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.

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.

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.

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.

Mosquitoes in urban green spaces and cemeteries in northern Spain.

BACKGROUND: Mosquitoes inhabiting urban green spaces and cemeteries in Europe represent a crucial facet of public health concern and contribute to the ecological balance. As urbanization intensifies, these areas increasingly serve as vital habitats for various mosquito species, fostering breeding grounds and increasing the risk of disease transmission. METHODS: A study was conducted in the three main cities (inland, coastal, and estuarine) of the Basque Country, northern Spain, to investigate the species composition, abundance, dynamic populations, larval habitats, and host preferences of mosquitoes in urban green spaces and cemeteries. CDC traps and dipping were used to collect mosquitoes for 2 years (2019-2020). RESULTS: A total of 21 mosquito species were identified, with Culex pipiens s.l. being the most abundant and widespread. The three ecological forms of Cx. pipiens were found, and Cx. pipiens pipiens was the most common in both green areas and cemeteries. Morphological identification together with molecular tools identified 65 COI sequences with high homology. The highest species richness was found in the inland city, followed by the coastal city and the estuarine city. Mosquito abundance was significantly higher in green areas compared to cemeteries and in the coastal and estuarine cities compared to the inland city. The investigation of larval breeding sites highlighted the dominance of Cx. pipiens s.l., particularly in semi-artificial ponds, diverse water-holding containers (tyres and buckets) and drainage systems in green areas; in cemeteries, most of the larvae were found in flowerpots and funerary urns. Seasonal activity exhibited variable peaks in mosquito abundance in the different cities, with a notable increase in July or August. Additionally, blood meal analysis revealed that Cx. pipiens s.l. fed on several common urban avian species. CONCLUSIONS: Studies on mosquitoes are essential to understand their role in disease transmission and to design targeted and sustainable management strategies to mitigate the associated risks.

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.

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.

SLESIS-R: an improved score for prediction of serious infection in patients with systemic lupus erythematosus based on the RELESSER prospective cohort.

OBJECTIVE: To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort. METHODS: We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance. RESULTS: A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777-0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48. CONCLUSIONS: SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures.

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.

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.

Effects of exercise on life satisfaction of people diagnosed with cancer: a systematic review and meta-analysis.

PURPOSE: A cancer diagnosis is commonly associated with a decline in patient's life satisfaction and more pessimistic expectations about the future. The identification of strategies to improve life satisfaction in patients with cancer is of great interest to health practitioners since it may be associated with a better prognosis of cancer and higher survival rates. Previous meta-analyses and reviews concluded that exercise could significantly improve health-related quality of life in this population, but the effects of exercise on life satisfaction are still not well-known. This review aims to analyse the effects of exercise programs on life satisfaction in people with cancer and individuals who have overcome cancer. METHODS: The present systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A thorough search of databases including Web of Science and PubMed/MEDLINE was carried out. Six studies (535 participants) in which the effect of an exercise program was compared to a non-exercise program control condition in patients with cancer were considered eligible. A subsequent meta-analysis was performed using the random effects model to calculate the standardized mean differences (SMD) and 95% confidence intervals (CI). RESULTS: Exercise intervention improved satisfaction with life compared with a control condition (SMD = 1.28; p = 0.02 with a 95% CI of 0.22 to 2.34). CONCLUSION: Exercise could be considered an effective tool to improve life satisfaction in patients with cancer. Hence, professionals might consider the possibility of integrating physical exercise into strategies aimed at enhancing the low life satisfaction often experienced by patients. PROSPERO: CRD42023438146.

The role of the brain renin-angiotensin system in Parkinson´s disease.

The renin-angiotensin system (RAS) was classically considered a circulating hormonal system that regulates blood pressure. However, different tissues and organs, including the brain, have a local paracrine RAS. Mutual regulation between the dopaminergic system and RAS has been observed in several tissues. Dysregulation of these interactions leads to renal and cardiovascular diseases, as well as progression of dopaminergic neuron degeneration in a major brain center of dopamine/angiotensin interaction such as the nigrostriatal system. A decrease in the dopaminergic function induces upregulation of the angiotensin type-1 (AT1) receptor activity, leading to recovery of dopamine levels. However, AT1 receptor overactivity in dopaminergic neurons and microglial cells upregulates the cellular NADPH-oxidase-superoxide axis and Ca2+ release, which mediate several key events in oxidative stress, neuroinflammation, and α-synuclein aggregation, involved in Parkinson's disease (PD) pathogenesis. An intraneuronal antioxidative/anti-inflammatory RAS counteracts the effects of the pro-oxidative AT1 receptor overactivity. Consistent with this, an imbalance in RAS activity towards the pro-oxidative/pro-inflammatory AT1 receptor axis has been observed in the substantia nigra and striatum of several animal models of high vulnerability to dopaminergic degeneration. Interestingly, autoantibodies against angiotensin-converting enzyme 2 and AT1 receptors are increased in PD models and PD patients and contribute to blood-brain barrier (BBB) dysregulation and nigrostriatal pro-inflammatory RAS upregulation. Therapeutic strategies addressed to the modulation of brain RAS, by AT1 receptor blockers (ARBs) and/or activation of the antioxidative axis (AT2, Mas receptors), may be neuroprotective for individuals with a high risk of developing PD or in prodromal stages of PD to reduce progression of the disease.

Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial.

BACKGROUND: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood. OBJECTIVES: Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors. METHODS: A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota. RESULTS: Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors. CONCLUSIONS: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

Association of the rs1966265 and rs351855 FGFR4 Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico.

The aim of this study was to associate FGFR4 rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors (p < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group (p < 0.05). Associations were observed between the rs1966265 GA genotype and patients with rectal cancer and stage III-IV disease. The rs351855 AA genotype was a risk factor for partial chemotherapy response, and the GA + AA genotype for age ≥ 50 years at diagnosis and rectal cancer was associated with a partial response to chemotherapy (p < 0.05). The AA haplotype was associated with increased susceptibility to CRC. In silico analysis indicated that the rs351855 variant is likely pathogenic (score = 0.998). Genotypic expression analysis in blood samples showed statistically significant differences (p < 0.05). EFNA4, SLC3A2, and HNF1A share signaling pathways with FGFR4. Therefore, rs1966265 and rs351855 may be potential CRC risk factors.

Effects of exogenous application of MeJA and SA on the physiological and molecular response of 'Dusa' avocado to Rosellinia necatrix.

Methyl jasmonate (MeJA) and salicylic acid (SA) are important in mediating plant responses to abiotic and biotic stresses and can act as elicitors by triggering plant defense responses similar to those induced by pathogens and may even provide long-term protection against them. Thus, exogenous application of MeJA and SA could protect susceptible avocado plants against white root rot (WRR) disease caused by the necrotrophic fungus Rosellinia necatrix, one of the main diseases affecting avocado orchards. This work evaluates the effects of MeJA or SA on the physiological and molecular response of susceptible 'Dusa' avocado rootstock, and their ability to provide some protection against WRR. MeJA and SA application in avocado increased photoprotective mechanisms (NPQ) and upregulated the glutathione S-transferase, suggesting the triggering of mechanisms closely related to oxidative stress relief and reactive oxygen species (ROS) scavenging. In contrast to SA, MeJA effects were more pronounced at the morpho-anatomical level, including functional traits such as high leaf mass area (LMA), high stomatal density, high root/shoot ratio, closely related to strategies to cope with water scarcity and WRR disease. Moreover, MeJA upregulated a greater number of defense-related genes than SA, including a glu protease inhibitor, a key gene in avocado defense against R. necatrix. The overall effects of MeJA increased 'Dusa' avocado tolerance to R. necatrix by inducing a primed state that delayed WRR disease symptoms. These findings point towards the use of MeJA application as an environmentally friendly strategy to mitigate the impact of this disease on susceptible avocado orchards.

Partial-accelerated irradiation with stereotactic radiotherapy at a dose of 30 Gy in 5 fractions in early breast cancer.

PURPOSE: To evaluate feasibility of accelerated partial breast irradiation (APBI) using stereotactic radiotherapy (SBRT) Thirty Gy delivered in 5 fractions for patients with early breast cancer. METHODS: Between January 1st, 2018, and December 31s, 2022, we conducted 117 treatments for patients with early-stage breast cancer. All patients underwent conservative surgery followed by APBI using stereotactic external beam radiotherapy. We analyzed local, regional, distant control, overall survival, toxicity, and cosmetic outcomes. RESULTS: The average age was 62 years. 21.3% ductal and 78.7% invasive carcinomas. Regarding the PTV volume, the median was 198.8 cc (38-794 cc). Treatments were completed in all cases. The median follow-up period was of 21 months (1-62 months). Regarding acute toxicity, no Grade 3-4 toxicities were recorded. One patient experienced Grade 2 neuropathic pain. One patient developed subacute fibrosis and two patients developed telangiectasia as subacute and chronic toxicity. Cosmetic results were "good" or "very good" in 96.3% of cases. None of the patients relapsed at any level (local, regional, or distant) and overall survival during follow.up was 100%. CONCLUSION: APBI with SBRT 30 Gy in 5 fractions in early-stage breast cancer is a feasible technique, very-well tolerated and has excellent oncologic and cosmetic outcome during our follow-up period.

Brain-Thymus Connections in Chagas Disease.

BACKGROUND: The brain and the immune systems represent the two primary adaptive systems within the body. Both are involved in a dynamic process of communication, vital for the preservation of mammalian homeostasis. This interplay involves two major pathways: the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. SUMMARY: The establishment of infection can affect immunoneuroendocrine interactions, with functional consequences for immune organs, particularly the thymus. Interestingly, the physiology of this primary organ is not only under the control of the central nervous system (CNS) but also exhibits autocrine/paracrine regulatory circuitries mediated by hormones and neuropeptides that can be altered in situations of infectious stress or chronic inflammation. In particular, Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), impacts upon immunoneuroendocrine circuits disrupting thymus physiology. Here, we discuss the most relevant findings reported in relation to brain-thymic connections during T. cruzi infection, as well as their possible implications for the immunopathology of human Chagas disease. KEY MESSAGES: During T. cruzi infection, the CNS influences thymus physiology through an intricate network involving hormones, neuropeptides, and pro-inflammatory cytokines. Despite some uncertainties in the mechanisms and the fact that the link between these abnormalities and chronic Chagasic cardiomyopathy is still unknown, it is evident that the precise control exerted by the brain over the thymus is markedly disrupted throughout the course of T. cruzi infection.

The Cranium I: Neurocranium.

The Sima de los Huesos (SH) site has provided a significant collection of hominin remains, including numerous cranial fragments, which have contributed to our understanding of the MP human population. The taxonomic classification of the SH hominins remains a topic of debate, with some studies suggesting a close relationship to Neandertals based on nuclear DNA analysis. The cranial morphology of the SH specimens exhibits a mix of Neandertal-like features and primitive traits observed in earlier Homo populations, providing insights into the evolutionary pattern of the Neanderthal lineage. This study focuses on the neurocranial traits of the SH population and describes three previously undescribed cranial individuals. The SH cranial collection now comprises 20 nearly complete crania, representing approximately two-thirds of the estimated population size. The analysis of the SH population reveals variations in robustness, frontal torus development, sagittal keeling, and occipital torus morphology, which may be related to sexual dimorphism and ontogenetic factors. The suprainiac region exhibits notable ontogenetic changes, while suture obliteration patterns do not strictly correlate with dental age. Metric measurements, particularly cranial breadths, highlight significant intrapopulation variation within the SH sample. Compared with other Middle Pleistocene (MP) hominins, the SH cranial vault displays archaic characteristics but differs from Homo erectus and Neandertals. The SH individuals have relatively short and tall cranial vaults, distinguishing them from other MP fossils. These findings contribute to our understanding of the MP human populations and their evolutionary trajectories.

Coxiella burnetii infection persistence in a goat herd during seven kidding seasons after an outbreak of abortions: the effect of vaccination.

Coxiella burnetii infection was monitored during seven kidding seasons (2017-2023) in a dairy goat herd that after an outbreak of Q fever abortions was vaccinated with an inactivated phase I vaccine. Due to the high infection rate just after the outbreak, only the replacement stock was vaccinated during the first three kidding seasons, and when the average herd immunity had decreased (fourth kidding season onwards), the whole herd was vaccinated. Vaginal swabs, feces, and milk were analyzed by PCR to monitor infection, and dust and aerosols were analyzed to measure C. burnetii environmental contamination. One year after the onset of the outbreak, a significant reduction in C. burnetii shedding loads was observed, but the percentage of shedding animals remained high until the third kidding season. By the seventh kidding season, no shedders were detected. The bacterial load excreted was significantly lower in vaccinated compared with unvaccinated animals, and in yearlings compared with multiparous. C. burnetii was detected by PCR in aerosols collected inside the animal premises throughout the study period except in the last season; whereas, aerosols collected outdoors tested negative in the last three kidding seasons. Viable C. burnetii was detectable in environmental dust collected inside the barn until the third kidding season following the outbreak. These results indicate that after an outbreak of Q fever, the risk of infection for humans and susceptible animals can remain high for at least three kidding seasons when the number of C. burnetii animal shedders is still high, even when bacterial excretion is low. IMPORTANCE: Q fever is a zoonosis distributed worldwide. Ruminants are the main reservoir, and infection can cause high rates of abortion. After entering a farm, Coxiella burnetii infection can persist in the animal population over several lambing/kidding periods. Once infection is established in a herd, vaccination with the inactivated Phase I vaccine significantly reduces bacterial shedding, but although at low levels, excretion may continue to occur for several lambing/kidding seasons. The time that C. burnetii remains viable in the farm environment after an outbreak of Q fever determines the period when risk of infection is high for the people in close contact. This work showed that this period extends at least three kidding seasons after the outbreak. These results provided valuable information on the epidemiology of C. burnetii infection in goat herds and may help to develop guidelines for controlling the disease and reducing infection risk for susceptible people and animals.