A Second Space Age Spanning Omics, Platforms, and Medicine Across Orbits.

The recent acceleration of commercial, private, and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit (LEO), concomitant with the highest-ever number of crewed missions entering space and preparations for exploration-class (>1 year) missions. Such rapid advancement into space from many new companies, countries, and space-related entities has enabled a"Second Space Age." This new era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, encompassing multi-omic, single-cell, and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring, and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics (PGx), as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this review, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration (NASA), Japan Aerospace Exploration Agency (JAXA), European Space Agency (ESA), and other space agencies, and also detail the commercial spaceflight sector's (e.g. SpaceX, Blue Origin, Axiom, Sierra Space) entrance into aerospace medicine and space biology, the first aerospace medicine biobank, and the myriad upcoming missions that will utilize these tools to ensure a permanent human presence beyond LEO, venturing out to other planets and moons.

Genomic investigations of unexplained acute hepatitis in children.

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

Monumental architecture at Aguada Fénix and the rise of Maya civilization.

Archaeologists have traditionally thought that the development of Maya civilization was gradual, assuming that small villages began to emerge during the Middle Preclassic period (1000-350 BC; dates are calibrated throughout) along with the use of ceramics and the adoption of sedentism1. Recent finds of early ceremonial complexes are beginning to challenge this model. Here we describe an airborne lidar survey and excavations of the previously unknown site of Aguada Fénix (Tabasco, Mexico) with an artificial plateau, which measures 1,400 m in length and 10 to 15 m in height and has 9 causeways radiating out from it. We dated this construction to between 1000 and 800 BC using a Bayesian analysis of radiocarbon dates. To our knowledge, this is the oldest monumental construction ever found in the Maya area and the largest in the entire pre-Hispanic history of the region. Although the site exhibits some similarities to the earlier Olmec centre of San Lorenzo, the community of Aguada Fénix probably did not have marked social inequality comparable to that of San Lorenzo. Aguada Fénix and other ceremonial complexes of the same period suggest the importance of communal work in the initial development of Maya civilization.

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Impact of intracardiac echocardiography versus transesophageal echocardiography guidance on left atrial appendage occlusion procedures: A meta-analysis.

BACKGROUND: Intracardiac echocardiography (ICE) is increasingly used during left atrial appendage occlusion (LAAO) as an alternative to transesophageal echocardiography (TEE). The objective of this study is to evaluate the impact of ICE versus TEE guidance during LAAO on procedural characteristics and acute outcomes, as well the presence of peri-device leaks and residual septal defects during follow-up. METHODS: All studies comparing ICE-guided versus TEE-guided LAAO were identified. The primary outcomes were procedural efficacy and occurrence of procedure-related complications. Secondary outcomes included lab efficiency (defined as a reduction in in-room time), procedural time, fluoroscopy time, and presence of peri-device leaks and residual interatrial septal defects (IASD) during follow-up. RESULTS: Twelve studies (n = 5637) were included. There were no differences in procedural success (98.3% vs. 97.8%; OR 0.73, 95% CI 0.42-1.27, p = .27; I2 = 0%) or adverse events (4.5% vs. 4.4%; OR 0.81 95% CI 0.56-1.16, p = .25; I2 = 0%) between the ICE-guided and TEE-guided groups. ICE guidance reduced in in-room time (mean-weighted 28.6-min reduction in in-room time) without differences in procedural time or fluoroscopy time. There were no differences in peri-device leak (OR 0.93, 95% CI 0.68-1.27, p = 0.64); however, an increased prevalence of residual IASD was observed with ICE-guided versus TEE-guided LAAO (46.3% vs. 34.2%; OR 2.23, 95% CI 1.05-4.75, p = 0.04). CONCLUSION: ICE guidance is associated with similar procedural efficacy and safety, but could result in improved lab efficiency (as established by a significant reduction in in-room time). No differences in the rate of periprocedural leaks were found. A higher prevalence of residual interatrial septal defects was observed with ICE guidance.

Real-world effectiveness and safety of insulin glargine 100 U/mL plus lixisenatide in adults with type 2 diabetes: An international, multicentre, 12-month, prospective observational study.

AIM: To assess the impact of insulin glargine (100 U/mL) and lixisenatide (iGlarLixi) fixed-ratio combination therapy on the overall management of glycaemia in patients with type 2 diabetes (T2D), previously inadequately controlled with oral antidiabetic drugs ± basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). MATERIALS AND METHODS: This 12-month, international, multicentre, prospective, observational study included patients (age ≥ 18 years) with T2D who had initiated iGlarLixi within 1 month prior to study inclusion. Data were collected at study inclusion, month 3, month 6 and month 12 from patient diaries, self-measured plasma glucose, and questionnaires. The primary endpoint was change in HbA1c from baseline to month 6. RESULTS: Of the 737 eligible participants (mean age: 57.8 [standard deviation: 11.2] years; male: 49%), 685 had baseline and post-baseline HbA1c data available. The least squares mean change in HbA1c from baseline to month 6 was -1.4% (standard error [95% confidence interval (CI)]: 0.05 [-1.5, -1.3]). The absolute change from baseline at month 12 was -1.7% ± 1.9% (95% CI: -1.9, -1.5). There were 72 hypoglycaemia events reported during the study period, with a very low incidence of severe hypoglycaemia (two participants [rate: 0.003 events per patient-year]). CONCLUSIONS: This real-world observational study shows that initiation of iGlarLixi in people with T2D inadequately controlled on oral antidiabetic drugs ± basal insulin or GLP-1 RAs improves glycaemic control with a low incidence of hypoglycaemia.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society .

Gut microbiota and inflammatory mediators differentiate IgE mediated and non-IgE mediated cases of cow's milk protein at diagnosis.

OBJECTIVE: Analyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers. PATIENTS AND METHODS: Fourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry. RESULTS: The fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients. CONCLUSIONS: The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.

Long chain capsaicin analogues synthetized by CALB-CLEAs show cytotoxicity on glioblastoma cell lines.

Glioblastoma is one of the most lethal tumors, displaying striking cellular heterogeneity and drug resistance. The prognosis of patients suffering from glioblastoma after 5 years is only 5%. In the present work, capsaicin analogues bearing modifications on the acyl chain with long-chain fatty acids showed promising anti-tumoral activity by its cytotoxicity on U-87 and U-138 glioblastoma multiforme cells. The capsaicin analogues were enzymatically synthetized with cross-linked enzyme aggregates of lipase B from Candida antarctica (CALB). The catalytic performance of recombinant CALB-CLEAs was compared to their immobilized form on a hydrophobic support. After 72 h of reaction, the synthesis of capsaicin analogues from linoleic acid, docosahexaenoic acid, and punicic acid achieved a maximum conversion of 69.7, 8.3 and 30.3% with CALB-CLEAs, respectively. Similar values were obtained with commercial CALB, with conversion yields of 58.3, 24.2 and 22% for capsaicin analogues from linoleic acid, DHA and punicic acid, respectively. Olvanil and dohevanil had a significant cytotoxic effect on both U-87 and U-138 glioblastoma cells. Irrespective of the immobilization form, CALB is an efficient biocatalyst for the synthesis of anti-tumoral capsaicin derivatives. KEY POINTS: • This is the first report concerning the enzymatic synthesis of capsaicin analogues from docosahexaenoic acid and punicic acid with CALB-CLEAs. • The viability U-87 and U-138 glioblastoma cells was significantly affected after incubation with olvanil and dohevanil. • Capsaicin analogues from fatty acids obtained by CALB-CLEAs are promising candidates for therapeutic use as cytotoxic agents in glioblastoma cancer cells.

Implementation feasibility of animal-assisted therapy in a pediatric intensive care unit: effectiveness on reduction of pain, fear, and anxiety.

Animal-assisted therapies are an innovative strategy within health care humanization initiatives, and they could play a role in the reduction of pain or anxiety. The main objective of this work was to evaluate the feasibility of implementing animal-assisted therapy in a pediatric intensive care unit and its effectiveness for the reduction of pain, fear, and anxiety. A prospective, quasi-experimental study of animal-assisted therapy was designed in the pediatric intensive care unit of the Hospital Universitario 12 de Octubre of Madrid, from January 2019 to December 2019. The study sample included patients who had been admitted to the unit and were over 3 years old. Satisfaction surveys were collected from the patients, family, and health personnel involved. Physiological variables and the level of pain (visual analog scale or Wong-Baker scale), fear (Child Medical Fear Scale), and anxiety (modified Yale Preoperatory Anxiety Scale) were evaluated before and after each session. Any existence of adverse events was recorded. A total of 74 therapy sessions were performed on 61 patients. All sessions were completed without any adverse effects. A total of 164 surveys were collected, providing an overall project rating of 9.69 out of a possible 10. The survey comments were found to be positive in most cases. No differences were found in the physiological variables measured before and after each session. There was a statistically significant decrease in pain, fear, and anxiety levels (p < 0.01).   Conclusion: The implementation of an animal-assisted therapy project in a pediatric intensive care unit is feasible and safe and has a high degree of acceptance among both participants and healthcare staff. Animal-assisted therapy is effective for the reduction of pain, fear, and anxiety, and therefore, it could be considered an adjunct to non-pharmacological therapy. What is Known: • Animal assisted therapies (AAT) are an innovative strategy that could be beneficial to help pediatrics patients cope with admission difficulties and could even play a role in reducing pain, anxiety and/or delirium. • To date there are not studies to analyze the effectiveness of AAT in the field of Pediatric Intesive Care. What is New: • Our study confirms the feasibility and effectiveness of the implementation of an AAT in the field of Pediatric Intensive Care with a high degree of acceptance by participants, caregivers and healthcare personnel. • AAT demonstrated a reduction in pain, fear and anxiety in pediatrics patients admitted to Pediatric Intensive Care Unit.

Accessibility to palliative care services in Colombia: an analysis of geographic disparities.

OBJECTIVES: Due to the increase in the prevalence of non-communicable diseases and the Colombian demographic transition, the necessity of palliative care has arisen. This study used accessibility and coverage indicators to measure the geographic barriers to palliative care. METHODS: Population-based observational study focused on urban areas and adult population from Colombia, which uses three measurements of geographic accessibility to services: a) density of palliative care services per 100,000 inhabitants, b) analysis of geographic distribution by territorial nodes of the country, and c) spatial analysis of palliative care services using Voronoi diagrams. ArcGIS Pro software was used to map services' locations and identify geographic disparities. RESULTS: A total of 504 palliative care services were identified, of which 77% were primary health care services. The density of palliative care services in Colombia is 1.8 primary care services per 100,000 inhabitants and 0.4 specialized services per 100,000 inhabitants. The average palliative care coverage is 41%, two regions of the country have a coverage below 30%. Twenty-eight percent of the services provide care for a population greater than 50,000 inhabitants within their coverage area, exceeding the acceptable limit by international standards. CONCLUSIONS: Palliative care services are concentrated in three main regions (Bogotá D.C., the Center, and the Caribbean) and are limited in the Orinoquia and Amazonia nodes. Density of specialized palliative care services is extremely low and there are regions without palliative services for adults with palliative needs.

Mucosal organs exhibit distinct response signatures to hydrogen sulphide in Atlantic salmon (Salmo salar).

Hydrogen sulphide (H2S) is considered an immunotoxicant, and its presence in the water can influence the mucosal barrier functions of fish. However, there is a significant knowledge gap on how fish mucosa responds to low environmental H2S levels. The present study investigated the consequences of prolonged exposure to sub-lethal levels of H2S on the mucosal defences of Atlantic salmon (Salmo salar). Fish were continuously exposed to two levels of H2S (low: 0.05 µM; and high: 0.12 µM) for 12 days. Unexposed fish served as control. Molecular and histological profiling focused on the changes in the skin, gills and olfactory rosette. In addition, metabolomics and proteomics were performed on the skin and gill mucus. The gene expression profile indicated that the gills and olfactory rosette were more sensitive to H2S than the skin. The olfactory rosette showed a dose-dependent response, but not the gills. Genes related to stress responses were triggered at mucosal sites by H2S. Moreover, H2S elicited strong inflammatory responses, particularly in the gills. All mucosal organs demonstrated the key molecular repertoire for sulphide detoxification, but their temporal and spatial expression was not substantially affected by sub-lethal H2S levels. Mucosal barrier integrity was not considerably affected by H2S. Mucus metabolomes of the skin and gills were unaffected, but a matrix-dependent response was identified. Comparing the high-concentration group's skin and gills mucus metabolomes identified altered amino acid biosynthesis and metabolism pathways. The skin and gill mucus exhibited distinct proteomic profiles. Enrichment analysis revealed that proteins related to immunity and metabolism were affected in both mucus matrices. The present study expands our knowledge of the defence mechanisms against H2S at mucosal sites in Atlantic salmon. The findings offer insights into the health and welfare consequences of sub-lethal H2S, which can be incorporated into the risk assessment protocols in salmon land-based farms.

Batch and semi-continuous treatment of cassava wastewater using microbial fuel cells and metataxonomic analysis.

The treatment of agroindustrial wastewater using microbial fuel cells (MFCs) is a technological strategy to harness its chemical energy while simultaneously purifying the water. This manuscript investigates the organic load effect as chemical oxygen demand (COD) on the production of electricity during the treatment of cassava wastewater by means of a dual-chamber microbial fuel cell in batch mode. Additionally, specific conditions were selected to evaluate the semi-continuous operational mode. The dynamics of microbial communities on the graphite anode were also investigated. The maximum power density delivered by the batch MFC (656.4 µW m - 2 ) was achieved at the highest evaluated organic load (6.8 g COD L - 1 ). Similarly, the largest COD removal efficiency (61.9%) was reached at the lowest organic load (1.17 g COD L - 1 ). Cyanide degradation percentages (50-70%) were achieved across treatments. The semi-continuous operation of the MFC for 2 months revealed that the voltage across the cell is dependent on the supply or suspension of the organic load feed. The electrode polarization resistance was observed to decreases over time, possibly due to the enrichment of the anode with electrogenic microbial communities. A metataxonomic analysis revealed a significant increase in bacteria from the phylum Firmicutes, primarily of the genus Enterococcus.

Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET).

BACKGROUND AND AIMS: Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. METHODS: Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. RESULTS: Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality. CONCLUSIONS: Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF.

Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trial.

BACKGROUND: Mediterranean and low-fat diets are effective in the primary prevention of cardiovascular disease. We did a long-term randomised trial to compare the effects of these two diets in secondary prevention of cardiovascular disease. METHODS: The CORDIOPREV study was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive a Mediterranean diet or a low-fat diet intervention, with a follow-up of 7 years. Clinical investigators (physicians, investigators, and clinical endpoint committee members) were masked to treatment assignment; participants were not. A team of dietitians did the dietary interventions. The primary outcome (assessed by intention to treat) was a composite of major cardiovascular events, including myocardial infarction, revascularisation, ischaemic stroke, peripheral artery disease, and cardiovascular death. This study is registered with ClinicalTrials.gov, NCT00924937. FINDINGS: From Oct 1, 2009, to Feb 28, 2012, a total of 1002 patients were enrolled, 500 (49·9%) in the low-fat diet group and 502 (50·1%) in the Mediterranean diet group. The mean age was 59·5 years (SD 8·7) and 827 (82·5%) of 1002 patients were men. The primary endpoint occurred in 198 participants: 87 in the Mediterranean diet group and 111 in the low-fat group (crude rate per 1000 person-years: 28·1 [95% CI 27·9-28·3] in the Mediterranean diet group vs 37·7 [37·5-37·9] in the low-fat group, log-rank p=0·039). Multivariable-adjusted hazard ratios (HRs) of the different models ranged from 0·719 (95% CI 0·541-0·957) to 0·753 (0·568-0·998) in favour of the Mediterranean diet. These effects were more evident in men, with primary endpoints occurring in 67 (16·2%) of 414 men in the Mediterranean diet group versus 94 (22·8%) of 413 men in the low-fat diet group (multiadjusted HR 0·669 [95% CI 0·489-0·915], log-rank p=0·013), than in 175 women for whom no difference was found between groups. INTERPRETATION: In secondary prevention, the Mediterranean diet was superior to the low-fat diet in preventing major cardiovascular events. Our results are relevant to clinical practice, supporting the use of the Mediterranean diet in secondary prevention. FUNDING: Fundacion Patrimonio Comunal Olivarero; Fundacion Centro para la Excelencia en Investigacion sobre Aceite de Oliva y Salud; local, regional, and national Spanish Governments; European Union.

Adherence to a Mediterranean lifestyle improves metabolic status in coronary heart disease patients: A prospective analysis from the CORDIOPREV study.

BACKGROUND AND OBJECTIVES: A Mediterranean lifestyle may prevent and mitigate cardiometabolic disorders. We explored whether adherence to a Mediterranean lifestyle was prospectively associated with the risk of metabolic syndrome (MetS) among coronary heart disease (CHD) patients. METHODS: The Coronary Diet Intervention with Olive Oil and Cardiovascular Prevention (CORDIOPREV) study was an interventional diet study to compare a Mediterranean diet with a low-fat diet, in 1002 CHD patients. The Mediterranean lifestyle (MEDLIFE) index was used to assess adherence to a MEDLIFE at baseline, and after 5 years, in 851 participants from the CORDIOPREV study. Subjects were classified as having high (>13 points), moderate (12-13 points), and low (<12 points) adherence to the MEDLIFE. Multivariable logistic regression models were used to determine the association between MEDLIFE adherence and the risk of MetS development or reversal. RESULTS: During the 5-year follow-up, CORDIOPREV participants with high adherence to MEDLIFE had a lower risk of MetS development (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.19-0.75, p < 0.01) and a higher likelihood of reversing preexisting MetS (OR 2.08 CI 95% 1.11-3.91, p = 0.02) compared with participants in the low MEDLIFE adherence group. Each additional one-point increment in the MEDLIFE index was associated with a 24% lower risk of MetS development (OR 0.76, 95% CI 0.64-0.90, p < 0.01) and a 21% higher likelihood of reversing preexisting MetS (OR 1.21 CI 95% 1.04-1.41, p = 0.01). CONCLUSIONS: Our results showed that greater adherence to a MEDLIFE reduced the risk of subsequent MetS development and increased the likelihood of reversing preexisting MetS among patients with CHD at baseline.

Outcomes of chlorhexidine lavage without capsulectomy versus complete capsulectomy after lead extraction for the treatment of cardiac implantable electronic device infection.

INTRODUCTION: Capsulectomy is recommended in patients with cardiac implantable electronic device (CIED) infection after transvenous lead extraction (TLE) but is time-consuming and requires extensive tissue debridement. In this study, we describe the outcomes of chlorhexidine gluconate (CHG) lavage in lieu of capsulectomy for the treatment of CIED infections. METHODS: This retrospective study included patients who underwent TLE for CIED-related infections in two institutions in Colombia. In the capsulectomy group, complete capsulectomy was performed after hardware removal. In the CHG group, exhaustive lavage of the generator pocket with 20 cc of CHG at 2% followed by irrigation with approximately 500 cc of normal saline (0.9% sodium chloride) was performed. The primary outcomes included reinfection and hematoma formation in the generator pocket. Secondary outcomes included the occurrence of any adverse reaction to chlorhexidine, the need for reintervention, infection-related mortality, and total procedural time. RESULTS: A total of 102 patients (mean age 67.2 ± 13 years, 32.4% female) underwent CIED extraction with either total capsulectomy (n = 54) or CHG (n = 48) lavage. Hematoma formation was significantly higher in the capsulectomy group versus the CHG group (13% vs. 0%, p = .014), with no significant differences in the reinfection rate. Capsulectomy was associated with longer procedural time (133.7 ± 78.5 vs. 89.9 ± 51.8 min, p = .002). No adverse reactions to CHG were found. Four patients (4.3%) died from worsening sepsis: three in the capsulectomy group and one in the CHG group (p = .346). CONCLUSIONS: In patients with CIED infections, the use of CHG without capsulectomy resulted in a lower risk of hematoma formation and shorter procedural times without an increased risk of reinfection or adverse events associated with CHG use.

Assisted reality device to guide cardiac implantable device programming in distant rural areas.

BACKGROUND: Patients with cardiac implantable electronic devices (CIEDs) living in rural areas have difficulty obtaining follow-up visits for device interrogation and programming in specialized healthcare facilities. OBJECTIVE: To describe the use of an assisted reality device designed to provide front-line workers with real-time online support from a remotely located specialist (Realwear HTM-1; Realwear) during CIED assistance in distant rural areas. METHODS: This is a prospective study of patients requiring CIED interrogation using the Realwear HMT-1 in a remote rural population in Colombia between April 2021 and June 2022. CIED interrogation and device programming were performed by a general practitioner and guided by a cardiac electrophysiologist. Non-CIED-related medical interventions were allowed and analyzed. The primary objective was to determine the incidence of clinically significant CIED alerts. Secondary objectives were the changes medical interventions used to treat the events found in the device interrogations regarding non-CIED related conditions. RESULTS: A total of 205 CIED interrogations were performed on 139 patients (age 69 ± 14 years; 54% female). Clinically significant CIED alerts were reported in 42% of CIED interrogations, consisting of the detection of significant arrhythmias (35%), lead malfunction (3%), and device in elective replacement interval (3.9%). Oral anticoagulation was initiated in 8% of patients and general medical/cardiac interventions unrelated to the CIED were performed in 52% of CIED encounters. CONCLUSION: Remote assistance using a commercially available assisted reality device has the potential to provide specialized healthcare to patients in difficult-to-reach areas, overcoming current difficulties associated with RM, including the inability to change device programming. Additionally, these interactions provided care beyond CIED-related interventions, thus delivering significant social and clinical impact to remote rural populations.

Plasma lipidic fingerprint associated with type 2 diabetes in patients with coronary heart disease: CORDIOPREV study.

OBJECTIVE: We aimed to identify a lipidic profile associated with type 2 diabetes mellitus (T2DM) development in coronary heart disease (CHD) patients, to provide a new, highly sensitive model which could be used in clinical practice to identify patients at T2DM risk. METHODS: This study considered the 462 patients of the CORDIOPREV study (CHD patients) who were not diabetic at the beginning of the intervention. In total, 107 of them developed T2DM after a median follow-up of 60 months. They were diagnosed using the American Diabetes Association criteria. A novel lipidomic methodology employing liquid chromatography (LC) separation followed by HESI, and detection by mass spectrometry (MS) was used to annotate the lipids at the isomer level. The patients were then classified into a Training and a Validation Set (60-40). Next, a Random Survival Forest (RSF) was carried out to detect the lipidic isomers with the lowest prediction error, these lipids were then used to build a Lipidomic Risk (LR) score which was evaluated through a Cox. Finally, a production model combining the clinical variables of interest, and the lipidic species was carried out. RESULTS: LC-tandem MS annotated 440 lipid species. From those, the RSF identified 15 lipid species with the lowest prediction error. These lipids were combined in an LR score which showed association with the development of T2DM. The LR hazard ratio per unit standard deviation was 2.87 and 1.43, in the Training and Validation Set respectively. Likewise, patients with higher LR Score values had lower insulin sensitivity (P = 0.006) and higher liver insulin resistance (P = 0.005). The receiver operating characteristic (ROC) curve obtained by combining clinical variables and the selected lipidic isomers using a generalised lineal model had an area under the curve (AUC) of 81.3%. CONCLUSION: Our study showed the potential of comprehensive lipidomic analysis in identifying patients at risk of developing T2DM. In addition, the lipid species combined with clinical variables provided a new, highly sensitive model which can be used in clinical practice to identify patients at T2DM risk. Moreover, these results also indicate that we need to look closely at isomers to understand the role of this specific compound in T2DM development. Trials registration NCT00924937.

Fine-mapping and evolutionary history of R-BPMV, a dominant resistance gene to Bean pod mottle virus in Phaseolus vulgaris L.

KEY MESSAGE: R-BPMV is located within a recently expanded TNL cluster in the Phaseolus genus with suppressed recombination and known for resistance to multiple pathogens including potyviruses controlled by the I gene. Bean pod mottle virus (BPMV) is a comovirus that infects common bean and legumes in general. BPMV is distributed throughout the world and is a major threat on soybean, a closely related species of common bean. In common bean, BAT93 was reported to carry the R-BPMV resistance gene conferring resistance to BPMV and linked with the I resistance gene. To fine map R-BPMV, 182 recombinant inbred lines (RILs) derived from the cross BAT93 × JaloEEP558 were genotyped with polymerase chain reaction (PCR)-based markers developed using genome assemblies from G19833 and BAT93, as well as BAT93 BAC clone sequences. Analysis of RILs carrying key recombination events positioned R-BPMV to a target region containing at least 16 TIR-NB-LRR (TNL) sequences in BAT93. Because the I cluster presents a suppression of recombination and a large number of repeated sequences, none of the 16 TNLs could be excluded as R-BPMV candidate gene. The evolutionary history of the TNLs for the I cluster were reconstructed using microsynteny and phylogenetic analyses within the legume family. A single I TNL was present in Medicago truncatula and lost in soybean, mirroring the absence of complete BPMV resistance in soybean. Amplification of TNLs in the I cluster predates the divergence of the Phaseolus species, in agreement with the emergence of R-BPMV before the separation of the common bean wild centers of diversity. This analysis provides PCR-based markers useful in marker-assisted selection (MAS) and laid the foundation for cloning of R-BPMV resistance gene in order to transfer the resistance into soybean.