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1.
CMAJ ; 196(18): E615-E623, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38740416

RESUMEN

BACKGROUND: Cancer surveillance data are essential to help understand where gaps exist and progress is being made in cancer control. We sought to summarize the expected impact of cancer in Canada in 2024, with projections of new cancer cases and deaths from cancer by sex and province or territory for all ages combined. METHODS: We obtained data on new cancer cases (i.e., incidence, 1984-2019) and deaths from cancer (i.e., mortality, 1984-2020) from the Canadian Cancer Registry and Canadian Vital Statistics Death Database, respectively. We projected cancer incidence and mortality counts and rates to 2024 for 23 types of cancer, overall, by sex, and by province or territory. We calculated age-standardized rates using data from the 2011 Canadian standard population. RESULTS: In 2024, the number of new cancer cases and deaths from cancer are expected to reach 247 100 and 88 100, respectively. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) are projected to decrease slightly from previous years for both males and females, with higher rates among males (ASIR 562.2 per 100 000 and ASMR 209.6 per 100 000 among males; ASIR 495.9 per 100 000 and ASMR 152.8 per 100 000 among females). The ASIRs and ASMRs of several common cancers are projected to continue to decrease (i.e., lung, colorectal, and prostate cancer), while those of several others are projected to increase (i.e., liver and intrahepatic bile duct cancer, kidney cancer, melanoma, and non-Hodgkin lymphoma). INTERPRETATION: Although the overall incidence of cancer and associated mortality are declining, new cases and deaths in Canada are expected to increase in 2024, largely because of the growing and aging population. Efforts in prevention, screening, and treatment have reduced the impact of some cancers, but these short-term projections highlight the potential effect of cancer on people and health care systems in Canada.


Asunto(s)
Neoplasias , Sistema de Registros , Humanos , Canadá/epidemiología , Neoplasias/epidemiología , Neoplasias/mortalidad , Masculino , Femenino , Incidencia , Distribución por Sexo , Predicción , Persona de Mediana Edad , Anciano , Distribución por Edad , Adulto , Mortalidad/tendencias
2.
Biophys J ; 122(2): 397-407, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36463407

RESUMEN

The crowdedness of the cell calls for adequate intracellular organization. Biomolecular condensates, formed by liquid-liquid phase separation of intrinsically disordered proteins and nucleic acids, are important organizers of cellular fluids. To underpin the molecular mechanisms of protein condensation, cell-free studies are often used where the role of crowding is not investigated in detail. Here, we investigate the effects of macromolecular crowding on the formation and material properties of a model heterotypic biomolecular condensate, consisting of nucleophosmin (NPM1) and ribosomal RNA (rRNA). We studied the effect of the macromolecular crowding agent poly(ethylene glycol) (PEG), which is often considered an inert crowding agent. We observed that PEG could induce both homotypic and heterotypic phase separation of NPM1 and NPM1-rRNA, respectively. Crowding increases the condensed concentration of NPM1 and decreases its equilibrium dilute phase concentration, although no significant change in the concentration of rRNA in the dilute phase was observed. Interestingly, the crowder itself is concentrated in the condensates, suggesting that co-condensation rather than excluded volume interactions underlie the enhanced phase separation by PEG. Fluorescence recovery after photobleaching measurements indicated that both NPM1 and rRNA become immobile at high PEG concentrations, indicative of a liquid-to-gel transition. Together, these results provide more insight into the role of synthetic crowding agents in phase separation and demonstrate that condensate properties determined in vitro depend strongly on the addition of crowding agents.


Asunto(s)
Fenómenos Bioquímicos , Ácidos Nucleicos , Nucleofosmina , ARN Ribosómico , Polietilenglicoles/química
3.
Health Rep ; 34(9): 14-21, 2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37729062

RESUMEN

Background: The lifetime probabilities of developing (LPdev) cancer and dying (LPdying) from cancer are useful summary statistics that describe the impact of cancer within a population. This study aims to present detailed LPdev and LPdying for cancer by sex and cancer type and to describe changes in these lifetime probabilities over time among the Canadian population. Data and methods: Cancer incidence data (1997 to 2018) were obtained from the Canadian Cancer Registry. All-cause and cancer mortality data (1997 to 2020) were obtained from the Canadian Vital Statistics - Death Database. LPdev and LPdying were calculated using the DevCan software, and trends over time were estimated using Joinpoint. Results: The LPdev for all cancers combined was 44.3% in Canada in 2018, with all results excluding Quebec. At the age of 60, the conditional probability of developing cancer was very similar (44.0% for males and 38.2% for females). The LPdying was 22.5% among the Canadian population in 2020, while the probability of dying from cancer conditional on surviving until age 60 was 25.1% for males and 20.5% for females. Generally, males experienced higher LPdev and LPdying for most specific cancers compared with females. Interpretation: LPdev and LPdying for cancer mirror cancer incidence and mortality rates. Cancer-specific changes in these probabilities over time are indicative of the cancer trends resulting from cancer prevention, screening, detection, and treatment. These changes in LPdev and LPdying provide insight into the shifting landscape of the Canadian cancer burden.


Asunto(s)
Neoplasias , Femenino , Masculino , Humanos , Persona de Mediana Edad , Canadá/epidemiología , Quebec , Bases de Datos Factuales , Probabilidad
4.
Sensors (Basel) ; 23(18)2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37766036

RESUMEN

Detecting volatile organic compounds is a fundamental step in water quality analysis. Methylisoborneol (MIB) provides a lousy odor to water, whereas geosmin (GEO) is responsible for its sour taste. A widely-used technique for their detection is gas-phase chromatography. On the other hand, an electronic nose from organic thin-film transistors is a cheaper and faster alternative. Poly(2,5-bis(3-tetradecyl-thiophen-2-yl)thieno[3,2-b]thiophene) (PBTTT-C14) features semiconducting properties suitable for organic electronics. However, in order to expose the active layer in a bottom-gate transistor structure with photolithographically patterned electrodes, a cross-linked dielectric such as poly(4-vinyl phenol) (PVP) is necessary. In this work, the cross-linking was demonstrated using FTIR and Raman spectroscopies, as well as high-k capacitors with a dielectric constant of 5.3. The presence of enhanced crystallinity with terrace formation in the semiconducting film was confirmed with UV-visible spectrophotometry, atomic force microscopy, and X-ray diffraction. Finally, for the first time, a PBTTT-C14 transistor on cross-linked PVP was shown to respond to isoborneol with a sensitivity of up to 6% change in mobility per ppm. Due to its similarity to MIB, a system comprising these sensors must be investigated in the future as a tool for sanitation companies in real-time water quality monitoring.

5.
Biophys J ; 121(20): 3962-3974, 2022 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-36004782

RESUMEN

Many cellular condensates are heterotypic mixtures of proteins and RNA formed in complex environments. Magnesium ions (Mg2+) and ATP can impact RNA folding, and local intracellular levels of these factors can vary significantly. However, the effect of ATP:Mg2+ on the material properties of protein-RNA condensates is largely unknown. Here, we use an in vitro condensate model of nucleoli, made from nucleophosmin 1 (NPM1) proteins and ribosomal RNA (rRNA), to study the effect of ATP:Mg2+. While NPM1 dynamics remain unchanged at increasing Mg2+ concentrations, the internal RNA dynamics dramatically slowed until a critical point, where gel-like states appeared, suggesting the RNA component alone forms a viscoelastic network that undergoes maturation driven by weak multivalent interactions. ATP reverses this arrest and liquefies the gel-like structures. ATP:Mg2+ also influenced the NPM1-rRNA composition of condensates and enhanced the partitioning of two clients: an arginine-rich peptide and a small nuclear RNA. By contrast, larger ribosome partitioning shows dependence on ATP:Mg2+ and can become reversibly trapped around NPM1-rRNA condensates. Lastly, we show that dissipative enzymatic reactions that deplete ATP can be used to control the shape, composition, and function of condensates. Our results illustrate how intracellular environments may regulate the state and client partitioning of RNA-containing condensates.


Asunto(s)
Proteínas Nucleares , ARN , Humanos , Proteínas Nucleares/metabolismo , Magnesio/farmacología , Nucleofosmina , ARN Ribosómico/genética , Péptidos , Arginina , Iones , ARN Nuclear Pequeño , Adenosina Trifosfato
6.
CMAJ ; 194(17): E601-E607, 2022 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-35500919

RESUMEN

BACKGROUND: Regular cancer surveillance is crucial for understanding where progress is being made and where more must be done. We sought to provide an overview of the expected burden of cancer in Canada in 2022. METHODS: We obtained data on new cancer incidence from the National Cancer Incidence Reporting System (1984-1991) and Canadian Cancer Registry (1992-2018). Mortality data (1984-2019) were obtained from the Canadian Vital Statistics - Death Database. We projected cancer incidence and mortality counts and rates to 2022 for 22 cancer types by sex and province or territory. Rates were age standardized to the 2011 Canadian standard population. RESULTS: An estimated 233 900 new cancer cases and 85 100 cancer deaths are expected in Canada in 2022. We expect the most commonly diagnosed cancers to be lung overall (30 000), breast in females (28 600) and prostate in males (24 600). We also expect lung cancer to be the leading cause of cancer death, accounting for 24.3% of all cancer deaths, followed by colorectal (11.0%), pancreatic (6.7%) and breast cancers (6.5%). Incidence and mortality rates are generally expected to be higher in the eastern provinces of Canada than the western provinces. INTERPRETATION: Although overall cancer rates are declining, the number of cases and deaths continues to climb, owing to population growth and the aging population. The projected high burden of lung cancer indicates a need for increased tobacco control and improvements in early detection and treatment. Success in breast and colorectal cancer screening and treatment likely account for the continued decline in their burden. The limited progress in early detection and new treatments for pancreatic cancer explains why it is expected to be the third leading cause of cancer death in Canada.


Asunto(s)
Neoplasias Pulmonares , Anciano , Canadá/epidemiología , Femenino , Predicción , Humanos , Incidencia , Neoplasias Pulmonares/epidemiología , Masculino , Sistema de Registros
7.
J Clin Monit Comput ; 36(4): 1131-1137, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34302578

RESUMEN

A more sensitive method than the train-of-four ratio seems required to detect low levels of residual neuromuscular blockade before tracheal extubation. The goal of the study was to determine the potential benefit of 5 s of 100 versus 200 Hz tetanic stimulation to quantify the residual block with mechanomyography in anesthetised patients. Twenty informed and consenting 18- to 80-year-old patients undergoing nose surgery were included. On the left hand, neuromuscular transmission was continuously monitored by acceleromyography. On the right side, a new mecanomyographic device (Isometric Thumb Force©) recorded the force of thumb adduction (N) developed during 5 s of 100- and 200 Hz tetanic stimulations of the ulnar nerve at three consecutive times: baseline before inducing the neuromuscular blockade, at the time of contralateral train-of-four ratio 0.9 recovery, and 3 min after additional sugammadex reversal. Tetanic Fade Ratios (TFR = F residual/F max) were compared between 100 and 200 Hz stimulations using Student's t test. At the time of TOF ratio 0.9 recovery, both 100 and 200 Hz TFR were significantly decreased compared to baseline (0.61 and 0.16 on average, respectively, p < 0.0001). The 200 Hz TFR was significantly lower than the 100 Hz TFR (p < 0.0001). There were no differences between baseline and post-reversal TFR. The 200 Hz TFR has the potential to better describe low levels of residual neuromuscular blockade than the TOF ratio and 100 Hz TFR and would benefit from further investigations. Retrospectively registered in the Australian and New Zealand Clinical Trials Registry ACTRN12619000273189.


Asunto(s)
Retraso en el Despertar Posanestésico , Bloqueo Neuromuscular , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Estimulación Eléctrica/métodos , Humanos , Persona de Mediana Edad , Unión Neuromuscular/fisiología , Proyectos Piloto , Adulto Joven
8.
Cancer ; 126(10): 2206-2216, 2020 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-32101643

RESUMEN

BACKGROUND: To the authors' knowledge, there are limited data regarding the epidemiology of malignant appendiceal tumors. It remains unknown whether the previously reported trends are occurring in different countries and/or continuing in recent years and/or whether they are possibly due to increasing rates of appendectomies. In the current study, the authors investigated the patterns and time trends of malignant appendiceal tumor diagnosis by age group, sex, stage of disease, and histology in Canada and the United States and concomitant rates of appendectomies in Canada. METHODS: The Canadian Cancer Registry and the US Surveillance, Epidemiology, and End Results incidence databases were used to identify incident patients of malignant appendiceal tumors in the 2 countries between 1992 and 2016. The Canadian national hospitals Discharge Abstract Database was used to identify appendectomies performed between 2004 and 2015. Joinpoint regression analyses were performed to determine time trends. RESULTS: There was an overall increase in the incidence of malignant appendiceal tumors of 232% in the United States and 292% in Canada between 2000 and 2016. The increase was noted for malignant adenocarcinomas and neuroendocrine appendiceal tumors in both countries. The increase occurred across all age groups, sexes, and stages of disease. The highest rate of increase was noted for appendiceal neuroendocrine malignant tumors diagnosed among the youngest age groups. The rate of appendectomies was stable in the recent time periods, resulting in a decreasing rate of appendectomies per malignant appendiceal tumor diagnosis. CONCLUSIONS: The incidence of malignant appendiceal tumor is continuing to increase, which is not likely due to the increasing diagnosis of asymptomatic tumors at the time of appendectomies.


Asunto(s)
Adenocarcinoma/epidemiología , Apendicectomía/estadística & datos numéricos , Neoplasias del Apéndice/epidemiología , Tumores Neuroendocrinos/epidemiología , Adenocarcinoma/cirugía , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Neoplasias del Apéndice/cirugía , Canadá/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/cirugía , Sistema de Registros , Estados Unidos/epidemiología , Adulto Joven
9.
CMAJ ; 192(9): E199-E205, 2020 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-32122974

RESUMEN

BACKGROUND: Cancer projections to the current year help in policy development, planning of programs and allocation of resources. We sought to provide an overview of the expected incidence and mortality of cancer in Canada in 2020 in follow-up to the Canadian Cancer Statistics 2019 report. METHODS: We obtained incidence data from the National Cancer Incidence Reporting System (1984-1991) and Canadian Cancer Registry (1992-2015). Mortality data (1984-2015) were obtained from the Canadian Vital Statistics - Death Database. All databases are maintained by Statistics Canada. Cancer incidence and mortality counts and age-standardized rates were projected to 2020 for 23 cancer types by sex and geographic region (provinces and territories) for all ages combined. RESULTS: An estimated 225 800 new cancer cases and 83 300 cancer deaths are expected in Canada in 2020. The most commonly diagnosed cancers are expected to be lung overall (29 800), breast in females (27 400) and prostate in males (23 300). Lung cancer is also expected to be the leading cause of cancer death, accounting for 25.5% of all cancer deaths, followed by colorectal (11.6%), pancreatic (6.4%) and breast (6.1%) cancers. Incidence and mortality rates will be generally higher in the eastern provinces than in the western provinces. INTERPRETATION: The number of cancer cases and deaths remains high in Canada and, owing to the growing and aging population, is expected to continue to increase. Although progress has been made in reducing deaths for most major cancers (breast, prostate and lung), there has been limited progress for pancreatic cancer, which is expected to be the third leading cause of cancer death in Canada in 2020. Additional efforts to improve uptake of existing programs, as well as to advance research, prevention, screening and treatment, are needed to address the cancer burden in Canada.


Asunto(s)
Neoplasias/epidemiología , Canadá , Femenino , Predicción , Humanos , Incidencia , Masculino , Neoplasias/mortalidad , Factores Sexuales
10.
Anaesthesia ; 75(3): 323-330, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31802485

RESUMEN

We aimed to compare the reliability of aspiration via a nasogastric tube with ultrasound for assessment of residual gastric volume. Sixty-one adult patients who were mechanically ventilated and received continuous enteral feeding through a nasogastric tube for > 48 h were included. A first qualitative and quantitative ultrasound examination of the gastric antrum was followed by gastric suctioning, performed by an operator blinded to the result of the ultrasound examination. A second ultrasound examination was performed thereafter, followed by re-injection of the aspirated gastric contents (≤ 250 ml) into the stomach. A third ultrasound assessment was then immediately performed. If the suctioned volume was ≥ 250 ml, 250 mg erythromycin was infused over 30 min. A fourth ultrasound was performed 90 min after the third. Sixty (98%) patients had a qualitatively assessed full stomach at first ultrasound examination vs. 52 (85%) after gastric suctioning (p = 0.016). The calculated gastric volume significantly decreased after gastric suctioning, without a significant decrease in the number of patients with volume ≥ 250 ml. Four of the nine patients with calculated gastric volume ≥ 250 ml had vomiting within the last 24 h (p = 0.013). The antral cross-sectional area significantly decreased between the third and the fourth ultrasound examination (p = 0.015). Erythromycin infusion did not make a significant difference to gastric volume (n = 10). Our results demonstrate that gastric suctioning is not a reliable tool for monitoring residual gastric volume. Gastric ultrasound is a feasible and promising tool for gastric volume monitoring in clinical practice.


Asunto(s)
Aspiración Respiratoria de Contenidos Gástricos/diagnóstico por imagen , Estómago/diagnóstico por imagen , Succión/métodos , Adulto , Anciano , Antibacterianos/efectos adversos , Estudios de Cohortes , Eritromicina/efectos adversos , Femenino , Vaciamiento Gástrico , Contenido Digestivo , Humanos , Intubación Gastrointestinal , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio , Estudios Prospectivos , Reproducibilidad de los Resultados , Estómago/anatomía & histología , Estómago/efectos de los fármacos , Ultrasonografía , Vómitos/etiología
11.
Int J Mol Sci ; 21(16)2020 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-32824618

RESUMEN

Biomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm and nucleoplasm. Most of these non-membranous organelles show liquid-like properties both in cells and when studied in vitro through liquid-liquid phase separation (LLPS) of purified proteins. In general, LLPS of proteins is known to be sensitive to variations in pH, temperature and ionic strength, but the role of crowding remains underappreciated. Several decades of research have shown that macromolecular crowding can have profound effects on protein interactions, folding and aggregation, and it must, by extension, also impact LLPS. However, the precise role of crowding in LLPS is far from trivial, as most condensate components have a disordered nature and exhibit multiple weak attractive interactions. Here, we discuss which factors determine the scope of LLPS in crowded environments, and we review the evidence for the impact of macromolecular crowding on phase boundaries, partitioning behavior and condensate properties. Based on a comparison of both in vivo and in vitro LLPS studies, we propose that phase separation in cells does not solely rely on attractive interactions, but shows important similarities to segregative phase separation.


Asunto(s)
Fraccionamiento Celular/métodos , Citosol/química , Proteínas Intrínsecamente Desordenadas/química , Animales , Cromatografía Liquida/métodos , Gránulos Citoplasmáticos/química , Humanos
12.
CMAJ ; 196(24): E836-E845, 2024 Jul 01.
Artículo en Francés | MEDLINE | ID: mdl-38955403

RESUMEN

CONTEXTE: Les données de surveillance du cancer sont essentielles pour mieux comprendre les lacunes et les progrès réalisés dans la lutte contre le cancer. Nous avons cherché à résumer les répercussions prévues du cancer au Canada en 2024, en effectuant des projections sur les nouveaux cas de cancer et les décès par cancer, par sexe et par province ou territoire, pour tous les âges confondus. MÉTHODES: Nous avons obtenu les données sur les nouveaux cas de cancer (c.-à-d., l'incidence, 1984­2019) et les décès par cancer (c.-à-d., la mortalité, 1984­2020) du Registre canadien du cancer et de la Base canadienne de données de l'état civil ­ Décès, respectivement. Nous avons projeté les chiffres et les taux d'incidence du cancer et de mortalité jusqu'en 2024 pour 23 types de cancer, par sexe et par province ou territoire. Nous avons calculé des taux normalisés selon l'âge au moyen de données de la population type canadienne de 2011. RÉSULTATS: En 2024, les nombres de nouveaux cas de cancer et de décès causés par le cancer devraient atteindre 247 100 et 88 100, respectivement. Le taux d'incidence normalisé selon l'âge (TINA) et le taux de mortalité normalisé selon l'âge (TMNA) devraient diminuer légèrement par rapport aux années précédentes, tant chez les hommes que chez les femmes, avec des taux plus élevés chez les hommes (TINA de 562,2 pour 100 000, et TMNA de 209,6 pour 100 000 chez les hommes; TINA de 495,9 pour 100 000 et TMNA de 152,8 pour 100 000 chez les femmes). Les TINA et les TMNA de plusieurs cancers courants devraient continuer à diminuer (p. ex., cancer du poumon, cancer colorectal et cancer de la prostate), tandis que ceux de plusieurs autres cancers devraient augmenter (p. ex., cancer du foie et des voies biliaires intrahépatiques, cancer du rein, mélanome et lymphome non hodgkinien). INTERPRÉTATION: Bien que l'incidence globale du cancer et la mortalité connexe sont en déclin, il devrait y avoir une augmentation des nouveaux cas et des décès au Canada en 2024, en grande partie en raison de la croissance et du vieillissement de la population. Les efforts en matière de prévention, de dépistage et de traitement ont atténué les répercussions de certains cancers, mais ces projections à court terme soulignent l'effet potentiel du cancer sur les gens et les systèmes de soins de santé au Canada.

14.
Int Urogynecol J ; 29(6): 803-810, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28921036

RESUMEN

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare outcomes after uterosacral ligament suspension (USLS) or sacrocolpopexy for symptomatic stage IV apical pelvic organ prolapse (POP) and evaluate predictors of prolapse recurrence. METHODS: The medical records of patients managed surgically for stage IV apical POP from January 2002 to June 2012 were reviewed. A follow-up survey was sent to these patients. The primary outcome, prolapse recurrence, was defined as recurrence of prolapse symptoms measured by validated questionnaire or surgical retreatment. Survival time free of prolapse recurrence was estimated using the Kaplan-Meier method, and Cox proportional hazards models evaluated factors for an association with recurrence. RESULTS: Of 2633 women treated for POP, 399 (15.2%) had stage IV apical prolapse and were managed with either USLS (n = 355) or sacrocolpopexy (n = 44). Those managed with USLS were significantly older (p < 0.001) and less likely to have a prior hysterectomy (39.7 vs 86.4%; p < 0.001) or prior apical prolapse repair (8.2 38.6%; p < 0.001). Median follow-up was 4.3 years [interquartile range (IQR) 1.1-7.7]. Survival free of recurrence was similar between USLS and sacrocolpopexy (p = 0.43), with 5-year rates of 88.7 and 97.6%, respectively. Younger age [adjusted hazard ratio (aHR) 1.55, 95% confidence interval (CI) 1.12-2.13; p = 0.008] and prior hysterectomy (aHR 2.8, 95% CI 1.39-5.64; p = 0.004) were associated with the risk of prolapse recurrence, whereas type of surgery approached statistical significance (aHR 2.76, 95% CI 0.80-9.60; p = 0.11). CONCLUSIONS: Younger age and history of prior hysterectomy were associated with an increased risk of recurrent prolapse symptoms. Notably, excellent survival free of prolapse recurrence were obtained with both surgical techniques.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Prolapso de Órgano Pélvico/cirugía , Complicaciones Posoperatorias/etiología , Vagina/cirugía , Adulto , Factores de Edad , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Histerectomía , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto Joven
15.
Annu Rev Microbiol ; 66: 521-50, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22803796

RESUMEN

Corynebacterium glutamicum exhibits numerous ideal intrinsic attributes as a factory of primary and secondary metabolites. The versatile capabilities of this organism have long been implemented at the industrial scale to produce an array of amino acids at high yields and conversion rates, thereby enabling the development of an entire industry. The postgenomic era provides a new technological platform not only to further optimize the intrinsic attributes of C. glutamicum whole cells as biocatalysts, but also to dramatically expand the product portfolio that can be manufactured by this organism, from amino acids to commodity chemicals. This review addresses the methods and strain optimization strategies enabled by genomic information and associated techniques. Their implementation has provided important additional incremental improvements to the economics of industry-scale manufacturing in which C. glutamicum and its episomal elements are used as a performing host-vector system.


Asunto(s)
Corynebacterium glutamicum/enzimología , Corynebacterium glutamicum/genética , Enzimas/genética , Enzimas/metabolismo , Biotecnología/métodos , Corynebacterium glutamicum/metabolismo , Microbiología Industrial/métodos , Ingeniería Metabólica/métodos , Redes y Vías Metabólicas/genética
16.
Cancer ; 122(8): 1254-60, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-26919270

RESUMEN

BACKGROUND: A rigorous assessment of the risk of colorectal cancer (CRC) among prostate cancer (PC) survivors that controls for important confounding factors and competing risks is necessary to determine the risk of CRC in this population and to inform screening guidelines. METHODS: With data from Manitoba, Canada, subjects diagnosed with PC as their first cancer between 1987 and 2009 were age-matched with up to 5 men with no history of invasive cancer on the PC diagnosis date. Subjects were followed to the date of diagnosis of CRC or another cancer, death, emigration, or the study endpoint (December 31, 2009). Competing risk proportional hazards models were used to compare the CRC incidence between those with PC and those without PC with the following model covariates: history of lower gastrointestinal endoscopy, frequency of health care visits, diabetes, and socioeconomic status. Mutually exclusive competing outcomes included CRC, another primary cancer, and death. RESULTS: For a total of 559,081 person-years, 14,164 men with PC and 69,051 men without PC were followed. Men diagnosed with PC had an increased risk of a subsequent diagnosis of CRC (all CRC: hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.02-1.27; rectal cancer: HR, 1.36; 95% CI, 1.09-1.71). The treatment of PC with radiation was associated with an increased risk for rectal cancer (HR, 2.06; 95% CI, 1.42-2.99) in comparison with PC cases not treated with radiation. CONCLUSIONS: The risk of CRC is increased after a diagnosis of PC and is highest for rectal cancer among those treated with radiation. CRC screening should be considered soon after the diagnosis of PC, especially for men planning for radiotherapy.


Asunto(s)
Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/epidemiología , Sistema de Registros , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Canadá , Estudios de Cohortes , Comorbilidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Valores de Referencia , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia
17.
Antimicrob Agents Chemother ; 60(10): 6407-10, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27480848

RESUMEN

The activity of ceftazidime-avibactam was compared with that of ceftazidime alone and meropenem against a collection of 190 Pseudomonas aeruginosa clinical isolates recovered from a multicenter study of bloodstream infections. The addition of avibactam increased ceftazidime susceptibility in the complete collection of strains (64.7% to 91.1%) and particularly among subsets of isolates showing AmpC hyperproduction (10.9% to 76.1%) or multidrug resistance (MDR) profiles (27% to 77.8%). The MICs of ceftazidime-avibactam, in contrast with those of ceftazidime or meropenem, remained at ≤4 µg/ml for a panel of 16 P. aeruginosa PAO1 isogenic mutants expressing multiple combinations of the most relevant ß-lactam resistance mechanisms.


Asunto(s)
Compuestos de Azabiciclo/farmacología , Ceftazidima/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Resistencia betalactámica/efectos de los fármacos , Combinación de Medicamentos , Humanos , Meropenem , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/aislamiento & purificación , Tienamicinas/farmacología
18.
Antimicrob Agents Chemother ; 60(12): 7415-7423, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27736752

RESUMEN

Whole-genome sequencing (WGS) was used for the characterization of the frequently extensively drug resistant (XDR) Pseudomonas aeruginosa sequence type 175 (ST175) high-risk clone. A total of 18 ST175 isolates recovered from 8 different Spanish hospitals were analyzed; 4 isolates from 4 different French hospitals were included for comparison. The typical resistance profile of ST175 included penicillins, cephalosporins, monobactams, carbapenems, aminoglycosides, and fluoroquinolones. In the phylogenetic analysis, the four French isolates clustered together with two isolates from one of the Spanish regions. Sequence variation was analyzed for 146 chromosomal genes related to antimicrobial resistance, and horizontally acquired genes were explored using online databases. The resistome of ST175 was determined mainly by mutational events; resistance traits common to all or nearly all of the strains included specific ampR mutations leading to ampC overexpression, specific mutations in oprD conferring carbapenem resistance, or a mexZ mutation leading to MexXY overexpression. All isolates additionally harbored an aadB gene conferring gentamicin and tobramycin resistance. Several other resistance traits were specific to certain geographic areas, such as a streptomycin resistance gene, aadA13, detected in all four isolates from France and in the two isolates from the Cantabria region and a glpT mutation conferring fosfomycin resistance, detected in all but these six isolates. Finally, several unique resistance mutations were detected in single isolates; particularly interesting were those in genes encoding penicillin-binding proteins (PBP1A, PBP3, and PBP4). Thus, these results provide information valuable for understanding the genetic basis of resistance and the dynamics of the dissemination and evolution of high-risk clones.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Genoma Bacteriano , Mutación , Filogenia , Pseudomonas aeruginosa/genética , Aminoglicósidos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Carbapenémicos/farmacología , Cefalosporinas/farmacología , Células Clonales , Fluoroquinolonas/farmacología , Francia/epidemiología , Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Hospitales , Humanos , Pruebas de Sensibilidad Microbiana , Monobactamas/farmacología , Penicilinas/farmacología , Porinas/genética , Porinas/metabolismo , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/clasificación , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , España/epidemiología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo
19.
Antimicrob Agents Chemother ; 59(2): 1334-6, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25421471

RESUMEN

We describe here the occurrence of blaVIM-2 in 10 carbapenem-resistant Pseudomonas monteilii strains isolated from different clinical samples from patients at the University Hospital Marqués de Valdecilla in northern Spain. All the blaVIM-2-harboring P. monteilii isolates possessed a class 1 integron, with the cassette array [intI1_blaVIM-2_aac(6')-Ib_qacEΔ1_sul1]. Our results show the emergence of VIM-2-producing multidrug-resistant species other than Pseudomonas aeruginosa or Pseudomonas putida in a Spanish hospital. P. monteilii, although sporadically isolated, should also be considered an important metallo-ß-lactamase (MBL) reservoir.


Asunto(s)
Centros de Atención Terciaria , Antibacterianos/farmacología , Humanos , Pseudomonas/efectos de los fármacos , Pseudomonas/enzimología , España , beta-Lactamasas/metabolismo
20.
Am J Gastroenterol ; 110(12): 1640-6, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26169513

RESUMEN

OBJECTIVES: We examined trends in colorectal cancer (CRC) screening (fecal occult blood test (FOBT), colonoscopy, and flexible sigmoidoscopy (FS)) and differences in CRC screening by income in a population with an organized CRC screening program and universal health-care coverage. METHODS: Individuals who had an FOBT, colonoscopy, or FS were identified from the provincial Physician Claims database and the population-based colon cancer screening registry. Trends in age-standardized rates were determined. Logistic regression was performed to explore the association between CRC screening and income quintiles by year. RESULTS: Up-to-date CRC screening (FOBT, colonoscopy, or FS) increased over time for men and women, all age groups, and all income quintiles. Up-to-date CRC screening was very high among 65- to 69- and 70- to 74-year-olds (70% and 73%, respectively). There was a shift toward the use of an FOBT for CRC screening for individuals in the lower income quintiles. The disparity in colonoscopy/FS coverage by income quintile was greater in 2012 than in 1995. Overall, there was no reduction in disparities by income in up-to-date CRC screening nor did the rate of increase in up-to-date CRC screening or FOBT use change after the introduction of the organized provincial CRC screening program. CONCLUSIONS: CRC screening is increasing over time for both men and women and all age groups. However, a disparity in up-to-date CRC screening by income persisted even with an organized CRC screening program in a universal health-care setting.


Asunto(s)
Neoplasias del Colon/prevención & control , Colonoscopía/estadística & datos numéricos , Detección Precoz del Cáncer , Renta , Tamizaje Masivo , Sangre Oculta , Cobertura Universal del Seguro de Salud , Distribución por Edad , Factores de Edad , Anciano , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/economía , Neoplasias del Colon/epidemiología , Colonoscopía/economía , Detección Precoz del Cáncer/economía , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricos , Detección Precoz del Cáncer/tendencias , Femenino , Humanos , Renta/estadística & datos numéricos , Estudios Longitudinales , Masculino , Manitoba/epidemiología , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Tamizaje Masivo/tendencias , Persona de Mediana Edad , Sigmoidoscopía/estadística & datos numéricos , Cobertura Universal del Seguro de Salud/estadística & datos numéricos
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