In silico Design for Systems-Based Metabolic Engineering for the Bioconversion of Valuable Compounds From Industrial By-Products.

Selecting appropriate metabolic engineering targets to build efficient cell factories maximizing the bioconversion of industrial by-products to valuable compounds taking into account time restrictions is a significant challenge in industrial biotechnology. Microbial metabolism engineering following a rational design has been widely studied. However, it is a cost-, time-, and laborious-intensive process because of the cell network complexity; thus, it is important to use tools that allow predicting gene deletions. An in silico experiment was performed to model and understand the metabolic engineering effects on the cell factory considering a second complexity level by transcriptomics data integration. In this study, a systems-based metabolic engineering target prediction was used to increase glycerol bioconversion to succinic acid based on Escherichia coli. Transcriptomics analysis suggests insights on how to increase cell glycerol utilization to further design efficient cell factories. Three E. coli models were used: a core model, a second model based on the integration of transcriptomics data obtained from growth in an optimized culture media, and a third one obtained after integration of transcriptomics data from adaptive laboratory evolution (ALE) experiments. A total of 2,402 strains were obtained with fumarase and pyruvate dehydrogenase being frequently predicted for all the models, suggesting these reactions as essential to increase succinic acid production. Finally, based on using flux balance analysis (FBA) results for all the mutants predicted, a machine learning method was developed to predict new mutants as well as to propose optimal metabolic engineering targets and mutants based on the measurement of the importance of each knockout's (feature's) contribution. Glycerol has become an interesting carbon source for industrial processes due to biodiesel business growth since it has shown promising results in terms of biomass/substrate yields. The combination of transcriptome, systems metabolic modeling, and machine learning analyses revealed the versatility of computational models to predict key metabolic engineering targets in a less cost-, time-, and laborious-intensive process. These data provide a platform to improve the prediction of metabolic engineering targets to design efficient cell factories. Our results may also work as a guide and platform for the selection/engineering of microorganisms for the production of interesting chemical compounds.

Heart failure admission across glomerular filtration rate categories in a community cohort of 125,053 individuals over 60 years of age.

A reduced estimated glomerular filtration rate (eGFR) has been described as a predictor of heart failure (HF). However, the increased risk across eGFR categories has not been fully evaluated, which is especially relevant in older individuals in whom both the prevalence of HF and decreased eGFR are higher. Furthermore, this association has not been studied in Mediterranean populations, where coronary heart disease (CHD), a frequent cause of HF, has a low prevalence. We performed a retrospective cohort study using the electronic medical records from primary and hospital settings in northeastern Spain. We included 125,053 individuals ≥60 years old with the determination of creatinine and without diagnosis or previous admission due to HF. The eGFR was calculated according to the CKD-EPI formula and classified by clinical categories. The association between eGFR, as a continuous and categorical variable, and the risk of admission due to HF was assessed by Cox proportional risk analysis, considering death as a competitive risk. During a median follow-up of 38.8 months, 2,176 individuals (1.74%) were hospitalized due to HF. The unadjusted admission rates were 4.02, 13.0, 26.0, and 48.6 per 1000 person-years for eGFR > 60, 45-59, 30-44, and 15-29 ml/min/1.73 m2, respectively. The corresponding hazard ratios (95% confidence interval; reference eGFR 60-89) were 1.38 (95% CI 1.23-1.55), 2.02 (95% CI 1.76-2.32) and 3.46 (95% CI 2.78-4.31). In this Mediterranean community-based cohort of individuals ≥60 years old without previous HF, the risk of admission due to HF gradually increased with decreasing eGFR.

Seguimiento de las recomendaciones en prevención secundaria cerebrovascular en atención primaria / Compliance with recommendations in secondary prevention of stroke in primary care

OBJETIVO: Conocer el grado de seguimiento de las recomendaciones en prevención secundaria cerebrovascular en atención primaria e identificar factores asociados. DISEÑO: Transversal multicéntrico. Emplazamiento: Centros de salud de atención primaria de un área metropolitana (944.280 habitantes). PARTICIPANTES: Pacientes mayores de 18 años con diagnóstico de enfermedad cerebrovascular antes de 6 meses del estudio. Mediciones principales: Extracción de historia clínica informatizada de variables demográficas, factores de riesgo y comorbilidad cardiovascular, fármacos, valores de presión arterial (PA), colesterolLDL y visitas por medicina y enfermería posteriores al episodio. Se consideró buen control: PA < 140/90mmHg, colesterolLDL < 100mg/dl, abstención tabáquica y prescripción de fármacos preventivos (antiagregantes/anticoagulantes, estatinas e IECA/ARAII o diurético) en los últimos 18 meses. RESULTADOS: Un total de 21.976 sujetos, media de edad 73,1 años (DE: 12,1), 48% mujeres, el 72,7% con accidente vascular cerebral establecido. Comorbilidad: 70,8% HTA, 55,1% dislipidemia, 30,9% DM, 14,1% fibrilación auricular, 13,5% cardiopatía isquémica, 12,5% insuficiencia renal crónica, 8,8% insuficiencia cardiaca, 6,2% arteriopatía periférica, 7,8% demencia. Sin registro de: hábito tabáquico 3,7%, PA 3,5% y colesterolLDL 6,5%. Grado de control: 75,4% abstención tabáquica, 65,7% PA < 140/90 y 41,0% colesterolLDL< 100mg/dl. Tratamiento: 86,2% antiagregantes/anticoagulantes, 61,3% estatinas y 61,8% IECA/ARAII o diurético. El registro/grado de control fue superior en el grupo de 66-79 años e inferior en el de 18-40 años. CONCLUSIONES: El seguimiento de las recomendaciones de las guías clínicas para la prevención de la enfermedad cerebrovascular en atención primaria es mejorable, especialmente en los más jóvenes. Son necesarios cambios organizativos e intervención más activa de los profesionales, así como estrategias para combatir la inercia terapéutica

OBJECTIVE: Knowing compliance with secondary prevention recommendations of stroke in primary care and to identify factors associated with compliance. DESIGN: Multi-centre cross-sectional. SETTING: Health primary care centres in a metropolitan area (944,280 inhabitants). PARTICIPANTS: Patients aged 18 years and over with ischemic brain disease diagnosis prior to 6months before the study. MAIN MEASUREMENTS: Clinical history records of demographic variables, risk factors and cardiovascular comorbidity, drugs, blood pressure values (BP), LDL-cholesterol and medical visits by doctor and nurses after the event. Good adherence was considered when BP < 140/90 mmHg, LDL-cholesterol < 100 mg/dL, smoking abstention and preventive drugs prescription (anti-platelet/anticoagulants, statins and angiotensin-converting-enzyme inhibitors/angiotensin-receptor-antagonists or diuretics) during the last 18 months. RESULTS: A total of 21,976 patients, mean age 73.12 years (SD: 12.13), 48% women, 72.7% with stroke. Co-morbidity: hypertension 70.8%, dyslipidemia 55.1%, DM 30.9%, atrial fibrillation 14.1%, ischemic heart disease 13.5%, chronic renal failure 12.5%, heart failure 8.8%, peripheral arterial disease 6.2%, dementia 7.8%. No record was found for smoking in 3.7%, for BP in 3.5% and for LDL in 6.5%. Optimal control: abstention smoking in 3.7%, BP < 140/90 in 65.7% and LDL < 100 mg/dL in 41.0%. Treatment: 86.2% anti-platelet/anticoagulants, 61.3% statins and 61.8% angiotensin-converting-enzyme inhibitors, angiotensin-receptor-antagonists or diuretic. Registration and risk factors control was higher in 66-79 years aged and lower in 18-40 years aged. CONCLUSIONS: The implementation of clinical guidelines recommendations for stroke prevention in primary care must be improved, especially among younger population. Organizational changes and more active involvement by professionals and strategies against therapeutic inertia must be taken

[Compliance with recommendations in secondary prevention of stroke in primary care]. / Seguimiento de las recomendaciones en prevención secundaria cerebrovascular en atención primaria.

OBJECTIVE: Knowing compliance with secondary prevention recommendations of stroke in primary care and to identify factors associated with compliance. DESIGN: Multi-centre cross-sectional. SETTING: Health primary care centres in a metropolitan area (944,280 inhabitants). PARTICIPANTS: Patients aged 18years and over with ischemic brain disease diagnosis prior to 6months before the study. MAIN MEASUREMENTS: Clinical history records of demographic variables, risk factors and cardiovascular comorbidity, drugs, blood pressure values (BP), LDL-cholesterol and medical visits by doctor and nurses after the event. Good adherence was considered when BP <140/90 mmHg, LDL-cholesterol <100 mg/dL, smoking abstention and preventive drugs prescription (anti-platelet/anticoagulants, statins and angiotensin-converting-enzyme inhibitors/angiotensin-receptor-antagonists or diuretics) during the last 18months. RESULTS: A total of 21,976 patients, mean age 73.12 years (SD: 12.13), 48% women, 72.7% with stroke. Co-morbidity: hypertension 70.8%, dyslipidemia 55.1%, DM 30.9%, atrial fibrillation 14.1%, ischemic heart disease 13.5%, chronic renal failure 12.5%, heart failure 8.8%, peripheral arterial disease 6.2%, dementia 7.8%. No record was found for smoking in 3.7%, for BP in 3.5% and for LDL in 6.5%. Optimal control: abstention smoking in 3.7%, BP <140/90 in 65.7% and LDL <100 mg/dL in 41.0%. TREATMENT: 86.2% anti-platelet/anticoagulants, 61.3% statins and 61.8% angiotensin-converting-enzyme inhibitors, angiotensin-receptor-antagonists or diuretic. Registration and risk factors control was higher in 66-79years aged and lower in 18-40years aged. CONCLUSIONS: The implementation of clinical guidelines recommendations for stroke prevention in primary care must be improved, especially among younger population. Organizational changes and more active involvement by professionals and strategies against therapeutic inertia must be taken.

Self-audit y la acreditación de tutores / Self-audit and tutor accreditation

ObjetivoDescribir la experiencia de utilización del self audit (SA) como criterio de acreditación de los tutores de medicina familiar y comunitaria, analizar el conocimiento que tienen los tutores de esta metodología de autoevaluación y recoger su opinión respecto a este método.DiseñoEstudio descriptivo retrospectivo y análisis de un cuestionario de opinión.EmplazamientoUnidades docentes (UU.DD.) de medicina familiar y comunitaria de Cataluña.ParticipantesTutores de las UU.DD. de medicina familiar y comunitaria de Cataluña (julio de 2001 a julio de 2008).IntervencionesFormación de los tutores en la metodología SA, creación de un grupo de referencia y circuito de corrección. Corrección por pares de los SA realizados por los tutores según unos criterios determinados previamente y envío posterior de un informe-feedback. Encuesta de opinión autoadministrada a un grupo de tutores de las UU.DD.Mediciones y resultados principalesSe realizaron 673 SA. El tema más frecuentemente escogido fue la diabetes mellitus (27,9% de los casos). La valoración global de los SA desde un punto de vista metodológico fue correcta en el 44,5% de los casos, mejorable en el 45,3% y deficiente en el 10,2%.Mediciones y resultados principalesEn relación con los cuestionarios de opinión, se enviaron 300. El índice de respuesta fue de 151/300 (50,3%). Ante la pregunta sobre la utilidad del SA para la práctica profesional, un 12% lo consideraba muy útil; un 56%, bastante útil y un 32%, poco o nada útil.Mediciones y resultados principalesRespecto de si era un buen criterio para la reacreditación y acreditación de tutores, un 63% opinaba que no...(AU)

ObjectiveTo describe the experience of using self-audit (SA) as a means of accrediting family and community medicine tutors, to analyse the knowledge that the tutors have on this self-assessment methodology, and to record their opinions on this method.DesignRetrospective descriptive study and analysis of an opinion questionnaire.SettingFamily and community medicine teaching units (TU) in Catalonia.ParticipantsTutors from family and community medicine TU in Catalonia (July 2001–July 2008).MethodsTraining of the tutors in SA methodology, creation of a reference group and a correction cycle. Correction by peers of the SAs performed by the tutors according to previously determined criteria and subsequent issue of a report-feedback. Self-administered questionnaire by a group of TU tutors.Measurements and main outcomesA total of 673 SA were performed. The most frequent topic selected was diabetes mellitus in 27.9% of cases. The overall evaluation of the SA from a methodological point of view was correct in 44.5% of cases, improvable in 45.3%, and deficient in 10.2%.Measurements and main outcomesA total of 300 opinion questionnaires were issued. The response rate was 151/300 (50.03%). On the question about the usefulness of the SA in professional practice, 12% considered it very useful, 56% adequate, and 32% of little use or not useful.Measurements and main outcomesAs regards whether it was a good means for the re-accreditation or accreditation of tutors, 66% considered that it was not.ConclusionsA high percentage of the SAs analysed are not carried out correctly, which indicates that tutors do not know this self-assessment method very well. They consider that SAs are a useful tool for improving clinical practice, but not a good means for accreditation and re-accreditation(AU)

[Self-audit and tutor accreditation]. / Self-audit y la acreditación de tutores.

OBJECTIVE: To describe the experience of using self-audit (SA) as a means of accrediting family and community medicine tutors, to analyse the knowledge that the tutors have on this self-assessment methodology, and to record their opinions on this method. DESIGN: Retrospective descriptive study and analysis of an opinion questionnaire. SETTING: Family and community medicine teaching units (TU) in Catalonia. PARTICIPANTS: Tutors from family and community medicine TU in Catalonia (July 2001-July 2008). METHODS: Training of the tutors in SA methodology, creation of a reference group and a correction cycle. Correction by peers of the SAs performed by the tutors according to previously determined criteria and subsequent issue of a report-feedback. Self-administered questionnaire by a group of TU tutors. MEASUREMENTS AND MAIN OUTCOMES: A total of 673 SA were performed. The most frequent topic selected was diabetes mellitus in 27.9% of cases. The overall evaluation of the SA from a methodological point of view was correct in 44.5% of cases, improvable in 45.3%, and deficient in 10.2%. A total of 300 opinion questionnaires were issued. The response rate was 151/300 (50.03%). On the question about the usefulness of the SA in professional practice, 12% considered it very useful, 56% adequate, and 32% of little use or not useful. As regards whether it was a good means for the re-accreditation or accreditation of tutors, 66% considered that it was not. CONCLUSIONS: A high percentage of the SAs analysed are not carried out correctly, which indicates that tutors do not know this self-assessment method very well. They consider that SAs are a useful tool for improving clinical practice, but not a good means for accreditation and re-accreditation.