Xunta de Galicia

In recent years, the gut microbiota and derived metabolites have emerged as relevant players in modulating several brain functions, including energy balance control1, 2–3. This form of distant communication mirrors that of metabolic hormones (for example, leptin, ghrelin), which convey information about the organism’s energy status by exerting effects on diverse brain regions, including the master homeostatic centre, the hypothalamus⁴. However, whether the hypothalamus is also able to influence gut microbiota composition remains enigmatic. Here we present a study designed to unravel this challenging question. To this aim, we used chemogenetics⁵ (to selectively activate or inhibit hypothalamic pro-opiomelanocortin or agouti-related peptide neurons) or centrally administered leptin or ghrelin to male mice. Subsequently, we conducted microbiota composition analysis throughout the gut using 16S rRNA gene sequencing. Our results showed that these brain interventions significantly changed the gut microbiota in an anatomical and short-term (2–4 h) fashion. Transcriptomic analysis indicated that these changes were associated with the reconfiguration of neuronal and synaptic pathways in the duodenum concomitant with increased sympathetic tone. Interestingly, diet-induced obesity attenuated the brain-mediated changes triggered by leptin in gut microbiota communities and sympathetic activation. Our findings reveal a previously unanticipated brain–gut axis that acutely attunes microbiota composition on fast timescales, with potential implications for meal-to-meal adjustments and systemic energy balance control.

Background Radioresistant tumours remain a challenge for conventional radiation therapy (RT), and often, only palliative treatment can be offered. Recently developed techniques, such as spatially fractionated radiation therapy (SFRT) could potentially improve treatment. However, current clinical SFRT implementations do not allow the full potential to be exploited. We further optimize SFRT, developing mini-GRID, which uses a flattening free filter accelerator. Methods The increase in normal tissue tolerances provided by mini-GRID compared to conventional RT and GRID therapy was validated in a rat model of brain irradiation in a longitudinal imaging study, behavioural tests and by histopathological evaluation. Results The implementation optimizes mini-GRID therapy, with beam widths around 2 mm². The peak-to-valley dose ratios and peak dose rates are around 4 and 7 Gy/min, respectively. Mini-GRID RT allows the use of high peak doses: 42 Gy in one fraction, a factor more than twice higher than the peak doses generally employed in conventional GRID therapy (20 Gy peak dose). This enables the use of more aggressive and potentially curative treatments. Infrared microspectroscopy analysis suggests different early biochemical changes in both modalities, with conventional RT leading to stronger modifications in the secondary protein structure, and higher oxidative damage than mini-GRID RT. Conclusions The possibility to treat both large and small tumours, and to perform safe and potentially curative dose escalations in previously untreatable cases, makes mini-GRID a promising approach to expand the clinical use of SFRT.

Adrenal mixed corticomedullary tumors (MCMTs) are rare lesions showing a mixture of two cell populations of cortical and medullary lineage. We describe an MCMT case presented in a 56-year-old woman with a history of arterial hypertension and high levels of aldosterone, accompanied by a review of the literature. The adrenalectomy specimen showed a well-circumscribed nodule of 30 mm in size, containing 60% of cells with a cortical phenotype (positive for α-inhibin and melan-A) and 40% of cells with a medullary phenotype (positive for chromogranin-A, GATA-3 and somatostatin receptor 2). There was no significant mitotic activity, necrosis, nor lymphovascular invasion. The GNAS p.(Arg844Cys) mutation, as well as variants of uncertain significance AKAP13 p.(His641Pro) and EPAS1 p.(Ser478del) were detected in the tumor. MCMT is more common in women (75%) with a mean age of 46.6 years (range 16–78). Most patients present with hypertension (79%), frequently associated with Cushing’s syndrome, (39%), diabetes (21%), aldosteronism (15%), and/or hyperandrogenism (6%). Laboratory data showed elevated levels of both cortisol and cathecholamines and/or their metabolites in more than 50% of cases, supporting the dual nature of the tumor. Most MCMTs are benign, but aggressive behavior was detected in four (12%) cases, all of them showing large size (80–220 mm), poor delimitation, venous invasion, necrosis, and/or high proliferation rates. The pathogenesis is unknown, but our findings suggest a tumor histogenesis from the cortical cellular component through the regulation of the protein kinase A pathway and secondary proliferation of the medullary component.

Simple Summary This study investigates how heat stress (HS) affects milk production, composition, and somatic cell count in Holstein cows in Galicia. The researchers used the temperature-humidity index (THI) to assess the climate conditions over several years (2016–2021) and their impact on dairy farming. The study found that when the THI exceeded certain thresholds, milk production decreased, and the quality of milk—especially its protein and fat content—was significantly affected. For example, for every unit increase in THI above the critical level, cows can lose up to 0.249 kg of milk per day. This shows that heat stress has a more pronounced effect on the composition of the milk than its volume. The impact of heat stress can last between 7 and 12 days and become more harmful if heat stress is accumulated over consecutive days, particularly for cows in the middle of their lactation cycle. While Galicia’s climate is milder than other regions, even moderate heat stress during the warmer months leads to substantial economic losses in the dairy sector. These findings emphasise growing concerns over climate change, as rising temperatures could further exacerbate the challenges faced by the dairy industry, highlighting the need for strategies to protect livestock and ensure sustainable milk production.

Background The clinical characterisation of SDHAF2-related familial paraganglioma syndrome remains elusive. The aim of this study is to contribute to the knowledge of this syndrome with valuable new information. Methods A total of 56 individuals with the p.(Gly78Arg) variant in the SDHAF2 gene were prospectively evaluated. Of the 33 subjects who developed paragangliomas (PGLs)/phaeochromocytomas (PCs) throughout follow-up, clinical, biochemical and imaging data were collected. [68Ga]Ga-DOTA-TOC and [18F]DOPA PET/CT scans were carried out on a subset of 22 patients with PGLs/PCs to compare their accuracy and surgical specimens (n=13) were microscopically evaluated to elucidate their potential malignant behaviour. Results Of the 33 patients (58.9%) with SDHAF2-related tumours, 17 (51.5%) were women, with a mean age at diagnosis of 38.6±17.2 years. Tumour development was found to be inherited paternally in all subjects. All the patients evaluated except one showed head and neck PGLs. Eleven patients (33.3%) showed mediastinal and abdominal extra-adrenal PGLs and two patients presented PCs. Multifocality was observed in 26 subjects (78.8%). Sixteen patients (48.5%) were asymptomatic at diagnosis. Only four patients with PGLs/PCs showed normetanephrine or 3-methoxytyramine secretion. Metastatic disease was observed in two patients (6.1%). GAPP score was ≥3 in 84.6% of tumours and PASS was ≥4 in 69.2%. [68Ga]Ga-DOTA-TOC PET/CT showed a greater detection rate (95.7%) of multifocal PGLs and metastatic lesions than [18F]DOPA PET/CT (79.3%), as well as higher mean SUVmax. Conclusions The current study offers new insights into the phenotypic characterisation of SDHAF2-related paraganglioma syndrome including the development of extra-cervical PGLs and metastatic transformation.

Glioblastoma multiforme (GBM) continues to be a hopeless case today. Its treatment involves the use of multiple modalities. One of them is radiation therapy (RT), that is limited by normal tissue tolerances in GBM patients. GBM is widely recognized to induce local and systemic immunosuppression, which is a hindrance to the use of immune-modulating therapies. One possible strategy is to ally immunotherapy (IT) with novel RT approaches able to revert the immunosuppressive nature of GBM. One example is minibeam radiation therapy (MBRT). Preclinical experiments have shown that MBRT leads to a remarkable widening of the therapeutic window for GBM and elicits an effective immune priming. The main hypothesis of this study is that the activation of the immune system by MBRT would synergize with IT enhancing tumour control and minimizing toxicities. To validate it, in vivo experiments in a glioma rat model were performed. The goal was to assess the gain in survival of animals treated with MBRT, MBRT plus an immune check point inhibitor (ICI) versus conventional RT (CRT) or ICI alone. All treatments (ICI alone, CRT, CRT + ICI, MBRT and MBRT + ICI) increased survival with respect to the non-irradiated controls. However, the high radiation dose (30 Gy) delivered in one fraction in CRT is highly detrimental for normal tissues contrary to MBRT. The combination of CRT plus ICI appeared to be toxic. MBRT + ICI surpassed the survival rate with respect to ICI alone. When ICI was used with high-dose conventional irradiation, tumor eradication was observed in 6 out 8 animals. However, the survival was statistically equivalent to MBRT plus ICI, with a tendency to reduce survival in comparison with CRT alone, suggesting acute toxicity associated with this multimodal treatment. In conclusion, our results suggest some advantages for MBRT in combination with ICI. We need to conduct further work to determine the optimal RT-IT combination and schedule for ICI injection and MBRT irradiation.

Despite remarkable advances, radiation therapy (RT) remains inefficient for some bulky tumors, radioresistant tumors, and certain pediatric tumors. Minibeam radiation therapy (MBRT) has emerged as a promising approach, reducing normal tissue toxicity while enhancing immune responses. Preclinical studies using X-rays and proton MBRT have demonstrated enhanced therapeutic index for aggressive tumor models. Combining MBRT’s advantages of spatial dose fractionation with the physical and biological benefits of carbon ions could be a step further toward unleashing the full potential of MBRT. This study aims to perform the first in vivo study of local and systemic responses of a subcutaneous mouse osteosarcoma (metastatic) model to carbon MBRT (C-MBRT) versus conventional carbon ion therapy (CT). Irradiations were conducted at the GSI Helmholtz Centre in Germany using 180 MeV/u ¹²C ions beam. All irradiated animals received an average dose (20 Gy) and displayed a significant and similar tumor growth delay in addition to a decreased metastasis score compared to the non-irradiated group. In the C-MBRT group, 70% of the tumor volume received the valley dose, which is a very low dose of 1.5 Gy. The remaining 30% of the tumor received the peak dose of 105 Gy, resulting in an average dose of 20 Gy. These results suggest that C-MBRT triggered distinct mechanisms from CT and encourage further investigations to confirm the potential of C-MBRT for efficient treatment of radioresistant tumors.

Objective: To assess the efficacy of a low-cost, Do-It-Yourself training material for emergency call simulation training, compared to a more traditional approach. Methods: A quasi-experimental design without pre-test was used. A final sample of 762 schoolchildren, aged three to twelve years, received two training programmes. The control group (C-G) received training using an adult dummy and an authentic smartphone (336 schoolchildren). The experimental group (ICall-G) was trained using a stuffed toy and the ICalled-DIY device, a low-cost simulation consisting of three sheets of paper held together by a ring that simulates a smartphone. The 20 min training was delivered by a nurse using a didactic–demonstration–simulation methodology. The evaluation consisted of a simulation scenario, in which participants had to identify the emergency and make a call and were then evaluated with a checklist. Results: No statistically significant differences were observed between the two groups in unlocking the phone (ICall-G: 84% vs. C-G: 83%; p = 0.78) or dialling 112 to make the call (ICall-G: 91% vs. C-G: 91%; p = 0.89). Hands-free activation in ICall-G was significantly higher (81%) compared to C-G (54%) (p < 0.001). At the pre-primary level, results were lower than those observed in primary education, with minimal differences between the first cycle of primary education and subsequent cycles. Conclusions: The use of a practical, low-cost and adapted tool for emergency call instruction was found to be comparable to a conventional approach. In addition, the use of the ICalled-DIY device was found to be more effective in facilitating the understanding of hands-free activation.

Economic sectors that drive nature decline are heavily subsidized and produce large environmental externalities, for which calls are increasing to reform or eliminate subsidies and internalize the environmental costs of these sectors. We compile data on subsidies and externalities across six key sectors linked to biodiversity loss— agriculture, fossil fuels, forestry, infrastructure, fisheries and aquaculture, and mining. The most updated estimates suggest that subsidies to these sectors total between US$1.7 and US$ 3.2 trillion annually, while environmental externalities range between US$10.5 and US$ 22.6 trillion annually. Moreover, data gaps suggest that these figures underestimate the global magnitude of subsidies and externalities. We discuss the need and opportunities of building a baseline counting the costs of subsidies and externalities of economic activities driving nature decline. A better understanding of the complexity, size, design, and effects of subsidies and externalities of economic sectors contributing to environmental degradation could facilitate and expedite discussions to strengthen multilateral rules.

Initial teacher education must envisage spaces that provide students with opportunities to experience a collaborative culture during their training, promoting the acquisition of cross-curricular competencies and the comprehension of links between theory and practice, and encouraging the integration of a gender perspective in educational practices. Through an interdisciplinary project in which three subjects of the teaching degree in primary education were involved, students produced a theatrical show for children. Although this type of practice is not frequent in the Spanish university context, the results suggest that implementing projects of this kind provides multiple benefits for the participants. The development of basic and cross-curricular competencies, such as collaboration, teamwork, adaptability, communication and creativity, are underscored. Furthermore, very enriching synergies are created between the different fields of knowledge that favour the development of a holistic and globalized education.

Background Breast cancer is the leading cause of female cancer mortality worldwide, accounting for 1 in 6 cancer deaths. Surgery, radiation, and systemic therapy are the three pillars of breast cancer treatment, with several strategies developed to combine them. The association of preoperative radiotherapy with immunotherapy may improve breast cancer tumor control by exploiting the tumor radio‐induced immune priming. However, this requires the use of hypofractionated radiotherapy (3 × 8 Gy), increasing the risk of toxicity. Mini‐GRID therapy (mini‐GRT) is an innovative form of spatially fractionated radiation therapy (SFRT) characterized by narrow beam widths between 1 to 2 mm that promises a significant increase in normal tissue dose tolerances and could thereby represent a new alternative for preoperative breast cancer treatment. Mini‐GRT has been successfully implemented at the Hospital de Santiago de Compostela (Spain) with a flattening filter‐free LINAC (megavoltage x‐rays). Purpose In this dosimetry proof‐of‐concept study, we evaluate the feasibility of photon mini‐GRT for preoperative breast cancer treatment. We also assess the clinical potential of mini‐GRT and compare it with the current treatment standard of intensity‐modulated radiotherapy (IMRT). Methods Seven unbiased breast cancer dosimetries of patients treated with stereotactic body radiotherapy (SBRT) (3 × 8 Gy, IMRT) were selected for the study. Photon mini‐GRT was compared with SBRT using three main criteria: (i) the dose to organs at risk (OARs), (ii) the dose constraints dictated by normal tissue tolerance, and (iii) the lateral penumbra in OARs. Tumor coverage was evaluated in terms of normalized total dose at 8 Gy‐fractions. The optimized SBRT by IMRT was realized at the Institut Curie, Paris, France. The dose in mini‐GRT was calculated by means of Monte Carlo simulations based on the mini‐GRT implementation realized at the University Hospital in Santiago de Compostela. Results Compared to SBRT plans, mini‐GRT resulted in a reduction of the mean dose to the lungs, heart, chest wall, and lymph nodes in the studied cases by a factor ranging from 50% to 100%. Additionally, valley, mean, and peak doses to normal tissues meet the dose tolerance limits for the considered OARs, the most challenging of all being the skin. The mean dose to the skin was reduced (20%–60% less) for most of the studied cases. Mini‐GRT also yielded sharper lateral penumbras in the skin and lungs (size reduced by at least 50%). Similar tumor integral doses were obtained for the two treatment modalities. Conclusion Mini‐GRT with megavoltage x‐rays is an innovative treatment approach already implemented in a clinical context. In this proof‐of‐concept study, we evaluated mini‐GRT for partial breast cancer irradiation, demonstrating its potential for preoperative treatment thanks to the high skin and normal tissue‐sparing capabilities. These initial results represent a first step towards clinical use and encourage further prospective clinical studies.

The veal niche market is gaining momentum in Brazil. Locally known as ‘Vitelão’, veal refers to the meat from calves slaughtered up to 12 months of age. In this study, we assessed the Galician Blond × Nelore cross as a candidate to produce veal. The aim of this study was to establish criteria for selecting 12-month-old calves suitable for slaughter. To find the best fit, we adjusted various growth models for calves up to 12 months of age. Once the best fit was determined, the selected growth model was then used to calculate the relative and instantaneous growth rates to evaluate the slaughtering potential at 12 months. Our study reveals that, under present conditions, the Logistic model is the best fit for characterizing and functionally analyzing growth from birth to 12 months of age in Galician Blond crosses with Nelore. Calves resulting from this cross experience rapid growth in their first 12 months of life, making them an excellent choice for producing high-quality veal while maintaining rusticity and adaptability to extreme environments. The results of this study could contribute to enhancing the growth management systems of Galician Blond and Nelore crosses in Brazilian grazing production systems. Additionally, they can be incorporated into genetic improvement programs as a tool for selecting animals with greater precocious growth without altering adult weight.

Coastal wetlands are vital habitats for human well-being because their ecosystem services are affected by multiple factors. In the quest to reduce the vulnerability of these valuable ecosystems for human beings, education is fundamental to facilitate analysis and answer questions. This paper presents an educational experience of the economic evaluation of El Culebrón Wetland (Coquimbo, Chile) to support decision-makers with new tools and arguments. Real-world experimentation was necessary to stimulate reflection in graduate students on complex problems and proposed solutions that challenged them to consider the different variables and beliefs involved in ecosystem services to put economic theory into practice. A study was developed based on an interdisciplinary educational experience based on two non-conventional methods of economic valuation: Contingent Valuation (CV) and Defensive Expenditure estimation (DE). The results of the 20-year valuation were US$5,750,000 (CV) and US$ 3,050,009 (DE). This experience is innovative and promising, allowing the estimation of the economic value of wetlands and reflecting on the opportunities and complexities involved in applying these methodologies. The study concludes that ethical questions were faced from the perspective of balancing economic, social, and environmental issues in pursuing sustainable development.

A bstract We study the production of a quark-antiquark antenna in the presence of a dense and anisotropic QCD medium. We assume the antenna to originate from an unpolarized gluon state, and consider both massless and massive final states. The medium anisotropy is captured by allowing the jet quenching coefficient to take different magnitudes in orthogonal directions with respect to the jet axis. We find that the final particle distribution is sensitive to the medium anisotropy, and more importantly, that this effect couples directly to the helicity/spin of the final states. We propose to look into these effects by performing a Fourier decomposition of the particle distribution inside the jet. In our medium model, we find that the spin independent terms contribute to the even harmonics of the cosine series. The helicity/spin dependence enters only through the sine Fourier series. We further explore the spin dependence by examining the degree of polarization of the final states in different directions. Our results indicate that the anisotropies present in the QCD matter produced in heavy ion collisions can be probed by studying azimuthal and spin observables inside jets.

The use of incretin agonists for managing metabolic dysfunction-associated steatohepatitis (MASH) is currently experiencing considerable interest. However, whether these compounds have a direct action on MASH is still under debate. This study aims to investigate whether GLP-1R/GIPR agonists act directly in hepatocytes and hepatic stellate cells (HSCs). For this, human hepatocyte and HSCs lines, as well as primary human hepatocytes and HSCs treated with Liraglutide, Acyl-GIP or the GLP-1/GIP dual agonist (MAR709) were used. We show that the concentrations of each compound, which were effective in insulin release, did not induce discernible alterations in either hepatocytes or HSCs. In hepatocytes displaying elevated fatty acid content after the treatment with oleic acid and palmitic acid, none of the three compounds reduced lipid concentration. Similarly, in HSCs activated with transforming growth factor-β (TGFb), Liraglutide, Acyl-GIP and MAR709 failed to ameliorate the elevated expression of fibrotic markers. The three compounds were also ineffective in phosphorylating CREB, which mediates insulinotropic actions, in both hepatocytes and HSCs. These findings indicate that incretin agonists have no direct actions in human hepatocytes or hepatic stellate cells, suggesting that their beneficial effects in patients with MASH are likely mediated indirectly, potentially through improvements in body weight, insulin resistance and glycemic control.

Over the past twenty years, brand communication strategies have evolved, particularly for younger audiences, with formats that blend advertising and entertainment content, often featuring influencers. This style of advertising presents challenges, notably the difficulty minors face in recognizing the commercial intent of messages. This article explores minors’ awareness and understanding of these advertising techniques, along with their moral and evaluative responses. We conducted 35 in-depth online interviews with minors aged 10–14 years in Spain. The findings reveal that recognition and understanding of such advertising increase with age. Although minors are accustomed to these practices, their primary reaction is indifference. The study emphasizes the importance of enhancing minors’ critical capacities to better navigate hybrid messages on social networks.

Spanish pear germplasm collections are crucial for preservation, research, and breeding efforts. However, genetic diversity and structure is unknown at national level. A coordinated national project analyzed 1251 accessions from 7 Spanish pear collections using an internationally recognized set of 14 SSRs to enhance the utilization of these collections. Key findings included the identification of 760 unique genotypes (490 diploids and 270 triploids). Notably, genotypes represented by a single accession accounted for 49% of the total, indicating high vulnerability of this material. Using a Bayesian clustering method revealed two main genetic groups, G1 containing most foreign cultivars and G2 retaining local Spanish cultivars, which were further divided into two other subgroups using a nested approach, revealing moderate but significant differentiation among them. The populations were renamed according to the origin of the reference samples assigned to each group as ‘South’ (G1.1), ‘Western Europe-1’ (G1.2), ‘Western Europe-2’ (G2.1) and ‘No-Pyrus communis’ (G2.2). The results led to the creation of a ‘generalist’ collection, aiming to maximize genetic diversity representativeness, starting with 68 genotypes but expanding to 111 to achieve better allele recovery. This core collection is a valuable resource for genetic studies and conservation, enhancing efforts to preserve pear biodiversity. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-77532-1.

We describe all Lorentzian semi-direct extensions of the Heisenberg group which are conformally Einstein. As a by side result, Bach-flat left-invariant Lorentzian metrics on semi-direct extensions of the Heisenberg group are classified, thus providing new background solutions in conformal gravity.