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1.
Proc Natl Acad Sci U S A ; 121(10): e2317832121, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38412136

RESUMEN

Non-Newtonian fluids can be used for the protection of flexible laminates. Understanding the coupling between the flow of the protecting fluid and the deformation of the protected solids is necessary in order to optimize this functionality. We present a scaling analysis of the problem based on a single coupling variable, the effective width of a squeeze flow between flat rigid plates, and predict that impact protection for laminates is optimized by using shear-thinning, and not shear-thickening, fluids. The prediction is verified experimentally by measuring the velocity and pressure in impact experiments. Our scaling analysis should be generically applicable for non-Newtonian fluid-solid interactions in diverse applications.

2.
Eur Arch Otorhinolaryngol ; 281(6): 3031-3037, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38356023

RESUMEN

PURPOSE: Septorhinoplasty (SR) is one of the most complex surgical procedures of the head and neck. As an elective procedure aiming to enhance patient quality of life, it can be difficult to perform in single-payer healthcare systems due to capacity pressures from acute and oncological surgical demand. We aimed to review national trends in the practice of SR to inform future healthcare planning. METHODS: This was a cross-sectional, population-based, longitudinal study of SR cases in Ireland's single-payer (public) healthcare system from 2005 to 2021. Time-series analysis using a linear regression model was performed to analyse trends by operation type, revision rates and length of stay. The impact of the COVID-19 pandemic and introduction of national surgical guidelines was analysed. RESULTS: 1952 SR were performed. Annual mean cases declined in both real (r = - 0.76, p < 0.01) and relative (r = - 0.87, p < 0.01) terms by 31% and 43%, respectively. Ambulatory SR, while initially rarely performed, increased to account for 55% of cases performed. The mean hospital length of stay declined significantly (r = - 0.84, p < 0.01) by 44%. CONCLUSIONS: SR increasingly struggles to find its place in Ireland's public healthcare system. New changes in SR practices including the rapid growth of ambulatory surgery and shorter lengths of hospital stay indicate positive responses to the mounting pressures faced by healthcare systems.


Asunto(s)
COVID-19 , Rinoplastia , Humanos , Irlanda , Estudios Transversales , Masculino , Femenino , Adulto , Rinoplastia/métodos , Rinoplastia/tendencias , Rinoplastia/estadística & datos numéricos , COVID-19/epidemiología , Persona de Mediana Edad , Tabique Nasal/cirugía , Estudios Longitudinales , Tiempo de Internación/estadística & datos numéricos , Adulto Joven , Adolescente , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Anciano
3.
Eur Arch Otorhinolaryngol ; 280(7): 3383-3392, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37005958

RESUMEN

PURPOSE: Non-conventional laryngeal malignancies (NSCC) often have limited published data to guide management despite individual histopathological subtypes often exhibiting heterogeneous behaviour, characteristics, and treatment responses compared to laryngeal squamous cell carcinoma (SCC). This study aimed to compare oncological outcomes with SCC, specifically disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). Secondary objectives were to compare treatment differences and perform a state of the art review. METHODS: This was a multicentre retrospective cohort study at four tertiary head and neck centres. Survival outcomes between NSCC and SCC patients were analysed with Kaplan-Meier curves and compared by log rank testing. Univariate Cox regression analysis was performed to predict survival by histopathological subgroup, T-stage, N-stage and M-stage. RESULTS: There were no significant differences in 3-year DFS (p = 0.499), DSS (p = 0.329), OS (p = 0.360) or Kaplan Meier survival curves (DSS/OS) between SCC and overall NSCC groups. However, univariate Cox regression analysis identified "rare" histopathologies (mostly small cell carcinoma) to be predictive of less favourable OS (p = 0.035) but this result was not observed for other NSCC histopathological subgroups. N-stage (p = 0.027) and M-stage (p = 0.048) also predicted OS for NSCC malignancies. Significant differences in treatment modalities were identified with treatment of NSCC typically involving surgical resection and SCC often managed non-surgically (e.g., primary radiotherapy). CONCLUSIONS: Although overall NSCC is managed differently compared to SCC, there do not appear to be differences in survival outcomes between these groups. N-stage and M-stage appear to be more predictive of OS than histopathology than many NSCC subtypes.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Laríngeas , Humanos , Neoplasias Laríngeas/patología , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Estadificación de Neoplasias , Neoplasias de Cabeza y Cuello/patología , Pronóstico
4.
New Solut ; 30(3): 237-248, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33121368

RESUMEN

The World Health Organization's (WHO) workplace health and safety guidelines on COVID-19 are unacceptably complacent in parts, patently dangerous in others, and contain serious gaps. Omissions include no mention of the essential role of labor inspection and enforcement, and a lack of recognition of potential interactions with other workplace hazards. WHO also omitted discussion of the necessity for wider employment protections to make safety and safe behavior a realistic prospect. Potential risks in outdoor work and the need to address the impact of job segregation related to inequalities in health outcomes are also absent. WHO's advice influences national practice, official guidance, and binding rules.The International Trade Union Confederation has assessed the flaws in WHO's arguments and has prepared a critique so they are understood and can be challenged.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Salud Laboral/normas , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Lugar de Trabajo/normas , Organización Mundial de la Salud/organización & administración , Betacoronavirus , COVID-19 , Humanos , Sindicatos/normas , Exposición Profesional/prevención & control , Exposición Profesional/normas , SARS-CoV-2
5.
Phys Rev Lett ; 123(12): 128002, 2019 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-31633967

RESUMEN

Dense suspensions often become more dilute as they move downstream through a constriction. We find that as a shear-thickening suspension is extruded through a narrow die and undergoes such liquid migration, the extrudate maintains a steady concentration ϕ_{out}^{LM}, independent of time or initial concentration. At low volumetric flow rate Q, ϕ_{out}^{LM} is a universal function of Q/r_{d}^{3}, a characteristic shear rate in the die of radius r_{d}, and coincides with the critical input concentration for the onset of LM, ϕ_{in}^{crit}. We predict this function by coupling the Wyart-Cates model for shear thickening and the "suspension balance model" for solvent permeation through particles.

6.
J Periodontol ; 90(1): 16-25, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30102767

RESUMEN

BACKGROUND: The aims of this study were to analyze the periodontal conditions among non-smokers, former smokers and current smokers in the two National Health and Nutrition Examination Surveys (NHANES) acquired between 2009 to 2012 and determine the association between time since quitting smoking and periodontal status. METHODS: Smoking status and periodontal examination data from NHANES 2009 to 2010 and 2011 to 2012 were analyzed. Respondents included in the analysis were aged ≥18 years, had undergone a complete NHANES Oral Health - Periodontal Exam with all measurements recorded as required for the periodontal classification algorithm, and had complete data from the NHANES Smoking - Cigarette Use questionnaire. Logistic regression was conducted with time since quitting as the exposure and presence of periodontitis as the outcome, and included adjustment for confounders. RESULTS: Smoking status was significantly associated with periodontal status (Chi-square; P < 0.0001). The rate of periodontitis was highest among smokers (35%), compared with former smokers (19%) and never smokers (13%). Among former smokers, after adjusting for confounders, each additional year since quitting smoking was associated with a significant reduction in the odds ratio (OR) for periodontitis by 3.9% (OR for each year 0.961, 95% confidence interval 0.948 to 0.975). CONCLUSIONS: Among former smokers, a longer time since quitting smoking was associated with a lower likelihood of periodontitis. Consequently, dental practitioners have a public health mandate to help their patients quit smoking. Future research should determine the best strategies for facilitating smoking cessation in dental patients.


Asunto(s)
Periodontitis , Cese del Hábito de Fumar , Adolescente , Adulto , Humanos , Encuestas Nutricionales , Fumadores , Fumar
7.
J Mater Sci Mater Med ; 27(2): 29, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26704546

RESUMEN

The aim of this study was to increase understanding of the mechanism and dominant drivers influencing phase separation during ram extrusion of calcium phosphate (CaP) paste for orthopaedic applications. The liquid content of extrudate was determined, and the flow of liquid and powder phases within the syringe barrel during extrusion were observed, subject to various extrusion parameters. Increasing the initial liquid-to-powder mass ratio, LPR, (0.4-0.45), plunger rate (5-20 mm/min), and tapering the barrel exit (45°-90°) significantly reduced the extent of phase separation. Phase separation values ranged from (6.22 ± 0.69 to 18.94 ± 0.69 %). However altering needle geometry had no significant effect on phase separation. From powder tracing and liquid content determination, static zones of powder and a non-uniform liquid distribution was observed within the barrel. Measurements of extrudate and paste LPR within the barrel indicated that extrudate LPR remained constant during extrusion, while LPR of paste within the barrel decreased steadily. These observations indicate the mechanism of phase separation was located within the syringe barrel. Therefore phase separation can be attributed to either; (1) the liquid being forced downstream by an increase in pore pressure as a result of powder consolidation due to the pressure exerted by the plunger or (2) the liquid being drawn from paste within the barrel, due to suction, driven by dilation of the solids matrix at the barrel exit. Differentiating between these two mechanisms is difficult; however results obtained suggest that suction is the dominant phase separation mechanism occurring during extrusion of CaP paste.


Asunto(s)
Cementos para Huesos/química , Fosfatos de Calcio/química , Inyecciones , Química Farmacéutica/métodos , Ensayo de Materiales , Pomadas , Tamaño de la Partícula , Transición de Fase , Polvos/química , Presión
8.
Clin Implant Dent Relat Res ; 15(4): 569-75, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22172048

RESUMEN

BACKGROUND: Tooth extraction is associated with dimensional changes in the alveolar ridge. The aim was to examine the effect of single versus contiguous teeth extractions on the alveolar ridge remodeling. MATERIAL AND METHODS: Five female beagle dogs were randomly divided into three groups on the basis of location (anterior or posterior) and number of teeth extracted - exctraction socket classification: group 1 (one dog): single-tooth extraction; group 2 (two dogs): extraction of two teeth; and group 3 (two dogs): extraction of three teeth in four anterior sites and four posterior sites in both jaws. The dogs were sacrificed after 4 months. Sagittal sectioning of each extraction site was performed and evaluated using microcomputed tomography. RESULTS: Buccolingual or palatal bone loss was observed 4 months after extraction in all three groups. The mean of the alveolar ridge width loss in group 1 (single-tooth extraction) was significantly less than those in groups 2 and 3 (p < .001) (multiple teeth extraction). Three-teeth extraction (group 3) had significantly more alveolar bone loss than two-teeth extraction (group 2) (p < .001). The three-teeth extraction group in the upper and lower showed more obvious resorption on the palatal/lingual side especially in the lower group posterior locations. CONCLUSION: Contiguous teeth extraction caused significantly more alveolar ridge bone loss as compared with when a single tooth is extracted.


Asunto(s)
Proceso Alveolar/fisiología , Remodelación Ósea/fisiología , Extracción Dental/métodos , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/fisiopatología , Proceso Alveolar/diagnóstico por imagen , Animales , Arco Dental/diagnóstico por imagen , Arco Dental/fisiología , Perros , Femenino , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Mandíbula/diagnóstico por imagen , Mandíbula/fisiología , Maxilar/diagnóstico por imagen , Maxilar/fisiología , Hueso Paladar/diagnóstico por imagen , Hueso Paladar/fisiología , Desbridamiento Periodontal/métodos , Piezocirugía/métodos , Distribución Aleatoria , Alveolo Dental/diagnóstico por imagen , Alveolo Dental/fisiología , Microtomografía por Rayos X/métodos
9.
Odontology ; 100(1): 61-6, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21567122

RESUMEN

The enamel matrix derivative (EMD) has been used extensively as an adjunct to root coverage procedures to achieve periodontal regeneration. However, its effect on gingival tissues has not been elucidated. The aim of this investigation was to evaluate histometrically the change in gingival soft tissue thickness around dehiscence-type defects treated with EMD. Five adult female beagle dogs were used. Buccal osseous dehiscences were surgically created on the maxillary canines and the second and fourth premolars. Thirty defect sites were randomly assigned to test and control groups (15 defect sites for each group). The test group received EMD application, whereas the control group did not. After 4 months of healing, the dogs were killed and tissue blocks were prepared. Histometric analysis showed that the mean thickness of gingival tissue was 1.76 ± 0.23 mm in EMD-treated sites compared to 0.72 ± 0.11 mm for control sites. The difference between the test and control groups was statistically significant (P < 0.0001). It appears that EMD has a positive influence on the increase in gingival tissue thickness when used in dehiscence-type defects in the beagle dog.


Asunto(s)
Proteínas del Esmalte Dental/farmacología , Encía/efectos de los fármacos , Animales , Proteínas del Esmalte Dental/uso terapéutico , Perros , Femenino , Recesión Gingival/tratamiento farmacológico , Distribución Aleatoria , Regeneración/efectos de los fármacos
10.
J Emerg Med ; 42(5): 503-10, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21549546

RESUMEN

BACKGROUND: Early goal-directed therapy (EGDT) has been shown to reduce mortality in patients with severe sepsis/septic shock, however, implementation of this protocol in the emergency department (ED) is sometimes difficult. OBJECTIVES: We evaluated our sepsis protocol to determine which EGDT elements were more difficult to implement in our community-based ED. METHODS: This was a non-concurrent cohort study of adult patients entered into a sepsis protocol at a single community hospital from July 2008 to March 2009. Charts were reviewed for the following process measures: a predefined crystalloid bolus, antibiotic administration, central venous catheter insertion, central venous pressure measurement, arterial line insertion, vasopressor utilization, central venous oxygen saturation measurement, and use of a standardized order set. We also compared the individual component adherence with survival to hospital discharge. RESULTS: A total of 98 patients presented over a 9-month period. Measures with the highest adherence were vasopressor administration (79%; 95% confidence interval [CI] 69-89%) and antibiotic use (78%; 95% CI 68-85%). Measures with the lowest adherence included arterial line placement (42%; 95% CI 32-52%), central venous pressure measurement (27%; 95% CI 18-36%), and central venous oxygen saturation measurement (15%; 95% CI 7-23%). Fifty-seven patients survived to hospital discharge (Mortality: 33%). The only element of EDGT to demonstrate a statistical significance in patients surviving to hospital discharge was the crystalloid bolus (79% vs. 46%) (respiratory rate [RR] = 1.76, 95% CI 1.11-2.58). CONCLUSION: In our community hospital, arterial line placement, central venous pressure measurement, and central venous oxygen saturation measurement were the most difficult elements of EGDT to implement. Patients who survived to hospital discharge were more likely to receive the crystalloid bolus.


Asunto(s)
Medicina de Emergencia/métodos , Sepsis/terapia , Anciano , Antibacterianos/uso terapéutico , Cateterismo Venoso Central , Protocolos Clínicos , Servicio de Urgencia en Hospital , Femenino , Fluidoterapia/métodos , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia
11.
Int Wound J ; 9(4): 436-41, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22182231

RESUMEN

The enamel matrix derivative (EMD) is a preparation of the enamel matrix proteins secreted by the Hertwig's epithelial root sheath. It has been shown that EMD promotes periodontal wound healing; however, the significance of the protein in repairing skin wounds is insufficiently addressed. The aim of this in vivo histomorphometric investigation was to analyse the effect of EMD protein on the healing of standardised epithelial wounds. Dorsal skin of 22-week-old female guinea pigs (n = 33) was scarified and divided into test- (topical application of EMD) and control-sites (sutured and allowed to heal). Animals were euthanised at specific time intervals and the specimens were then evaluated histomorphometrically. The mean widths of the external wound gaps (WGs) in the test- and control-sites at the 5th, 20th and 35th day of healing were 5·89, 3·6 and 1·01 mm and 6·41, 5·02 and 3·43 mm, respectively. Histomorphometric analysis showed a statistically significant difference in the WGs between the test- and control-sites. A significant increase in the formation of organised connective tissue matrix, collagen fibres and early muscle formation was observed in the test-sites as compared with the control-sites. Within the limits of this study, it is concluded that topical application of the EMD on standardised epithelial allows early wound closure and promotes healing as compared to when the defects are merely sutured.


Asunto(s)
Proteínas del Esmalte Dental/farmacología , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/patología , Análisis de Varianza , Animales , Biopsia con Aguja , Modelos Animales de Enfermedad , Epitelio/lesiones , Epitelio/patología , Femenino , Cobayas , Inmunohistoquímica , Puntaje de Gravedad del Traumatismo , Distribución Aleatoria , Valores de Referencia , Resultado del Tratamiento , Cicatrización de Heridas/fisiología
12.
J Emerg Med ; 43(4): 641-4, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20542397

RESUMEN

BACKGROUND: Lead dislodgement has been shown to be the most common complication in the first 30 days after pacemaker insertion. Although it is rare, pneumopericardium with tamponade can also result. OBJECTIVES: We present a case of an extremely rare delay from cardiac pacemaker insertion to lead migration with resulting pneumopericardium and cardiac tamponade. CASE REPORT: A 65-year-old woman with a past medical history significant for congestive heart failure, chronic obstructive pulmonary disease, and third-degree heart block, requiring pacemaker insertion 2 years prior with a revision 1 year prior, presented to the Emergency Department complaining of sudden-onset pleuritic chest pain. Her work-up revealed a pneumopericardium with atrial pacemaker lead migration into the right middle lobe of the lung. She suddenly developed hypotension and respiratory distress and required pericardiocentesis and, ultimately, surgical repair for a perforated right atrium. CONCLUSION: Pacemaker migration can lead to pneumopericardium and tamponade, even up to 1 year after placement.


Asunto(s)
Taponamiento Cardíaco/etiología , Marcapaso Artificial/efectos adversos , Neumopericardio/etiología , Implantación de Prótesis/efectos adversos , Anciano , Taponamiento Cardíaco/cirugía , Dolor en el Pecho/etiología , Femenino , Atrios Cardíacos/lesiones , Lesiones Cardíacas/etiología , Lesiones Cardíacas/cirugía , Humanos , Neumopericardio/cirugía , Falla de Prótesis
13.
J Can Dent Assoc ; 77: b6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21385536

RESUMEN

Odontogenic keratocyst (OKC) is a developmental, noninflammatory chronic cyst that may be unilocular or multilocular. Histologic features of OKC are pathognomonic. A 41-year-old male patient presented for emergency evaluation of a buccal gingival swelling in the area of teeth 34 and 35. Incision and drainage were followed 3 weeks later by surgical curettage and guided tissue regeneration using Puros allograft and resorbable membrane. Biopsy of the excised tissue revealed OKC. At 1-year follow-up, the patient was comfortable and complete resolution of the radiolucent pathology was evident. Periodic examination is required because of the high rate of recurrence of OKC.


Asunto(s)
Enfermedades de las Encías/diagnóstico , Enfermedades de las Encías/cirugía , Regeneración Tisular Guiada Periodontal , Enfermedades Mandibulares/diagnóstico , Enfermedades Mandibulares/cirugía , Quistes Odontogénicos/diagnóstico , Quistes Odontogénicos/cirugía , Adulto , Enfermedades de las Encías/patología , Humanos , Masculino , Enfermedades Mandibulares/patología , Membranas Artificiales , Quistes Odontogénicos/patología , Colgajos Quirúrgicos
14.
Nucleic Acids Res ; 39(7): 2593-603, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21112870

RESUMEN

Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating enzyme in the base-excision repair pathway. As with other DNA glycosylases, the abasic product is potentially more harmful than the initial lesion. Since Mug is known to bind its product tightly, inhibiting enzyme turnover, understanding how Mug binds DNA is of significance when considering how Mug interacts with downstream enzymes in the base-excision repair pathway. We have demonstrated differential binding modes of Mug between its substrate and abasic DNA product using both band shift and fluorescence anisotropy assays. Mug binds its product cooperatively, and a stoichiometric analysis of DNA binding, catalytic activity and salt-dependence indicates that dimer formation is of functional significance in both catalytic activity and product binding. This is the first report of cooperativity in the uracil DNA glycosylase superfamily of enzymes, and forms the basis of product inhibition in Mug. It therefore provides a new perspective on abasic site protection and the findings are discussed in the context of downstream lesion processing and enzyme communication in the base excision repair pathway.


Asunto(s)
Reparación del ADN , ADN/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/enzimología , Timina ADN Glicosilasa/metabolismo , Uracil-ADN Glicosidasa/metabolismo , Unión Competitiva , ADN/química , Daño del ADN , Polarización de Fluorescencia , Unión Proteica , Cloruro de Sodio/química
16.
Int J Periodontics Restorative Dent ; 29(4): 425-33, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19639063

RESUMEN

The goal of this investigation was to evaluate histologically and histometrically the healing process in dehiscence-type defects treated by enamel matrix derivative (EMD). Five adult female beagle dogs were used. Buccal osseous dehiscences were surgically created on the maxillary canines and the second and fourth premolars. Thirty defect sites were randomly assigned to treatment and control groups (15 defect sites for each group). The treatment group received EMD application, while the control groups received no EMD. After 4 months of healing, the dogs were sacrificed and tissue blocks were prepared. Histometric parameters were employed to evaluate the type of periodontal tissues that formed in the defects. All created dehiscence defects in the test sites treated by EMD had formed functional connective tissue fibers inserted into regenerated cellular cementum. The mean amount of apicocoronal regenerated cementum was 3.74 +/- 0.43 mm in EMD- treated sites, whereas the control sites had not formed cementum in the created dehiscence defects (P < .000). Statistically significant differences were found between treatment and control sites. Within the limits of this study, it can be concluded that EMD alone effectively promoted new cementum and functionally oriented connective tissue formation.


Asunto(s)
Cemento Dental/fisiología , Proteínas del Esmalte Dental/farmacología , Regeneración/efectos de los fármacos , Proceso Alveolar/cirugía , Animales , Tejido Conectivo/fisiología , Perros , Femenino , Maxilar/cirugía , Distribución Aleatoria , Dehiscencia de la Herida Operatoria
17.
J Mol Biol ; 383(4): 762-71, 2008 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-18761016

RESUMEN

Archaeal family-B DNA polymerases bind tightly to uracil and hypoxanthine (the deamination products of cytosine and adenine), resulting in profound inhibition of DNA replication. Investigation of the mechanism of inhibition, using single-turnover kinetics with polymerase in excess of DNA, indicated that deoxy-NTPs were efficiently bound to the polymerase-DNA complex but very poorly incorporated into the extending chain. Addition of the processivity factor proliferating cell nuclear antigen (PCNA) resulted in increased affinity of the polymerase for all primer-templates, producing extremely tight complexes when uracil (K(d)=16 pM) or hypoxanthine (K(d)=65 pM) was present. Analytical ultracentrifugation confirmed the stability of these complexes and revealed a polymerase/PCNA/DNA stoichiometry of 1:1:1. However, PCNA had no influence on the ability of the polymerase to read through uracil and hypoxanthine, the same kinetic parameters being observed with or without the processivity factor. The specificity constants determined using single-turnover kinetics showed that uracil and hypoxanthine slowed the polymerase by factors of approximately 5000 and 3000, respectively. Uracil and hypoxanthine are removed from DNA by base excision repair, initiated by uracil-DNA glycosylase and endonuclease V, respectively. Both enzymes are profoundly inhibited by the simultaneous binding of both PCNA and polymerase to primer-templates, with polymerase alone being much less effective. Thus, when the PCNA-polymerase complex encounters uracil/hypoxanthine in DNA templates, base excision repair is switched off, protecting the complex from a repair pathway that is dangerous in the context of single-stranded DNA formed during replication.


Asunto(s)
Proteínas Arqueales/metabolismo , Reparación del ADN , Replicación del ADN , ADN Polimerasa Dirigida por ADN/metabolismo , Hipoxantina/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Pyrococcus furiosus , Uracilo/metabolismo , Proteínas Arqueales/genética , ADN de Archaea/genética , ADN de Archaea/metabolismo , ADN Polimerasa Dirigida por ADN/química , ADN Polimerasa Dirigida por ADN/genética , Desoxirribonucleasa (Dímero de Pirimidina)/genética , Desoxirribonucleasa (Dímero de Pirimidina)/metabolismo , Sustancias Macromoleculares/química , Sustancias Macromoleculares/metabolismo , Modelos Moleculares , Antígeno Nuclear de Célula en Proliferación/genética , Pyrococcus furiosus/genética , Pyrococcus furiosus/metabolismo , Moldes Genéticos , Uracil-ADN Glicosidasa/genética , Uracil-ADN Glicosidasa/metabolismo
18.
Int J Occup Environ Health ; 13(4): 428-36, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-18085056

RESUMEN

The U.K. authorities are failing to acknowledge or deal effectively with an epidemic of work-related cancers. The government's Health and Safety Executive (HSE) underestimates the exposed population, the risks faced as a result of those exposures, and the potential for prevention. The HSE fails to acknowledge the social inequality in occupational cancer risk, which is concentrated in manual workers and lower employment grades, or the greater likelihood these groups will experience multiple exposures to work-related carcinogens. It continues to neglect the largely uninvestigated and unprioritized risk to women and currently has neither a requirement nor a strategy for reducing the numbers and volumes of cancer-causing substances, processes, and environments at work. The result is that the U.K. faces at least 20,000 and possibly in excess of 40,000 new cases of work-related cancer every year, leading to thousands of deaths and an annual cost to the economy of between pounds 29.5bn and pounds 59bn. This paper outlines flaws in the HSE's approach and makes recommendations to address effectively the U.K.'s occupational cancer crisis.


Asunto(s)
Brotes de Enfermedades/prevención & control , Política de Salud , Neoplasias/epidemiología , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Exposición a Riesgos Ambientales/prevención & control , Exposición a Riesgos Ambientales/normas , Femenino , Humanos , Masculino , Neoplasias/etiología , Enfermedades Profesionales/etiología , Exposición Profesional/prevención & control , Exposición Profesional/normas , Ocupaciones , Clase Social , Reino Unido/epidemiología , Salud de la Mujer , Indemnización para Trabajadores
19.
J Mol Biol ; 372(4): 855-863, 2007 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-17692870

RESUMEN

The interaction of archaeal family B DNA polymerases with deaminated bases has been examined. As determined previously by our group, the polymerase binds tightly to uracil (the deamination product of cytosine), in single-stranded DNA, and stalls replication on encountering this base. DNA polymerisation was also inhibited by the presence of hypoxanthine, the deamination product of adenine. Quantitative binding assays showed that the polymerase bound DNA containing uracil 1.5-4.5-fold more strongly than hypoxanthine and site-directed mutagenesis suggested that the same pocket was used for interaction with both deaminated bases. In contrast the polymerase was insensitive to xanthine, the deamination product of guanine. Traces of uracil and hypoxanthine in DNA can lead to inhibition of the PCR by archaeal DNA polymerases, an important consideration for biotechnology applications. Dual recognition of uracil and hypoxanthine may be facilitated by binding the bases with the glycosidic bond in the anti and syn conformation, respectively.


Asunto(s)
Proteínas Arqueales/metabolismo , ADN Polimerasa Dirigida por ADN/metabolismo , Hipoxantina/metabolismo , Pyrococcus furiosus/enzimología , Uracilo/metabolismo , Xantina/metabolismo , Proteínas Arqueales/genética , ADN/química , ADN Polimerasa Dirigida por ADN/genética , Desaminación , Estructura Molecular , Reacción en Cadena de la Polimerasa , Unión Proteica
20.
Int J Occup Environ Health ; 12(3): 254-8, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16967833

RESUMEN

The Finnish Institute of Occupational Health (FIOH) has received support from the World Health Organization (WHO) and the International Labor Office (ILO) to publish the African Newsletter on Occupational Health and Safety. The African Newsletter on Occupational Health and Safety should not be a medium for industry propaganda, or the source of misinformation among the workers of Africa. Instead, FIOH should provide the same level of scientific information in Africa that it does in Finland and other developed countries.


Asunto(s)
Amianto/efectos adversos , Comunicación , Políticas Editoriales , Exposición Profesional/efectos adversos , Salud Laboral , Publicaciones Periódicas como Asunto/ética , Industria Química/normas , Conflicto de Intereses , Finlandia , Humanos , Exposición Profesional/normas , Propaganda , Organización Mundial de la Salud , Zimbabwe
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