Erectile dysfunction in cardiovascular patients: A prospective study of the eNOS gene T-786C, G894T, and INTRON variable number of the tandem repeat functional interaction.

BACKGROUND: Cardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood. OBJECTIVES: Exploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high-risk cardiovascular disease patients. MATERIALS AND METHODS: Patients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T-786C), genotyped by fluorescence polarization assays, were registered. The 27-bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Association analyses were run with the R-3.2.0 software. RESULTS: A significant association between endothelial nitric oxide synthase 786-TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 ± 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3-months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 ± 16 scores, the International Index of Erectile Function-Erectile Function 21 ± 10 scores, p < 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 ± 23 scores, p < 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894-T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction. CONCLUSIONS: Our study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high-risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.

Circulating miRNA-21 is an innovative biomarker for cardiovascular events in erectile dysfunction patients.

Introduction: It is well-known that circulating microRNAs (miRNAs) play a relevant role in many kinds of diseases by regulating the expression of genes involved in various pathophysiologic processes, including erectile dysfunction (ED) and cardiovascular diseases (CVD). Purpose: This study aimed to identify the miRNA-21 profile in the blood samples of patients with ED, CVD, and the combination of both pathologies to elucidate the potential function of miRNA-21. Methods: A total of 45 patients with CVD and/or who underwent the erectile function test were included and divided into the following categories: CVD with ED (cases, n = 29) and controls (n = 16) with either ED or CVD. Real-time polymerase chain reaction analysis verified the results. miRNA-21 expression was quantified, and informatics analysis was applied to predict the functions of this differentially expressed miRNA-21. Results: A total of 64% of cases (63 ± 9 years, 66% with severe ED, 56% with CV ejection fraction) first presented ED as the sentinel clinical manifestation. Serum miRNA-21 levels in the control ED were significant, up to 10-fold higher than in the CVD controls and cases. A significant inverse (p = 0.0368, ß = -2.046) correlation was found between erectile function and miRNA-21 levels. Conclusions: Our study provides comprehensive insights into the functional interaction between miRNA-21 and ED in CVD patients. Its relevance lies in the potential of miRNA as a biomarker to be applied in the cardiovascular predictive medicine field.

Microbial biotechnology and beyond: A roadmap for sustainable development and climate mitigation in the transition from fossil fuels to green chemistry.

Our planet, which operates as a closed system, is facing increasing entropy due to human activities such as the overexploitation of natural resources and fossil fuel use. The COP28 in Dubai emphasized the urgency to abandon fossil fuels, recognizing them as the primary cause of human-induced environmental changes, while highlighting the need to transition to renewable energies. We promote the crucial role of microbes for sustaining biogenic cycles to combat climate change and the economic potential of synthetic biology tools for producing diverse non-fossil fuels and chemicals, thus contributing to emission reduction in transport and industry. The shift to 'green chemistry' encounters challenges, derived from the availability of non-food residues and waste (mainly lignocellulosic) as raw material, the construction of cost-effective bioprocessing plants, product recovery from fermentation broths and the utilization of leftover lignin residues for synthesizing new chemicals, aligning with circular economy and sustainable development goals. To meet the Paris Agreement goals, an urgent global shift to low-carbon, renewable sources is imperative, ultimately leading to the cessation of our reliance on fossil fuels.

Insights From the Histopathologic Analysis of Acquired and Genetic Thoracic Aortic Aneurysms and Dissections.

OBJECTIVE: The purpose of this study was to apply contemporary consensus criteria developed by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology to the evaluation of aortic pathology, with the expectation that the additional pathologic information may enhance the understanding and management of aortic diseases. METHODS: A scoring system was applied to ascending aortic specimens from 42 patients with heritable thoracic aortic disease and known genetic variations and from 86 patients from a single year, including patients with known genetic variations (n = 12) and patients with sporadic disease (n = 74). RESULTS: The various types of lesions of medial degeneration and the overall severity of medial degeneration overlapped considerably between those patients with heritable disease and those with sporadic disease; however, patients with heritable thoracic aortic disease had significantly more overall medial degeneration (P = .004) and higher levels of elastic fiber fragmentation (P = .03) and mucoid extracellular matrix accumulation (P = .04) than patients with sporadic thoracic aortic disease. Heritable thoracic aortic disease with known genetic variation was more prevalent in women than in men (27.2% vs 9.8%; P = .04), and women had more severe medial degeneration than men (P = .04). Medial degeneration scores were significantly lower for patients with bicuspid aortic valves than for patients with tricuspid aortic valves (P = .03). CONCLUSION: The study's findings indicate considerable overlap in the pattern, extent, and severity of medial degeneration between sporadic and hereditary types of thoracic aortic disease. This finding suggests that histopathologic medial degeneration represents the final common outcome of diverse pathogenetic factors and mechanisms.

EASIER: A new model for online learning of minimally invasive surgery skills.

INTRODUCTION: Technology Enhanced Learning (TEL) can provide the tools to safely master minimally invasive surgery (MIS) skills in patient-free environments and receive immediate objective feedback without the constant presence of an instructor. However, TEL-based systems tend to work isolated from one another, focus on different skills, and fail to provide contents without a sound pedagogical background. OBJECTIVE: The objective of this descriptive study is to present in detail EASIER, an innovative TEL platform for surgical and interventional training, as well as the results of its validation. METHODS: EASIER provides a Learning Management System (LMS) for institutions and content creators that can connect and integrate TEL "external assets" (virtual reality simulators, augmented box trainers, augmented videos, etc.) addressing different skills. The platform integrates all skills under an Assessment Module that measures skills' progress in different courses. Finally, it provides content creators with a pedagogical model to scaffold contents while retaining flexibility to approach course design with different training philosophies in mind. Three courses were developed and hosted in the platform to validate it with end-users in terms of usability, performance, learning results in the courses and student self-perception on learning. RESULTS: In total 111 volunteers completed the validation. The study was limited due to the COVID-19 pandemic, which limited access to external assets (virtual reality simulators). Nevertheless, usability was rated with 73.1 in the System Usability Scale. Most positive aspects on performance were easiness to access the platform, easiness to change the configuration and not requiring additional plug-ins to use the platform. The platform was rated above average in the six scales of the User Experience Questionnaire. Overall, student results improved significantly across the three courses (p < 0.05). CONCLUSIONS: This study provides, within its limitations, evidence on the usefulness of the EASIER platform for distance learning of MIS skills. Results show the potential impact of the platform and are an encouraging boost for the future, especially in the aftermath of the COVID-19 pandemic.

Percepción y conocimiento sobre sepsis en pobladores de Lima, Perú durante la pandemia de la Covid-19 / Knowledge and perception on sepsis in Lima settlers, Peru during COVID-19 pandemic

RESUMEN Objetivo: Determinar la percepción y nivel de conocimiento sobre sepsis durante la pandemia de la Covid-19 en pobladores de Lima, Perú. Material y métodos: Estudio descriptivo transversal utilizando encuestas electrónicas. Se incluyó a personas mayores de 18 años, residentes en Lima entre diciembre de 2020 y abril de 2021. Se excluyeron a personas relacionadas al área de salud. Resultados: Se realizaron 289 encuestas, la edad media de los encuestados fue 38±15 años y 63% fueron mujeres. El 64% respondió que había escuchado alguna vez la palabra sepsis; 63% tuvo la percepción de que sepsis es una infección potencialmente mortal, 18% no sabía, 8% inflamación severa y 7% como una reacción alérgica severa. El 53% no sabía que la Covid-19 puede desencadenar sepsis, mientras que 68% sabía que la sepsis puede desencadenar la muerte. Conclusión: La percepción más frecuente de sepsis en pobladores de Lima fue infección potencialmente mortal, sin embargo, más de la mitad no supo que la Covid-19 puede desencadenar sepsis.

SUMMARY Objective: To determine the level of knowledge and perception of settlers of Lima, Peru on sepsis during the COVID-19 pandemic. Methods: A cross-sectional study was carried-out using electronic survey among Lima settlers above 18 years of age from December 2020 and April 2021. We excluded health care workers. Results: 289 surveys were conducted; mean age of participants was 38±15 years; 63% were females; 64% had heard about sepsis; 63% had the perception that sepsis was potentially lethal; 18% did not know about it; 8% said that it is a severe inflammation and 7% responded that it is an allergic reaction. Fifty three percent did not know that COVID-19 could lead to sepsis but 68% knew that sepsis may cause mortality. Conclusion: The most common perception on sepsis by Lima settlers was of an infection potentially lethal, but more than half of participants did not know that COVID-19 could lead to sepsis.

LuxR402 of Novosphingobium sp. HR1a regulates the correct configuration of cell envelopes.

Although there is some evidence to suggest that LuxR-solo proteins participate in inter-species or even inter-kingdom communication, most of the LuxR-solo protein functions are unknown. We have characterized the LuxR402 regulator of Novosphingobium sp. HR1a, a bacterial strain with the ability to establish high numbers in the plant rhizosphere and able to degrade a wide range of polycyclic aromatic hydrocarbons. LuxR402 controls the aggregation state of the bacterial culture; cultures of a mutant strain lacking this regulator flocculate in less than 3 h without agitation. We have demonstrated that the bacterial surface of the mutant is highly hydrophobic and that the mutant cells assimilate sugars slower than the wild-type. The flocculation mechanism has been demonstrated to be involved in the survival of the strain under unfavorable conditions; the luxR402 gene is repressed and produces flocculation in the presence of salicylate, a substrate that, although being assimilated by Novosphingobium, is toxic to cells at high concentrations. The flocculation of cultures in industrial setups has mainly been achieved through the addition of chemicals; these studies open up the possibility of controlling the flocculation by regulating the level of expression of the luxR402 gene.

Past, present and future trends in the remediation of heavy-metal contaminated soil - Remediation techniques applied in real soil-contamination events.

Most worldwide policy frameworks, including the United Nations Sustainable Development Goals, highlight soil as a key non-renewable natural resource which should be rigorously preserved to achieve long-term global sustainability. Although some soil is naturally enriched with heavy metals (HMs), a series of anthropogenic activities are known to contribute to their redistribution, which may entail potentially harmful environmental and/or human health effects if certain concentrations are exceeded. If this occurs, the implementation of rehabilitation strategies is highly recommended. Although there are many publications dealing with the elimination of HMs using different methodologies, most of those works have been done in laboratories and there are not many comprehensive reviews about the results obtained under field conditions. Throughout this review, we examine the different methodologies that have been used in real scenarios and, based on representative case studies, we present the evolution and outcomes of the remediation strategies applied in real soil-contamination events where legacies of past metal mining activities or mine spills have posed a serious threat for soil conservation. So far, the best efficiencies at field-scale have been reported when using combined strategies such as physical containment and assisted-phytoremediation. We have also introduced the emerging problem of the heavy metal contamination of agricultural soils and the different strategies implemented to tackle this problem. Although remediation techniques used in real scenarios have not changed much in the last decades, there are also encouraging facts for the advances in this field. Thus, a growing number of mining companies publicise in their webpages their soil remediation strategies and efforts; moreover, the number of scientific publications about innovative highly-efficient and environmental-friendly methods is also increasing. In any case, better cooperation between scientists and other soil-related stakeholders is still required to improve remediation performance.

Rio Tinto as a niche for acidophilus enzymes of industrial relevance.

Lignocellulosic residues are amongst the most abundant waste products on Earth. Therefore, there is an increasing interest in the utilization of these residues for bioethanol production and for biorefineries to produce compounds of industrial interest. Enzymes that breakdown cellulose and hemicellulose into oligomers and monosaccharides are required in these processes and cellulolytic enzymes with optimum activity at a low pH area are desirable for industrial processes. Here, we explore the fungal biodiversity of Rio Tinto, the largest acidic ecosystem on Earth, as far as the secretion of cellulolytic enzymes is concerned. Using colorimetric and industrial substrates, we show that a high proportion of the fungi present in this extremophilic environment secrete a wide range of enzymes that are able to hydrolyze cellulose and hemicellulose at acidic pH (4.5-5). Shotgun proteomic analysis of the secretomes of some of these fungi has identified different cellulases and hemicellulolytic enzymes as well as a number of auxiliary enzymes. Supplementation of pre-industrial cocktails from Myceliophtora with Rio Tinto secretomes increased the amount of monosaccharides released from corn stover or sugar cane straw. We conclude that the Rio Tinto fungi display a good variety of hydrolytic enzymes with high industrial potential.

Can microbiology help to make aviation more sustainable?

Production of sustainable aviation fuels (SAFs) using microbes still requires huge research efforts to fulfill the needs of aviation, both in the biological utilization of raw materials as well as in the biological processes to convert these materials (oils, sugars, aromatic compounds and others) into SAFs. However, we should also be aware of the microbiology constraints that, in some cases, will not allow us to reach the commercial level and that, by creating false expectations we will harm the credibility of microbiologists. However, in our opinion microbiologists can and should continue to find new avenues for producing SAFs, and for evaluating the advantages and feasibility of their production. This last step will require a close collaboration between researchers and industry.

Rare delayed cardiac tamponade in a pig after cardiac surgery.

OBJECTIVE: Delayed cardiac tamponade, a life-threatening complication of pericardial effusion in humans, has rarely been described in large animal models. We report here a pig with cardiac tamponade that developed 29 days after cardiac surgery. STUDY DESIGN: Case report. ANIMALS: One 45-kg domestic pig. METHODS: Open-chest surgery was performed on a pig to induce chronic heart failure. At 15 days after surgery, the pig's breathing appeared laboured; induced heart failure was considered the cause. Routine heart failure medications were administered. RESULTS: On day 28, the pig's status deteriorated. On day 29, echocardiography performed just before the pig's death showed a large pericardial effusion, mainly in the lateral and anterior walls of the right heart, with several fibre exudation bands. The right heart was severely compressed with an extremely small right ventricle. An emergency sternotomy was unsuccessful. Pathologic examination showed a severely thickened, fibrous pericardium. The pericardial sac was distended (up to 4.5 cm) and was full of dark brown, soft, friable material. Epicardial haemorrhage with a fresh, organised thrombus was noted in the pericardium. CONCLUSION: Delayed tamponade occurring at least 15 days after open-chest surgery is easy to misdiagnose or overlook in large animal models where attention is often focused on primary pathological model changes. To decrease mortality in animal models, researchers should be aware of potential complications and use the same level of follow-up monitoring of large animals as in clinical care.

CoVITEST: A Fast and Reliable Method to Monitor Anti-SARS-CoV-2 Specific T Cells From Whole Blood.

Cellular and humoral immune responses are essential for COVID-19 recovery and protection against SARS-CoV-2 reinfection. To date, the evaluation of SARS-CoV-2 immune protection has mainly focused on antibody detection, generally disregarding the cellular response, or placing it in a secondary position. This phenomenon may be explained by the complex nature of the assays needed to analyze cellular immunity compared with the technically simple and automated detection of antibodies. Nevertheless, a large body of evidence supports the relevance of the T cell's role in protection against SARS-CoV-2, especially in vulnerable individuals with a weakened immune system (such as the population over 65 and patients with immunodeficiencies). Here we propose to use CoVITEST (Covid19 anti-Viral Immunity based on T cells for Evaluation in a Simple Test), a fast, affordable and accessible in-house assay that, together with a diagnostic matrix, allows us to determine those patients who might be protected with SARS-CoV-2-reactive T cells. The method was established using healthy SARS-CoV-2-naïve donors pre- and post-vaccination (n=30), and further validated with convalescent COVID-19 donors (n=51) in a side-by-side comparison with the gold standard IFN-γ ELISpot. We demonstrated that our CoVITEST presented reliable and comparable results to those obtained with the ELISpot technique in a considerably shorter time (less than 8 hours). In conclusion, we present a simple but reliable assay to determine cellular immunity against SARS-CoV-2 that can be used routinely during this pandemic to monitor the immune status in vulnerable patients and thereby adjust their therapeutic approaches. This method might indeed help to optimize and improve decision-making protocols for re-vaccination against SARS-CoV-2, at least for some population subsets.

Can effective pedagogy be ensured in minimally invasive surgery e-learning?

INTRODUCTION: Effectiveness of e-learning diminishes without the support of a pedagogical model to guide its use. In minimally invasive surgery (MIS), this has been reported as a limitation when technology is used to deliver contents without a sound pedagogical background. MATERIAL AND METHODS: We describe how a generic pedagogical model, the 3D pedagogy framework, can be used for setting learning outcomes and activities in e-learning platforms focused on MIS cognitive skills. A demonstrator course on Nissen fundoplication was developed following the model step-by-step in the MISTELA learning platform. Course design was informed by Kolb's Experiential learning model. Content validation was performed by 13 MIS experts. RESULTS: Ten experts agreed on the suitability of content structuring done according to the pedagogical model. All experts agreed that the course provides means to assess the intended learning outcomes. CONCLUSIONS: This work showcases how a general-purpose e-learning framework can be accommodated to the needs of MIS training without limiting the course designers' pedagogical approach. Key advances for its success include: (1) proving the validity of the model in the wider scope of MIS skills and (2) raising awareness amongst stakeholders on the need of developing training plans with explicit, rather than assumed, pedagogical foundations. Abbreviations: MIS: minimally invasive surgery; TEL: technology enhanced learning.

Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol?

OBJECTIVE: as scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices. MATERIAL AND METHODS: prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images. RESULTS: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (p<001) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (p<001). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (p<001) than two-day-protocol (no significant results; p=0.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; p<001). CONCLUSIONS: most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful. In patients with joint prostheses, an increase in percentage variation above 9% obtained maximum sensitivity and negative predictive value.

Ultrastructural Adaptation of the Cardiomyocyte to Chronic Mitral Regurgitation.

Introduction: Mitral regurgitation (MR) imposes volume overload on the left ventricle (LV) and elevates wall stress, triggering its adverse remodeling. Pronounced LV dilation, minimal wall thinning, and a gradual decline in cardiac ejection fraction (EF) are observed. The structural changes in the myocardium that define these gross, organ level remodeling are not known. Cardiomyocyte elongation and slippage have both been hypothesized, but neither are confirmed, nor are the changes to the cardiomyocyte structure known. Using a rodent model of MR, we used immunohistochemistry and transmission electron microscopy (TEM) to describe the ultrastructural remodeling of the cardiomyocyte. Methods: Twenty-four male Sprague-Dawley rats (350-400 g) were assigned to two groups: group (1) rats induced with severe MR (n = 18) and group (2) control rats that were healthy and age and weight matched (n = 6). MR was induced in the beating heart using a 23-G ultrasound-guided, transapical needle to perforate the anterior mitral leaflet, and the rats were followed to 2, 10, and 20 weeks (n = 6/time-point). Echocardiography was performed to quantify MR severity and to measure LV volume and function at each time-point. Explanted myocardial tissue were examined with TEM and immunohistochemistry to investigate the ultrastructural changes. Results: MR induced rapid and significant increase in end-diastolic volume (EDV), with a 50% increase by 2 weeks, compared with control. Rise in end-systolic volume (ESV) was more gradual; however, by 20 weeks, both EDV and ESV in MR rats were increased by 126% compared with control. A significant decline in EF was measured at 10 weeks of MR. At the ultrastructural level, as early as 2 weeks after MR, cardiomyocyte elongation and increase in cross-sectional area were observed. TEM depicted sarcomere shortening, with loss of Z-line and I-band. Desmin, a cytoskeletal protein that is uniformly distributed along the length of the cardiomyocyte, was disorganized and localized to the intercalated disc, in the rats induced with MR and not in the controls. In the rats with MR, the linear registry of the mitochondrial arrangement along the sarcomeres was lost, with mitochondrial fragmentation, aggregation around the nucleus, and irregularities in the cristae. Discussion: In the setting of chronic mitral regurgitation, LV dilatation occured by cardiomyocyte elongation, which manifests at the subcellular level as distinct ultrastructural alterations of the sarcomere, cytoskeleton, and mitochondria. Since the cytoskeleton not only provides tensegrity but has functional consequences on myocyte function, further investigation into the impact of cytoskeletal remodeling on progressive heart failure or recovery of function upon correcting the valve lesion are needed.

Biochemical and Metabolic Plant Responses toward Polycyclic Aromatic Hydrocarbons and Heavy Metals Present in Atmospheric Pollution.

Heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) are toxic components of atmospheric particles. These pollutants induce a wide variety of responses in plants, leading to tolerance or toxicity. Their effects on plants depend on many different environmental conditions, not only the type and concentration of contaminant, temperature or soil pH, but also on the physiological or genetic status of the plant. The main detoxification process in plants is the accumulation of the contaminant in vacuoles or cell walls. PAHs are normally transformed by enzymatic plant machinery prior to conjugation and immobilization; heavy metals are frequently chelated by some molecules, with glutathione, phytochelatins and metallothioneins being the main players in heavy metal detoxification. Besides these detoxification mechanisms, the presence of contaminants leads to the production of the reactive oxygen species (ROS) and the dynamic of ROS production and detoxification renders different outcomes in different scenarios, from cellular death to the induction of stress resistances. ROS responses have been extensively studied; the complexity of the ROS response and the subsequent cascade of effects on phytohormones and metabolic changes, which depend on local concentrations in different organelles and on the lifetime of each ROS species, allow the plant to modulate its responses to different environmental clues. Basic knowledge of plant responses toward pollutants is key to improving phytoremediation technologies.