Perturbed development of calb2b expressing dI6 interneurons and motor neurons underlies locomotor defects observed in calretinin knock-down zebrafish larvae.

Calcium binding proteins are essential for neural development and cellular activity. Calretinin, encoded by calb2a and calb2b, plays a role during early zebrafish development and has been proposed as a marker for distinct neuronal populations within the locomotor network. We generated a calb2b:hs:eGFP transgenic reporter line to characterize calretinin expressing cells in the developing spinal cord and describe morphological and behavioral defects in calretinin knock-down larvae. eGFP was detected in primary and secondary motor neurons, as well as in dI6 and V0v interneurons. Knock-down of calretinin lead to disturbed development of motor neurons and dI6 interneurons, revealing a crucial role during early development of the locomotor network. Primary motor neurons showed delayed axon outgrowth and the distinct inhibitory CoLo neurons, originating from the dI6 lineage, were absent. These observations explain the locomotor defects we observed in calretinin knock-down animals where the velocity, acceleration and coordination were affected during escapes. Altogether, our analysis suggests an essential role for calretinin during the development of the circuits regulating escape responses and fast movements within the locomotor network.

Preclinical characterization of a non-peptidomimetic HIV protease inhibitor with improved metabolic stability.

Protease inhibitors (PIs) remain an important component of antiretroviral therapy for the treatment of HIV-1 infection due to their high genetic barrier to resistance development. Nevertheless, the two most commonly prescribed HIV PIs, atazanavir and darunavir, still require co-administration with a pharmacokinetic boosting agent to maintain sufficient drug plasma levels which can lead to undesirable drug-drug interactions. Herein, we describe GS-9770, a novel investigational non-peptidomimetic HIV PI with unboosted once-daily oral dosing potential due to improvements in its metabolic stability and its pharmacokinetic properties in preclinical animal species. This compound demonstrates potent inhibitory activity and high on-target selectivity for recombinant HIV-1 protease versus other aspartic proteases tested. In cell culture, GS-9770 inhibits Gag polyprotein cleavage and shows nanomolar anti-HIV-1 potency in primary human cells permissive to HIV-1 infection and against a broad range of HIV subtypes. GS-9770 demonstrates an improved resistance profile against a panel of patient-derived HIV-1 isolates with resistance to atazanavir and darunavir. In resistance selection experiments, GS-9770 prevented the emergence of breakthrough HIV-1 variants at all fixed drug concentrations tested and required multiple protease substitutions to enable outgrowth of virus exposed to escalating concentrations of GS-9770. This compound also remained fully active against viruses resistant to drugs from other antiviral classes and showed no in vitro antagonism when combined pairwise with drugs from other antiretroviral classes. Collectively, these preclinical data identify GS-9770 as a potent, non-peptidomimetic once-daily oral HIV PI with potential to overcome the persistent requirement for pharmacological boosting with this class of antiretroviral agents.

Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study.

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.

Magnetic resonance spectroscopy in MELAS syndrome: correlation with CSF and plasma metabolite levels and change after glutamine supplementation.

PURPOSE: MELAS syndrome is a genetic disorder caused by mitochondrial DNA mutations. We previously described that MELAS patients had increased CSF glutamate and decreased CSF glutamine levels and that oral glutamine supplementation restores these values. Proton magnetic resonance spectroscopy (1H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare 1H-MRS of MELAS patients with controls, the 1H-MRS after glutamine supplementation in the MELAS group, and investigate the association between 1H-MRS and CSF lactate, glutamate, and glutamine levels. METHODS: We conducted an observational case-control study and an open-label, single-cohort study with single-voxel MRS (TE 144/35 ms). We assessed the brain metabolism changes in the prefrontal (PFC) and parieto-occipital) cortex (POC) after oral glutamine supplementation in MELAS patients. MR spectra were analyzed with jMRUI software. RESULTS: Nine patients with MELAS syndrome (35.8 ± 3.2 years) and nine sex- and age-matched controls were recruited. Lactate/creatine levels were increased in MELAS patients in both PFC and POC (0.40 ± 0.05 vs. 0, p < 0.001; 0.32 ± 0.03 vs. 0, p < 0.001, respectively). No differences were observed between groups in glutamate and glutamine (Glx/creatine), either in PFC (p = 0.930) or POC (p = 0.310). No differences were observed after glutamine supplementation. A positive correlation was found between CSF lactate and lactate/creatine only in POC (0.85, p = 0.003). CONCLUSION: No significant metabolite changes were observed in the brains of MELAS patients after glutamine supplementation. While we found a positive correlation between lactate levels in CSF and 1H-MRS in MELAS patients, we could not monitor treatment response over short periods with this tool. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04948138; initial release 24/06/2021; first patient enrolled on 1/07/2021. https://clinicaltrials.gov/ct2/show/NCT04948138.

Challenges in Psoriasis Research: A Systematic Review of Preclinical Models.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. METHODS: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. RESULTS: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. CONCLUSIONS: Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.

What can we learn from general practitioners who left Spain? A mixed methods international study.

BACKGROUND: International mobility of health workforce affects the performance of health systems and has major relevance in human resources for health policy and planning. To date, there has been little research exploring the reasons why general practitioners (GPs) migrate. This mixed methods study aimed to investigate the reasons why Spain-trained GPs migrate and develop GP retention and recruitment health policy recommendations relevant to Spanish primary care. METHODS: The study followed an explanatory sequential mixed methods study design combining surveys with semi-structured interviews and focus groups with GPs who qualified in Spain and were living overseas at the time of the study. The survey data examined the reasons why GPs left Spain and their intention to return and were analysed using quantitative methods. The transcripts from interviews and focus groups centred on GPs' insights to enhance retention and recruitment in Spain and were analysed thematically. RESULTS: The survey had 158 respondents with an estimated 25.4% response rate. Insufficient salary (75.3%), job insecurity and temporality (67.7%), excessive workload (67.7%), poor primary care governance (55.7%), lack of flexibility in the workplace (43.7%) and personal circumstances (43.7%) were the main reasons for leaving Spain. Almost half of the respondents (48.7%) would consider returning to Spanish general practice if their working conditions improved. Interviews and focus groups with respondents (n = 24) pointed towards the need to improve the quality of employment contracts, working conditions, opportunities for professional development, and governance in primary care for effective retention and recruitment. CONCLUSION: Efforts to improve GP retention and recruitment in Spain should focus on salary, job security, flexibility, protected workload, professional development, and governance. We draw ten GP retention and recruitment recommendations expected to inform urgent policy action to tackle existing and predicted GP shortages in Spanish primary care.

Radiological insights into rheumatoid meningitis - a rare central nervous system manifestation of rheumatoid arthritis: a retrospective review of six cases.

BACKGROUND: The objective is to analyze and review the clinical, laboratory, and neuroimaging characteristics of rheumatoid meningitis (RM) in six patients with known rheumatoid arthritis (RA). METHODS: We performed a retrospective review of patients diagnosed with RM from August 2012 to June 2023. To identify the cases, we used medical term search engines and the hospital´s radiology case database. Clinical information and laboratory findings were gathered from the medical records. A neuroradiologist with five years of experience reviewed and analyzed the RM to determine the characteristics findings of RM. RESULTS: Six patients with RM are included. Seizures along with headaches were among the clinical signs that were documented. All the patients had high levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (ACPA) in the peripheral blood. Biopsy in two cases confirmed typical rheumatoid nodules. Leptomeningeal enhancement was found bilaterally in all cases and was predominantly found in the frontoparietal region. "Mismatch DWI/FLAIR" was found in five patients. Bilateral subdural collections could be found in two patients. Brain PET scan revealed increased metabolism in two cases. CONCLUSION: Rheumatoid meningitis is a rare complication of rheumatoid arthritis (RA) with challenging clinical diagnosis due to non-specific symptoms. This study highlights the importance of MR in detecting characteristic neuroimaging patterns, including "mismatch DWI/FLAIR", to aid in early diagnosis. Increased awareness of this condition may facilitate timely intervention and improve prognosis. These results still need to be verified by large studies.

Exploring value creation in a virtual community of practice: a framework analysis for knowledge and skills development among primary care professionals.

BACKGROUND: Healthcare professionals traditional education reflects constraints to face the complex needs of people with chronic diseases in primary care settings. Since more innovative and practical solutions are required, Virtual Community of Practices (vCoP) seem to better respond to learning updates, improving professional and organizational knowledge. However, little is known about the value created in vCoPs as social learning environments. The objective of this project was to explore the value creation process of a gamified vCoP ("e-mpodera vCoP") aimed at improving the knowledge and attitudes of primary healthcare professionals (PCPs) (nurses and general practitioners) to the empowerment of people with chronic conditions. METHODS: A framework analysis assessed the value creation process using a mixed methods approach. The framework provided awareness about knowledge and usefulness in a learning community through five cycles: (1) immediate value, (2) potential value, (3) applied value, (4) realized value, and (5) reframing value. Quantitative data included vCoP analytics such as logins, contributions, points, badges, and performance metrics. Qualitative data consisted of PCPs' forum contributions from Madrid, Catalonia, and Canary Islands over 14 months. RESULTS: A total of 185 PCPs had access to the e-mpodera vCoPs. The vCoP showed the dynamic participation of 146 PCPs, along 63 content activities posted, including a total of 3,571 contributions (including text, images, links to webpages, and other files). Regarding the value creation process, the e-mpodera vCoP seems to encompass a broad spectrum of value cycles, with indicators mostly related to cycle 1 (immediate value - activities and interactions) and cycle 2 (potential value - knowledge capital); and to a lesser extent for cycle 3 (applied value - changes in practice) and for cycle 4 (realized value - performance improvement). The presence of indicators related to cycle 5 (reframing value), was minimal, due to few individual redefinitions of success. CONCLUSION: To reach a wider range of value possibilities, a combination of learning objectives, competence framework, challenged-based gamified platform, and pathway model of skill development seems crucial. However, additional research is required to gain clearer insights into organizational values, professionals' lifelong educational needs in healthcare, and the long-term sustainability of performance improvement. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02757781. Registered on 02/05/2016.

Medical deserts in Spain-Insights from an international project.

INTRODUCTION: Medical deserts are a growing phenomenon across many European countries. They are usually defined as (i) rural areas, (ii) underserved areas or (iii) by applying a measure of distance/time to a facility or a combination of the three characteristics. The objective was to define medical deserts in Spain as well as map their driving factors and approaches to mitigate them. METHODS: A mixed methods approach was applied following the project "A Roadmap out of medical deserts into supportive health workforce initiatives and policies" work plan. It included the following elements: (i) a scoping literature review; (ii) a questionnaire survey; (iii) national stakeholders' workshop; (iv) a descriptive case study on medical deserts in Spain. RESULTS: Medical deserts in Spain exist in the form of mostly rural areas with limited access to health care. The main challenge in their identification and monitoring is local data availability. Diversity of both factors contributing to medical deserts and solutions applied to eliminate or mitigate them can be identified in Spain. They can be related to demand for or supply of health care services. More national data, analyses and/or initiatives seem to be focused on the health care supply dimension. CONCLUSIONS: Addressing medical deserts in Spain requires a comprehensive and multidimensional approach. Effective policies are needed to address both the medical staff education and planning system, working conditions, as well as more intersectoral approach to the population health management.

NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer.

Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies.

Developing customized fuel models for shrub and bracken communities in Galicia (NW Spain).

Geospatial fire behaviour and fire hazard simulators, fire effects models and smoke emission software commonly use standard fuel models in order to simplify data collection and the inclusion of complex fuel scenarios. These fuel models are often mapped using remotely sensed data. However, given the great complexity of fuelbeds, with properties that vary widely in both time and space, the use of these standard fuel models can greatly limit accurate fuel mapping. This affects fuel hazard assessment, fuel reduction treatment plans, fire management decision-making and evaluation of the environmental impact of wildfire. In this study, we developed unique customized fire behaviour fuel models for shrub and bracken communities, by using k-medoids clustering analysis based on both fuel structural characteristics and potential fire behaviour. We used an original database of 722 destructive sample plots in nine different shrub and bracken communities covering the entire distribution area in Galicia (NW Spain), one of the regions in Europe most affected by forest fires. Measurements of cover, height and fuel fractions loads differentiated by size and vegetative state (live or dead) were used to estimate the potential rate of fire spread with five different models including fireline intensity, heat per unit area and the flame length for each sampling site and considering extreme environmental conditions. The optimal number of clusters was established by combining practical knowledge about the shrubland communities under study and their associated fire behaviour, with maximization of the mean value of the silhouette variable and minimization of the within-cluster sum of squares. The structural characteristics of the medoids derived from the analysis were associated with each of the proposed customized fuel models. Finally, a simple dichotomous classification based only on shrub height was developed to enable construction of spatially explicit fuel model maps based on remotely sensed data. Thus, the methodology applied allows generation of a more realistic representation of fuel distribution in the landscape, based on fuel structure measurements of natural regional ecosystems rather than on the use of standard models. We believe that the proposed methodology is generally applicable to communities composed of other shrub and fern species in different biogeographical regions.

Occurrence of Pseudomonas syringae pvs. actinidiae, actinidifoliorum and Other P. syringae Strains on Kiwifruit in Northern Spain.

Pseudomonas syringae pv. actinidiae (Psa), the agent causing bacterial canker of kiwifruit, has been present in the Principality of Asturias (PA), Northern Spain, since 2013, although with restricted distribution. In this study, 53 strains collected in kiwifruit orchards in PA during the period 2014-2020 were characterized by a polyphasic approach including biochemical and phylogenetic analysis. Thirty-three strains, previously identified by PCR as Psa, have been found to be a homogeneous group in phylogenetic analysis, which seems to indicate that there have been few introductions of the pathogen into the region. Two strains were confirmed as P. syringae pv. actinidifoliorum (Pfm), so this is the first report of Pfm in the PA. The remaining 18 strains were found to be close to P. avellanae and P. syringae pv. antirrhini or to strains described as Pfm look-alikes. Pathogenicity tests carried out on peppers with a selection of strains have shown that both Psa and Pfm caused clear damage, while the 18 atypical strains caused variable lesions. It would be necessary to carry out pathogenicity testing of atypical strains on kiwifruit plants to study the role of these strains in the kiwifruit pathosystem to evaluate their pathogenic potential in this crop.

The nature of training in flavor preference learning determines the underlying associative structure.

Pairing a palatable flavor (US) with an initially neutral flavor cue (CS) results in an acquired conditioned preference for the latter. Two main associations have been proposed to explain the acquisition of flavor preferences: Flavor-Flavor and Flavor-Nutrient learning. Although the hedonic reaction triggered by US consumption has also been suggested as a possible additional component underlying acquired flavor preference, this issue has received little attention. Here we explored whether the amount of training to the CS-US compound can favor the formation of a Flavor-Hedonic reaction association using rats as subjects and sucrose as the US. We expected that the more exposure to the CS-US compound, the stronger the S-R type association. Since S-R associations are not sensitive to devaluation procedures, we used a Sensory-Specific Satiety procedure to devalue the US after conditioning and then measured preferences for the CS. On Experiment 1 with a short restrictive training (classic procedure), preference for the CS was decreased after devaluation of the US compared to the control condition. On Experiment 2, with short unrestrictive training, preference for the CS was again weakened. Experiment 3 with a long unrestrictive training, rats expressed preference for the CS regardless of the devaluation procedure. These results suggest that, as with an instrumental paradigm, extensive training in flavor preference learning undermines the US devaluation effect.

Infantile Hemangioma in Infancy: A Case Study on the Natural Course and Therapeutic Management.

Infantile hemangiomas (IHs) are common benign vascular tumors that affect infants. In this case report, we detail the natural course of an IH in an infant monitored over four months without medical intervention, illustrating the benign progression and potential for spontaneous stabilization of such lesions. The aim was to observe changes in the size and morphology of the hemangioma, alongside the infant's overall health and developmental milestones, through regular clinical assessments. This case presented a challenge as the patient's parents lacked English fluency, lacked healthcare access, and had low socioeconomic status. It highlights the importance of individualized patient care, advocating for careful observation and restraint in the application of pharmacological treatments when clinically unnecessary. The report contributes to existing pediatric dermatology knowledge by emphasizing the natural benign behavior of IH and the need for a balanced approach to treatment decisions, ensuring safe and favorable long-term outcomes for patients.

Uncommon Etiologies of Acute Abdominal Pain: A Case Report on Omental Infarction.

Omental infarction is an uncommon cause of abdominal pain. The condition is often misdiagnosed due to its clinical similarity to more common abdominal pathologies like appendicitis and cholecystitis. This report presents the case of a 57-year-old female with a one-week history of left-sided abdominal pain, initially aggravated by eating and defecation. The patient, a long-term smoker with a complex medical history that includes deep vein thrombosis and pulmonary embolism, was hemodynamically stable on presentation. A CT scan revealed a nodular infiltration consistent with an omental infarct. Conservative management was pursued, resulting in symptom resolution by the third day of hospitalization. This case underscores the diagnostic challenges associated with omental infarction, particularly its differentiation from other causes of acute abdominal pain. It highlights the importance of considering rare etiologies in patients with atypical presentations and emphasizes the role of imaging, particularly CT scans, in accurate diagnosis. The patient's successful conservative management aligns with current recommendations, which advocate for non-surgical treatment in most cases. This approach avoids unnecessary surgical interventions and ensures a favorable prognosis with low complication rates in patients with prompt and appropriate management.

Surviving in a multistressor world: Gene expression changes in earthworms exposed to heat, desiccation, and chemicals.

An investigation of the effects of anthropogenic stress on terrestrial ecosystems is urgently needed. In this work, we explored how exposure to heat, desiccation, and chemical stress alters the expression of genes that encode heat shock proteins (HSPs), an enzyme that responds to oxidative stress (CAT), hypoxia-related proteins (HIF1 and HYOU), and a DNA repair-related protein (PARP1) in the earthworm Eisenia fetida. Exposure to heat (31°C) for 24 h upregulated HSPs and hypoxia-related genes, suggesting possible acquired thermotolerance. Desiccation showed a similar expression profile; however, the HSP response was activated to a lesser extent. Heat and desiccation activated the small HSP at 24 h, suggesting that they may play a role in adaptation. Simultaneous exposure to endosulfan and temperature for 7 h upregulated all of the evaluated genes, implicating a coordinated response involving multiple biological processes to ensure survival and acclimation. These results highlight the relevance of multistress analysis in terrestrial invertebrates.

Illuminating the Mysteries of the Smallest Birds: Hummingbird Population Health, Disease Ecology, and Genomics.

Hummingbirds share biologically distinctive traits: sustained hovering flight, the smallest bird body size, and high metabolic rates fueled partially by nectar feeding that provides pollination to plant species. Being insectivorous and sometimes serving as prey to larger birds, they fulfill additional important ecological roles. Hummingbird species evolved and radiated into nearly every habitat in the Americas, with a core of species diversity in South America. Population declines of some of their species are increasing their risk of extinction. Threats to population health and genetic diversity are just beginning to be identified, including diseases and hazards caused by humans. We review the disciplines of population health, disease ecology, and genomics as they relate to hummingbirds. We appraise knowledge gaps, causes of morbidity and mortality including disease, and threats to population viability. Finally, we highlight areas of research need and provide ideas for future studies aimed at facilitating hummingbird conservation.

Use of Transesophageal Echocardiography During Orthotopic Liver Transplantation: Simplifying the Procedure.

The intraoperative management of patients undergoing orthotopic liver transplantation (OLT) is influenced by the cardiovascular manifestations typically found in the context of end-stage liver disease, by the presence of concomitant cardiovascular disease, and by the significant hemodynamic changes that occur during surgery. Hypotension and intraoperative blood pressure fluctuations during OLT are associated with liver graft dysfunction, acute kidney failure, and increased risk of 30-d mortality. Patients also frequently present hemodynamic instability due to various causes, including cardiac arrest. Recent evidence has shown transesophageal echocardiography (TEE) to be a useful minimally invasive monitoring tool in patients undergoing OLT that gives valuable real-time information on biventricular function and volume status and can help to detect OLT-specific complications or situations. TEE also facilitates rapid diagnosis of life-threatening conditions in each stage of OLT, which is difficult to identify with other types of monitoring commonly used. Although there is no consensus on the best approach to intraoperative monitoring in these patients, intraoperative TEE is safe and useful and should be recommended during OLT, according to experts, for assessing hemodynamic changes, identifying possible complications, and guiding treatment with fluids and inotropes to achieve optimal patient care.

Exploring floral morphoanatomy and embryology in wild populations of Chrysolaena flexuosa (Vernonia, Asteraceae): a contribution to understanding its ornamental potential.

Chrysolaena flexuosa (Sims.) H. Rob. is a South American species in the tribe Vernonieae, with potential ornamental value: it has attractive inflorescences, is suitable for pot cultivation, and its cypselae are useful for dried flower arrangements. Apart from studies on the growth dynamics of this species under cultivation, chromosome number, DNA content, ploidy level, size, pollen viability, and the characterization of phenotypic and genetic variability, it is noteworthy that other aspects regarding the floral architecture, reproductive mode, and gametophyte formation of C. flexuosa have not yet been studied. For this reason, our study encompasses a floral morphoanatomical survey and a comprehensive assessment of gametophyte development in the species. As a result of this study, we report new floral morphotypes, confirming that the morphological variability of the species might be greater than speculated. The morphoanatomy of the androecium and gynoecium and the male and female gametophyte developmental characteristics are uniform in all the populations studied despite the different ploidy levels. Chrysolaena flexuosa has five tetrasporangiate stamens of the dicotyledonous type of development; all the populations studied displayed a unilocular inferior ovary with a single anatropous, unitegumented, and tenuinucellar ovule. Given that all the embryo sacs observed were of the Polygonum-type development regardless of the ploidy level, we infer that the populations analyzed are fertile and undergo sexual reproduction. Our results not only contribute further research in the field of breeding systems and propagation of this species, but also promote the successful introduction of C. flexuosa to the plant ornamental market.