Early and sustained increase in time in range 1 year after initiation of hybrid close loop therapy via telemedicine in type 1 diabetes patients.

BACKGROUND AND AIMS: Evidence supports the efficacy and safety of the Hybrid Close loop (HCL) system in patients with type 1 diabetes (T1D). However, limited data are available on the long-term outcomes of patients on HCL with telemedicine follow-up. METHODS: A prospective observational cohort study including T1D patients, who were upgrading to HCL system. Virtual training and follow-up were done through telemedicine. CGM data were analyzed to compare the baseline time in range (TIR), time below range (TBR), glycemic variability and auto mode (AM), with measurements performed at 3, 6 and 12 months. RESULTS: 134 patients were included with baseline A1c 7.6% ± 1.1. 40.5% had a severe hypoglycemia event in the last year. Baseline TIR, measured two weeks after starting AM was 78.6 ± 9.94%. No changes were evident at three (Mean difference - 0.15;CI-2.47,2.17;p = 0.96), six (MD-1.09;CI-3.42,1.24;p = 0.12) and 12 months (MD-1.30;CI-3.64,1.04;p = 0.08). No significant changes were found in TBR or glycemic variability throughout the follow-up. Use of AM was 85.6 ± 17.5% and percentage of use of sensor was 88.75 ± 9.5% at 12 months. No severe hypoglycemic (SH) events were reported. CONCLUSIONS: HCL systems allow to improve TIR, TBR and glycemic variability safely, early and sustained up to 1 year of follow-up in patients with T1D and high risk of hypoglycemia followed through telemedicine.

Characterization of bovine ruminal content focusing on energetic potential use and valorization opportunities.

This work characterized the bovine ruminal content excluding stomach tissue obtained from a slaughterhouse plant located in Cordoba, Colombia. The goal is to establish possible energetic uses and valorization potential instead of risky local current contaminant practices. Samples of ruminal content (RC) were collected under two conditions as-fresh and dry. Microbiological and bromatological quality, density, proximate and elemental analysis, and calorific power values were measured. There were complemented with optical microscopy, SEM, XEDS, FTIR, TGA, and TGA-MS analysis for both conditions. Ashes of combustion products from mixtures of natural gas and RC were studied, using XRD and XRF techniques. Results showed that fresh-state RC has an important microbiological quality without some human risk pathogens, such as Salmonella sp, E. coli, and vegetable risk pathogens, such as nematodes. Dry and sieved state RC is lignin-cellulosic heterogeneous biomass, with a real density of 164 kg/m3, a calorific power between 12 and 15 kJ/kg, and ashes rich in alkaline-earth elements. These results indicate that RC might have a good potential in co-combustion, gasification, and other energy processes. However, important considerations should be done about management of RC, because its direct application as fertilizer could carry out a negative effect, which was demonstratred in the growth of a model plant.

Design and Usability of an Avatar-Based Learning Program to Support Diabetes Education: Quality Improvement Study in Colombia.

BACKGROUND: This quality improvement study, entitled Avatar-Based LEarning for Diabetes Optimal Control (ABLEDOC), explored the feasibility of delivering an educational program to people with diabetes in Colombia. The aim was to discover how this approach could be used to improve awareness and understanding of the condition, the effects of treatment, and strategies for effective management of blood-glucose control. METHODS: Individuals with diabetes were recruited by Colombian endocrinologists to a human-centered study to codesign the educational program, using the Double Diamond model. Participants contributed to two phases. The first phase focused on gathering unmet educational needs and choice of curriculum. Three prototypes were developed as a result. During phase 2, a different group of participants engaged with the program for several weeks, before reporting back. RESULTS: Thirty-six participants completed a Web survey during phase 1, and five were also interviewed by telephone. The majority (33 of 36; 91%) were receptive to the prospect of educational interventions and ranked the chosen topic of hypoglycemia highly. In phase 2, the three prototypes were tested by 17 participants, 10 of whom also gave feedback in focus groups. The response was overwhelmingly positive, with 16 of 17 (94%) stating they would use a program like this again. The 3D version was the most highly rated. CONCLUSIONS: Immersive, avatar-based programs, delivered through smartphone, have the potential to deliver educational information that is trusted, engaging, and useful. Future work includes expansion of the curriculum, evaluation with a larger group, and exploration of the prospective role of artificial intelligence in personalizing this form of educational intervention.

Efficacy of the mHealth application in patients with type 2 diabetes transitioning from inpatient to outpatient care: A randomized controlled clinical trial.

INTRODUCTION: No studies have assessed the efficacy of telemedicine using a platform for recording and adjusting insulin doses in patients with diabetes mellitus type 2 (DM2) transitioning from inpatient to outpatient care. This study aimed to assess, in a population of patients with DM2, discharged from a tertiary referral hospital, whether treatment based on the use of an mHealth application was associated with better glycemic control at the 3-month follow-up, than standard care. METHODS: This open, randomized, controlled clinical trial included adult DM2 patients who were transitioning from inpatient to outpatient care. The efficacy and safety of patient management with and without mHealth was compared at the 3-month follow-up. The primary outcome was the change in the Glycosylated hemoglobin (HbA1c) levels. The secondary outcomes were the rates of hypoglycemic and hyperglycemic events and treatment satisfaction measured using the Insulin Treatment Satisfaction Questionnaire (ITSQ). RESULTS: In total, 86 patients (41 using mHealth) were included in the clinical trial. HbA1c levels showed a significant decrease in both groups. The mean HbA1c level was significantly lower in the mHealth group. Patients using mHealth showed decreased incidence rate ratios of hypoglycemia 3.0 mmol/L [<54 mg/dl], hypoglycemia ranging from 3.0 to 3.8 mmol/L [54 to 70 mg/dl] and severe hypoglycemia. The level of satisfaction assessed using the ITSQ was higher in the mHealth group. CONCLUSION: Using mHealth in patients with DM2 transitioning from inpatient to outpatient care improves metabolic control and may reduce the hypoglycemia rates.

Is a cloud-based platform useful for diabetes management in Colombia? The Tidepool experience.

BACKGROUND: There are several medical devices used in Colombia for diabetes management, most of which have an associated telemedicine platform to access the data. In this work, we present the results of a pilot study evaluating the use of the Tidepool telemedicine platform for providing remote diabetes health services in Colombia across multiple devices. METHOD: Individuals with Type 1 and Type 2 diabetes using multiple diabetes devices were recruited to evaluate the user experience with Tidepool over three months. Two endocrinologists used the Tidepool software to maintain a weekly communication with participants reviewing the devices data remotely. Demographic, clinical, psychological and usability data were collected at several stages of the study. RESULTS: Six participants, from ten at the baseline (five MDI and five CSII), completed this pilot study. Three different diabetes devices were employed by the participants: a glucose meter (Abbot), an intermittently-scanned glucose monitor (Abbot), and an insulin pump (Medtronic). A score of 81.3 in the system usability scale revealed that overall, most participants found the system easy to use, especially the web interface. The system also compared highly favourably against the proprietary platforms. The ability to upload and share data and communicate remotely with the clinicians was raised consistently by participants. Clinicians cited the lockdown imposed by the Covid-19 pandemic as a valuable test for this platform. Inability to upload data from mobile devices was identified as one of the main limitations. CONCLUSION: Tidepool has the potential to be used as a tool to facilitate remote diabetes care in Colombia. Users, both participants and clinicians, agreed to recommend the use of platforms like Tidepool to achieve better disease management and communication with the health care team. Some improvements were identified to enhance the user experience.

Glycemic control metrics using flash glucose monitoring and hospital complications in patients with COVID-19.

BACKGROUND AND AIMS: Few studies have reported on the use of continuous glucose monitoring (CGM) during the Covid-19 pandemic. We aimed to examine glycemic control metrics using flash glucose monitoring during insulin treatment and the clinical outcome in hospitalized patients with COVID-19. METHODS: Prospective, single-center cohort of adult patients diagnosed with type 2 diabetes or hyperglycemia and COVID-19 infection treated with basal bolus insulin regimen. Glycemic control was assessed with the use of intermittent Freestyle Libre flash glucose monitoring during the hospital stay. Outcome of interest were time in range [TIR], time above [TAR] and below [TBR] range, glycemic variability [coefficient of variation [% CV]), and differences in a composite of complications including ICU admission, acute respiratory distress syndrome (ARDS) and acute kidney injury. RESULTS: A total of 60 patients were included (44 known diabetes and 16 new onset hyperglycemia). In total 190,080 data points of CGM were available, of which 72.5% of values were within the target area [TIR (70-180 mg/dL)], 22% TAR (>180 mg/dL), and 3% were TBR (<70 mg/dL). During treatment, the coefficient of variation (% CV) was 30%. There were no association with TIR, but patients with TAR >180 mg/dl had higher rates of a composite of complications (22.5% vs 16%, p = 0.04). CONCLUSIONS: Basal bolus insulin regimen was safe and effective in achieving inpatient glycemic control in most patients with COVID-19. The association between TAR and complications indicates the need for improved inpatient glycemic control in hospitalized patients with COVID-19.

Virtual training on the hybrid close loop system in people with type 1 diabetes (T1D) during the COVID-19 pandemic.

BACKGROUND AND AIMS: In Colombia, the government established mandatory isolation after the first case of COVID-19 was reported. As a diabetes care center specialized in technology, we developed a virtual training program for patients with type 1 diabetes (T1D) who were upgrading to hybrid closed loop (HCL) system. The aim of this study is to describe the efficacy and safety outcomes of the virtual training program. METHOD: ology: A prospective observational cohort study was performed, including patients with diagnosis of T1D previously treated with multiple doses of insulin (MDI) or sensor augmented pump therapy (SAP) who were updating to HCL system, from March to July 2020. Virtual training and follow-up were done through the Zoom video conferencing application and Medtronic Carelink System version 3.1 software. CGM data were analyzed to compare the time in range (TIR), time below range (TBR) and glycemic variability, during the first two weeks corresponding to manual mode with the final two weeks of follow-up in automatic mode. RESULTS: 91 patients were included. Mean TIR achieved with manual mode was 77.3 ± 11.3, increasing to 81.6% ± 7.6 (p < 0.001) after two weeks of auto mode use. A significant reduction in TBR <70 mg/dL (2,7% ± 2,28 vs 1,83% ± 1,67, p < 0,001) and in glycemic variability (% coefficient of variation 32.4 vs 29.7, p < 0.001) was evident, independently of baseline therapy. CONCLUSION: HCL systems allows T1D patients to improve TIR, TBR and glycemic variability independently of previous treatment. Virtual training can be used during situations that limit the access of patients to follow-up centers.

Factors associated with clinically significant hypoglycemia in patients with type 1 diabetes using sensor-augmented pump therapy with predictive low-glucose management: A multicentric study on iberoamerica.

BACKGROUND AND AIMS: Despite using sensor-augmented pump therapy (SAPT) with predictive low-glucose management (PLGM), hypoglycemia is still an issue in patients with type 1 Diabetes (T1D). Our aim was to determine factors associated with clinically significant hypoglycemia (<54 mg/dl) in persons with T1D treated with PLGM-SAPT. METHOD: ology: This is a multicentric prospective real-life study performed in Colombia, Chile and Spain. Patients with T1D treated with PLGM-SAPT, using sensor ≥70% of time, were included. Data regarding pump and sensor use patterns and carbohydrate intake from 28 consecutive days were collected. A bivariate and multivariate Poisson regression analysis was carried out, to evaluate the association between the number of events of <54 mg/dl with the clinical variables and patterns of sensor and pump use. RESULTS: 188 subjects were included (41 ± 13.8 years-old, 23 ± 12 years disease duration, A1c 7.2% ± 0.9). The median of events <54 mg/dl was four events/patient/month (IQR 1-10), 77% of these events occurred during day time. Multivariate analysis showed that the number of events of hypoglycemia were higher in patients with previous severe hypoglycemia (IRR1.38; 95% CI 1.19-1.61; p < 0.001), high glycemic variability defined as Coefficient of Variation (CV%) > 36% (IRR 2.09; 95%CI 1.79-2.45; p < 0.001) and hypoglycemia unawareness. A protector effect was identified for adequate sensor calibration (IRR 0.77; 95%CI 0.66-0.90; p:0.001), and the use of bolus wizard >60% (IRR 0.74; 95%CI 0.58-0.95; p:0.017). CONCLUSION: In spite of using advanced SAPT, clinically significant hypoglycemia is still a non-negligible risk. Only the identification and intervention of modifiable factors could help to prevent and reduce hypoglycemia in clinical practice.

Cuidados de enfermería para la persona adulta, diabética con hipoglucemia: revisión integrativa / Nursing care for the adult diabetic experiencing hypoglycemia: an integrative review

Introducción:La hipoglucemia es la complicación más frecuente del tratamiento con insulina en adultos. Los eventos de hipoglucemia severa se asocian con complicaciones a corto, mediano y largo plazo en pacientes con diabetes mellitus. Una de las estrategias para reducir la frecuencia de hipoglucemia son las intervenciones de enfermería y aunque hay pocos estudios que las enuncian de manera explícita, se ha publicado respecto a las necesidades de dichos pacientes, que permiten determinar diagnósticos de enfermería y a partir de ellos establecer metas e intervenciones para el cuidado de dichos pacientes. Objetivo: identificar los cuidados de enfermería para prevenir y controlar los eventos de hipoglucemia en pacientes adultos diagnosticados con diabetes mellitus. Metodología: revisión integrativa, se realizó en seis fases: planteamiento de la pregunta PICO; búsqueda en bases de datos y metabuscadores; lectura crítica; análisis, clasificación, validación por nivel de evidencia y grado de recomendación, y presentación de la información. Resultados: la revisión reportó cinco categorías: factores de riesgo y protectores, miedo a la hipoglucemia, atención brindada al paciente, disminución de la hipoglucemia y descripcióndel impacto de la hipoglucemia en los pacientes. Conclusiones: a partir de las necesidades reportadas en las 5 categorías de los resultados se determinaron características definitorias y factores relacionados que permitieron formular diagnósticos de enfermería y determinar como principales intervenciones: enseñanza del proceso de enfermedad, medicamentos prescritos, entrenamiento de asertividad, manejo de la hipoglicemia, nutricional y de la medicación, mejorar el afrontamiento, enseñanza individual, facilitar el aprendizaje y potenciación de la disposición de aprendizaje.

ntroduction: hypoglycemia is the most common complication of insulin therapy in adults. Events of severe hypoglycemia are associated with short, medium and long term complications in patients with diabetes mellitus (DM). One of the strategies to reduce the frequency of hypoglycemia are nursing interventions and although there are few studies that explicitly describe them, there are publications on the needs of such patients, allowing the determination of nursing diagnoses and based on them, setting goals and interventions to deliver care for these patients. Objective: to identify nursing care interventions to prevent and control hypoglycemic events in adult patients diagnosed with DM. Methodology: an integrative review was conducted in six phases: posing the PICOT question; search in databases and metasearch engines; critical reading; analysis, classification, validation by level of evidence and degree of recommendation, and data presentation. Results: the review reported five categories: risk and protective factors, fear of hypoglycemia, care provided to the patient, decrease in hypoglycemia and description of the impact of hypoglycemia on patients. Conclusions: Based on the needs reported in the resulting five categories, defining characteristics and related factors were determined allowing the formulation of nursing diagnoses and identifying the following as the main nursing interventions for hypoglycemia management: teaching of the disease process, prescribed medication, assertiveness training, hypoglycemia management, nutritional and medication therapy, improving coping, individual teaching, facilitating learning and empowering the willingness to learn.

Impact of sensor-augmented pump therapy with predictive low-glucose management on hypoglycemia and glycemic control in patients with type 1 diabetes mellitus: 1-year follow-up.

AIMS: To describe real-life experience with sensor-augmented pump therapy with predictive low-glucose management (SAPT-PLGM), in terms of hypoglycemia and glycemic control after one year of follow-up in T1D patients with hypoglycemia as the main indication of therapy. METHODS: Retrospective cohort study under real life conditions. Baseline and one-year follow-up variables of glycemic control, hypoglycemia and glycemic variability were compared. RESULTS: Fifty patients were included, 31 on prior treatment with SAPT with low-glucose suspend (LGS) feature and 19 on multiple dose insulin injections (MDI). Mean HbA1c decreased in the MDI group (8.24%-7.08%; p = 0.0001). HbA1c change was not significant in the SAPT-LGS group. Area under the curve (AUC) below 70 mg/dl improved in both SAPT-LGS and MDI groups while AUC, %time and events below 54 mg/dl decreased in SAPT-LGS group. Glycemic variability improved in the MDI group. Less patients presented severe hypoglycemia with SAPT-PLGM in both groups, however the change was non-significant. CONCLUSIONS: Under real life conditions, SAPT-PLGM reduced metrics of hypoglycemia in patients previously treaded with MDI and SAPT-LGS without deteriorating glycemic control in SAPT-LGS patients, while improving it in patients treated with MDI.

Defining High Glycemic Variability in Type 1 Diabetes: Comparison of Multiple Indexes to Identify Patients at Risk of Hypoglycemia.

Background: International consensus on the use of continuous glucose monitoring (CGM) recommends coefficient of variation (CV) as the metric of choice to express glycemic variability (GV) with a cutoff of 36% to define unstable diabetes. Even though, CV is associated with hypoglycemia in type 2 diabetes patients, the evidence on the use of one particular measure of GV in type 1 diabetes (T1DM) patients as a predictor of hypoglycemia is limited. Methods: A cohort of T1DM ambulatory patients was evaluated using CGM. Number and incidence rate of events <54 and <70 mg/dL were calculated. Bivariate and multivariate analysis of different glycemic indexes and clinical variables were performed to identify those associated with hypoglycemia. Receiver operating characteristic (ROC) curve analysis for each of the glycemic indexes was performed to define the best index and its optimal cutoff threshold to discriminate patients with events of hypoglycemia. Results: Seventy-three patients were included. A total of 128 events <54 mg/dL were recorded in 34 patients, and 350 events <70 mg/dL were registered in 51 patients. CV was the only variable significantly associated with hypoglycemia <54 mg/dL in the multivariate analysis (adjusted relative risk [aRR] 1.44, 95% confidence interval [CI]: 1.10-1.88, P = 0.008). CV, HbA1c (glycated hemoglobin), and mean glucose were associated with events <70 mg/dL. ROC curve analysis showed that, among GV metrics, CV had the best performance to discriminate patients with events <54 mg/dL (area under the curve [AUC] 0.87, 95% CI: 0.79-0.95) and events <70 mg/dL (AUC 0.79, 95% CI: 0.68-0.90) with optimal cutoff thresholds values of 34% and 31%, respectively. Among glycemic risk (GR) indexes, low blood glucose index (LBGI) showed the best performance. Conclusions: This analysis shows that CV is the best GV index, and LBGI the best GR index, to identify patients at risk of clinically significant hypoglycemia and hypoglycemia alert events in T1DM patients.

Patient Values and Preferences Regarding Continuous Subcutaneous Insulin Infusion and Artificial Pancreas in Adults with Type 1 Diabetes: A Systematic Review of Quantitative and Qualitative Data.

OBJECTIVE: We produced, through a systematic review of quantitative and qualitative evidence, a synthesis of the issues of importance (values and preferences) to adult patients with type 1 diabetes regarding treatment with automated insulin delivery systems. METHODS: We searched MEDLINE, CINAHL, EMBASE, and PsycINFO from the inception of each database through September 2018. We included studies examining patient values and preferences for outcomes related to continuous subcutaneous insulin infusion or artificial pancreas treatment. We compiled structured summaries of the results and assessed the relative importance of each outcome. GRADE (Grading of Recommendations, Assessment Development, and Evaluation) and CERQual (Confidence in Evidence from Reviews of Qualitative research) approaches provided the structure for the evaluation of the quality of evidence and confidence in the findings. A mixed-methods result-based convergent design provided the structure for integration and presentation of results. RESULTS: We reviewed 1665 unique citations; 19 studies (8 quantitative and 11 qualitative) proved eligible. Glycemic control is the key attribute that drives patients' preference. Reduction of glycemic variability and decreased incidence of hypoglycemia and chronic complications proved of intermediate importance and were ranked similarly to components of treatment burden, including the size and appearance of devices, cost, ease of use, and the embarrassment of public use. CONCLUSIONS: Clinician guidance may play a crucial role in determining patient values and preferences (for instance, patients' priority in glucose control rather than avoiding diabetic complications). Our results provide guidance for clinicians in discussing preferred insulin delivery systems with patients with type 1 diabetes.

Efficacy and safety of sensor-augmented pump therapy (SAPT) with predictive low-glucose management in patients diagnosed with type 1 diabetes mellitus previously treated with SAPT and low glucose suspend / Eficacia y seguridad del tratamiento con bomba de insulina con sensor (SAPT) con gestión predictiva de la hipoglucemia en pacientes con diagnóstico de diabetes mellitus tipo 1 tratados previamente con SAPT y suspensión por hipoglucemia

Background: Sensor-augmented insulin pump therapy (SAPT) with low-glucose suspend (LGS) is an effective and safe alternative for treating patients with type 1 diabetes mellitus (T1DM). New predictive low-glucose management (PLGM) systems decrease the severity and duration of hypoglycemic events. However, evidence of benefits in patients previously treated with SAPT-LGS is limited. Methods: A prospective before-after study was conducted in patients with T1DM treated with SAPT-LGS, who were switched to the Minimed(R) 640G system with SmartGuard(R) to assess the impact on A1c levels, severe hypoglycemia (SH), hypoglycemia unawareness (HU), and area under the curve (AUC) <70mg/dL after three months of follow-up. Results: Fifty-five patients with T1DM with a mean age of 37.9 (IQR 6, 79) years and a mean baseline A1c level of 7.52±1.11% were enrolled. After three months under PLGM, A1c levels significantly decreased to 7.18±0.91% (p=0.004). SH rate decreased from 2.47 (CI 0.44, 4.90) to 0.87 (CI 0.22, 1.52) events/patient-year (Incidence rate ratio 0.353, 95% CI 0.178, 0.637), AUC <70mg/dL decreased from 0.59±0.76 to 0.35±0.65mg/dL x minute (p=0.030). HU determined by Clarke questionnaire resolved in 23 out of 30 patients (p=0.002). Conclusions: This study suggests that SAPT with PLGM decreases the frequency of SH, HU, exposure to glucose levels below 70mg/dL, and A1c levels. Based on these results, this therapy should be considered in T1DM patients previously treated with SAPT-LGS with persistent SH and HU. Further clinical trials comparing the efficacy and safety of these features are required

Introducción: La terapia con bomba de insulina integrada a sistema de monitoreo continuo con suspensión en hipoglucemia (SAPT-LGS) es una alternativa efectiva y segura para el tratamiento en pacientes con diabetes tipo 1 (DM1). La función de suspensión antes del límite bajo (PLGM) reduce la gravedad y la duración de los eventos hipoglucémicos. Sin embargo, la evidencia del beneficio en pacientes tratados previamente con SAPT-LGS es limitada. Métodos: Se realizó un estudio longitudinal antes y después con pacientes DM1 tratados con SAPT-LGS que se cambiaron al sistema Minimed(R) 640G con SmartGuard(R), con el fin de evaluar el impacto en los niveles de A1c, hipoglucemia severa (HS), hipoglucemia asintomática (HA) y área bajo la curva (AUC) <70mg/dl después de tres meses de seguimiento. Resultados: Se incluyeron 55 pacientes con DM1, de 37.9 (IQR 6, 79) años, A1c basal de 7.52±1.11%. A los 3 meses bajo PLGM, la A1c se redujo significativamente a 7.18%±0.91% (p=0.004). La tasa de HS se redujo de 2.47 (CI 0.44,4.90) a 0.87 (CI 0.22,1.52) eventos/año del paciente (índice de incidencia 0.353 IC 95%, 0.178, 0.637), el AUC <70mg/dl se redujo de 0,59±0,76 a 0,35±0,65mg/dl x minuto (p = 0,030). HA determinado por el cuestionario Clarke resolvió en 23 de 30 pacientes (p=0,002). Conclusiones: Este estudio sugiere que PLGM reduce la frecuencia de HS, HA, la exposición a niveles de glucosa por debajo de 70mg/dl y A1c. Con base a estos resultados, esta terapia debería considerarse en pacientes con DM1 tratados previamente con SAPT-LGS que persisten con HS e HA. Se requieren ensayos clínicos adicionales que comparen la eficacia y la seguridad de estas características

A Genome-Scale Metabolic Reconstruction of Phytophthora infestans With the Integration of Transcriptional Data Reveals the Key Metabolic Patterns Involved in the Interaction of Its Host.

Phytophthora infestans, the causal agent of late blight disease, affects potatoes and tomatoes worldwide. This plant pathogen has a hemibiotrophic lifestyle, having an initial biotrophic infection phase during which the pathogen spreads within the host tissue, followed by a necrotrophic phase in which host cell death is induced. Although increasing information is available on the molecular mechanisms, underlying the distinct phases of the hemibiotrophic lifestyle, studies that consider the entire metabolic processes in the pathogen while undergoing the biotrophic, transition to necrotrophic, and necrotrophic phases have not been conducted. In this study, the genome-scale metabolic reconstruction of P. infestans was achieved. Subsequently, transcriptional data (microarrays, RNA-seq) was integrated into the metabolic reconstruction to obtain context-specific (metabolic) models (CSMs) of the infection process, using constraint-based reconstruction and analysis. The goal was to identify specific metabolic markers for distinct stages of the pathogen's life cycle. Results indicate that the overall metabolism show significant changes during infection. The most significant changes in metabolism were observed at the latest time points of infection. Metabolic activity associated with purine, pyrimidine, fatty acid, fructose and mannose, arginine, glycine, serine, and threonine amino acids appeared to be the most important metabolisms of the pathogen during the course of the infection, showing high number of reactions associated with them and expression switches at important stages of the life cycle. This study provides a framework for future throughput studies of the metabolic changes during the hemibiotrophic life cycle of this important plant pathogen.

Identification, Characterization, Immunolocalization, and Biological Activity of Lucilin Peptide.

Maggots from the Lucilia sp. genus are used for debridement of infected and necrotic wounds. Broad-spectrum antimicrobial activity has been described in the excretion/secretions (ES1) of these larvae. This study identifies the genetic sequence of a cecropin-like antimicrobial peptide from Lucilia eximia. Total RNA was extracted and used for PCR-RACE amplification of a cecropin, the native peptide was immunolocalized in the tissues and secretions of the larvae, and a synthetic analog was used to explore its antimicrobial, cytotoxic, LPS neutralizing and wound-healing activities in vitro. The genetic cDNA sequence of a cecropin-like antimicrobial peptide in L. eximia called "Lucilin" was amplified, corresponding to 63 aa completed protein and 40 aa mature peptide; the structure of the mature peptide was predicted as an α-helix. The peptide was immunolocalized in the salivary glands, fat body, the ES, and hemolymph of the maggots. Lucilin synthetic peptide analog was active against E. coli DH10B with a MIC2 of 7.8 µg/mL, E. coli extended spectrum b-lactamase (ESBL) (MIC: 15.6 µg/mL), and Enterobacter cloacae (MIC: 125 µg/mL), but it was not active against Pseudomonas aeruginosa and Staphylococcus epidermidis; and had no cytotoxic or hemolytic activity. It showed immunomodulatory activity against human peripheral blood mononuclear cells (PBMCs) stimulated with LPS, reducing the TNF-α production when treated at 17 µg/mL and induces cell migration of Hacat at 5 and 50 µg/mL. Lucilin is a cecropin-like peptide from L. eximia with antimicrobial activity against Gram negative bacteria and immunomodulatory activities, decreasing the TNF-α production in PBMCs and inducing cellular migration in human keratinocytes.

Efficacy and safety of sensor-augmented pump therapy (SAPT) with predictive low-glucose management in patients diagnosed with type 1 diabetes mellitus previously treated with SAPT and low glucose suspend.

BACKGROUND: Sensor-augmented insulin pump therapy (SAPT) with low-glucose suspend (LGS) is an effective and safe alternative for treating patients with type 1 diabetes mellitus (T1DM). New predictive low-glucose management (PLGM) systems decrease the severity and duration of hypoglycemic events. However, evidence of benefits in patients previously treated with SAPT-LGS is limited. METHODS: A prospective before-after study was conducted in patients with T1DM treated with SAPT-LGS, who were switched to the Minimed® 640G system with SmartGuard® to assess the impact on A1c levels, severe hypoglycemia (SH), hypoglycemia unawareness (HU), and area under the curve (AUC) <70mg/dL after three months of follow-up. RESULTS: Fifty-five patients with T1DM with a mean age of 37.9 (IQR 6, 79) years and a mean baseline A1c level of 7.52±1.11% were enrolled. After three months under PLGM, A1c levels significantly decreased to 7.18±0.91% (p=0.004). SH rate decreased from 2.47 (CI 0.44, 4.90) to 0.87 (CI 0.22, 1.52) events/patient-year (Incidence rate ratio 0.353, 95% CI 0.178, 0.637), AUC <70mg/dL decreased from 0.59±0.76 to 0.35±0.65mg/dL x minute (p=0.030). HU determined by Clarke questionnaire resolved in 23 out of 30 patients (p=0.002). CONCLUSIONS: This study suggests that SAPT with PLGM decreases the frequency of SH, HU, exposure to glucose levels below 70mg/dL, and A1c levels. Based on these results, this therapy should be considered in T1DM patients previously treated with SAPT-LGS with persistent SH and HU. Further clinical trials comparing the efficacy and safety of these features are required.

Photo-oxidation of Dimethyl Malonate Initiated by Chlorine Atoms in Gas Phase: Kinetics and Mechanism.

The rate coefficient for the gas-phase reaction of chlorine atoms with dimethyl malonate (DMM, CH3OC(O)CH2C(O)OCH3) was determined at 298 K using relative methods giving a value of (3.8 ± 0.4) × 10-12, cm3 molecule-1 s-1). The photo-oxidation mechanism of DMM was also investigated. The main products were identified by infrared spectroscopy, and computational calculations were performed in order to support the experimental data. The results reveal that the photo-oxidation occurs mainly by the abstraction of an H atom from the methyl groups. The CH3OC(O)CH2C(O)OCH2O• radical formed subsequently reacts according to three competitive paths: reaction with molecular oxygen to yield CH3OC(O)CH2C(O)OC(O)H, isomerization-unimolecular decomposition to lead finally to CH3OC(O)C(O)H, CO2, and HC(O)OH, and α-ester rearrangement to form monomethyl malonate and carbon monoxide. The yield of products as a function of oxygen pressure was also determined.

Photooxidation of Di-tert-butyl Malonate in the Presence and Absence of Nitrogen Dioxide.

The rate constant for the reaction of di-tert-butyl malonate (DTBM) with chlorine atoms in the gas phase was measured using cyclohexane and pentane as references. The measurements lead to a value of (1.5 ± 0.1) × 10-10 cm3 molecule-1 s-1. The subsequent photo-oxidation mechanism of DTBM in the absence and presence of nitrogen dioxide was investigated. The main carbonated products identified in the first case were acetone, formic acid, carbon monoxide, and carbon dioxide. The addition of nitrogen dioxide lead besides to the formation of (CH3)3CC(O)OONO2 and (CH3)3CONO2. The proposed photo-oxidation mechanism was supported both experimentally and computationally. The results reveal that the (CH3)3COC(O)CH2C(O)OC(CH3)2O• radical formed reacts according to two competitive reactions: decomposition to yield acetone and (CH3)3COC(O)CH2C(O)O• radical 55 ± 2%, and migration of the H atom of the methylene group to the terminal oxygen atom 40 ± 3%.

The performance of integrated health care networks in continuity of care: a qualitative multiple case study of COPD patients.

BACKGROUND: Integrated health care networks (IHN) are promoted in numerous countries as a response to fragmented care delivery by providing a coordinated continuum of services to a defined population. However, evidence on their effectiveness and outcome is scarce, particularly considering continuity across levels of care; that is the patient's experience of connected and coherent care received from professionals of the different care levels over time. The objective was to analyse the chronic obstructive pulmonary disease (COPD) patients' perceptions of continuity of clinical management and information across care levels and continuity of relation in IHN of the public health care system of Catalonia. METHODS: A qualitative multiple case study was conducted, where the cases are COPD patients. A theoretical sample was selected in two stages: (1) study contexts: IHN and (2) study cases consisting of COPD patients. Data were collected by means of individual, semi-structured interviews to the patients, their general practitioners and pulmonologists and review of records. A thematic content analysis segmented by IHN and cases with a triangulation of sources and analysists was carried out. RESULTS: COPD patients of all networks perceived that continuity of clinical management was existent due to clear distribution of roles for COPD care across levels, rapid access to care during exacerbations and referrals to secondary care when needed; nevertheless, patients of some networks highlighted too long waiting times to non-urgent secondary care. Physicians generally agreed with patients, however, also indicated unclear distribution of roles, some inadequate referrals and long waiting times to primary care in some networks. Concerning continuity of information, patients across networks considered that their clinical information was transferred across levels via computer and that physicians also used informal communication mechanisms (e-mail, telephone); whereas physicians highlighted numerous problems of the information system, thus the need to use informal communication channels. Finally, regarding continuity of relation, patients of some networks pointed out high turnover of personnel - being frequently seen by locum doctors or assigned to new physicians - which hindered the development of a trusting relationship. CONCLUSION: Study findings suggest a generally perceived adequate performance of IHN in continuity of care but also the existence of a series of difficulties related to all continuity types. Results can provide opportunities to improving the care process of COPD patients but also of patients with other conditions who receive care across the primary and secondary care level.

Factores asociados a mortalidad en pacientes con falla cardiaca descompensada / Factors associated with mortality in patients with decompensated heart failure

Introducción: la falla cardiaca (FC) es una de las principales causas de morbimortalidad a nivel mundial, la cual ha experimentado aumento gradual de su incidencia sin variación importante en su desenlace en las dos últimas décadas. En Colombia muy pocos estudios evalúan factores asociados a mortalidad por falla cardiaca. Métodos: estudio de cohorte prospectivo en el que se incluyeron pacientes con diagnóstico de falla cardiaca descompensada al momento del ingreso a urgencias, entre febrero de 2010 y marzo de 2013. Se calculó el tamaño de muestra y se realizó un análisis multivariado para la evaluación de los factores de riesgo asociados a mortalidad intrahospitalaria y a 30 días. Resultados: se incluyeron 462 pacientes. La mortalidad hospitalaria fue de 8.9% y a 30 días de 13.8%, en el modelo multivariado para el desenlace mortalidad intrahospitalaria se observó que la única variable con significancia estadística fue el BUN ≥43 mg/dL (OR, 3.45 [IC 95% 1.54-7.74], p= 0.003). Para la mortalidad a 30 días, la estancia hospitalaria >5 días (OR, 2.23 [IC 95% 1.20-4.12], p= 0.011), el BUN ≥43 mg/dL (OR, 2.55 [IC 95% 1.31-4.94], p= 0.005) y el NT-proBNP ≥ 4630 pg/dL (OR, 2.47 [IC 95% 1.30-4.70], p= 0.006). Conclusiones: la mortalidad intrahospitalaria de los pacientes con falla cardiaca descompensada en la población evaluada fue alta. En los análisis multivariados, se encontró que el BUN ≥ 43 mg/dL fue el único factor de riesgo independiente asociado a mortalidad intrahospitalaria; mientras que la mortalidad a 30 días se relacionó además con el NT-proBNP y la estancia hospitalaria superior a cinco días.

Introduction: heart failure is one of the main causes of morbidity and mortality worldwide; it has experienced a gradual increase in incidence with no significant variation in outcome in the last two decades. In Colombia there are no studies to evaluate risk factors for mortality, which is the subject of this study. Methods: prospective cohort study in which patients with diagnosis of decompensated heart failure on admission to the emergency department between February 2010 and March 2013 were included. The sample size was calculated and a multivariate analysis was performed to evaluate the risk factors associated with in-hospital and 30-day mortality. Results: 462 patients were included. Hospital mortality was 8.9% and 30-day mortality 13.8%; in the multivariate model for hospital mortality outcome was observed that the only variable with statistic significance was BUN ≥ 43 mg/dL (OR, 3.45 [95% CI 1.54- 7.74], p = 0.003). For 30 day mortality, hospital stay > 5 days (OR, 2.23 [95% CI 1.20-4.12], p = 0.011), BUN ≥43 mg/dL (OR, 2.55 [95% CI 1.31-4.94] , p = 0.005) and NT-proBNP ≥ 4630 pg/dL (OR, 2.47 [95% CI 1.30-4.70], p = 0.006). Conclusions: in-hospital mortality in patients with decompensated heart failure in the study population was high. In multivariate analysis, it was found that BUN ≥ 43 mg/dL was the only independent risk factor associated with hospital mortality, while the 30-day mortality was also associated with NT-proBNP and hospital stay greater than five days.