Recent Insights Into Native Valve Infective Endocarditis: JACC Focus Seminar 4/4.

This focused review highlights the latest issues in native valve infective endocarditis. Native valve disease moderately increases the risk of developing infective endocarditis. In 2023, new diagnostic criteria were published by the Duke-International Society of Cardiovascular Infectious Diseases group. New pathogens were designated as typical, and findings on computed tomography imaging were included as diagnostic criteria. It is now recognized that a multidisciplinary approach to care is vital, and the role of an "endocarditis team" is highlighted. Recent studies have suggested that a transition from intravenous to oral antibiotics in selected patients may be reasonable, and the role of long-acting antibiotics is discussed. It is also now clear that an aggressive surgical approach can be life-saving in some patients. Finally, results of several recent studies have suggested there is an association between dental and other invasive procedures and an increased risk of developing infective endocarditis. Moreover, data indicate that antibiotic prophylaxis may be effective in some scenarios.

Photobiomodulation increases brain metabolic activity through a combination of 810 and 660 wavelengths: a comparative study in male and female rats.

Photobiomodulation (PBM), an emerging and non-invasive intervention, has been shown to benefit the nervous system by modifying the mitochondrial cytochrome c-oxidase (CCO) enzyme, which has red (620-680 nm) or infrared (760-825 nm) spectral absorption peaks. The effect of a single 810-nm wavelength with a combination of 810 nm and 660 nm lights in the brain metabolic activity of male and female rats was compared. PBM, with a wavelength of 810 nm and a combination of 810 nm and 660 nm, was applied for 5 days on the prefrontal cortex. Then, brain metabolic activity in the prefrontal area, hippocampus, retrosplenial, and parietal cortex was explored. Sex differences were found in cortical and subcortical regions, indicating higher male brain oxidative metabolism, regardless of treatment. CCO activity in the cingulate and prelimbic area, dentate gyrus, retrosplenial and parietal cortex was enhanced in both treatments (810 + 660 nm and 810 nm). Moreover, using the combination of waves, CCO increased in the infralimbic area, and in CA1 and CA3 of the hippocampus. Thus, employment of a single NIR treatment or a combination of red to NIR treatment led to slight differences in CCO activity across the limbic system, suggesting that a combination of lights of the spectrum may be relevant.

Pericardiocentesis Outcomes in Patients With Pulmonary Hypertension: A Nationwide Analysis from the United States.

Pericardiocentesis (PC) in patients with pulmonary hypertension (PH) and pericardial effusions has unclear benefits because it has been associated with acute hemodynamic collapse and increased mortality. Data on in-hospital outcomes in this population are limited. The National Inpatient Sample database was used to identify adult patients who underwent PC during hospitalizations between 2016 and 2020. Data were stratified by the presence or absence of PH. A multivariate regression model and case-control matching was used to estimate the association of PH with PC in-hospital outcomes. A total of 95,665 adults with a procedure diagnosis of PC were included, of whom 7,770 had PH. Patients with PH tended to be older (aged 67 ± 15.7 years) and female (56%) and less frequently presented with tamponade (44.9% vs 52.4%). Patients with PH had significantly higher rates of chronic kidney disease, coronary artery disease, heart failure, and chronic lung disease, among other co-morbidities. In the multivariate analysis, PC in PH was associated with higher all-cause mortality (adjusted odds ratio [aOR] 1.40, confidence interval [CI] 1.30 to 1.51) and higher rates of postprocedure shock (aOR 1.53, CI 1.30 to 1.81) than patients without PH. Mortality was higher in those with pulmonary arterial hypertension than other nonpulmonary arterial hypertension PH groups (aOR 2.35, 95% CI 1.46 to 3.80, p <0.001). The rates of cardiogenic shock (aOR 1.49, 95% CI 1.38 to 1.61), acute respiratory failure (aOR 1.56, 95% CI 1.48 to 1.64), and mechanical circulatory support use (aOR 1.86, 95% CI 1.63 to 2.12) were also higher in patients with PH. There was no significant volume-outcome relation between hospitals with a high per-annum pericardiocentesis volume compared with low-volume hospitals in these patients. In conclusion, PC is associated with increased in-hospital mortality and higher rates of cardiovascular complications in patients with PH, regardless of the World Health Organization PH group.

Advances in automated and reactive flow cytometry for synthetic biotechnology.

Automated flow cytometry (FC) has been initially considered for bioprocess monitoring and optimization. More recently, new physical and software interfaces have been made available, facilitating the access to this technology for labs and industries. It also comes with new capabilities, such as being able to act on the cultivation conditions based on population data. This approach, known as reactive FC, extended the range of applications of automated FC to bioprocess control and the stabilization of cocultures, but also to the broad field of synthetic and systems biology for the characterization of gene circuits. However, several issues must be addressed before automated and reactive FC can be considered standard and modular technologies.

Species designation of streptococci causing infective endocarditis in patients with mitral valve prolapse.

OBJECTIVES: Viridans group streptococci (VGS) have been previously linked to infective endocarditis (IE) in patients with mitral valve prolapse (MVP). The species identification of VGS is now available in clinical laboratories; however, it has not been examined in MVP IE. Therefore, we detailed the clinical profile, species designations, and antibiotic susceptibility of VGS isolates from patients with MVP IE. METHODS: We retrospectively queried all adults with MVP and a definite or possible IE diagnosis seen at medical centers of the Mayo Clinic Enterprise from January 2009 to December 2021. Data, including clinical characteristics, comorbidities, microbiology, and outcomes, were extracted from electronic health records. VGS isolates from patients with MVP and IE were subclassified into mutans, salivarius, anginosus, sanguinis, and mitis groups. RESULTS: A total of 38 patients with MVP with IE due to streptococcal species were included. Overall, median age was 62.4 years and 32% of patients were females. The most prevalent comorbidities were diabetes mellitus (26%), hypertension (21%), heart failure (16%), and malignancy (16%). A total of (37%) patients presented with an embolic event at the time of their IE diagnosis, 27 (66%) required valve surgery, and no patient died within the hospital stay. The Streptococcus mitis group was the predominant (n = 17, 45%) species designation; S. anginosus and S. sanguinis were identified in three (8%) each; S. mutans in two (5%); and S. salivarius in one (3%). Non-VGS streptococcal pathogens included S. agalactiae in three patients (8%), S. equi in two (5%), and S. dysgalactiae and S. bovis in one each (3%). VGS were identified in five (13%) patients, but species designation was not done. No penicillin resistance was identified among the isolates. CONCLUSION: The S. mitis group was the predominant species in our investigation. Continued evaluation of VGS species should be considered to profile the IE risk based on species identification.

Impact of Chronic Heart Failure on Acute Pulmonary Embolism in-Hospital Outcomes (From a Contemporary Study).

There is a paucity of evidence on the impact of chronic heart failure (HF) on acute pulmonary embolism (PE) hospitalization outcomes. The aim of this study was to evaluate the in-hospital outcomes of patients with chronic HF and acute PE. A total of 1,391,145 hospitalizations with acute PE from the National Inpatient Sample Database from 2011 to 2019 were included. The database was queried for relevant International Classification of Diseases, Ninth and Tenth Revisions procedural and diagnostic codes. Baseline characteristics and in-hospital outcomes for patients with acute PE were compared in patients with and without a history of chronic HF. Multivariate logistic regression analyses were performed, adjusting for age, race, gender, and statistically significant co-morbidities between cohorts. A p value <0.001 was considered significant. Overall, the mean age was 65.2±16 years; 50.9% of patients were women, and 230,875 patients (16.6%) had chronic HF. The patients in the chronic HF cohort were predominantly older (mean age 69.0 vs 61.4 years) and male (49.9% vs 48.3%). In the multivariate model, chronic HF was associated with increased all-cause mortality (odds ratio [OR] 1.6, 95% confidence interval [CI], 1.57 to 1.63, 10.4% vs 5.7%), acute respiratory distress (OR 1.7, 95% CI 1.70 to 1.74, 39.5% vs 22.1%), cardiac arrest (OR 1.4, 95% CI 1.40 to 1.49, 3.9% vs 2.2%), and cardiogenic shock (OR 3.0, 95% CI 2.85 to 3.06, 4.2% vs 1.2%). All p values were <0.001. In conclusion, patients with PE and chronicHF are associated with increased in-hospital complications compared with patients with PE and without chronic HF. Prospective studies are needed to evaluate optimal management strategies in this population at high risk.

Staphylococcus aureus bacteraemia and mortality: a population-based study in Olmsted County, Minnesota, from 2006 to 2020.

OBJECTIVES: To provide an evaluation of predictors of 6-month mortality in incident Staphylococcus aureus bacteraemia cases. METHODS: A retrospective population-based study of 541 adult residents of Olmsted County, MN with monomicrobial S. aureus bacteraemia from 1 January 2006 through 31 December 2020. Multivariable Cox regression was used to investigate risk factors of 6-month mortality. RESULTS: The median (interquartile range [IQR]) age of 541 patients with S. aureus bacteraemia was 66.8 (54.4-78.5) years and 39.6% were female. The median (IQR) Charlson Comorbidity Index was 6 (3-9). Overall, 144 patients died during the six-month period following their initial episode (30-day and 6-month mortality = 16.5% and 26.7%, respectively). In a multivariable analysis, older age, ICU admission, and unknown source of infection were significant predictors of increased 6-month mortality. In contrast, having an infectious diseases (ID) consultation was associated with reduced mortality in the first 2 weeks of follow-up. Secondary analyses revealed an early benefit of ID consultation during the first 30 days of follow-up and that infective endocarditis was an additional predictor of 6-month mortality. CONCLUSIONS: To our knowledge, this investigation represents the only US population-based study evaluating predictors of mortality in patients with S. aureus bacteraemia. The finding of a short-term survival benefit associated with early ID consultation may be due to more extensive diagnostic efforts.

A Population-Based Evaluation of Polymicrobial Staphylococcus aureus Bacteremia.

OBJECTIVE: To provide an evaluation of incidence and six-month mortality rates of polymicrobial Staphylococcus aureus bacteremia (p-SAB) in the United States (US). METHODS: A retrospective population-based study of all incident adults with monomicrobial SAB (m-SAB) and p-SAB in Olmsted County, Minnesota (MN) from 1 January 2006, through 31 December 2020, was conducted. Demographics, clinical characteristics, in-hospital outcomes, and six-month survival were compared between groups. RESULTS: Overall, 31 incident p-SAB cases occurred during the 15-year study period, corresponding to an overall age- and sex-standardized incidence rate of 1.9/100,000 person-years (95% CI, 1.3-2.6). One-third of p-SAB cases were due to MRSA, and almost one-half (15/31) were caused by Gram-positive bacteria. As compared to the 541 cases with incident m-SAB, p-SAB patients were more likely to have a catheter-related infection (p = 0.008) and less likely to be community-acquired cases (p = 0.027). The unadjusted risk of six-month mortality was greater in the p-SAB group (14/31, 45.2%) compared to the m-SAB group (144/541, 26.6%) (HR = 1.94, 95% CI = 1.12-3.36, p = 0.018). After adjusting for relevant covariates, this difference approached significance (HR = 1.93, 95% = CI 0.96-3.87, p = 0.064). CONCLUSIONS: To our knowledge, the current investigation represents the only US population-based study evaluating p-SAB patients. We found lower incidence rates for p-SAB than previously reported, with almost one-half of the cases caused by Gram-positive bacteria. Furthermore, these patients had poor survival compared to incident m-SAB cases.

Pulmonary artery capacitance and pulmonary vascular resistance as prognostic indicators in acute pulmonary embolism.

Aims: The non-invasive calculation of right ventricular (RV) haemodynamics as pulmonary artery (PA) capacitance (PAC) and pulmonary vascular resistance (PVR) have proved to be feasible, easy to perform, and of high prognostic value. We, therefore, evaluated whether baseline PAC and PVR could predict clinical outcomes for patients with acute pulmonary embolism (PE). Methods and results: We prospectively followed 373 patients [mean (standard deviation) age, 64.1 (14.9) years; 58.4% were men, and 27.9% had cancer] who had acute PE and transthoracic echocardiography within 1 day of diagnosis from 1 March 2013 through 30 June 2020. Pulmonary artery capacitance was calculated as left ventricular stroke volume/(PA systolic pressure - PA diastolic pressure). Pulmonary vascular resistance was calculated as (tricuspid regurgitant velocity/RV outflow tract velocity time integral) × 10 + 0.16. These two variables were calculated retrospectively from the values obtained with transthoracic echocardiography. Pulmonary artery capacitance was acquired in 99 (27%) patients and PVR in 65 (17%) patients. Univariable and bivariable logistic regression analyses, and receiver operating characteristic curves were used to evaluate the ability of these haemodynamic measurements to predict mortality up to 6 months. After using bivariable models to adjust individually for age, cancer, and pulmonary hypertension. Pulmonary vascular resistance was associated with all-cause mortality at 3 months [area under the curve (AUC) 0.75, 95% confidence interval (CI) 0.61-0.86; P = 0.01], and 6 months (AUC 0.81; 95% CI 0.69-0.91; P ≤ 0.03). Pulmonary artery capacitance was associated with all-cause mortality at 30 days (AUC 0.95; 95% CI 0.82-0.99; P < 0.001) and 3 months (AUC 0.84; 95% CI 0.65-0.99; P = 0.003). Conclusion: Non-invasive measurement of RV haemodynamics could provide prognostic information of patients with acute PE. Pulmonary artery capacitance and PVR are potentially important predictors of all-cause mortality in these patients and should be explored in future studies.

Incidence Trends and Epidemiology of Staphylococcus aureus Bacteremia: A Systematic Review of Population-Based Studies.

OBJECTIVES: To determine incidence trends of Staphylococcus aureus bacteremia (SAB) from population-based studies from multiple countries. METHODS: A contemporary systematic review was conducted using Ovid Cochrane Central Register of Controlled Trials (1991+), Ovid Embase (1974+), Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE) (1946+ including epub ahead of print, in-process & other non-indexed citations), and Web of Science Core Collection (Science Citation Index Expanded 1975+ and Emerging Sources Citation Index 2015+). Two authors (J.R.H. and J.A.Q.M.) independently reviewed all studies and included those that reported population-based incidence of SAB in patients aged 18 years and older. RESULTS: Twenty-six studies met inclusion criteria with the highest number (n=6) of studies conducted in Canada. The incidence of SAB ranged from 9.3 to 65 cases/100,000/year. The median age of patients with SAB ranged from 62 to 72 years and SAB cases were more commonly observed in men than in women. The most common infection sources were intravascular catheters and skin and soft tissue infections. SAB incidence trends demonstrated high variability for geographic regions and calendar years. Overall, there was no change in the incidence trend across all studies during the past two decades. CONCLUSION: Multiple factors, both pros, and cons are likely responsible for the overall stable SAB incidence in countries included in this systematic review. Some of these factors vary in geographic location and prompt additional investigations from countries not included in the current review so that a more global characterization is defined.

Incidence of Monomicrobial Staphylococcus aureus Bacteremia: A Population-Based Study in Olmsted County, Minnesota-2006 to 2020.

Background: Population-based studies of Staphylococcus aureus bacteremia (SAB) in the United States are limited. We provide a contemporary evaluation of SAB incidence in Olmsted County, Minnesota, from 2006 to 2020. Methods: This was a retrospective population-based study of all adult patients with SAB residing in Olmsted County from 1 January 2006 through 31 December 2020. Initial episodes of SAB were identified using the microbiology laboratory databases at both Olmsted Medical Center and Mayo Clinic Rochester. Results: Overall, 541 incident SAB cases were identified with a median age of 66.8 (interquartile range, 54.4-78.5) years, and 60.4% were male. Among these cases, 298 (56.2%) were due to methicillin-susceptible S aureus (MSSA) and 232 (43.8%) cases of methicillin-resistant S aureus (MRSA). The overall age- and sex-adjusted SAB incidence rate (IR) was 33.9 (95% confidence interval [CI], 31.0-36.8) cases/100 000 person-years (PY). Males had a higher age-adjusted IR of 46.0 (95% CI, 41.0-51.0) cases/100 000 PY compared to females (IR, 24.4 [95% CI, 21.1-27.7] cases/100 000 PY). Age- and sex-adjusted SAB IRs due to MSSA and MRSA were 18.7 and 14.6 cases/100 000 PY, respectively, and the percentage of incident SAB cases due to MRSA fluctuated across the study period. There was no apparent temporal trend in SAB incidence over the study period (P = .093). Conclusions: Our investigation represents the only contemporary population-based study in the United States. Despite the impression that SAB incidence may have increased based on Centers for Disease Control and Prevention surveillance data, our finding of no change in SAB incidence was somewhat unanticipated.

No Effects of Photobiomodulation on Prefrontal Cortex and Hippocampal Cytochrome C Oxidase Activity and Expression of c-Fos Protein of Young Male and Female Rats.

The role of light in our biological processes and systems is extensively known. In addition, the use of light devices has been introduced in the field of healthcare as an opportunity to administer power light at specific wavelengths to improve our body functions and counteract light deficiency. One of these techniques is photobiomodulation (PBM), which uses red to infrared light in a non-invasive way to stimulate, heal, regenerate, and protect tissue. The main proposed mechanism of action is the stimulation of the cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial electron transport chain. PBM has achieved positive effects on brain activity and behavioral function of several adult animal models of health and disease, the potential use of this technique in developing stages is not surprising. This research aims to examine the effects of PBM on the prefrontal cortex and hippocampus of 23 day-old healthy male (n = 31) and female (n = 30) Wistar rats. Three groups of each sex were used: a PBM group which received 5 days of PBM, a device group submitted to the same conditions but without light radiation, and a control basal group. CCO histochemistry and c-Fos immunostaining were used to analyze brain metabolic activity and immediate early genes activation, respectively. Results displayed no metabolic differences between the three groups in both sexes. The same results were found in the analysis of c-Fos positive cells, reporting no differences between groups. This research, in contrast to the PBM consequences reported in healthy adult subjects, showed a lack of PBM effects in the brain markers we examined in young healthy rat brains. At this stage, brain function, specifically brain mitochondrial function, is not disturbed so it could be that the action of PBM in the mitochondria may not be detectable using the analysis of CCO activity and c-Fos protein expression. Further studies are needed to examine in depth the effects of PBM in brain development, cognitive functions and postnatal disorders, along with the exploration of the optimal light parameters.

Contemporary demographics, diagnostics and outcomes in non-bacterial thrombotic endocarditis.

OBJECTIVE: Non-bacterial thrombotic endocarditis (NBTE) is a syndrome characterised by cardiac valve vegetations and/or thickening due to non-infective mechanisms. Nowadays, a premortem diagnosis of NBTE is possible based on echocardiographic findings. Therefore, to better characterise this disease, we performed a contemporary review of the epidemiology, demographics, diagnosis and clinical outcomes of these patients. METHODS: Adults with a diagnosis of NBTE seen within the Mayo Clinic Enterprise from December 2014 to December 2021 were included. NBTE diagnosis was identified by clinicians representing at least two specialties including cardiology, infectious diseases, rheumatology and oncology. Patients with positive blood cultures, infective endocarditis, culture-negative endocarditis and denial of research authorisation were excluded. All patients had a 1-year follow-up. RESULTS: Forty-eight cases were identified; mean age was 60.0±13.8 years, 75% were female. The most prevalent comorbidities were malignancy (52.1%) and connective tissue disease (37.5%). Valvular abnormalities included 41 (85.4%) patients with vegetations, 43 (89.6%) patients with thickening and 26 (54.2%) with moderate to severe regurgitation. Thirty-eight (79.2%) patients had an embolic event (stroke in 26 (54.2%) patients) within 1 month of NBTE diagnosis and 16 (33.3%) patients died within 1 year of NBTE diagnosis. Metastatic tumours and lung cancer were associated with 1-year all-cause mortality (p=0.0017 and p=0.0004, respectively). CONCLUSIONS: NBTE was more prevalent in females and embolic complications were the most frequent clinical finding. Overall, patients with NBTE had a poor prognosis, particularly in those with lung cancer or metastatic tumours. Further studies in patients with NBTE are needed given its morbidity and mortality.

A clinical profile of infective endocarditis in patients with recent COVID-19: A systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can progress to cardiovascular complications which are linked to higher in-hospital mortality rates. Infective endocarditis (IE) can develop in patients with recent COVID-19 infections, however, characterization of IE following COVID-19 infection has been lacking. To better characterize this disease, we performed a systematic review with descriptive analysis of the clinical features and outcomes of these patients. METHODS: Our search was conducted in 8 databases for all published reports of probable or definite IE in patients with a prior COVID-19 confirmed diagnosis. After ensuring an appropriate inclusion of the articles, we extracted data related to clinical characteristics, modified duke criteria, microbiology, outcomes, and procedures. RESULTS: Searches generated a total of 323 published reports, and 20 articles met our inclusion criteria. The mean age of patients was 52.2 ± 16.9 years and 76.2% were males. Staphylococcus aureus was isolated in 8 (38.1%) patients, Enterococcus faecalis in 3 patients (14.3%) and Streptococcus mitis/oralis in 2 (9.5%) patients. The mean time interval between COVID-19 and IE diagnoses was 16.7 ± 15 days. Six (28.6%) patients required critical care due to IE, 7 patients (33.3%) underwent IE-related cardiac surgery and 5 patients (23.8%) died during their IE hospitalization. CONCLUSIONS: Our systematic review provides a profile of clinical features and outcomes of patients with a prior COVID-19 infection diagnosis who subsequently developed IE. Due to the ongoing COVID-19 pandemic, it is essential that clinicians appreciate the possibility of IE as a unique complication of COVID-19 infection.

Nimotuzumab for COVID-19: case series.

Background: In COVID-19, EGFR production is upregulated in the alveolar epithelial cells. EGFR overexpression further activates STAT-3 and increases lung pathology. The EGFR pathway is also one of the major nodes in pulmonary fibrosis. Methods: Nimotuzumab, a humanized anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was well tolerated. IL-6 decreased from the first antibody infusion. Clinical symptoms significantly improved after nimotuzumab administration, and the CT scans at discharge showed major resolution of the lung lesions and no signs of fibrosis. Conclusion: Safe anti-EGFR antibodies like nimotuzumab may modulate COVID-19-associated hyperinflammation and prevent fibrosis. Clinical Trial Registration: RPCEC00000369 (RPCEC rpcec.sld.cu).

Lay abstract Background: In COVID-19, the protein EGFR is overactive in the infected lung cells. Methods: Nimotuzumab, an anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was safe. The most important inflammatory markers decreased from the first administration. The patients' clinical symptoms and imaging results improved significantly. Conclusion: Anti-EGFR antibodies like nimotuzumab may contribute to the recovery of COVID-19 patients without long-term consequences.

Climate-Aware and IoT-Enabled Selection of the Most Suitable Stone Fruit Tree Variety.

The application of new technologies such as the Internet of Things offers the opportunity to improve current agricultural development, facilitate daily tasks, and turn farms into efficient and sustainable production systems. The use of these new technologies enables the digital transformation process demanded by the sector and provides agricultural collectives with more optimized analysis and prediction tools. Due to climate change, one of the farm industry's problems is the advance or decay in the cycle of stone fruit trees. The objective is to recommend whether a specific area meets the minimum climatic requirements for planting certain stone fruit trees based on climatic data and bioclimatic indicators. The methodology used implements a large amount of meteorological data to generate information on specific climatic conditions and interactions on crops. In this work, a pilot study has been carried out in the Region of Murcia using an IoT platform. We simulate scenarios for the development of stone fruit varieties better adapted to the environment. Based on the standard, open interfaces, and protocols, the platform integrates heterogeneous information sources and interoperability with other third-party solutions to exchange and exploit such information.

Reducing phenotypic instabilities of a microbial population during continuous cultivation based on cell switching dynamics.

Predicting the fate of individual cells among a microbial population (i.e., growth and gene expression) remains a challenge, especially when this population is exposed to very dynamic environmental conditions, such as those encountered during continuous cultivation. Indeed, the dynamic nature of a continuous cultivation process implies the potential diversification of the microbial population resulting in genotypic and phenotypic heterogeneity. The present work focused on the induction of the arabinose operon in Escherichia coli as a model system to study this diversification process in continuous cultivations. As a preliminary step, the green fluorescent protein (GFP) level triggered by an arabinose-inducible ParaBAD promoter was tracked by flow cytometry in chemostat cultivations with glucose-arabinose co-feeding. For a wide range of glucose-arabinose co-feeding concentrations in the chemostats, the simultaneous occurrence of GFP positive and negative subpopulation was observed. In the second set of experiments, continuous cultivation was performed by adding glucose continuously and arabinose based on the capability of individual cells to switch from low GFP to high GFP expression states, performed with a technology setup called segregostat. In the segregostat cultivation mode, on-line flow cytometry analysis was used for adjusting the arabinose/glucose transitions based on the phenotypic switching profiles of the microbial population. This strategy allowed finding an appropriate arabinose pulsing frequency, leading to prolonged maintenance of the induction level with a limited increase in the phenotypic diversity for more than 60 generations. The results suggest that the steady forcing of individual cells into a given phenotypic trajectory may not be the best strategy for controlling cell populations. Instead, allowing individual cells to switch periodically around a predefined threshold seems to be a more robust strategy leading to oscillations, but within a predictable cell population behavior range.

IoTCrawler: Challenges and Solutions for Searching the Internet of Things.

Due to the rapid development of the Internet of Things (IoT) and consequently, the availability of more and more IoT data sources, mechanisms for searching and integrating IoT data sources become essential to leverage all relevant data for improving processes and services. This paper presents the IoT search framework IoTCrawler. The IoTCrawler framework is not only another IoT framework, it is a system of systems which connects existing solutions to offer interoperability and to overcome data fragmentation. In addition to its domain-independent design, IoTCrawler features a layered approach, offering solutions for crawling, indexing and searching IoT data sources, while ensuring privacy and security, adaptivity and reliability. The concept is proven by addressing a list of requirements defined for searching the IoT and an extensive evaluation. In addition, real world use cases showcase the applicability of the framework and provide examples of how it can be instantiated for new scenarios.

Infarto agudo de miocardio en cuatro hospitales de atención secundaria en Cuba en la era COVID-19 / Acute myocardial infarction in four secondary care hospitals in Cuba in the COVID-19 era

RESUMEN Introducción: Las características clínico-epidemiológicas en el diagnóstico, evolución y tratamiento de los pacientes con infarto agudo de miocardio en la era COVID-19 dependen de varios factores. Objetivos: Precisar el comportamiento de algunas variables clínico-epidemiológicas en la atención y tratamiento de los pacientes con infarto agudo de miocardio en el curso de la COVID-19. Método: Se realizó un estudio observacional en cuatro hospitales de atención secundaria en Cuba. Se utilizaron las siguientes variables: número de ingresos por infartos, mortalidad hospitalaria, tiempo de demora mayor de 4 horas desde el inicio de los síntomas y la llegada a la primera asistencia médica y el porcentaje de trombólisis. Se definieron dos grupos, los ingresados entre el 1 de marzo al 30 de septiembre de 2019 (Grupo I) y los ingresados en igual período pero del 2020 (Grupo II). Las comparaciones entre ambos grupos se realizaron utilizando el test de Chi cuadrado. Resultados: Existió una disminución de 53 ingresos por infarto agudo de miocardio en Las Tunas (112 vs. 159, p<0.05), con un incremento del número de ingresos en el Hospital Enrique Cabrera en los pacientes del grupo II (98 vs. 68, p<0.05). Se incrementó el número de fallecidos y la mortalidad hospitalaria en el grupo II en todos los centros con relación al grupo I. En la mayoría de los centros se incrementó la demora desde el inicio de los síntomas y la llegada al lugar de la primera asistencia médica. El porciento de trombólisis fue superior al 50% en la mayoría de los centros en el grupo II. Conclusiones: Las características de la COVID-19 pueden modificar aspectos clínicos y epidemiológicos en la atención y tratamiento de los pacientes con infarto agudo de miocardio.

ABSTRACT Introduction: The clinico-epidemiological characteristics in the diagnosis, evolution and treatment of patients with acute myocardial infarction in the COVID-19 era depend on several factors. Objectives: To determine the behavior of some clinico-epidemiological variables in the management of patients with acute myocardial infarction during de COVID-19 pandemic. Methods: An observational study was carried out in four secondary care hospitals in Cuba. The following variables were used: number of admission due to acute myocardial infarction, hospital mortality, delay longer than four hours from the beginning of the symptoms to the arrival to the first medical assistance, and thrombolysis percentage. Two groups were defined, those admitted from March 1st to September 30th, 2019 (Group I) and those admitted in the same period, but from 2020 (Group II). Comparisons between both groups were made using the chi square test. Results: There was a decrease of 53 admissions due to acute myocardial infarction in Las Tunas (112 vs. 159; p<0.05), with an increase in the number of admissions in the Hospital Enrique Cabrera in patients from Group II (98 vs. 68; p<0.05). The number of deaths and hospital mortality in Group II increased in all the centers in relation to Group I. In most of the hospitals there was an increase of the time elapsed from the beginning of the symptoms to the arrival to the first medical assistance. Thrombolysis percentage in Group II was higher than 50% in most of the centers. Conclusions: The characteristics of COVID-19 may modify the clinical and epidemiological aspects in the management of patients with acute myocardial infarction.