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1.
Am J Manag Care ; 30(2): 66-72, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38381541

RESUMO

OBJECTIVES: We examined the association between electronic health information sharing and repeat imaging in readmissions among older adults with and without Alzheimer disease (AD). STUDY DESIGN: Cohort study using national Medicare data. METHODS: Among Medicare beneficiaries with 30-day readmissions in 2018, we examined repeat imaging on the same body system during the readmission. This was evaluated between fragmented and nonfragmented (same-hospital) readmissions and across categories of electronic information sharing via health information exchanges (HIEs) in fragmented readmissions: admission and readmission hospitals share the same HIE, admission and readmission hospitals participate in different HIEs, one or both do not participate in HIE, or HIE data missing. This relationship was evaluated using unadjusted and adjusted logistic regression. RESULTS: Overall, 14.3% of beneficiaries experienced repeat imaging during their readmission. Compared with nonfragmented readmissions, fragmented readmissions were associated with 5% higher odds of repeat imaging on the same body system in older adults without AD. This was not mitigated by the presence of electronic information sharing: Fragmented readmissions to hospitals that shared an HIE had 6% higher odds of repeat imaging (adjusted OR, 1.06; 95% CI, 1.00-1.13). There was no difference seen in the odds of repeat imaging for older adults with AD. CONCLUSIONS: Despite substantial investment, HIEs as currently deployed and used are not associated with decreased odds of repeat imaging in readmissions.


Assuntos
Medicare , Readmissão do Paciente , Humanos , Idoso , Estados Unidos , Estudos de Coortes , Estudos Retrospectivos , Hospitalização
2.
Benef Microbes ; 11(5): 411-455, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32865024

RESUMO

Evidence is accumulating that short chain fatty acids (SCFA) play an important role in the maintenance of gut and metabolic health. The SCFA acetate, propionate and butyrate are produced from the microbial fermentation of indigestible carbohydrates and appear to be key mediators of the beneficial effects elicited by the gut microbiome. Microbial SCFA production is essential for gut integrity by regulating the luminal pH, mucus production, providing fuel for epithelial cells and effects on mucosal immune function. SCFA also directly modulate host metabolic health through a range of tissue-specific mechanisms related to appetite regulation, energy expenditure, glucose homeostasis and immunomodulation. Therefore, an increased microbial SCFA production can be considered as a health benefit, but data are mainly based on animal studies, whereas well-controlled human studies are limited. In this review an expert group by ILSI Europe's Prebiotics Task Force discussed the current scientific knowledge on SCFA to consider the relationship between SCFA and gut and metabolic health with a particular focus on human evidence. Overall, the available mechanistic data and limited human data on the metabolic consequences of elevated gut-derived SCFA production strongly suggest that increasing SCFA production could be a valuable strategy in the preventing gastro-intestinal dysfunction, obesity and type 2 diabetes mellitus. Nevertheless, there is an urgent need for well controlled longer term human SCFA intervention studies, including measurement of SCFA fluxes and kinetics, the heterogeneity in response based on metabolic phenotype, the type of dietary fibre and fermentation site in fibre intervention studies and the control for factors that could shape the microbiome like diet, physical activity and use of medication.


Assuntos
Ácidos Graxos Voláteis/metabolismo , Gastroenteropatias/prevenção & controle , Microbioma Gastrointestinal , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Animais , Metabolismo dos Carboidratos , Diabetes Mellitus Tipo 2/prevenção & controle , Interações entre Hospedeiro e Microrganismos , Humanos , Obesidade/prevenção & controle , Prebióticos
3.
Can J Anaesth ; 67(5): 515-520, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32152886

RESUMO

PURPOSE: Upper airway injury and sympathetic activation may be related to the forces applied during laryngoscopy. We compared the applied forces during laryngoscopy using direct and indirect visualization of a standardized mannequin glottis. METHODS: Force transducers were applied to the concave surface of a GlideScope T-MAC Macintosh-style video laryngoscope that can also be used as a conventional direct-view laryngoscope. Thirty-four anesthesiologists performed four laryngoscopies (two direct and two indirect views) on an Ambu mannequin in a randomized sequence. During each laryngoscopy, participants were instructed to obtain views corresponding to > 80% and 50% of the glottic opening aperture. Peak and impulse forces were measured for each view. RESULTS: To achieve a 50% glottic opening view, the top 10th percentile force was higher with direct vs indirect laryngoscopy in terms of peak (difference, 9.1 newton; 99% confidence interval [CI], 7.4 to 13.9) and impulse (difference, 56.4 newton·sec; 99% CI, 49.0 to 81.7) forces. To achieve >80% view of the glottic opening, median force was higher with direct vs indirect laryngoscopy in terms of peak (difference, 3.6 newton; 99% CI, 1.6 to 7.3) and impulse (difference, 20.4 newton·sec; 99% CI, 11.7 to 35.1) forces. CONCLUSIONS: In this mannequin study, lower forces applied during indirect vs direct laryngoscopy may reflect an advantage of video laryngoscopy, but additional studies using patients are required to confirm the clinical implications of these findings.


RéSUMé: OBJECTIF: Les lésions aux voies aériennes supérieures et l'activation du système sympathique pourraient être dues aux forces appliquées pendant la laryngoscopie. Nous avons comparé les forces appliquées pendant une laryngoscopie avec visualisation directe vs indirecte d'une glotte standardisée sur mannequin. MéTHODE: Des transducteurs ont été appliqués à la surface concave d'un vidéolaryngoscope de type Macintosh GlideScope T-MAC, un dispositif qui peut également être utilisé comme laryngoscope conventionnel avec visualisation directe. Trente-quatre anesthésiologistes ont chacun réalisé quatre laryngoscopies (deux visualisations directes et deux indirectes) sur un mannequin Ambu en suivant une séquence randomisée. Pendant chaque laryngoscopie, les participants avaient pour consigne d'obtenir des vues correspondant à > 80 % et 50 % de l'ouverture glottique. Les forces maximales et impulsions ont été mesurées pour chaque visualisation. RéSULTATS: Pour obtenir une visualisation à 50 % de l'ouverture glottique, le 10e percentile maximal était plus élevé en cas de laryngoscopie directe qu'en cas de laryngoscopie indirecte tant au maximum de la force (différence, 9,1 newton; intervalle de confiance [IC] 99 %, 7,4 à 13,9) qu'à l'impulsion (différence, 56,4 newton·sec; IC 99 %, 49,0 à 81,7). Pour obtenir une visualisation à > 80 % de l'ouverture glottique, la médiane était également plus élevée en cas de laryngoscopie directe qu'en cas de laryngoscopie indirecte, tant au maximum de la force (différence, 3,6 newton; intervalle de confiance [IC] 99 %, 1,6 à 7,3) qu'à l'impulsion (différence, 20,4 newton·sec; IC 99 %, 11,7 à 35,1). CONCLUSION: Dans cette étude sur mannequin, les forces et impulsions moins prononcées appliquées pendant la laryngoscopie indirecte plutôt que directe pourraient refléter un avantage de la vidéolaryngoscopie, mais des études supplémentaires sur patient sont nécessaires afin de confirmer les implications cliniques de ces résultats.


Assuntos
Laringoscópios , Laringoscopia , Glote , Humanos , Intubação Intratraqueal , Manequins , Gravação em Vídeo
4.
Benef Microbes ; 11(2): 101-129, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32073295

RESUMO

The inherent and diverse capacity of dietary fibres, nondigestible oligosaccharides (NDOs) and prebiotics to modify the gut microbiota and markedly influence health status of the host has attracted rising interest. Research and collective initiatives to determine the composition and diversity of the human gut microbiota have increased over the past decade due to great advances in high-throughput technologies, particularly the 16S ribosomal RNA (rRNA) sequencing. Here we reviewed the application of 16S rRNA-based molecular technologies, both community wide (sequencing and phylogenetic microarrays) and targeted methodologies (quantitative PCR, fluorescent in situ hybridisation) to study the effect of chicory inulin-type fructans, NDOs and specific added fibres, such as resistant starches, on the human intestinal microbiota. Overall, such technologies facilitated the monitoring of microbiota shifts due to prebiotic/fibre consumption, though there are limited community-wide sequencing studies so far. Molecular studies confirmed the selective bifidogenic effect of fructans and galactooligosaccharides (GOS) in human intervention studies. Fructans only occasionally decreased relative abundance of Bacteroidetes or stimulated other groups. The sequencing studies for various resistant starches, polydextrose and beta-glucan showed broader effects with more and different types of gut microbial species being enhanced, often including phylotypes of Ruminococcaceae. There was substantial variation in terms of magnitude of response and in individual responses to a specific fibre or NDO which may be due to numerous factors, such as initial presence and relative abundance of a microbial type, diet, genetics of the host, and intervention parameters, such as intervention duration and fibre dose. The field will clearly benefit from a more systematic approach that will support defining the impact of prebiotics and fibres on the gut microbiome, identify biomarkers that link gut microbes to health, and address the personalised response of an individual's microbiota to prebiotics and dietary fibres.


Assuntos
Dieta , Fibras na Dieta , Frutanos , Microbioma Gastrointestinal/genética , Prebióticos , Fezes/microbiologia , Humanos , Filogenia , RNA Ribossômico 16S/genética
5.
Cell Transplant ; 27(8): 1210-1221, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30016879

RESUMO

Intramuscular administration of mesenchymal stromal cells (MSCs) represents a therapeutic option for diabetic critical limb ischemia. Autologous or allogeneic approaches may be used but disease-induced cell dysfunction may limit therapeutic efficacy in the former. Our aim was to compare the efficacy of allogeneic and autologous MSC transplantation in a model of hindlimb ischemia in diabetes mellitus and to determine whether allogeneic transplantation would result in the activation of an immune response. MSCs were isolated from C57BL/6 (B6) and diabetic obese C57BKSdb/db mice. Phosphate-buffered saline (control group), and MSCs (1 × 106) from B6 (allogeneic group) or C57BKSdb/db (syngeneic group) were administered intramuscularly into the ischemic thigh of C57BKSdb/db mice following the induction of hindlimb ischemia. MSCs derived from both mouse strains secrete several angiogenic factors, suggesting that the potential therapeutic effect is due to paracrine signaling. Administration of allogeneic MSCs significantly improved blood perfusion as compared with the control group on week 2 and 3, post-operatively. In comparison with the control group, syngeneic MSCs significantly improved blood perfusion at week 2 only. There was no statistical difference in blood perfusion between allogeneic and syngeneic MSC groups at any stages. There was no statistical difference in ambulatory and necrosis score among the three groups. Amputation of toes was only observed in the control group (one out of seven animals). Alloantibody was detected in three out of the eight mice that received allogeneic MSCs but was not observed in the other groups. In summary, we demonstrated comparable efficacy after transplantation of autologous and allogeneic MSCs in a diabetic animal model despite generation of an immune response.


Assuntos
Complicações do Diabetes/complicações , Membro Posterior/irrigação sanguínea , Isquemia/complicações , Isquemia/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Neovascularização Fisiológica , Animais , Células Cultivadas , Complicações do Diabetes/sangue , Complicações do Diabetes/imunologia , Modelos Animais de Doenças , Membro Posterior/imunologia , Isquemia/sangue , Isquemia/imunologia , Isoanticorpos/sangue , Isoanticorpos/imunologia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Camundongos Endogâmicos C57BL , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos
6.
Urology ; 85(3): 490, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25733257
8.
Ann R Coll Surg Engl ; 96(2): e19-20, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24780660

RESUMO

The internet provides the public with unregulated access to a wide range of medications. We present the case of a 43-year-old man who purchased oral tadalafil gel on the internet and injected it into his left radial artery. He presented 48 hours after injection with signs of ischaemia distal to the injection site requiring a combination of medical and surgical treatment. This unique case highlights the potential dangers of unregulated access to medication and the consequences of intravascular injection of oral gels.


Assuntos
Carbolinas/efeitos adversos , Dedos/irrigação sanguínea , Isquemia/induzido quimicamente , Inibidores da Fosfodiesterase 5/efeitos adversos , Uso Indevido de Medicamentos sob Prescrição/efeitos adversos , Artéria Radial/lesões , Adulto , Amputação Traumática/induzido quimicamente , Anticoagulantes/uso terapêutico , Géis , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Iloprosta/uso terapêutico , Injeções Intra-Arteriais , Isquemia/tratamento farmacológico , Masculino , Tadalafila , Vasodilatadores/uso terapêutico
9.
Prostate ; 74(3): 250-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24166488

RESUMO

BACKGROUND: Current diagnostic testing for prostate cancer results in numerous unnecessary biopsy procedures and creates a substantial financial burden. A statistical prediction model for prostate cancer has been developed, based on four Kallikrein markers in blood. This systematic review and meta-analysis examines the aggregated results from published studies of the Kallikrein Panel. METHODS: Literature searches to identify relevant studies were conducted. A meta-analysis of the results was performed using inverse variance, mean difference with corresponding 95% confidence intervals (CI). The results of the meta-analysis were used to assess the Kallikrein Panel's effect on healthcare costs. RESULTS: The Kallikrein Panel has been evaluated in more than 8,500 patients (2,780 with prostate cancer and 598 with high grade prostate cancer). Meta-analysis demonstrates a statistically significant improvement of 8-10% in predictive accuracy. In addition, 48% to 56% of current prostate biopsies could be avoided. Use of the Kallikrein Panel could result in annual US savings approaching $1 billion. CONCLUSIONS: The Kallikrein Panel has the potential to improve patient outcomes and reduce costs. The panel provides significantly improved specificity. Because the Kallikrein Panel has been studied in a range of clinical settings, it is a test that could be readily and widely used in practice.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/economia , Calicreínas/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/economia , Algoritmos , Biópsia/economia , Redução de Custos , Custos e Análise de Custo , Detecção Precoce de Câncer/economia , Humanos , Masculino , Antígeno Prostático Específico/sangue , Sensibilidade e Especificidade , Calicreínas Teciduais/sangue , Estados Unidos
10.
J Agric Food Chem ; 60(45): 11331-42, 2012 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-23072624

RESUMO

The colonic microbial degradation of a polyphenol-rich black tea extract (BTE) and red wine/grape juice extract (RWGE) was compared in a five-stage in vitro gastrointestinal model (TWINSHIME). Microbial metabolism of BTE and RWGE polyphenols in the TWINSHIME was studied subsequently in single- and continuous-dose experiments. A combination of liquid or gas chromatography with mass spectrometry (LC-MS or GC-MS) and NMR-based metabolic profiling was used to measure selected parent polyphenols, their microbial degradation into phenolic acids, and the production of short-chain fatty acids (SCFAs) in different colon compartments. Acetate production was increased by continuous feeding of BTE but not RWGE. During RWGE feeding, gallic acid and 4-hydroxyphenylpropionic acid remained elevated throughout the colon, while during BTE feeding, they were consumed in the distal colon, while 3-phenylpropionic acid was strongly produced. Gut microbial production of phenolics and SCFAs is dependent on colon location and polyphenol source, which may influence potential health benefits.


Assuntos
Bactérias/metabolismo , Camellia sinensis/metabolismo , Colo/metabolismo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Extratos Vegetais/metabolismo , Polifenóis/metabolismo , Vitis/metabolismo , Vinho/análise , Camellia sinensis/química , Colo/microbiologia , Humanos , Metagenoma , Modelos Biológicos , Extratos Vegetais/análise , Especificidade da Espécie , Chá/metabolismo , Vitis/química
11.
J Urol ; 188(3): 757-61, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22818135

RESUMO

PURPOSE: We examined the effect of 5α-reductase inhibitor therapy on prostate cancer detection in men with persistently increased or fluctuating prostate specific antigen and prior negative prostate cancer biopsy. MATERIALS AND METHODS: A total of 276 men with prostate specific antigen greater than 4 ng/ml (208) or a prostate specific antigen velocity change of 0.75 ng/ml (68) and a normal digital rectal examination who had previously undergone biopsy a minimum of 2 times with prostate cancer not detected were given 5 mg finasteride (154) or dutasteride (122) daily. In phase 1, 97 patients had prostate specific antigen measured at 6 and 12 months with repeat transrectal ultrasonography and biopsy (12 cores) performed at 1 year. In phase 2, 179 patients underwent biopsy triggered by a change in nadir prostate specific antigen of more than 0.4 ng/ml. RESULTS: In phase 1 at 1 year prostate specific antigen had decreased by 2.4 ng/ml (-46.7%), and prostate volume had decreased 7.1 ml (-17.9%). Prostate cancer was detected in 27 of 97 (27.8%) patients and the mean minimum prostate specific antigen velocity from a nadir of 0.4 ng/ml was 0.6 ng/ml. In phase 2, 48 of 179 (26.8%) men underwent repeat biopsy at a mean of 14.6 months. Of these 48 men 26 (54.1%) were found to have prostate cancer. Of the 26 men in whom prostate cancer was detected 20 (76.9%) were found to have Gleason score 7 or greater disease. CONCLUSIONS: The magnitude of change in serum prostate specific antigen after 5α-reductase inhibitor therapy may be useful in diagnosing prostate cancer in patients with persistently increased or fluctuating prostate specific antigen and prior negative prostate biopsy.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Azasteroides/farmacologia , Finasterida/farmacologia , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/efeitos dos fármacos , Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Biópsia , Dutasterida , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico
12.
Cell Transplant ; 21(6): 1095-107, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22304991

RESUMO

Tissue necrosis resulting from critical limb ischemia (CLI) leads to amputation in a significant number of patients. Autologous cell therapy using angiogenic cells such as endothelial progenitor cells (EPCs) holds promise as a treatment for CLI but a limitation of this treatment is that the underlying disease etiology that resulted in CLI may also contribute to dysfunction of the therapeutic EPCs. This study aimed to elucidate the mechanism of EPC dysfunction using diabetes mellitus as a model and to determine whether correction of this defect in dysfunctional EPCs ex vivo would improve the outcome after cell transplantation in the murine hind limb ischemia model. EPC dysfunction was confirmed in a homogenous population of patients with type 1 diabetes mellitus and a microarray study was preformed to identify dysregulated genes. Notably, the secreted proangiogenic protein osteopontin (OPN) was significantly downregulated in diabetic EPCs. Furthermore, OPN-deficient mice showed impaired recovery following hind limb ischemia, suggesting a critical role for OPN in postnatal neovascularization. EPCs isolated from OPN KO mice showed decreased ability to adhere to endothelial cells as well as impaired angiogenic potential. However, this dysfunction was reversed upon exposure to recombinant OPN, suggesting that OPN may act in an autocrine manner on EPCs. Indeed, exposure of OPN knockout (KO) EPCs to OPN was sufficient to induce the secretion of angiogenic proteins (IL-6, TGF-α, and FGF-α). We also demonstrated that vascular regeneration following hind limb ischemia in OPN KO mice was significantly improved upon injection of EPCs preexposed to OPN. We concluded that OPN acts in an autocrine manner on EPCs to induce the secretion of angiogenic proteins, thereby playing a critical role in EPC-mediated neovascularization. Modification of cells by exposure to OPN may improve the efficacy of autologous EPC transplantation via the enhanced secretion of angiogenic proteins.


Assuntos
Células Endoteliais/citologia , Osteopontina/farmacologia , Doenças Vasculares Periféricas/terapia , Células-Tronco/efeitos dos fármacos , Adulto , Animais , Terapia Baseada em Transplante de Células e Tecidos , Células Cultivadas , Diabetes Mellitus Tipo 1/patologia , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Membro Posterior/irrigação sanguínea , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-6/metabolismo , Isquemia/metabolismo , Isquemia/terapia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Fisiológica/efeitos dos fármacos , Osteopontina/genética , Osteopontina/metabolismo , Doenças Vasculares Periféricas/metabolismo , Coelhos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Regeneração , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco/metabolismo , Fator de Crescimento Transformador alfa/metabolismo , Adulto Jovem
13.
Br J Oral Maxillofac Surg ; 50(1): 13-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21168246

RESUMO

Reconstruction of surgical defects in the head and neck using microvascular free tissue transfer is reliable with success rates in excess of 95%. Our previous audit (1992-1998) showed that 16% of patients required an early return to theatre, and the overall free flap salvage rate was 73%. The medical records of 37 patients who had required early return to theatre (within 7 days) after free tissue transfer were analysed to ascertain the indication for reoperation, and whether surgical intervention had been successful, taking into account the timing and cause of compromise. The results of a retrospective re-audit (1999-2004 and 2005-2009) showed that the return to theatre rate had reduced to 4% overall because of a reduction in the number of cases: those that required evacuation of a neck haematoma, and venous compromise of fasciocutaneous or perforator free flaps. Salvage of flaps was most successful when done within the first 24h, and in cases of venous compromise. Three percent of free flaps failed without attempted salvage; most were late failures. Overall survival (1992-2009) for composite free flaps (93%) was lower than for fasciocutaneous or perforator free flaps (96%). Between 2005 and 2009 our overall free flap survival rate was 98%.


Assuntos
Auditoria Odontológica , Retalhos de Tecido Biológico/tendências , Procedimentos Cirúrgicos Bucais/tendências , Procedimentos de Cirurgia Plástica/tendências , Estudos de Coortes , Inglaterra/epidemiologia , Fáscia/transplante , Seguimentos , Retalhos de Tecido Biológico/irrigação sanguínea , Retalhos de Tecido Biológico/estatística & dados numéricos , Sobrevivência de Enxerto , Hematoma/epidemiologia , Humanos , Complicações Intraoperatórias/epidemiologia , Procedimentos Cirúrgicos Bucais/estatística & dados numéricos , Procedimentos de Cirurgia Plástica/estatística & dados numéricos , Reoperação , Estudos Retrospectivos , Transplante de Pele/estatística & dados numéricos , Transplante de Pele/tendências , Trombose/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa/epidemiologia
14.
Gene Ther ; 19(3): 338-46, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21716302

RESUMO

For non-viral gene delivery to be successful, plasmids must move through the cytoplasm to the nucleus in order to be transcribed. While the cytoskeletal meshwork acts as a barrier to plasmid DNA movement in the cytoplasm, the microtubule network is required for directed plasmid trafficking to the nucleus. We have shown previously that plasmid-microtubule interactions require cytoplasmic adapter proteins such as molecular motors, transcription factors (TFs) and importins. However, not all plasmid sequences support these interactions to allow movement to the nucleus. We now demonstrate that microtubule-DNA interactions can show sequence specificity with promoters containing binding sites for cyclic AMP response-element binding protein (CREB), including the cytomegalovirus immediate early promoter (CMV(iep)). Plasmids containing CREB-binding sites showed stringent interactions in an in vitro microtubule-binding assay. Using microinjection and real-time particle tracking, we show that the inclusion of TF binding sites within plasmids permits cytoplasmic trafficking of plasmids during gene transfer. We found that CREB-binding sites are bound by CREB in the cytoplasm during transfection, and allow for enhanced rates of movement and subsequent nuclear accumulation. Moreover, small interfering RNA knockdown of CREB prevented this enhanced trafficking. Therefore, TF binding sites within plasmids are necessary for interactions with microtubules and enhance movement to the nucleus.


Assuntos
Técnicas de Transferência de Genes , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Microtúbulos/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , Fatores de Transcrição/metabolismo , Sítios de Ligação , Transporte Biológico , Linhagem Celular , Núcleo Celular/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Citoplasma/metabolismo , Elementos Facilitadores Genéticos , Humanos , Modelos Biológicos , Regiões Promotoras Genéticas , Ligação Proteica
15.
Microbiology (Reading) ; 156(Pt 11): 3224-3231, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20724384

RESUMO

Polyphenols, ubiquitously present in the food we consume, may modify the gut microbial composition and/or activity, and moreover, may be converted by the colonic microbiota to bioactive compounds that influence host health. The polyphenol content of fruit and vegetables and derived products is implicated in some of the health benefits bestowed on eating fruit and vegetables. Elucidating the mechanisms behind polyphenol metabolism is an important step in understanding their health effects. Yet, this is no trivial assignment due to the diversity encountered in both polyphenols and the gut microbial composition, which is further confounded by the interactions with the host. Only a limited number of studies have investigated the impact of dietary polyphenols on the complex human gut microbiota and these were mainly focused on single polyphenol molecules and selected bacterial populations. Our knowledge of gut microbial genes and pathways for polyphenol bioconversion and interactions is poor. Application of specific in vitro or in vivo models mimicking the human gut environment is required to analyse these diverse interactions. A particular benefit can now be gained from next-generation analytical tools such as metagenomics and metatranscriptomics allowing a wider, more holistic approach to the analysis of polyphenol metabolism. Understanding the polyphenol-gut microbiota interactions and gut microbial bioconversion capacity will facilitate studies on bioavailability of polyphenols in the host, provide more insight into the health effects of polyphenols and potentially open avenues for modulation of polyphenol bioactivity for host health.


Assuntos
Bactérias/metabolismo , Dieta , Flavonoides/metabolismo , Trato Gastrointestinal/microbiologia , Metagenoma , Fenóis/metabolismo , Animais , Disponibilidade Biológica , Frutas , Perfilação da Expressão Gênica , Humanos , Modelos Animais , Polifenóis , Proteômica , Verduras
16.
BJU Int ; 106(9): 1364-73, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20377582

RESUMO

OBJECTIVE: To describe a novel synchronous approach to apical dissection during robotic-assisted radical prostatectomy (RARP) which augments circumferential visual appreciation of the prostatic apex and membranous urethra anatomy, and assess its effect on apical margin positivity. PATIENTS AND METHODS: Positive surgical margins (PSM) during RP predispose to earlier biochemical recurrence, and occur most frequently at the prostatic apex. Conventional apical transection after early ligation of the dorsal venous complex (DVC) remains suboptimal, as this approach obscures visualization of the intersection between prostatic apex and membranous urethra, leading to inadvertent apical capsulotomy and eventual margin positivity. A synchronous urethral transection commenced via a retro-apical approach was adopted in 209 consecutive patients undergoing RARP by one surgeon (A.T.) between April to September 2009. The apical margin rates for this group were compared with those of 1665 previous patients who received conventional urethral transection via an anterior approach after DVC ligation. Outcomes were adjusted for differences in clinicopathological variables. All RP specimens were processed according to institutional protocols, and examined by dedicated genitourinary pathologists. The location of PSMs was identified as apex, posterior, posterolateral, bladder neck, anterior, base, or multifocal. RESULTS: Patients receiving synchronous urethral transection had significantly lower apical PSM rates than the control group (1.4% vs 4.4%, P = 0.04). This marked improvement in the retro-apical group occurred despite a significantly higher incidence of aggressive cancer (≥ pT3a) documented on final specimen pathology (16% vs 10%, P = 0.027).Technical difficulty was encountered in three of 209 study patients, in whom urethral transection had to be completed using the classic anterior approach. CONCLUSION: Improved circumferential visualization of the prostatic apex, membranous urethra and their anatomical intersection facilitates precise dissection of the apex and its surrounding neural scaffold, and optimizes membranous urethral preservation. This has significantly ameliorated apical PSM rates in patients undergoing RARP, despite having to deal with more aggressive cancer on final specimen pathology.


Assuntos
Recidiva Local de Neoplasia/prevenção & controle , Próstata/patologia , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Robótica , Uretra/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Próstata/cirurgia , Neoplasias da Próstata/prevenção & controle , Neoplasias da Próstata/cirurgia , Resultado do Tratamento , Uretra/cirurgia
17.
BJU Int ; 106(4): 528-36, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20192955

RESUMO

OBJECTIVE: To analyse consecutive cases of robotic-assisted laparoscopic prostatectomy (RALP), present the incidence of nerve-sparing-related positive surgical margins (SM+), include visual cues that might assist in smoothly changing to the robotic platform, and discuss the scientific rationale for 'intersensory integration' which might explain the 'reverse Braille' phenomenon, i.e. the ability to feel when vision is greatly enhanced, as the lack of tactile feedback during RALP is often cited as a disadvantage of robotic surgery, interfering with a surgeon's ability to make intraoperative oncological decisions. PATIENTS AND METHODS: Data from 1340 consecutive patients undergoing RALP from one institution were analysed and trends for positive posterolateral SM+ (PLSM+) were correlated with oncological variables before and after RALP. A sample of patient slides were reviewed by a extramural pathologist. Multivariate regression modelling was used to compare the projected rates of PLSM+ vs the actual rate, given the effect of a conscious effort to use visual cues. Finally, video recordings of the procedure were systematically reviewed and correlated with anatomical and histopathological images in an integrated session involving the surgeon and the pathology team. RESULTS: The incidence of PLSM+ was 2.1%, which gradually declined to 1.0% in the last 100 patients. The reduction in PLSM+ occurred despite an increased rate of high-risk tumours operated on during this period. Forecasting analysis showed that the actual PLSM+ rate declined by half in the most recent 1000 patients, due to an integrated effort involving the use of visual cues during surgery. The following visual cues were considered important; appreciation of periprostatic (lateral prostatic) fascial compartments; colour and texture of the tissue; periprostatic veins as a landmark for athermal dissection; signs of inflammation; and a freely separating bloodless plane showing loose shiny areolar tissue. CONCLUSION: Adapting to the robotic platform is easy and there is no compromise of the oncological safety of this procedure. Experienced surgeons can use visual cues to assist during nerve-sparing RALP and achieve low PLSM+ rates.


Assuntos
Competência Clínica , Retroalimentação Sensorial/fisiologia , Laparoscopia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Robótica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/patologia , Tato
18.
Head Neck ; 32(6): 714-22, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19827119

RESUMO

BACKGROUND: Extracapsular spread (ECS) in the cervical lymph nodes represents the most significant adverse prognostic indicator in oral squamous cell carcinoma (OSCC). METHODS: In a consecutive cohort of OSCC treated by primary surgery, ECS was seen in 25% (101) of 400 patients. RESULTS: ECS doubled the incidence of local recurrence and distant metastases, but tripled regional failure. The recurrences occurred sooner in ECS than in non-ECS cases (206 vs 334 days, p = .04). Patients with macroscopic ECS had a 5-year overall survival (OS) of 19% compared with 31% in microscopic ECS. MRI neck staging offered poor sensitivity, especially in microscopic ECS. Age >75 years, smoking, and heavy use of alcohol were independent predictors of ECS, which may implicate a failure of immunosurveillance by the host as much as adverse biology of the tumor. CONCLUSIONS: Reporting of ECS is essential in accurate prognostication, and we advocate that all patients with OSCC and ECS should be grouped as pN3 on the basis of their prognosis. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2010.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Idoso , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Excisão de Linfonodo , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Neoplasias Bucais/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Fatores de Risco
20.
Oral Oncol ; 45(4-5): 421-30, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19362049

RESUMO

Free tissue transfer with microvascular anastomosis has transformed surgical outcomes for head and neck cancer patients. Microvascular reconstruction has allowed surgeons to perform more aggressive ablative surgery. This paper considers the extent to which this method of reconstruction has improved functional outcomes in these patients.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Anastomose Cirúrgica/métodos , Sobrevivência de Enxerto , Humanos , Laringe/cirurgia , Ilustração Médica , Microcirculação , Microcirurgia/métodos , Recuperação de Função Fisiológica , Sistema Estomatognático/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Resultado do Tratamento
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