noncoding sequence variants and epigenetic alterations significantly influence gene regulation and could contribute to cancer development. However, exploring noncoding regions in hereditary cancer susceptibility demands cutting-edge methodologies for functionally characterizing genomic discoveries. Additionally, comprehending the impact on cancer development of variants in noncoding DNA and the epigenome necessitates integrating diverse data through bioinformatic analyses. As novel technologies and analytical methods continue to advance, this realm of research is rapidly gaining traction. Within this mini-review, we delve into future research domains concerning aberrations in noncoding DNA regions, such as pseudoexons, promoter variants and cis-epimutations.
[Box: see text].
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Epigênese Genética , Predisposição Genética para Doença , Mutação , Neoplasias , Humanos , Neoplasias/genética , Variação Genética , DNA Intergênico/genética , Regiões Promotoras Genéticas , Biologia Computacional/métodos , Genômica/métodosRESUMO
Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. The dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA-binding motif single-stranded interacting protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. RBMS1 polymorphism has been shown to be associated with obesity and type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of the differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in the adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes.
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Adipócitos , Adipogenia , Animais , Camundongos , Células 3T3-L1 , Adipócitos/metabolismo , Adipogenia/genética , Diferenciação Celular/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo dos Lipídeos/genética , Obesidade/metabolismo , Proteômica , TranscriptomaRESUMO
Secondary caries is one of the leading causes of resin-based dental restoration failure. It is initiated at the interface of an existing restoration and the restored tooth surface. It is mainly caused by an imbalance between two processes of mineral loss (demineralization) and mineral gain (remineralization). A plethora of evidence has explored incorporating several bioactive compounds into resin-based materials to prevent bacterial biofilm attachment and the onset of the disease. In this review, the most recent advances in the design of remineralizing compounds and their functionalization to different resin-based materials' formulations were overviewed. Inorganic compounds, such as nano-sized amorphous calcium phosphate (NACP), calcium fluoride (CaF2), bioactive glass (BAG), hydroxyapatite (HA), fluorapatite (FA), and boron nitride (BN), displayed promising results concerning remineralization, and direct and indirect impact on biofilm growth. The effects of these compounds varied based on these compounds' structure, the incorporated amount or percentage, and the intended clinical application. The remineralizing effects were presented as direct effects, such as an increase in the mineral content of the dental tissue, or indirect effects, such as an increase in the pH around the material. In some of the reported investigations, inorganic remineralizing compounds were combined with other bioactive agents, such as quaternary ammonium compounds (QACs), to maximize the remineralization outcomes and the antibacterial action against the cariogenic biofilms. The reviewed literature was mainly based on laboratory studies, highlighting the need to shift more toward testing the performance of these remineralizing compounds in clinical settings.
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Cárie Dentária , Metacrilatos , Humanos , Metacrilatos/química , Fosfatos de Cálcio/química , Compostos de Amônio Quaternário/farmacologia , Biofilmes , Minerais/farmacologia , Resinas Vegetais , Cárie Dentária/tratamento farmacológico , Cárie Dentária/prevenção & controle , Antibacterianos/farmacologia , Materiais Dentários/farmacologiaRESUMO
PURPOSE OF REVIEW: Optimizing deceased donor organ utilization is gaining recognition as a topical and important issue, both in the United Kingdom (UK) and globally. This review discusses pertinent issues in the field of organ utilization, with specific reference to UK data and recent developments within the UK. RECENT FINDINGS: A multifaceted approach is likely required in order to improve organ utilization. Having a solid evidence-base upon which transplant clinicians and patients on national waiting lists can base decisions regarding organ utilization is imperative in order to bridge gaps in knowledge regarding the optimal use of each donated organ. A better understanding of the risks and benefits of the uses of higher risk organs, along with innovations such as novel machine perfusion technologies, can help clinician decision-making and may ultimately reduce the unnecessary discard of precious deceased donor organs. SUMMARY: The issues facing the UK with regards to organ utilization are likely to be similar to those in many other developed countries. Discussions around these issues within organ donation and transplantation communities may help facilitate shared learning, lead to improvements in the usage of scarce deceased donor organs, and enable better outcomes for patients waiting for transplants.
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Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Transplantes , Humanos , Perfusão , Reino Unido , Listas de Espera , Doadores de TecidosRESUMO
BACKGROUND: The distinctive properties and high activity of calcium titanate nanoparticles (CaTiO3-NPs) increase their use in many products. However, the cytotoxic and genotoxic effects of CaTiO3-NPs in human cancer cell lines have not been well studied. Therefore, this study was conducted to explore CaTiO3-NPs induced cytotoxicity, genomic instability and apoptosis in human breast cancer (MCF-7) cells. METHODS: Sulforhodamine B (SRB) and the alkaline comet assays were done to study cell viability and DNA damage induction, respectively. Apoptosis induction and cell cycle distribution were analyzed using flow cytometry. The level of intracellular reactive oxygen species (ROS) was studied, and the expression levels of p53, Bax and Bcl2 genes were also measured. RESULTS: The results of the Sulforhodamine B (SRB) cytotoxicity assay showed that viability of MCF-7 cells was not affected by CaTiO3-NPs treatment for 24 h, however, exposure to CaTiO3-NPs for 72 h caused concentrations dependent death of MCF-7 cells. Treatment with CaTiO3-NPs for 72 h caused marked increases in intracellular ROS level and induced DNA damage. Treatment of MCF-7 cells with CaTiO3-NPs also caused MCF-7 cell cycle arrest at the G0 and S phases and s triggered apoptosis of MCF-7 cells by causing simultaneous increases in the expression levels of apoptotic p53 and Bax genes and a decrease in the expression level of anti-apoptotic Bcl2 gene. CONCLUSION: Collectively, it was concluded that CaTiO3-NPs cause time- and concentration-dependent cytotoxic effects in human MCF-7 cells through induction of ROS generation, genomic instability and apoptosis. Thus it is recommended that further in vitro and in vivo studies are therefore recommended to understand the cytotoxic and biological effects of CaTiO3-NPs.
RESUMO
BACKGROUND: Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilization, survival and function. METHODS: We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥2+ on dipstick testing, on kidney utilization, early graft function, graft failure and estimated glomerular filtration rate (eGFR). RESULTS: Eighteen percent (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% versus 82%; odds ratio 0.70, 95% confidence interval 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (hazard ratio 0.91, 95% confidence interval 0.74 to 1.11). There was also no association with delayed graft function, patient survival or eGFR at 1 or 3 years. CONCLUSIONS: Our study suggests reluctance in the UK to utilize kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilization without negatively impacting transplant outcomes.
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Transplante de Rim , Obtenção de Tecidos e Órgãos , Humanos , Adulto , Transplante de Rim/efeitos adversos , Estudos de Coortes , Albuminúria/etiologia , Doadores de Tecidos , Sobrevivência de Enxerto , Reino Unido/epidemiologia , Resultado do TratamentoRESUMO
Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF < 7 days, 576 (31·2%) had DGF 7-14 days, and 345 (18·7%) had DGF >14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14 days is a novel early biomarker for significantly worse longer-term outcomes.
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Transplante de Rim , Obtenção de Tecidos e Órgãos , Adulto , Estudos de Coortes , Função Retardada do Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Reino Unido/epidemiologiaRESUMO
There are concerns that simultaneous pancreas-kidney (SPK) transplants from donation after circulatory death (DCD) donors have a higher risk of graft failure than those from donation after brain death (DBD) donors. A UK registry analysis of SPK transplants between 2005 and 2018 was performed. Pancreas survivals of those receiving organs from DCD or DBD donors were compared. Multivariable analyses were used to adjust for baseline differences between the two groups and to identify factors associated with pancreas graft loss. A total of 2228 SPK transplants were implanted; 403 (18.1%) were from DCD donors. DCD donors were generally younger, slimmer, less likely to have stroke as a cause of death, with lower terminal creatinines and shorter pancreas cold ischemic times than DBD donors. Median (IQR) follow-up was 4.2 (1.6-8.1) years. On univariable analysis, there were no statistically significant differences in 5-year death-censored pancreas graft survival between the two donor types (79.5% versus 80.4%; p = .86). Multivariable analysis showed no statistically significant differences in 5-year pancreas graft loss between transplants from DCD (n = 343) and DBD (n = 1492) donors (hazard ratio 1.26, 95% CI 0.76-1.23; p = .12). The findings from this study support the increased use of SPK transplants from DCD donors.
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Transplante de Rim , Obtenção de Tecidos e Órgãos , Morte Encefálica , Morte , Sobrevivência de Enxerto , Humanos , Pâncreas , Sistema de Registros , Estudos Retrospectivos , Doadores de Tecidos , Reino UnidoRESUMO
Donor-transmitted cancer (DTC) has major implications for the affected patient as well as other recipients of organs from the same donor. Unlike heterotopic transplant recipients, there may be limited treatment options for orthotopic transplant recipients with DTC. We systematically reviewed the evidence on DTC in orthotopic solid organ transplant recipients (SOTRs). We searched MEDLINE, EMBASE, PubMed, Scopus, and Web of Science in January 2020. We included cases where the outcome was reported and excluded donor-derived cancers. We assessed study quality using published checklists. Our domains of interest were presentation, time to diagnosis, cancer extent, management, and survival. There were 73 DTC cases in liver (n = 51), heart (n = 10), lung (n = 10) and multi-organ (n = 2) recipients from 58 publications. Study quality was variable. Median time to diagnosis was 8 months; 42% were widespread at diagnosis. Of 13 cases that underwent re-transplantation, three tumours recurred. Mortality was 75%; median survival 7 months. Survival was worst in transmitted melanoma and central nervous system tumours. The prognosis of DTC in orthotopic SOTRs is poor. Although re-transplantation offers the best chance of cure, some tumours still recur. Publication bias and clinical heterogeneity limit the available evidence. From our findings, we suggest refinements to clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020165001, Prospero Registration Number: CRD42020165001.
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Transplante de Órgãos , Transplantes , Humanos , Recidiva Local de Neoplasia , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos , TransplantadosRESUMO
Improved biomarkers are needed for prostate cancer, as the current gold standards have poor predictive value. Tests for circulating prostate-specific antigen (PSA) levels are susceptible to various noncancer comorbidities in the prostate and do not provide prognostic information, whereas physical biopsies are invasive, must be performed repeatedly, and only sample a fraction of the prostate. Injectable biosensors may provide a new paradigm for prostate cancer biomarkers by querying the status of the prostate via a noninvasive readout. Proteases are an important class of enzymes that play a role in every hallmark of cancer; their activities could be leveraged as biomarkers. We identified a panel of prostate cancer proteases through transcriptomic and proteomic analysis. Using this panel, we developed a nanosensor library that measures protease activity in vitro using fluorescence and in vivo using urinary readouts. In xenograft mouse models, we applied this nanosensor library to classify aggressive prostate cancer and to select predictive substrates. Last, we coformulated a subset of nanosensors with integrin-targeting ligands to increase sensitivity. These targeted nanosensors robustly classified prostate cancer aggressiveness and outperformed PSA. This activity-based nanosensor library could be useful throughout clinical management of prostate cancer, with both diagnostic and prognostic utility.
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Biomarcadores Tumorais , Perfilação da Expressão Gênica , Biblioteca Gênica , Neoplasias Experimentais , Neoplasias da Próstata , Animais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Experimentais/classificação , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias da Próstata/classificação , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismoRESUMO
INTRODUCTION: Faecal Immunohistochemistry Testing (FIT) is recommended as an adjunct to guide referrals from Primary Care for individuals without rectal bleeding, who do not meet the suspected cancer pathway referral guidelines. It has largely replaced Faecal Occult Blood Testing. AIMS: To assess the specificity of FIT. To understand the characteristics of FIT negative cancer patients and whether they have predominantly right sided cancers. Evaluating the efficacy of FIT and Iron deficiency anaemia in combination to capture patients with colorectal cancers. METHODS: A study of 1000 symptomatic patients, undergoing FIT by Clinicians during the 'Digital rectal examination'. Inclusion criteria; all patients referred via our cancer referral pathway. FIT positivity was set at 10 µg g of faeces. RESULTS: There were 7 FIT negative cancers in this cohort; 1 was a lymphoma and the other 6 were caecal adenocarcinomas. 5 were anaemic. The positive predictive value of IDA was 34% compared with 'other symptoms'; 18%. The negative predictive value of FIT was 99.05% in this cohort. Specificity for FIT was 86.9% (CI 96%). CONCLUSION: Two separate referral pathways for IDA and FIT positive tests, would have captured all patients except 2; the lymphoma and 1 advanced caecal adenocarcinoma. FIT is an excellent triage tool prior to colonoscopy however capturing right sided disease remains a weak point. Multivariate analysis of patients in addition to IDA and FIT should improve capture of this subgroup.
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Anemia Ferropriva , Neoplasias Colorretais , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/etiologia , Colonoscopia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Humanos , Imuno-Histoquímica , Programas de Rastreamento , Sangue OcultoRESUMO
The two erythropoietin (EPO) receptor forms mediate different cellular responses to erythropoietin. While hematopoiesis is mediated via the homodimeric EPO receptor (EPOR), tissue protection is conferred via a heteromer composed of EPOR and CD131. In the skeletal system, EPO stimulates osteoclast precursors and induces bone loss. However, the underlying molecular mechanisms are still elusive. Here, we evaluated the role of the heteromeric complex in bone metabolism in vivo and in vitro by using Cibinetide (CIB), a non-erythropoietic EPO analogue that exclusively binds the heteromeric receptor. CIB is administered either alone or in combination with EPO. One month of CIB treatment significantly increased the cortical (~5.8%) and trabecular (~5.2%) bone mineral density in C57BL/6J WT female mice. Similarly, administration of CIB for five consecutive days to female mice that concurrently received EPO on days one and four, reduced the number of osteoclast progenitors, defined by flow cytometry as Lin-CD11b-Ly6Chi CD115+, by 42.8% compared to treatment with EPO alone. In addition, CIB alone or in combination with EPO inhibited osteoclastogenesis in vitro. Our findings introduce CIB either as a stand-alone treatment, or in combination with EPO, as an appealing candidate for the treatment of the bone loss that accompanies EPO treatment.
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Densidade Óssea/efeitos dos fármacos , Eritropoetina/metabolismo , Oligopeptídeos/farmacologia , Osteogênese/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Hematopoese/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismoRESUMO
In transplant, meaningful international comparisons in organ utilization are needed. This collaborative study between the United Kingdom (UK) and the United States (US) aimed to develop a kidney utilization metric allowing for legitimate intercountry comparisons. Data from the UK and US transplant registries, including all deceased donor kidneys recovered from 2006 to 2017, were analyzed. To identify a potentially comparable kidney utilization rate (UR), several denominators were assessed. We discovered that the proportion of transplanted kidneys from elderly donors in the UK (10.7%) was 18 times greater than that in the US (0.6%). Conversely, en bloc pediatric kidney transplant was more common in the US. Donation after circulatory death utilization has risen in both countries but is twice as prevalent in the UK (39% of transplants) vs the US (20%). In addition, US and UK URs are not directly comparable due to fundamental system differences. However, using a suite of URs revealed practice areas likely to yield the most benefit if improved, such as efforts to increase kidney offer acceptance in the US and to reduce postacceptance discard in the UK. Methods used in this study, including novel intracountry risk-adjusted UR trend logistic regression analyses, can be translated to other international transplant registries in pursuit of further global learning opportunities.
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Obtenção de Tecidos e Órgãos , Idoso , Criança , Sobrevivência de Enxerto , Humanos , Rim , Doadores de Tecidos , Resultado do Tratamento , Reino Unido , Estados UnidosRESUMO
OBJECTIVES: The purpose of the study was twofold: (1) to test the hypothesis that tooth loss is independently associated with carotid atherosclerotic burden (CAB) among individuals with ischemic stroke (IS) or transient ischemic attack (TIA) and (2) to test the association between tooth loss and disability following the occurrence of cerebral ischemia. MATERIALS AND METHODS: This observational study included 418 patients with IS or TIA. Tooth loss and the CAB were measured through a head and neck multidetector computed tomography angiography. CAB was analyzed in both common, internal, and external carotid arteries and classified in five levels of vascular occlusion. The modified Rankin Scale (mRS) was used to evaluate the functional outcome at patient discharge. Health records provided information on sociodemographic and medical covariates. The association between CAB and tooth loss, as well as between tooth loss and subtypes of cerebral ischemia were estimated through Poisson regression. Cox regression was carried out to evaluate the association between tooth loss and the mRS, with α = 5%. RESULTS: Mean age was 65.6 ± 13.8 years, with 52.4% males. Multivariate analyses revealed that severe tooth loss (> 23 missing teeth) was independently associated with CAB ≥ 50% (PR = 2.86, 95% CI = 1.19-6.89) and mRS scores (> 2) (HR = 1.97, 95% CI = 1.10-3.75). CONCLUSION: Tooth loss was independently associated with CAB and predicted a poorer functional outcome among IS and TIA patients. CLINICAL RELEVANCE: Clinical assessment of tooth loss may provide important information on risk for CAB and poorer functional outcome among stroke patients.
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Aterosclerose , Isquemia Encefálica , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Perda de Dente , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Feminino , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Perda de Dente/epidemiologia , Resultado do TratamentoRESUMO
Caries-related biofilms and associated complications are significant threats in dentistry, especially when biofilms grow over dental restorations. The inhibition of cariogenic biofilm associated with the onset of carious lesions is crucial for preventing disease recurrence after treatment. This in vitro study defined optimized parameters for using a photosensitizer, toluidine blue O (TBO), activated via a red light-emitting diode (LED)-based wireless device to control the growth of cariogenic biofilms. The effect of TBO concentrations (50, 100, 150, and 200 µg/mL) exposed to light or incubated in the dark was investigated in successive cytotoxicity assays. Then, a mature Streptococcus mutans biofilm model under sucrose challenge was treated with different TBO concentrations (50, 100, and 150 µg/mL), different light energy doses (36, 108, and 180 J/cm2), and different incubation times before irradiation (1, 3, and 5 min). The untreated biofilm, irradiation with no TBO, and TBO incubation with no activation represented the controls. After treatments, biofilms were analyzed via S. mutans colony-forming units (CFUs) and live/dead assay. The percentage of cell viability was within the normal range compared to the control when 50 and 100 µg/mL of TBO were used. Increasing the TBO concentration and energy dose was associated with biofilm inhibition (p < 0.001), while increasing incubation time did not contribute to bacterial elimination (p > 0.05). Irradiating the S. mutans biofilm via 100 µg/mL of TBO and ≈180 J/cm2 energy dose resulted in ≈3-log reduction and a higher amount of dead/compromised S. mutans colonies in live/dead assay compared to the control (p < 0.001). The light energy dose and TBO concentration optimized the bacterial elimination of S. mutans biofilms. These results provide a perspective on the determining parameters for highly effective photo-killing of caries-related biofilms and display the limitations imposed by the toxicity of the antibacterial photodynamic therapy's chemical components. Future studies should support investigations on new approaches to improve or overcome the constraints of opportunities offered by photodynamic inactivation of caries-related biofilms.
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Biofilmes/efeitos da radiação , Lâmpadas de Polimerização Dentária , Cárie Dentária/terapia , Streptococcus mutans/efeitos da radiação , Animais , Contagem de Colônia Microbiana , Cárie Dentária/microbiologia , Relação Dose-Resposta à Radiação , Camundongos , Fármacos Fotossensibilizantes/efeitos adversos , Células RAW 264.7 , Streptococcus mutans/patogenicidade , Streptococcus mutans/fisiologia , Cloreto de Tolônio/efeitos adversosRESUMO
At present, bioactive glasses (BAGs) are demonstrating promising results in the remineralization of hard tissues. Their bioactive properties can potentially overcome the demineralization effect accompanying orthodontic treatment. This review aimed to evaluate the effectiveness of bioactive glass enhanced orthodontic bonding resins on enamel remineralization, in addition to their antibacterial, ion release and acid neutralization effect. Four databases (PubMed, MEDLINE, Web of Science and Scopus) were searched. Two hundred and fifty-one full-text articles were screened independently, out of which seven studies satisfied the inclusion criteria. Quality appraisal was performed by two independent reviewers. Methodologies used to assess the anti-demineralization effect included Micro-Computed Tomography, Polarized Light Microscopy and Hardness Testing (Knoop and Berkovich). All seven articles confirmed the superior remineralization effect of BAG orthodontic bonding resins compared to their non-BAG counterparts. A proportional relationship was proved between BAG concentrations and increased anti-demineralization effect. The addition of antibacterial agents to BAG does not necessarily improve its anti-demineralization effect. Although studies have confirmed the effectiveness of BAG orthodontic bonding resins on enamel remineralization, there was a degree of heterogeneity across studies due to the lack of an in vitro studies standardized protocol.
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Vidro/química , Microscopia de Polarização , Microtomografia por Raio-XRESUMO
Brown tumours affecting the cervical spine are a rare but recognised complication of renal failure-related secondary hyperparathyroidism. We present a case of a 26 year-old female with radiculopathy who was managed successfully with 360° cervical spine fixation and parathyroidectomy.
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Vértebras Cervicais/cirurgia , Hiperparatireoidismo Secundário/complicações , Osteíte Fibrosa Cística/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Feminino , Humanos , Hiperparatireoidismo Secundário/cirurgia , Osteíte Fibrosa Cística/complicações , Paratireoidectomia/métodos , Radiculopatia/etiologia , Radiculopatia/cirurgia , Neoplasias da Coluna Vertebral/complicaçõesRESUMO
This JAMA Guide to Statistics and Methods article discusses accounting for competing risks in clinical research.
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Pesquisa Biomédica , Ensaios Clínicos como Assunto , Risco , Humanos , Medição de Risco , Análise de Sobrevida , Modelos de Riscos Proporcionais , Probabilidade , Modelos EstatísticosRESUMO
Cariogenic oral biofilms are strongly linked to dental caries around dental sealants. Quaternary ammonium monomers copolymerized with dental resin systems have been increasingly explored for modulation of biofilm growth. Here, we investigated the effect of dimethylaminohexadecyl methacrylate (DMAHDM) on the cariogenic pathogenicity of Streptococcus mutans (S. mutans) biofilms. DMAHDM at 5 mass% was incorporated into a parental formulation containing 20 mass% nanoparticles of amorphous calcium phosphate (NACP). S. mutans biofilms were grown on the formulations, and biofilm inhibition and virulence properties were assessed. The tolerances to acid stress and hydrogen peroxide stress were also evaluated. Our findings suggest that incorporating 5% DMAHDM into 20% NACP-containing sealants (1) imparts a detrimental biological effect on S. mutans by reducing colony-forming unit counts, metabolic activity and exopolysaccharide synthesis; and (2) reduces overall acid production and tolerance to oxygen stress, two major virulence factors of this microorganism. These results provide a perspective on the value of integrating bioactive restorative materials with traditional caries management approaches in clinical practice. Contact-killing strategies via dental materials aiming to prevent or at least reduce high numbers of cariogenic bacteria may be a promising approach to decrease caries in patients at high risk.