RESUMEN
OBJECTIVES: The Modern Innovative Solutions to Improve Outcomes in Asthma, Breathlessness and Chronic Obstructive Pulmonary Disease (COPD) (MABC) service aimed to enhance disease management for chronic respiratory conditions through specialist multidisciplinary clinics, predominantly in the community. This study assesses the outcomes of these clinics. DESIGN: This study used a prospective, longitudinal, participatory action research approach. SETTING: The study was conducted in primary care practices across Hampshire, UK. PARTICIPANTS: Adults aged 16 years and above with poorly controlled asthma or COPD, as well as those with undifferentiated breathlessness not under specialist care, were included. INTERVENTIONS: Participants received care through the multidisciplinary, specialist-led MABC clinics. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes included disease activity, quality of life and healthcare utilisation. Secondary outcomes encompassed clinic attendance, diagnostic changes, patient activation, participant and healthcare professional experiences and cost-effectiveness. RESULTS: A total of 441 participants from 11 general practitioner practices were recruited. Ninety-six per cent of participants would recommend MABC clinics. MABC assessments led to diagnosis changes for 64 (17%) participants with asthma and COPD and treatment adjustments for 252 participants (57%). Exacerbations decreased significantly from 236 to 30 after attending the clinics (p<0.005), with a mean reduction of 0.53 exacerbation events per participant. Reductions were also seen in unscheduled and out-of-hours primary care attendance, emergency department visits and hospital admissions (all p<0.005). Cost savings from reduced exacerbations and healthcare utilisation offset increased medication costs and clinic expenses. CONCLUSIONS: Specialist-supported multidisciplinary teams in MABC clinics improved diagnosis accuracy and adherence to guidelines. High patient satisfaction, disease control improvements and reduced exacerbations resulted in decreased unscheduled healthcare use and cost savings. TRIAL REGISTRATION NUMBER: NCT03096509.
Asunto(s)
Asma , Médicos Generales , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Humanos , Estudios Prospectivos , Calidad de Vida , Asma/terapia , Enfermedad Pulmonar Obstructiva Crónica/terapia , Instituciones de Atención Ambulatoria , DisneaRESUMEN
On November 5th, 2015 the worst environmental disaster in Brazil spilled 60 million m3 of iron mining residue into Gualaxo do Norte River (Minas Gerais State), an affluent of the highest River Basin of the Brazilian Southeast (Doce River Basin), reaching the Atlantic Ocean. To assess the impact of the iron residue on the aquatic plant metabolism, we performed macrophyte growth experiments under controlled light and temperature conditions using two species (Egeria densa and Chara sp.). The plants' growth data were fitted in a kinetic model to obtain the biomass yields (K) and growth rates (µ). Turbidity and electrical conductivity of the water were measured over time. Both plants showed the highest growth rates in the contaminated condition (0.056 d-1 for E. densa and 0.45 d-1 for Chara sp.) and the biomass increased in the short-term (≈20 days). The control condition (i.e. no impacted water) supported the biomass increasing over time and the development of vegetative buddings with high daily rates (1.75 cm d-1 for E. densa and 0.13 cm d-1 for Chara sp). Turbidity showed a sharp decrease in 48 h and had no effects in the plants growth in the contaminated condition. The contamination affected the plants' yields in the long-term affecting the biomass development. This study provides preliminary information about the ecological consequences of a mining dam rupture aiming to collaborate with monitoring and risk assessments.
Asunto(s)
Chara/crecimiento & desarrollo , Hydrocharitaceae/crecimiento & desarrollo , Hierro , Minería , Ríos/química , Contaminantes Químicos del Agua/toxicidad , Océano Atlántico , Biomasa , Brasil , Chara/efectos de los fármacos , Hydrocharitaceae/efectos de los fármacos , Desarrollo de la Planta/efectos de los fármacos , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: The human gut contains approximately 1014 bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. RESULTS: In this model, cross-feeding interactions emerge readily, despite the species' ability to metabolize sugars autonomously. Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. The microbial diversity and stratification collapse if the flux through the gut is enhanced to mimic diarrhea. CONCLUSIONS: In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. It can be extended to include, e.g., complex nutrient sources, and host-microbiota interactions via the intestinal wall.
Asunto(s)
Biodiversidad , Microbioma Gastrointestinal , Modelos Biológicos , Evolución Molecular , Humanos , Análisis de Flujos Metabólicos , Análisis Espacio-TemporalRESUMEN
BACKGROUND: Low-yield metabolism is a puzzling phenomenon in many unicellular and multicellular organisms. In abundance of glucose, many cells use a highly wasteful fermentation pathway despite the availability of a high-yield pathway, producing many ATP molecules per glucose, e.g., oxidative phosphorylation. Some of these organisms, including the lactic acid bacterium Lactococcus lactis, downregulate their high-yield pathway in favor of the low-yield pathway. Other organisms, including Escherichia coli do not reduce the flux through the high-yield pathway, employing the low-yield pathway in parallel with a fully active high-yield pathway. For what reasons do some species use the high-yield and low-yield pathways concurrently and what makes others downregulate the high-yield pathway? A classic rationale for metabolic fermentation is overflow metabolism. Because the throughput of metabolic pathways is limited, influx of glucose exceeding the pathway's throughput capacity is thought to be redirected into an alternative, low-yield pathway. This overflow metabolism rationale suggests that cells would only use fermentation once the high-yield pathway runs at maximum rate, but it cannot explain why cells would decrease the flux through the high-yield pathway. RESULTS: Using flux balance analysis with molecular crowding (FBAwMC), a recent extension to flux balance analysis (FBA) that assumes that the total flux through the metabolic network is limited, we investigate the differences between Saccharomyces cerevisiae and L. lactis that downregulate the high-yield pathway at increasing glucose concentrations, and E. coli, which keeps the high-yield pathway functioning at maximal rate. FBAwMC correctly predicts the metabolic switching mode in these three organisms, suggesting that metabolic network architecture is responsible for differences in metabolic switching mode. Based on our analysis, we expect gradual, "overflow-like" switching behavior in organisms that have an additional energy-yielding pathway that does not consume NADH (e.g., acetate production in E. coli). Flux decrease through the high-yield pathway is expected in organisms in which the high-yield and low-yield pathways compete for NADH. In support of this analysis, a simplified model of metabolic switching suggests that the extra energy generated during acetate production produces an additional optimal growth mode that smoothens the metabolic switch in E. coli. CONCLUSIONS: Maintaining redox balance is key to explaining why some microbes decrease the flux through the high-yield pathway, while other microbes use "overflow-like" low-yield metabolism.
Asunto(s)
Biología Computacional/métodos , Escherichia coli/metabolismo , Lactococcus lactis/metabolismo , Saccharomyces cerevisiae/metabolismo , Acetatos/metabolismo , Glucosa/metabolismo , Oxidación-ReducciónRESUMEN
The purpose of this case report is to describe the regression of vascular calcifications (VC) in a patient with secondary hyperparathyroidism (SHPT) after having added cinacalcet to her treatment. We present the clinical case of a 48-year-old woman with chronic renal failure secondary to tubulointerstitial disease. She was being treated with long-term haemodialysis (HD) and underwent two kidney transplants with transplantectomies. The patient presented with severe SHPT caused by parathyroid gland hypertrophy. The radiology test showed signs of VC in the radial and interdigital arteries, and VC in a linear arrangement were observed in both breasts on the mammography. Cinacalcet was added to her treatment with vitamin D derivatives and phosphate-binding agents, which resulted in a good control of mineral metabolism. The radiology test showed that the calcification in the interdigital artery had disappeared and that the bone appeared to be more structured. The mammography also showed regression of the VC. To conclude, cinacalcet may have potential for regression of VC in patients with SHPT.
Asunto(s)
Calcimiméticos/uso terapéutico , Hiperparatiroidismo Secundario/tratamiento farmacológico , Naftalenos/uso terapéutico , Calcificación Vascular/tratamiento farmacológico , Mama/irrigación sanguínea , Calcitriol/uso terapéutico , Carbonato de Calcio/uso terapéutico , Quelantes/uso terapéutico , Cinacalcet , Quimioterapia Combinada , Femenino , Rechazo de Injerto/cirugía , Mano/irrigación sanguínea , Humanos , Hidroxicolecalciferoles/uso terapéutico , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/patología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/terapia , Trasplante de Riñón , Mamografía , Persona de Mediana Edad , Nefritis Intersticial/complicaciones , Fósforo , Poliaminas/uso terapéutico , Diálisis Renal , Reoperación , Sevelamer , Calcificación Vascular/diagnóstico por imagenRESUMEN
El propósito de este informe de caso es describir la regresión de las calcificaciones vasculares (CV) en una paciente con hiperparatiroidismo secundario (HPTS) tras añadir cinacalcet a su tratamiento. Presentamos un caso clínico de una mujer de 48 años de edad con insuficiencia renal crónica secundaria a nefropatía túbulo-intersticial, tratada con hemodiálisis (HD) de larga duración y sometida a dos trasplantes renales con trasplantectomías. La paciente presentaba HPTS grave causado por la hipertrofia de la glándula paratiroidea; la radiología mostró signos de CV en las arterias radiales e interdigitales y la mamografía, CV lineales múltiples en ambas mamas. Se añadió cinacalcet al tratamiento previo con derivados de la vitamina D y agentes quelantes del fósforo, lo que dio como resultado un buen control del metabolismo mineral. La radiología mostró que las calcificaciones de la arteria interdigital habían desaparecido y que el hueso presentaba un aspecto más estructurado. La mamografía también mostró una regresión de las CV. En conclusión, cinacalcet puede tener potencial para la regresión de las CV en pacientes con HPTS (AU)
The purpose of this case report is to describe the regression of vascular calcifications (VC) in a patient with secondary hyperparathyroidism (SHPT) after having added cinacalcet to her treatment. We present the clinical case of a 48-year-old woman with chronic renal failure secondary to tubulointerstitial disease. She was being treated with long-term haemodialysis (HD) and underwent two kidney transplants with transplantectomies. The patient presented with severe SHPT caused by parathyroid gland hypertrophy. The radiology test showed signs of VC in the radial and interdigital arteries, and VC in a linear arrangement were observed in both breasts on the mammography. Cinacalcet was added to her treatment with vitamin D derivatives and phosphate-binding agents, which resulted in a good control of mineral metabolism. The radiology test showed that the calcification in the interdigital artery had disappeared and that the bone appeared to be more structured. The mammography also showed regression of the VC. To conclude, cinacalcet may have potential for regression of VC in patients with SHPT (AU)
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Insuficiencia Renal Crónica/complicaciones , Calcificación Vascular/complicaciones , Diálisis Renal , Hiperparatiroidismo Secundario/complicaciones , Nefritis Intersticial/complicaciones , MamografíaRESUMEN
Whole genome duplications (WGDs) have been hypothesized to be responsible for major transitions in evolution. However, the effects of WGD and subsequent gene loss on cellular behavior and metabolism are still poorly understood. Here we develop a genome scale evolutionary model to study the dynamics of gene loss and metabolic adaptation after WGD. Using the metabolic network of Saccharomyces cerevisiae as an example, we primarily study the outcome of WGD on yeast as it currently is. However, similar results were obtained using a recontructed hypothetical metabolic network of the pre-WGD ancestor. We show that the retention of genes in duplicate in the model, corresponds nicely with those retained in duplicate after the ancestral WGD in S. cerevisiae. Also, we observe that transporter and glycolytic genes have a higher probability to be retained in duplicate after WGD and subsequent gene loss, both in the model as in S. cerevisiae, which leads to an increase in glycolytic flux after WGD. Furthermore, the model shows that WGD leads to better adaptation than small-scale duplications, in environments for which duplication of a whole pathway instead of single reactions is needed to increase fitness. This is indeed the case for adaptation to high glucose levels. Thus, our model confirms the hypothesis that WGD has been important in the adaptation of yeast to the new, glucose-rich environment that arose after the appearance of angiosperms. Moreover, the model shows that WGD is almost always detrimental on the short term in environments to which the lineage is preadapted, but can have immediate fitness benefits in "new" environments. This explains why WGD, while pivotal in the evolution of many lineages and an apparent "easy" genetic operator, occurs relatively rarely.
Asunto(s)
Evolución Molecular , Duplicación de Gen , Genoma Fúngico/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Biología de Sistemas/métodosRESUMEN
Genome shrinkage occurs after whole genome duplications (WGDs) and in the evolution of parasitic or symbiotic species. The dynamics of this process, whether it occurs by single gene deletions or also by larger deletions are however unknown. In yeast, genome shrinkage has occurred after a WGD. Using a computational model of genome evolution, we show that in a random genome single gene deletions cannot explain the observed pattern of gene loss in yeast. The distribution of genes deleted per event can be very well described by a geometric distribution, with a mean of 1.1 genes per event. In terms of deletions of a stretch of base pairs, we find that a geometric distribution with an average of 500-600 base pairs per event describes the data very well. Moreover, in the model, as in the data, gene pairs that have a small intergenic distance are more likely to be both deleted. This proves that simultaneous deletion of multiple genes causes the observed pattern of gene deletions, rather than deletion of functionally clustered genes by selection. Furthermore, we found that in the bacterium Buchnera aphidicola larger deletions than in yeast are necessary to explain the clustering of deleted genes. We show that the excess clustering of deleted genes in B. aphidicola can be explained by the clustering of genes in operons. Therefore, we show that selection has little effect on the clustering of deleted genes after the WGD in yeast, while it has during genome shrinkage in B. aphidicola.
Asunto(s)
Eliminación de Gen , Genoma Bacteriano/genética , Genoma Fúngico/genética , Buchnera/genética , Evolución Molecular , Duplicación de Gen , Modelos Genéticos , Saccharomyces cerevisiae/genéticaRESUMEN
La prevalencia de insuficiencia cardíaca (ICC) en hemodiálisis (HD) es elevada,se ha relacionado con disfunción sistólica, pero su relación con disfuncióndiastólica (DD) no ha sido estudiada.Objetivos: Analizar la incidencia de ICC en una población prevalente en HD yfactores asociados, incluyendo DD.Pacientes y metodo: 79 pacientes en HD; edad: 48 ± 15 años; tiempo en HD:83 ± 62 meses; 55,7% tenía calcificaciones arteriales (CVP) (series radiológicas)y 26% Cardiopatía isquémica (CIsq). Se recogieron parámetros analíticos y clínicosde riesgo cardiovascular, y mediante ecocardiografía se estudiaron: calcificacionesvalvulares (CV), hipertrofia ventricular izquierda (HVI), dilatación VI, disfunciónsistólica y diastólica (DD). Los pacientes se siguieron prospectivamentedos años, recogiendo: incidencia de CIsq, ICC y mortalidad de origen cardíaco.Resultados: Hallazgos ecocardiográficos más frecuentes: HVI (93%) y DD (relajaciónmiocárdica alterada (RMA): 63,5%). El 38,3% presentó ICC, asociándosea mayor tiempo en HD (130/72 meses), mayores niveles de CaxP (74/65), PTH(677/376), fosfatasa alcalina ósea (27/16), aluminio (35/25) y PA sistólica(145/130 mmHg) (p < 0,05), así como a la presencia de CIsq, CVP, CV, HVI yRMA (p < 0,01). La fracción de eyección era normal en ambos grupos. El estudiode regresión logística identificó como factores predictores de ICC: RMA (OR:9,5), CIsq (OR: 15) y PA sistólica (OR: 2,2).Los pacientes con RMA tenían mayor edad (55/37), más tiempo en HD (76/60meses), CVP y CV (p < 0,001). Edad (OR: 2,13) y CVP (OR: 3,9) se comportaroncomo factores predictores de RMA.Conclusiones: Los pacientes en HD presentan elevada incidencia de ICC. La cardiopatíaisquémica, la DD (relajación ventricular alterada) y la PA sistólica se comportancomo factores predictores de su aparición. La DD tiene muy alta prevalencia,y se relaciona con la edad y con la presencia de CVP
Heart failure (CHF) and diastolic dysfuction (DD) relationship has received poorattention in hemodialysis patients (HD).Objetive: To analyse the incidence of CHF in our HD patients, the relationshipwith DD and impact on mortality.Methods: We studied 79 patients: 48 ± 15 years old, mean time on HD 83 ±63 months. Vascular calcification (PVC) was evaluated by radiologic series(55.7%). We analyzed the presence of clinical and analytical cardiovascular factors.All patients underwent M-mode, two-dimensional, Doppler echocardiography.Patients were followed for two years. Clinical information collected: incidence ofischemic heart disease (IHD), CHF, and mortality due to cardiovascular events.Results: Most frequent finding was Left Ventricular Hypertrophy (LVH) (93%),followed by DD (63.5% had anormal LV relaxation) (ALVR). Incidence of CHFwas 38.3%; and was significantly associated with higher: time on HD (130/72months), Ca x P (74/65), PTH (677/376), bone alkaline phosphatase (27/16), andsystolic BP (145 vs 130 mmHg); IHD, PVC, valvular calcification (VC), LVH andALVR (p < 0.01). Systolic function was normal in both groups (with/without CHF).Logistic regression identified as risk factors for CHF: ALVR (OR: 9.5), IHD (OR:15) and systolic BP (OR: 2.2).ALVR was associated with greater age (55/37), longer time on HD (76/60), PVCand VC (p < 0.001). Predictor factors identified were age (OR: 2.13) and PVC(OR: 3.9).Conclusions: HD patients showed a high incidence of CHF. IHD, systolic BPand DD (ALVR) have behave as risk factors for CHF. Vascular calcifications wereintimately related to these findings and, therefore, they contribute to the greatermortality of these patients
Asunto(s)
Persona de Mediana Edad , Humanos , Diástole , Corazón/fisiopatología , Insuficiencia Cardíaca/epidemiología , Diálisis Renal , Estudios Transversales , Incidencia , Factores de RiesgoRESUMEN
UNLABELLED: Heart failure (CHF) and diastolic dysfuction (DD) relationship has received poor attention in hemodialysis patients (HD). OBJECTIVE: To analyse the incidence of CHF in our HD patients, the relationship with DD and impact on mortality. METHODS: We studied 79 patients: 48 +/- 15 years old, mean time on HD 83 +/- 63 months. Vascular calcification (PVC) was evaluated by radiologic series (55.7%). We analyzed the presence of clinical and analytical cardiovascular factors. All patients underwent M-mode, two-dimensional, Doppler echocardiography. Patients were followed for two years. Clinical information collected: incidence of ischemic heart disease (IHD), CHF, and mortality due to cardiovascular events. RESULTS: Most frequent finding was Left Ventricular Hypertrophy (LVH) (93%), followed by DD (63.5% had anormal LV relaxation) (ALVR). Incidence of CHF was 38.3%; and was significantly associated with higher: time on HD (130/72 months), Ca x P (74/65), PTH (677/376), bone alkaline phosphatase (27/16), and systolic BP (145 vs 130 mmHg); IHD, PVC, valvular calcification (VC), LVH and ALVR (p < 0.01). Systolic function was normal in both groups (with/without CHF). Logistic regression identified as risk factors for CHF: ALVR (OR: 9.5), IHD (OR: 15) and systolic BP (OR: 2.2). ALVR was associated with greater age (55/37), longer time on HD (76/60), PVC and VC (p < 0.001). Predictor factors identified were age (OR: 2.13) and PVC (OR: 3.9). CONCLUSIONS: HD patients showed a high incidence of CHF. IHD, systolic BP and DD (ALVR) have behave as risk factors for CHF. Vascular calcifications were intimately related to these findings and, therefore, they contribute to the greater mortality of these patients.
Asunto(s)
Diástole , Insuficiencia Cardíaca/epidemiología , Corazón/fisiopatología , Diálisis Renal , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoAsunto(s)
Fallo Renal Crónico/terapia , Terapia de Reemplazo Renal/métodos , Distribución por Edad , Factores de Edad , Análisis de Varianza , Femenino , Hemodiálisis en el Domicilio/estadística & datos numéricos , Humanos , Trasplante de Riñón/estadística & datos numéricos , Masculino , Diálisis Peritoneal/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Diálisis Renal/estadística & datos numéricos , Terapia de Reemplazo Renal/estadística & datos numéricos , Factores Sexuales , EspañaRESUMEN
We compared the survival of 842 patients on centre haemodialysis to 272 patients on continuous ambulatory peritoneal dialysis (CAPD). All patients selected had begun treatment between 1 January 1984 and 30 June 1988 and were from six centres which participate in a regional renal patients registry. Patients on CAPD were older and had a greater proportion of diabetes and other associated diseases. Age, diabetes, and cardiovascular diseases were associated with a shorter survival on treatment in all the patients studied. Without adjustment for risk factors, patient 3-year survival was higher in centre haemodialysis than in CAPD, 80% versus 64% respectively. However, no significant differences could be shown in the survival rates of the two treatment modalities after accounting for the heterogeneity of the patients in the two groups, either by stratification or by multivariate analysis (Cox). Age was the main predictive factor for CAPD patient survival, while the influence of diabetes and cardiovascular diseases was less clear. Technique survival was much better in centre haemodialysis (94% versus 56% in CAPD, 3-year survival). Older age and diabetes mellitus were associated with a greater risk of switching from centre haemodialysis to CAPD and a trend to retain those patients on CAPD.
Asunto(s)
Diálisis Peritoneal Ambulatoria Continua/mortalidad , Diálisis Renal/mortalidad , Adolescente , Adulto , Anciano , Causas de Muerte , Niño , Preescolar , Femenino , Unidades de Hemodiálisis en Hospital , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
A 27-year-old, full-term pregnant woman with progressive systemic sclerosis (PSS) came to the hospital with marked proteinuria and edema. Two days later, she gave birth to a normal baby. After delivery and during the next 48 hours, renal failure developed. A renal biopsy specimen disclosed findings characteristic of PSS, and immunofluorescence studies displayed nonspecific deposits of fibrinogen and complement. The patient's general condition deteriorated, with development of pericarditis and pulmonary failure; after several peritoneal dialysis treatments, a peritoneal infection developed, and the patient died of Gram-negative sepsis. The association of PSS and nephrotic syndrome is unusual.