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1.
Dev Dyn ; 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37847071

RESUMO

BACKGROUND: Male-specific lethal 3 (Msl3) is a member of the chromatin-associated male-specific lethal MSL complex, which is responsible for the transcriptional upregulation of genes on the X chromosome in males of Drosophila. Although the dosage complex operates differently in mammals, the Msl3 gene is conserved from flies to humans. Msl3 is required for meiotic entry during Drosophila oogenesis. Recent reports indicate that also in primates, Msl3 is expressed in undifferentiated germline cells before meiotic entry. However, if Msl3 plays a role in the meiotic entry of mammals has yet to be explored. RESULTS: To understand, if Msl3a plays a role in the meiotic entry of mammals, we used mouse spermatogenesis as a study model. Analyses of single-cell RNA-seq data revealed that, in mice, Msl3 is mostly expressed in meiotic cells. To test the role of Msl3 in meiosis, we used a male germline-specific Stra8-iCre driver and a newly generated Msl3flox conditional knock-out mouse line. Msl3 conditional loss-of-function in spermatogonia did not cause spermatogenesis defects or changes in the expression of genes related to meiosis. CONCLUSIONS: Our data suggest that, in mice, Msl3 exhibits delayed expression compared to Drosophila and primates, and loss-of-function mutations disrupting the chromodomain of Msl3 alone do not impede meiotic entry in rodents.

2.
J Oral Maxillofac Surg ; 72(1): 35-40, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24210930

RESUMO

PURPOSE: Most of the current understanding of articular cartilage maintenance and degradation is derived from large load-bearing synovial joints, in particular the knee joint. The aim of this study was to identify valuable degradation markers for cartilage degradation in the temporomandibular joint (TMJ) by comparing the relative concentrations of carboxyterminal telopeptides of collagen types I and II (CTX-I and CTX-II), cartilage oligomeric matrix protein (COMP), and prostaglandin E2 (PGE2) in synovial fluid (SF) of TMJ and knee joints with cartilage degradation. MATERIALS AND METHODS: In this cross-sectional comparative study, participants were recruited from the University Medical Center Groningen, The Netherlands. Patients with TMJ osteoarthritis were compared with patients with knee osteoarthritis. The outcome variables were the relative SF concentrations of CTX-I, CTX-II, COMP, and PGE2. An independent samples Mann-Whitney U test was used to compare the relative concentrations. RESULTS: Thirty consecutive patients (9 male, 21 female; mean age, 40.1 yr; standard deviation, 15.3 yr) with TMJ osteoarthritis and 31 consecutive patients (20 male, 11 female; mean age, 37.4 yr; standard deviation, 13.7 yr) who were scheduled for arthroscopy of the knee joint participated in this study. Significant differences were found between relative concentrations of COMP (P = .000) and PGE2 (P = .005), and no significant differences were found between relative concentrations of CTX-I (P = .720) and CTX-II (P = .242). CONCLUSIONS: Relative SF concentrations of COMP and PGE2 showed significant differences between the TMJ and the knee joint, suggesting that there are differences in pathophysiology and that the inflammatory component may be more distinct in the TMJ.


Assuntos
Osteoartrite do Joelho/patologia , Osteoartrite/patologia , Transtornos da Articulação Temporomandibular/patologia , Adulto , Artroscopia/métodos , Proteína de Matriz Oligomérica de Cartilagem/análise , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Colágeno Tipo I/análise , Colágeno Tipo II/análise , Estudos Transversais , Dinoprostona/análise , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Masculino , Osteoartrite/metabolismo , Osteoartrite do Joelho/metabolismo , Paracentese/métodos , Peptídeos/análise , Líquido Sinovial/química , Transtornos da Articulação Temporomandibular/metabolismo
3.
Ann Plast Surg ; 72(6): 666-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23241804

RESUMO

INTRODUCTION: Scapular flaps are a reliable system for reconstruction. Disadvantages of reconstruction with these flaps include unsightly scars at the donor site due to wound healing under excessive tension and the use of skin grafts. Minimally invasive harvesting techniques may reduce potential donor-site morbidity. There has been no report on endoscopically assisted harvesting of the scapular adipofascial flap. METHODS: Two patients with large defects are reviewed. Endoscopically assisted minimally invasive techniques for harvest of scapular adipofascial flaps were used in reconstruction of these soft-tissue defects. RESULTS: Both defects were successfully reconstructed in the primary setting without any donor-site wound complications. CONCLUSIONS: This is the first time that a scapular flap has been harvested successfully with a minimally invasive technique for reconstruction. This technique allows the use of a scapular flap as a pedicled flap or as a free flap. Minimally invasive harvest of the adipofascial scapular flap has the advantages of short incision and better cosmesis of the donor site, for scarring is minimized and the incision can be closed primarily without skin grafting therefore reducing donor-site morbidity compared with the traditional open technique.


Assuntos
Fasciite/cirurgia , Úlcera da Perna/cirurgia , Retalhos Cirúrgicos , Coleta de Tecidos e Órgãos/métodos , Endoscopia , Feminino , Humanos , Pessoa de Meia-Idade
4.
Am J Orthod Dentofacial Orthop ; 145(1): 108-15, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24373661

RESUMO

INTRODUCTION: Rapid prototyping is a fast-developing technique that might play a significant role in the eventual replacement of plaster dental models. The aim of this study was to investigate the accuracy and reproducibility of physical dental models reconstructed from digital data by several rapid prototyping techniques. METHODS: Twelve mandibular and maxillary conventional plaster models from randomly chosen subjects were selected and served as the gold standard. The plaster models were scanned to form high-resolution 3-dimensional surface models in .stl files. These files were converted into physical models using 3 rapid prototyping techniques: digital light processing, jetted photopolymer, and 3-dimensional printing. Linear measurements on the plaster models were compared with linear measurements on the rapid prototyping models. One observer measured the height and width of the clinical crowns of all teeth (first molar to first molar) on all models (plaster and replicas) using a digital caliper. All models were measured 5 times with a 2-week interval between measurements. RESULTS: The intraobserver agreement was high (intraclass correlation coefficient >0.94). The mean systematic differences for the measurements of the height of the clinical crowns were -0.02 mm for the jetted photopolymer models, 0.04 mm for the digital light processing models, and 0.25 mm for the 3-dimensional printing models. For the width of the teeth, the mean systematic differences were -0.08 mm for the jetted photopolymer models, -0.05 mm for the digital light processing models, and -0.05 mm for the 3-dimensional printing models. CONCLUSIONS: Dental models reconstructed by the tested rapid prototyping techniques are considered clinically acceptable in terms of accuracy and reproducibility and might be appropriate for selected applications in orthodontics.


Assuntos
Desenho Assistido por Computador/estatística & dados numéricos , Modelos Dentários/estatística & dados numéricos , Dente Pré-Molar/anatomia & histologia , Sulfato de Cálcio/química , Cefalometria/estatística & dados numéricos , Dente Canino/anatomia & histologia , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Imageamento Tridimensional/métodos , Incisivo/anatomia & histologia , Mandíbula/anatomia & histologia , Maxila/anatomia & histologia , Dente Molar/anatomia & histologia , Odontometria/estatística & dados numéricos , Polímeros/química , Impressão/métodos , Reprodutibilidade dos Testes , Software , Propriedades de Superfície , Tecnologia Odontológica/estatística & dados numéricos , Coroa do Dente/anatomia & histologia
5.
J Clin Periodontol ; 40(2): 186-95, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23211012

RESUMO

AIM: The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. MATERIAL & METHODS: Thirty patients (79 implants) with peri-implantitis were treated with resective surgical treatment consisting of apically re-positioned flap, bone re-contouring and surface debridement and decontamination. Patients were randomly allocated to decontamination with 0.12% CHX + 0.05% CPC (test-group) or a placebo-solution (without CHX/CPC, placebo-group). Microbiological parameters were recorded during surgery; clinical and radiographical parameters were recorded before (pre-) treatment (baseline), and at 3, 6 and 12 months after treatment. RESULTS: Nine implants in two patients in the placebo-group were lost due to severe persisting peri-implantitis. Both decontamination procedures resulted in significant reductions of bacterial load on the implant surface, but the test-group showed a significantly greater reduction than the placebo-group (log 4.21 ± 1.89 versus log 2.77 ± 2.12, p = 0.006). Multilevel analysis showed no differences between both groups in the effect of the intervention on bleeding, suppuration, probing pocket depth and radiographical bone loss over time. CONCLUSION: Implant surface decontamination with 0.12% CHX + 0.05% CPC in resective surgical treatment of peri-implantitis leads to a greater immediate suppression of anaerobic bacteria on the implant surface than a placebo-solution, but does not lead to superior clinical results. The long-term microbiological effect remains unknown.


Assuntos
Anti-Infecciosos Locais/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Cetilpiridínio/farmacologia , Clorexidina/farmacologia , Descontaminação/métodos , Implantes Dentários/microbiologia , Peri-Implantite/tratamento farmacológico , Peri-Implantite/cirurgia , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/cirurgia , Anti-Infecciosos Locais/uso terapêutico , Cetilpiridínio/uso terapêutico , Clorexidina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multinível , Desbridamento Periodontal , Índice Periodontal , Radiografia
6.
J Orofac Pain ; 27(2): 171-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23630689

RESUMO

AIMS: To carry out a systematic review of randomized controlled trials (RCTs) to investigate in patients with arthralgia of the temporomandibular joint (TMJ) the effectiveness of TMJ lavage compared to nonsurgical treatment with regard to pain intensity and mandibular range of motion. METHODS: The electronic databases Cochrane Controlled Trials Register (1960-2012), PubMed÷Medline (1966-2012), and Embase (1966-2012) were systematically searched for relevant RCTs. References of relevant articles were searched for additional studies, as well as citing reports. Two authors independently performed data extraction by using predefined quality indicators. Relevant outcome data included reduction in pain, as assessed by a visual analog scale (VAS) or a pain score, and maximal mouth opening (MMO) before and 6 months after treatment. Included trials were combined using fixed and random effects meta-analysis. RESULTS: Three RCTs (222 patients) were included for meta-analysis. The statistically significant overall standardized mean difference (SMD) (P < .001) with regard to pain intensity was -1.07 (95% CI = -1.38, - 0.76) in favor of TMJ lavage. The MMO did not change significantly (P > .05, SMD = .05 [95% CI = -0.33, 0.23]). CONCLUSIONS: The results suggest that lavage of the TMJ may be slightly more effective than nonsurgical treatment for pain reduction. However, this difference is not likely to be clinically relevant.


Assuntos
Artralgia/terapia , Dor Facial/terapia , Transtornos da Articulação Temporomandibular/terapia , Artroscopia , Humanos , Funções Verossimilhança , Medição da Dor , Modalidades de Fisioterapia , Psicoterapia , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular , Irrigação Terapêutica , Resultado do Tratamento
7.
J Oral Maxillofac Surg ; 71(10): 1659-64, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23932112

RESUMO

PURPOSE: There is a growing interest in markers for cartilage degradation in synovial joints because of their potential diagnostic and prognostic value. Therefore, the aim of this study was to identify valuable degradation markers for temporomandibular joint (TMJ) osteoarthritis (OA) by comparing the relative concentrations of carboxyterminal telopeptides type I and II (CTX-I and II), cartilage oligomeric matrix protein (COMP), and prostaglandin E2 (PGE2) in the synovial fluid (SF) of TMJs with OA with those of healthy symptom-free TMJs. MATERIALS AND METHODS: In this cross-sectional case-control study, participants were recruited from the University Medical Center Groningen (Groningen, the Netherlands). Cases were defined as patients with TMJ OA, and control patients had symptom-free TMJs. The outcome variables were the relative concentrations of CTX-I, CTX-II, COMP, and PGE2 in osteoarthritic TMJ SF compared with symptom-free joints. An independent-samples Mann-Whitney U test was used to compare the relative concentrations. RESULTS: Thirty cases (9 male, 21 female; mean age, 40.1 yr; standard deviation, 15.3 yr) and 10 controls (5 male, 5 female; mean age, 30.3 yr; standard deviation, 10.8 yr) were studied. No significant differences in relative concentrations of CTX-I (P = .548), CTX-II (P = .842), COMP (P = .140), and PGE2 (P = .450) were found between the groups. Unexpected low relative concentrations of CTX-I and high relative concentrations of CTX-II were observed. CONCLUSIONS: Assumed changes in the SF concentration of CTX-I, CTX-II, COMP, and PGE2 in TMJ OA seem to occur proportionally. Furthermore, the unexpected large contribution of CTX-II suggests that this marker may be useful to quantify cartilage degradation in TMJ OA.


Assuntos
Proteína de Matriz Oligomérica de Cartilagem/análise , Colágeno Tipo II/análise , Colágeno Tipo I/análise , Dinoprostona/análise , Osteoartrite/metabolismo , Peptídeos/análise , Transtornos da Articulação Temporomandibular/metabolismo , Adulto , Biomarcadores/análise , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Paracentese , Líquido Sinovial/química , Articulação Temporomandibular/metabolismo
8.
J Orofac Pain ; 26(3): 233-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22838008

RESUMO

AIMS: To determine the available evidence in the literature for whether hypoxia-reperfusion injury plays a role in the pathogenesis of joint diseases in general and of osteoarthritis (OA) of the temporomandibular joint (TMJ) in particular. METHODS: The electronic databases CENTRAL, PubMed, and EMBASE were systematically searched. The search strategy combined thesaurus terms "reperfusion injury" and "joints" and excluded "tourniquet," which possibly induces iatrogenic reperfusion injury. Inclusion and exclusion criteria were applied, data were extracted, and quality was assessed. RESULTS: Four studies could be included, investigating four different aspects of the hypoxia-reperfusion mechanism in joints. All studies investigated several arthritides in the knee or shoulder joint and were observational studies, except for one section of one of the studies, which was a randomized controlled trial. These studies do not provide any evidence to support or reject the hypothesis that hypoxia reperfusion occurs in TMJ OA. Positive but weak evidence is provided to support the hypothesis that hypoxia-reperfusion injury occurs in OA of the knee joint. Furthermore, some results of the included studies suggest differences between OA and other types of arthritis in relation to the hypoxia-reperfusion mechanism. CONCLUSION: There is no evidence to support or reject the hypothesis that hypoxia reperfusion occurs in TMJ OA, and limited evidence is provided to support that hypoxia-reperfusion injury occurs in OA of the knee joint. Since the studies suggest differences between OA and other types of arthritis in relation to hypoxia-reperfusion mechanisms, further research in this field needs to distinguish OA from other types of arthritis.


Assuntos
Osteoartrite/fisiopatologia , Traumatismo por Reperfusão , Transtornos da Articulação Temporomandibular/fisiopatologia , Humanos , Cápsula Articular/irrigação sanguínea , Osteoartrite do Joelho/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Fluxo Sanguíneo Regional
9.
Clin Oral Investig ; 16(3): 689-97, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21538074

RESUMO

The objective of this study was to assess variations in the occurrence of temporomandibular disorders (TMDs) and the risk of developing pain and function impairment of the temporomandibular complex in obstructive sleep apnea syndrome (OSAS) patients treated with either an oral appliance (mandibular advancement device) or continuous positive airway pressure (CPAP) in a 2-year follow-up study. In addition, we assessed the relationship between the mean mandibular protrusion and the frequency of wearing the appliance during follow-up with the occurrence of pain and function impairment of the temporomandibular complex. Fifty-one patients were randomized to oral appliance therapy and 52 patients to CPAP therapy. TMDs (diagnosed according to the Axis I Research Diagnostic Criteria for TMD), pain intensity and disability and mandibular function impairment were recorded at baseline, after 2 months, 1 year and 2 years of therapy. Only in the initial period of treatment the occurrence of pain-related TMDs was considerably higher (24%) in the oral appliance group compared to CPAP (6%). Oral appliance therapy furthermore resulted in more temporomandibular pain compared to CPAP (odds ratio 2.33, 95% confidence interval (1.22-4.43)). However, there were no limitations in mandibular function in both groups during the (entire) follow-up period. Although generally not serious and of transient nature, oral appliance therapy results in more pain-related TMDs in the initial period of use compared with CPAP therapy. Oral appliance therapy is associated with increased pain in the temporomandibular complex in the initial period of use. Because of the transient nature, this pain is not a reason to contra-indicate an oral appliance in OSAS patients. Moreover, TMDs and the risk of developing pain and function impairment of the temporomandibular complex appear limited with long-term oral appliance use.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Placas Oclusais/efeitos adversos , Apneia Obstrutiva do Sono/terapia , Transtornos da Articulação Temporomandibular/etiologia , Adulto , Artralgia/etiologia , Dor Facial/etiologia , Feminino , Humanos , Modelos Lineares , Masculino , Mandíbula/crescimento & desenvolvimento , Avanço Mandibular/instrumentação , Pessoa de Meia-Idade , Medição da Dor , Cooperação do Paciente , Inquéritos e Questionários , Fatores de Tempo
10.
J Clin Periodontol ; 38(7): 667-76, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21564158

RESUMO

AIM: This study evaluated, through a systematic review of the literature, the estimated implant survival rate of short (<10 mm) dental implants installed in partially edentulous patients. MATERIALS AND METHODS: A systematic search was conducted in the electronic databases of MEDLINE (1980-October 2009) and EMBASE (1980-October 2009) to identify eligible studies. Two reviewers independently assessed the methodological quality of the articles using specific study design-related quality assessment forms. RESULTS: Twenty-nine methodologically acceptable studies were selected. A total of 2611 short implants (lengths 5-9.5 mm) were analysed. An increase in implant length was associated with an increase in implant survival (from 93.1% to 98.6%). Heterogeneity between studies was explored by subgroup analyses. The cumulative estimated failure rate of studies performed in the maxilla was 0.010 implants/year, compared with 0.003 found in the studies in the mandible. For studies that also included smokers, the failure rate was 0.008 compared with 0.004 found in studies that excluded smokers. Surface topography and augmentation procedure were not sources of heterogeneity. CONCLUSION: There is fair evidence that short (<10 mm) implants can be placed successfully in the partially edentulous patient, although with a tendency towards an increasing survival rate per implant length, and the prognosis may be better in the mandible of non smoking patients.


Assuntos
Implantes Dentários , Planejamento de Prótese Dentária , Arcada Parcialmente Edêntula/cirurgia , Falha de Restauração Dentária , Humanos , Arcada Parcialmente Edêntula/reabilitação , Mandíbula/cirurgia , Maxila/cirurgia , Prognóstico , Propriedades de Superfície , Análise de Sobrevida , Resultado do Tratamento
11.
Am J Orthod Dentofacial Orthop ; 140(3): e107-14, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21889058

RESUMO

INTRODUCTION: The aim of this study was to determine the reliability and the measurement error (by means of the smallest detectable error) of 17 commonly used cephalometric measurements made on 3-dimensional (3D) cone-beam computed tomography images. METHODS: Twenty-five cone-beam computed tomography scans were randomly selected, and 3D images were rendered, segmented, and traced with the SimPlant Ortho Pro software (version 2.1, Materialise Dental, Leuven, Belgium). This was repeated twice by 2 observers during 2 sessions at least 1 week apart. Measurement error was determined by means of the smallest detectable difference. Differences were analyzed with Wilcoxon signed rank tests. Intraobserver and interobserver reliability values were calculated by means of intraclass correlation coefficients (ICC) based on absolute agreement. RESULTS: There were great variations of measurement errors between the angular (range, 0.88°-6.29°) and linear (range, 1.33-3.56 mm) variables. The greatest measuring error was associated with the dental measurements U1-FHPL, L1-MdPL. and L1-FHPL (range, 3.80°-6.29°). ANB angle was the only variable with a measuring error of 1° or less for both observers. The intraobserver agreement of all measurements was very good (ICC, 0.86-0.99). Except for SN-FHPL (ICC, 0.76), interobserver agreement was very good (ICC, >0.88). CONCLUSIONS: The measurement errors of 3D cephalometric measurements (except for the ANB angle) can be considered clinically relevant. This questions the use of linear and angular 3D measurements to detect true treatment effects when a high level of accuracy is required.


Assuntos
Cefalometria/métodos , Tomografia Computadorizada de Feixe Cônico , Imageamento Tridimensional/métodos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Avaliação de Resultados em Cuidados de Saúde/métodos , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Adulto Jovem
12.
Alzheimers Dement (N Y) ; 7(1): e12169, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34027023

RESUMO

INTRODUCTION: Containment measures implemented to minimize the spread of coronavirus disease 2019 (COVID-19) are reported to be negatively affecting mental health, diet, and alcohol consumption. These factors, as well as poor cardiometabolic health and insufficient physical and cognitive activity, are known to increase the risk of developing dementia. COVID-19 "lockdown" measures may have exacerbated these dementia risk factors among people in mid-to-later life. METHODS: We compared longitudinal data from before (October 2019) and during (April-June 2020) the first COVID-19 lockdown period in Tasmania, Australia. Participants (n = 1671) were 50+ years of age and engaged in a public health program targeting dementia risk reduction, with one-third participating in the Preventing Dementia Massive Open Online Course (PD-MOOC). Regression models were used to assess changes in smoking, alcohol use, body mass index (BMI), diet, physical exercise, cognitive and social activity, anxiety and depression, and management of cholesterol, diabetes, and blood pressure. Where significant changes were noted, the moderating influence of being in current employment, living with others, and completing the PD-MOOC was tested. RESULTS: Although friend networks contracted marginally during lockdown, no detrimental effects on modifiable dementia risk factors were noted. Anxiety levels and alcohol consumption decreased, there was no change in depression scores, and small but significant improvements were observed in cognitive and physical activity, smoking, diet, and BMI. Stronger improvements in cognitive activity were observed among people who were cohabiting (not living alone) and both cognitive activity and adherence to the MIND diet (Mediterranean-DASH diet Intervention for Neurological Delay) improved more for people who participated in the PD-MOOC. DISCUSSION: Longitudinal data did not show widespread negative effects of COVID-19 lockdown on modifiable dementia risk factors in this sample. The results counter the dominant narratives of universal pandemic-related distress and suggest that engaging at-risk populations in proactive health promotion and education campaigns during lockdown events could be a protective public health strategy.

13.
Nat Microbiol ; 6(6): 746-756, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958766

RESUMO

Transcription initiates at promoters, DNA regions recognized by a DNA-dependent RNA polymerase. We previously identified horizontally acquired Escherichia coli promoters from which the direction of transcription was unclear. In the present study, we show that more than half of these promoters are bidirectional and drive divergent transcription. Using genome-scale approaches, we demonstrate that 19% of all transcription start sites detected in E. coli are associated with a bidirectional promoter. Bidirectional promoters are similarly common in diverse bacteria and archaea, and have inherent symmetry: specific bases required for transcription initiation are reciprocally co-located on opposite DNA strands. Bidirectional promoters enable co-regulation of divergent genes and are enriched in both intergenic and horizontally acquired regions. Divergent transcription is conserved among bacteria, archaea and eukaryotes, but the underlying mechanisms for bidirectionality are different.


Assuntos
Archaea/genética , DNA Arqueal/genética , DNA Bacteriano/genética , Escherichia coli/genética , Regiões Promotoras Genéticas , Sítio de Iniciação de Transcrição , Sequência de Bases , Transferência Genética Horizontal
14.
J Med Chem ; 64(15): 10711-10741, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34260229

RESUMO

Herein, a series of 2,3-dihydrobenzofurans have been developed as highly potent bromo and extra-terminal domain (BET) inhibitors with 1000-fold selectivity for the second bromodomain (BD2) over the first bromodomain (BD1). Investment in the development of two orthogonal synthetic routes delivered inhibitors that were potent and selective but had raised in vitro clearance and suboptimal solubility. Insertion of a quaternary center into the 2,3-dihydrobenzofuran core blocked a key site of metabolism and improved the solubility. This led to the development of inhibitor 71 (GSK852): a potent, 1000-fold-selective, highly soluble compound with good in vivo rat and dog pharmacokinetics.


Assuntos
Benzofuranos/farmacologia , Proteínas/antagonistas & inibidores , Benzofuranos/síntese química , Benzofuranos/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Proteínas/metabolismo , Solubilidade , Relação Estrutura-Atividade
15.
Am J Orthod Dentofacial Orthop ; 137(1): 16.e1-6; discussion 16-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20122425

RESUMO

INTRODUCTION: The aims of this study were to determine the linear accuracy of 3-dimensional surface models derived from a commercially available cone-beam computed tomography (CBCT) dental imaging system and volumetric rendering software and to investigate the influence of voxel resolution on the linear accuracy of CBCT surface models. METHODS: Glass sphere markers were fixed on 10 dry mandibles. The mandibles were scanned with 0.40 and 0.25 voxel size resolutions in 3 sessions. Anatomic truth was established with 6 direct digital caliper measurements. The surface models were rendered by a volumetric rendering program, and the CBCT measurements were established as the mean of the 3 measurements. RESULTS: The intraclass correlation coefficients between the physical measurements and the measurements of the CBCT images of 0.40 and 0.25 voxels were all more than 0.99. All CBCT measurements were accurate. There was no difference between the accuracy of the measurements between the 0.40 and 0.25 voxel size groups. The smallest detectable differences of the CBCT measurements were minimal, confirming the accuracy of the CBCT measurement procedure. CONCLUSIONS: The measurements on 3-dimensional surface models of 0.25 and 0.40 voxel size data sets made with the 3D eXam CBCT scanner (KaVo Dental GmbH, Bismarckring, Germany) and SimPlant Ortho Pro software (version 2.00, Materialise Dental, Leuven, Belgium) are accurate compared with direct caliper measurements. An increased voxel resolution did not result in greater accuracy of the surface model measurments.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Mandíbula/diagnóstico por imagem , Modelos Dentários , Radiografia Dentária Digital/métodos , Adulto , Cadáver , Humanos , Imageamento Tridimensional/métodos , Mandíbula/anatomia & histologia , Valores de Referência , Software
16.
Am J Orthod Dentofacial Orthop ; 138(5): 546.e1-8; discussion 546-7, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21055590

RESUMO

INTRODUCTION: The aim of this study was to determine the reliability and the measuring error (by means of the smallest detectable error) of 11 angular and 4 linear measurements commonly used for cephalometric analysis. METHODS: Twenty-five digital lateral cephalograms were randomly selected and traced with Viewbox software (version 3.1.1.13, dHAL Software, Kifissia, Greece). This was repeated 3 times by 2 observers during 3 sessions. There was at least 1 week between each session. Differences were analyzed with a repeated measurement analysis of variance (ANOVA). Intraobserver and interobserver reliabilities were calculated with intraclass correlation coefficients (ICC) based on absolute agreement. Measurement error was determined by means of the smallest detectable difference. RESULTS: The intraobserver agreement of the measurements was good (ICC >0.82). SNA, SNB, ANB, and ANS-Me had the smallest intraobserver errors for both observers (>1.86 mm or degrees). Except for SN-FH (ICC = 0.76), interobserver agreement was good (ICC >0.87). CONCLUSIONS: Determining the appropriate measuring error of cephalometric measurements by means of the smallest detectable difference is necessary to find the true difference between the start and the end of active treatment. Depending on the magnitude of clinical significance, the measuring error was possibly clinically significant for all variables tested and, therefore, questions the use of these variables to detect the true treatment effect.


Assuntos
Cefalometria/estatística & dados numéricos , Adolescente , Viés , Dente Pré-Molar/patologia , Criança , Queixo/patologia , Meato Acústico Externo/patologia , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Incisivo/patologia , Mandíbula/patologia , Côndilo Mandibular/patologia , Maxila/patologia , Dente Molar/patologia , Osso Nasal/patologia , Variações Dependentes do Observador , Órbita/patologia , Reprodutibilidade dos Testes , Sela Túrcica/patologia , Software
17.
Matrix Biol ; 85-86: 15-33, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295578

RESUMO

Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we present a "blank slate" culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture platform provides full control over biochemical and physical properties, allowing the impact of biochemical composition and tissue mechanics to be separately evaluated in vitro. Here, we demonstrate that the peptide gels support the growth of a range of cells including human induced pluripotent stem cells and human cancer cell lines. Furthermore, we present proof-of-concept that the peptide gels can be used to build disease-relevant models. Controlling the peptide gelator concentration allows peptide gel stiffness to be matched to normal breast (<1 kPa) or breast tumour tissue (>1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, the peptide gels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions affect the size, shape and organisation of breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and other diseases.


Assuntos
Neoplasias da Mama/metabolismo , Mama/citologia , Técnicas de Cocultura/métodos , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Hidrogéis/química , Peptídeos/metabolismo , Animais , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/patologia , Comunicação Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Feminino , Fibroblastos/metabolismo , Células HCT116 , Humanos , Células MCF-7 , Camundongos , Modelos Biológicos , Peptídeos/química
18.
Rheumatology (Oxford) ; 48(9): 1077-82, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19553376

RESUMO

OBJECTIVE: To compare health-related quality of life (HR-QOL), employment and disability of primary and secondary SS (pSS and sSS, respectively) patients with the general Dutch population. METHODS: HR-QOL, employment and disability were assessed in SS patients regularly attending the University Medical Center Groningen (n = 235). HR-QOL, employment and disability were evaluated with the Short Form-36 questionnaire (SF-36) and an employment and disability questionnaire. Results were compared with Dutch population data (matched for sex and age). Demographical and clinical data associated with HR-QOL, employment and disability were assessed. RESULTS: Response rate was 83%. SS patients scored lower on HR-QOL than the general Dutch population. sSS patients scored lower on physical functioning, bodily pain and general health than pSS patients. Predictors for reduced HR-QOL were fatigue, tendomyalgia, articular involvement, use of artificial saliva, use of anti-depressants, comorbidity, male sex and eligibility for disability compensation (DC). Employment was lower and DC rates were higher in SS patients compared with the Dutch population. CONCLUSION: SS has a large impact on HR-QOL, employment and disability.


Assuntos
Emprego , Qualidade de Vida , Síndrome de Sjogren/reabilitação , Adulto , Idoso , Avaliação da Deficiência , Escolaridade , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/psicologia , Classe Social
19.
J Clin Periodontol ; 35(12): 1073-86, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19040585

RESUMO

AIM: This study evaluated, through a systematic review of the literature, the outcome of single-implant restorations in the aesthetic zone with natural adjacent teeth, thereby addressing immediate, early and conventional implant approaches. MATERIAL AND METHODS: MEDLINE (1950-2008), EMBASE (1966-2008), and CENTRAL (1800-2008) were searched to identify eligible studies. Two reviewers independently assessed the methodological quality using specific study-design-related assessment forms. RESULTS: Out of 86 primarily selected articles, 19 studies fulfilled the inclusion criteria. A meta-analysis showed an overall survival rate of 95.5% [95% confidence interval: (93.0-97.1)] after 1 year. A stratified meta-analysis revealed no differences in survival between immediate, early and conventional implant strategies. Little marginal peri-implant bone resorption was found together with low incidence of biological and technical complications. No significant differences in outcome measures were reported in clinical trials comparing immediate, early or conventional implant strategies. CONCLUSION: The included literature suggested that promising short-term results could be achieved for immediate, early and conventional single-implants in the aesthetic zone. However, important parameters as aesthetic outcome, soft-tissue aspects, and patient satisfaction were clearly underexposed. The question whether immediate and early single-implant therapies would result in better treatment outcomes remained inconclusive due to lack of well-designed controlled clinical studies.


Assuntos
Implantação Dentária Endóssea/métodos , Implantes Dentários para Um Único Dente , Prótese Dentária Fixada por Implante , Perda do Osso Alveolar/diagnóstico por imagem , Dente Pré-Molar , Dente Canino , Falha de Restauração Dentária , Estética Dentária , Gengiva/anatomia & histologia , Humanos , Incisivo , Satisfação do Paciente , Radiografia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Alvéolo Dental/cirurgia , Resultado do Tratamento
20.
Hemodial Int ; 22(2): 261-269, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29024379

RESUMO

INTRODUCTION: Ultrasound of the inferior vena cava (IVC-US) has been used to estimate intravascular volume status and fluid removal during a hemodialysis session. Usually, renal nurses rely on other, imprecise methods to determine ultrafiltration. To date, no study has examined whether renal nurses can reliably perform ultrasound for volume assessment and for potential prevention of intradialytic hypotension. This pilot study aimed to determine if a renal nurse could master the skill of performing and correctly interpreting Point of Care Ultrasound on patients receiving hemodialysis. METHODS: After receiving theoretical training and performing 100 training scans, a renal nurse performed 60 ultrasound scans on 10 patients. These were categorized by the nurse into hypovolemic, euvolemic, or hypervolemic through measurement of the maximal diameter and degree of collapse of the IVC. Scans were subsequently assessed for adequacy and quality by two sonologists, who were blinded to each other's and the nurse's results. FINDINGS: The interrater reliability of 60 scans was good, with intraclass correlation 0.79 (95% confidence interval (CI) =0.63-0.87) and with a good interrater agreement for the following estimation of intravascular volume (Cohen's weighted Kappa κw = 0.62), when comparing the nurse to an expert sonographer. DISCUSSION: A renal nurse can reliably perform ultrasound of the IVC in hemodialysis patients, obtaining high quality scans for volume assessment of hemodialysis patients. This novel approach could be more routinely applied by other renal nurses to obtain objective measures of patient volume status in the dialysis setting.


Assuntos
Diálise Renal/métodos , Ultrassonografia/métodos , Veia Cava Inferior/diagnóstico por imagem , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Enfermeiras e Enfermeiros
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