Physical activity shifts gut microbiota structure in aged subjects with overweight/obesity and metabolic syndrome.

We aimed to identify how physical activity (PA), within the context of a Mediterranean diet, affects metabolic variables and gut microbiota in older individuals with overweight/obesity and metabolic syndrome. Observational analysis was conducted as part of the PREDIMED-Plus study with 152 males and 145 females with overweight/obesity and metabolic syndrome. General assessments, anthropometric and biochemical measurements, and gut microbial 16S rRNA sequencing data were analyzed at baseline and 1-year of follow-up. Participants were stratified by tertiles of 1-year change in total PA-related energy expenditure ranging from -98.77 to 1099.99 METs (min/week). The total PA percentage of change was reduced in tertile 1 (-44.83 ± 24.94), increased in tertile 2 (28.96 ± 23.33) and tertile 3 (273.64 ± 221.42). Beta diversity analysis showed differences in the gut microbiota population within each tertile group. Significant differences were found at phylum, family, and genus levels in the gut microbiota of the three tertile groups at baseline and 1-year timepoint. Tertile 3, the group with the greatest increase in PA, was characterized by increases in their levels of Sutterella, Bilophila, and Lachnospira bacteria as well as a reduction in Collinsella. Moreover, this tertile showed a different pattern in its predicted metabolic capacities to the other groups. Our results have demonstrated that changes in PA such as lifestyle and Mediterranean diet induces specific variations in the gut microbiota profile. This modulation of gut microbiome populations and their metabolic capacities may contribute to the health of the aged individuals with overweight/obesity and metabolic syndrome.

Spatiotemporal dynamics of Ixodes ricinus abundance in northern Spain.

Ixodes ricinus is the most medically relevant tick species in Europe because it transmits the pathogens that cause Lyme borreliosis and tick-borne encephalitis. Northern Spain represents the southernmost margin of its main European range and has the highest rate of Lyme borreliosis hospitalisations in the country. Currently, the environmental determinants of the spatiotemporal patterns of I. ricinus abundance remain unknown in this region and these may differ from drivers in highly favourable areas for the species in Europe. Therefore, our study aimed to understand the main factors modulating questing I. ricinus population dynamics to map abundance patterns in northern Spain. From 2012 to 2014, monthly/fortnightly samplings were conducted at 13 sites in two regions of northern Spain to estimate spatiotemporal variation in I. ricinus questing abundance. Local abundance of I. ricinus was modelled in relation to variation in local biotic and abiotic environmental conditions by constructing generalised linear mixed models with a zero-inflated negative binomial distribution for overdispersed data. The different developmental stages of I. ricinus were most active at different times of the year. Adults and nymphs showed a peak of abundance in spring, while questing larvae were more frequent in summer. The main determinants affecting the spatiotemporal abundance of the different stages were related to humidity and temperature. For adults and larvae, summer seemed to be the most influential period for their abundance, while for nymphs, winter conditions and those of the preceding months seemed to be determining factors. The highest abundances of nymphs and adults were predicted for the regions of northern Spain with the highest rate of Lyme borreliosis hospitalisations. Our models could be the basis on which to build more accurate predictive models to identify the spatiotemporal windows of greatest potential interaction between animals/humans and I. ricinus that may lead to the transmission of I. ricinus-borne pathogens.

Nobody's land? The oldest evidence of early Upper Paleolithic settlements in inland Iberia.

The Iberian Peninsula is a key region for unraveling human settlement histories of Eurasia during the period spanning the decline of Neandertals and the emergence of anatomically modern humans (AMH). There is no evidence of human occupation in central Iberia after the disappearance of Neandertals ~42,000 years ago until approximately 26,000 years ago, rendering the region "nobody's land" during the Aurignacian period. The Abrigo de la Malia provides irrefutable evidence of human settlements dating back to 36,200 to 31,760 calibrated years before the present (cal B.P.) This site also records additional levels of occupation around 32,420 to 26,260 cal B.P., suggesting repeated settlement of this territory. Our multiproxy examination identifies a change in climate trending toward colder and more arid conditions. However, this climatic deterioration does not appear to have affected AMH subsistence strategies or their capacity to inhabit this region. These findings reveal the ability of AMH groups to colonize regions hitherto considered uninhabitable, reopening the debate on early Upper Paleolithic population dynamics of southwestern Europe.

Preliminary Screening on Antibacterial Crude Secondary Metabolites Extracted from Bacterial Symbionts and Identification of Functional Bioactive Compounds by FTIR, HPLC and Gas Chromatography-Mass Spectrometry.

Secondary metabolites, bioactive compounds produced by living organisms, can unveil symbiotic relationships in nature. In this study, soilborne entomopathogenic nematodes associated with symbiotic bacteria (Xenorhabdus stockiae and Photorhabdus luminescens) were extracted from solvent supernatant containing secondary metabolites, demonstrating significant inhibitory effects against E. coli, S. aureus, B. subtilus, P. mirabilis, E. faecalis, and P. stutzeri. The characterization of these secondary metabolites by Fourier transforms infrared spectroscopy revealed amine groups of proteins, hydroxyl and carboxyl groups of polyphenols, hydroxyl groups of polysaccharides, and carboxyl groups of organic acids. Furthermore, the obtained crude extracts were analyzed by high-performance liquid chromatography for the basic identification of potential bioactive peptides. Gas chromatography-mass spectrometry analysis of ethyl acetate extracts from Xenorhabdus stockiae identified major compounds including nonanoic acid derivatives, proline, paromycin, octodecanal derivatives, trioxa-5-aza-1-silabicyclo, 4-octadecenal, methyl ester, oleic acid, and 1,2-benzenedicarboxylicacid. Additional extraction from Photorhabdus luminescens yielded functional compounds such as indole-3-acetic acid, phthalic acid, 1-tetradecanol, nemorosonol, 1-eicosanol, and unsaturated fatty acids. These findings support the potential development of novel natural antimicrobial agents for future pathogen suppression.

Immune checkpoint inhibitors-associated thrombosis in patients with head and neck cancer: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS: /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identification of variables predictive of VTE/AT. RESULTS: A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no significant differences (p = 0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0-22.9) and the group that did not (median 9.86 months, 95% CI 6.3-13.4). The presence of liver metastases was predictive of VTE/AT (p < 0.05). CONCLUSIONS: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not significantly impact survival. The presence of liver metastases can predict these events.

Ionizable nanoemulsions for RNA delivery into the central nervous system - importance of diffusivity.

Lipid nanoparticles (LNPs) currently dominate the RNA delivery landscape; however their limited diffusivity hampers targeted tissue dissemination, and, hence, their capacity for intracellular drug delivery. This is especially relevant for tissues such as the central nervous system (CNS), where overcoming proactive brain barriers is crucial for the efficacy of genetic therapeutics. This research aimed to create ionizable nanoemulsions (iNEs), a new generation of RNA delivery systems with enhanced diffusivity. The developed iNEs (consisting of the combination of C12-200, DOPE, Vitamin E, and DMG-PEG) with a size below 100 nm, neutral surface charge, and high RNA loading capacity, showed excellent cell viability and transfection efficiency in various cellular models, including neurons, astrocytes, and microglia. Subsequently, iNEs containing mRNA GFP were tested for CNS transfection, highlighting their exceptional diffusivity and selective transfection of neurons following intra-parenchymal administration.

Characterizing Hepatitis Delta in Spain and the gaps in its management.

BACKGROUND AND AIMS: Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated HDV prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. METHOD: Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. RESULTS: We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. CONCLUSION: One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present.

Applications of the Methylotrophic Yeast Komagataella phaffii in the Context of Modern Biotechnology.

Komagataella phaffii (formerly Pichia pastoris) is a methylotrophic yeast widely used in laboratories around the world to produce recombinant proteins. Given its advantageous features, it has also gained much interest in the context of modern biotechnology. In this review, we present the utilization of K. phaffii as a platform to produce several products of economic interest such as biopharmaceuticals, renewable chemicals, fuels, biomaterials, and food/feed products. Finally, we present synthetic biology approaches currently used for strain engineering, aiming at the production of new bioproducts.

Internet Gaming Disorder and the Incidence of Suicide-Related Ideation and Behaviors in College Students.

OBJECTIVES: The longitudinal associations between DSM-5 Internet Gaming Disorder (IGD) and suicide-related ideation and behaviors have not been explored. In this study, we therefore seek to examine the association between baseline IGD and incident suicide ideation, plans, and attempts. METHODS: This is a prospective cohort study of 2586 Mexican college students followed up from September 2018 to June 2022. We estimated hazards ratios modeling incidence of suicide ideation, plans, and attempts by fitting proportional hazards Cox models with person-time scaled in years. RESULTS: Among 2140 students without suicide ideation at baseline, there were 467 incident cases in 3987.6 person-years; ideation incidence rates were 179 cases per 1000 person-years among students with IGD and 114 cases per 1000 person-years among those without IGD. Incidence rates for suicide plans were 67 and 39 per 1000 among IGD and non-IGD students, and 15 and 10 per 1000, respectively for attempts. After controlling for age, sex, and mood, anxiety, and substance use disorders, IGD was associated with an 83% increased risk of suicide ideation. Although incidence rate estimates for plans and attempts were higher among students with IGD, results were not statistically significant. CONCLUSIONS: This study helps to raise awareness of the increased risk of at least suicidal ideation in people experiencing IGD. Clinicians treating patients with IGD may encounter complaints of suicide ideation over time, and even reports of suicidal behavior that should not be disregarded. Identifying these patients and treating/referring them for underlying suicidality should form part of IGD treatment.

Acute Hepatitis in Children Due to Rat Hepatitis E Virus.

Two of 11 children with acute hepatitis of unknown origin were found to have rat hepatitis E virus infection. This infection should be considered in the differential diagnosis of children with acute hepatitis of unknown origin.

TwinsMX: Exploring the Genetic and Environmental Influences on Health Traits in the Mexican Population.

TwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and mental health traits among the country's population. With a multidisciplinary approach, TwinsMX aims to advance our knowledge of the genetic and environmental mechanisms underlying ethnic variations in complex traits and diseases, including behavioral, psychometric, anthropometric, metabolic, cardiovascular and mental disorders. With information gathered from over 2800 twins, this article updates the prevalence of several complex traits; and describes the advances and novel ideas we have implemented such as magnetic resonance imaging. The future expansion of the TwinsMX registry will enhance our comprehension of the intricate interplay between genetics and environment in shaping health and disease in the Mexican population. Overall, this report describes the progress in the building of a solid database that will allow the study of complex traits in the Mexican population, valuable not only for our consortium, but also for the worldwide scientific community, by providing new insights of understudied genetically admixed populations.

Developing an Approach for Integrating Chemical Analysis and Transcriptional Changes to Assess Contaminants in Water, Sediment, and Fish.

Pharmaceuticals in aquatic environments pose threats to aquatic organisms because of their continuous release and potential accumulation. Monitoring methods for these contaminants are inadequate, with targeted analyses falling short in assessing water quality's impact on biota. The present study advocates for integrated strategies combining suspect and targeted chemical analyses with molecular biomarker approaches to better understand the risks posed by complex chemical mixtures to nontarget organisms. The research aimed to integrate chemical analysis and transcriptome changes in fathead minnows to prioritize contaminants, assess their effects, and apply this strategy in Wascana Creek, Canada. Analysis revealed higher pharmaceutical concentrations downstream of a wastewater-treatment plant, with clozapine being the most abundant in fathead minnows, showing notable bioavailability from water and sediment sources. Considering the importance of bioaccumulation factor and biota-sediment accumulation factor in risk assessment, these coefficients were calculated based on field data collected during spring, summer, and fall seasons in 2021. Bioaccumulation was classified as very bioaccumulative with values >5000 L kg-1, suggesting the ability of pharmaceuticals to accumulate in aquatic organisms. The study highlighted the intricate relationship between nutrient availability, water quality, and key pathways affected by pharmaceuticals, personal care products, and rubber components. Prioritization of these chemicals was done through suspect analysis, supported by identifying perturbed pathways (specifically signaling and cellular processes) using transcriptomic analysis in exposed fish. This strategy not only aids in environmental risk assessment but also serves as a practical model for other watersheds, streamlining risk-assessment processes to identify environmental hazards and work toward reducing risks from contaminants of emerging concern. Environ Toxicol Chem 2024;00:1-22. © 2024 SETAC.

Bioactive Compounds from Organic Waste.

The reuse and reincorporation of waste are the principles of circular economies. Compost, biofuels, animal feed, dyes, and bioactive compounds can be obtained from the revaluation of organic waste. Research on this subject is scarce and limited to specific sectors, such as agriculture and agroindustry, leaving aside others that generate large quantities of organic waste, such as floriculture. The remains of these sectors have a low decomposition rate compared to other organic wastes. They are a source of bioactive compounds (e.g., essential oils, pigments, phenols) that can be reincorporated into the production chain of various industries. This review describes the composition of waste from agroindustry, agriculture, and floriculture, analyzing their potential revalorization as a source of bioactive compounds and an alternative supply source.

Non-HLA angiotensin-type-1 receptor autoantibodies mediate the long-term loss of grafted neurons in Parkinson's disease models.

BACKGROUND: Clinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host tissue, and alleviate motor symptoms in Parkinson´s disease (PD). In some patients, deterioration of graft function occurred several months after observing a graft-derived functional improvement. Rejection of peripheral organs was initially related to HLA-specific antibodies. However, the role of non-HLA antibodies is now considered also relevant for rejection. Angiotensin-II type-1 receptor autoantibodies (AT1-AA) act as agonists of the AT1 receptors. AT1-AA are the non-HLA antibodies most widely associated with graft dysfunction or rejection after transplantation of different solid organs and hematopoietic stem cells. However, it is not known about the presence and possible functional effects of AT1-AA in dopaminergic grafts, and the effects of treatment with AT1 receptor blockers (ARBs) such as candesartan on graft survival. METHODS: In a 6-hydroxydopamine PD rat model, we studied the short-term (10 days)- and long-term (3 months) effects of chronic treatment with the ARB candesartan on survival of grafted dopaminergic neurons and microglial graft infiltration, as well as the effects of dopaminergic denervation and grafting on serum and CSF AT1-AA levels. The expression of AT1 receptors in grafted neurons was determined by laser capture microdissection. RESULTS: At the early period post-grafting, the number of grafted dopaminergic neurons that survived was not significantly different between treated and untreated hosts (i.e., control rats and rats treated with candesartan), probably because, just after grafting, other deleterious factors are predominant for dopaminergic cell death, such as mechanical trauma, lack of growth factors/nutrients and ischemia. However, several months post-grafting, we observed a significantly higher number of surviving dopaminergic neurons and a higher density of striatal dopaminergic terminals in the candesartan-treated group. For several months, grafted rats showed blood and cerebrospinal fluid levels of AT1-AA higher than normal controls, and also higher AT1-AA levels than non-grafted parkinsonian rats. CONCLUSIONS: The results suggest the use of ARBs such as candesartan in PD patients, particularly before and after dopaminergic grafts, and the need to monitor AT1-AA levels in PD patients, particularly in those candidates for dopaminergic grafting.

Supportive care needs among older Mexican adults with metastatic cancer.

INTRODUCTION: Supportive care needs may vary according to age. The purpose of this research is to describe and compare supportive care needs between older adults with metastatic cancer (age ≥ 65 years) and their younger counterparts. MATERIALS AND METHODS: We conducted a retrospective secondary analysis of a cohort of patients with newly diagnosed metastatic solid tumors. Supportive care needs were assessed at baseline and at a three-month follow-up. Patients were divided into two groups (aged ≥65/<65 years). Differences in clinical characteristics and supportive care needs were compared utilizing descriptive statistics. Multivariate logistic regression models were employed to identify patient characteristics associated with specific supportive care needs. RESULTS: Between 2018 and 2022, 375 patients were enrolled. Median age was 66 years (interquartile range 19-94). At baseline, older adults had a higher number of supportive care needs (4.8 vs. 4.2, p = 0.01) and were at higher risk of malnutrition (75 vs. 65%, p = 0.05). Increasing age (odds ratio [OR] 1.02 (95% confidence interval [CI] 1.0-1.04, p = 0.03) and an estimated life expectancy <6 months (OR 3.0, 95%CI 1.5-6.1; p < 0.01) were associated with higher odds of malnutrition, while a higher educational level was associated with decreased odds (OR 0.68, 95%CI 0.5-0.8; p < 0.01). At three-month follow-up, older adults still had a higher number of supportive care needs (3.8 vs.2.6, p < 0.01) and were more likely to have fatigue (62 vs. 47%, p = 0.02). An estimated life expectancy of <6 months was associated with increased odds of fatigue (OR 3.0, 95%CI 1.5-6.3; p < 0.01). DISCUSSION: Older adults reported significantly more supportive care needs, particularly risk of malnutrition and fatigue. This information can help in the creation of supportive care services tailored to the needs of older individuals.

Evolutionary analysis of indeterminate cytology and risk of malignancy in a thyroid nodule unit.

OBJECTIVE: The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods. METHODS: 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006-2008, 2012-2014, 2017-2019). Distribution of diagnostic cytologies, risk of malignancy, diagnostic performance indices of FNA, and cytologic-histologic correlation in indeterminate cytologies were analyzed. RESULTS: only 2.2% of cytology tests were insufficient for a diagnosis. 86.9% cytologies were benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006-2008), 10.1% (2012-2014), and 10% (2017-2019). Surgery was performed in 13% of benign cytology, result-ing in malignant histology in 2.7%. All malignant and suspicious cytologies underwent surgery: malig-nancy confirmed in 98% and 77% of cases, respectively. All 'indeterminate with atypia' cytologies (2006-2008) and Bethesda IV (2012-2014; 2017-2019) un-derwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the 'inde-terminate without atypia' category (2006-2008) and Bethesda III (2012-2014; 2017-2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6% with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods. CONCLUSION: Bethesda system reduces indeterminate cytologies and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

Hypotension prediction index guided goal-directed therapy to reduce postoperative acute kidney injury during major abdominal surgery: study protocol for a multicenter randomized controlled clinical trial.

BACKGROUND: Acute kidney injury (AKI) is a significant postoperative complication associated with increased mortality and hospital costs. Hemodynamic strategies, such as goal-directed therapy, might reduce AKI risk. Predicting and proactively managing intraoperative hypotension may be helpful. This trial aims to investigate if a preemptive hemodynamic strategy guided by the hypotension prediction index (HPI) can decrease the incidence of moderate-to-severe AKI within 30 days following major elective abdominal surgery. METHODS: This is an open-label, controlled, multicenter, randomized clinical trial that involves daily patient follow-up until hospital discharge. Inclusion criteria are patients aged over 65 and/or categorized as ASA III or IV physical status, undergoing major elective abdominal surgery (general, urological, or gynecological procedures) via laparoscopic or open approach under general or combined anesthesia. INTERVENTION: In the intervention group, hemodynamic management will be based on the HPI and the advanced functional hemodynamic variables provided by the Hemosphere platform and the AcumenIQ® sensor (Edwards Lifesciences). The primary outcome is the incidence of moderate-to-severe AKI within 7 days post-surgery. Secondary outcomes include postoperative complications and 30-day mortality. DISCUSSION: This study explores the potential of HPI-guided hemodynamic management in reducing AKI after major elective abdominal surgery, with implications for postoperative outcomes and patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05569265. Registered on October 6, 2022.

Modelling the spatial risk of malaria through probability distribution of Anopheles maculipennis s.l. and imported cases.

Malaria remains one of the most important infectious diseases globally due to its high incidence and mortality rates. The influx of infected cases from endemic to non-endemic malaria regions like Europe has resulted in a public health concern over sporadic local outbreaks. This is facilitated by the continued presence of competent Anopheles vectors in non-endemic countries.We modelled the potential distribution of the main malaria vector across Spain using the ensemble of eight modelling techniques based on environmental parameters and the Anopheles maculipennis s.l. presence/absence data collected from 2000 to 2020. We then combined this map with the number of imported malaria cases in each municipality to detect the geographic hot spots with a higher risk of local malaria transmission.The malaria vector occurred preferentially in irrigated lands characterized by warm climate conditions and moderate annual precipitation. Some areas surrounding irrigated lands in northern Spain (e.g. Zaragoza, Logroño), mainland areas (e.g. Madrid, Toledo) and in the South (e.g. Huelva), presented a significant likelihood of A. maculipennis s.l. occurrence, with a large overlap with the presence of imported cases of malaria.While the risk of malaria re-emergence in Spain is low, it is not evenly distributed throughout the country. The four recorded local cases of mosquito-borne transmission occurred in areas with a high overlap of imported cases and mosquito presence. Integrating mosquito distribution with human incidence cases provides an effective tool for the quantification of large-scale geographic variation in transmission risk and pinpointing priority areas for targeted surveillance and prevention.

Systemic inflammatory Th1 cytokines during Trypanosoma cruzi infection disrupt the typical anatomical cell distribution and phenotypic/functional characteristics of various cell subsets within the thymus.

The thymus plays a crucial role in T cell differentiation, a complex process influenced by various factors such as antigens, the microenvironment and thymic architecture. The way the thymus resolves infections is critical, as chronic persistence of microbes or inflammatory mediators can obstruct the differentiation. Here, we illustrate that following inflammatory T helper 1 infectious processes like those caused by Candida albicans or Trypanosoma cruzi, single positive thymocytes adopt a mature phenotype. Further investigations focused on T. cruzi infection, reveal a substantial existence of CD44+ cells in both the cortical and medullary areas of the thymus at the onset of infection. This disturbance coincides with heightened interferon gamma (IFNγ) production by thymocytes and an increased cytotoxic capacity against T. cruzi-infected macrophages. Additionally, we observe a reduced exportation capacity in T. cruzi-infected mice. Some alterations can be reversed in IFNγ knockout mice (KO). Notably, the majority of these effects can be replicated by systemic expression of interleukin (IL)-12+IL-18, underlining the predominantly inflammatory rather than pathogen-specific nature of these phenomena. Understanding the mechanisms through which systemic inflammation disrupts normal T cell development, as well as subsequent T cell exportation to secondary lymphoid organs (SLO) is pivotal for comprehending susceptibility to diseases in different pathological scenarios.

Radiofrequency ablation as a novel modality in Ecuador for treating toxic thyroid nodules: a case series.

Background: Treating hyperthyroidism induced by autonomously functioning thyroid nodules (AFTNs) through radioactive iodine and surgery often results in undesirable hypothyroidism. Radiofrequency ablation (RFA) has arisen as a favorable option. European guidelines recommend RFA for small AFTN in young patients, aiming to restore normal thyroid function and avoid irradiation. The procedure, costing between 500 and 1,000 euros, is conducted in outpatient clinics and takes 15 to 40 minutes. We aimed to describe the clinical outcomes of AFTN patients treated with RFA in Ecuador. Case Description: We included eight patients with toxic thyroid nodules suppressed thyroid-stimulating hormone (TSH), with symptomatic hyperthyroidism. The mean age was 41.63 years [standard deviation (SD): 14.97 years]. The median follow-up time was 8 months. Nodules were solid (37.5%) or predominantly solid (62.5%). The mean volume pre-RFA was 5.27 mL [interquartile range (IQR), 0.70-9.66 mL]. After ablation, the median volumes at 1, 3, and 6 months were [2.25 (SD: 1.67; P<0.12), 1.28 (SD: 1.1; P=0.013), and 1.37 (SD: 1; P=0.23) mL], respectively. The volume reduction (VR) was 45.8%, 75.1%, and 69.7% at 1-, 3-, and 6-month follow-up, respectively. Conclusions: RFA holds promise as a potential therapeutic approach for managing AFTNs. The success and the feasibility of RFA in this series are consistent with other studies as a treatment option in young patients with small AFTN. However, more research is needed to establish comprehensive guidelines and protocols to maximize the benefits of RFA in AFTNs.