Leptin/Ghrelin Axis and Antibodies Reactive to Both Hormones in Relation to Metabolic Syndrome Components in Mexican Children.

Background: Metabolic syndrome (MetS) in children is a rising health issue that is strongly associated with cardiovascular diseases and type 2 diabetes mellitus development. Low-affinity antibodies reactive to leptin and ghrelin are suggested to regulate hormone stability and function; nevertheless, the role of the leptin/ghrelin axis and antibodies reactive to both hormones in relation to MetS or its components in the pediatric population remains unknown. Methods: Fifty-eight children (7-12 years) were included and categorized according to the presence of one or more criteria for the diagnosis of MetS or according to body mass index. Body composition, biochemical variables, and metabolic risk indexes were determined. Antibodies reactive to leptin and ghrelin were quantified by an in-house enzyme-linked immunosorbent assay test. Ratios of leptin/ghrelin hormones and anti-leptin/anti-ghrelin immune complexes were obtained. Results: The biochemical variables glucose (P = 0.0009), insulin (P = 0.0001), leptin (P = 0.0036), HOMA-IR (homeostatic model assessment for insulin resistance) (P < 0.0001), and plasma atherogenic index (P < 0.0001) were significantly higher in children with two or three components of MetS (MetS 2-3) in comparison to children with none or one component (MetS 0-1). Ratios of leptin/ghrelin (P = 0.0307) and anti-leptin/anti-ghrelin immune complexes (P = 0.0338) were higher in MetS 2-3 group versus MetS 0-1 group. In MetS 2-3 group, both insulin (r = 0.4361, P = 0.0293) and HOMA-IR (r = 0.4761, P = 0.0161) were positively correlated with the leptin/ghrelin hormone ratio. Conclusions: The higher leptin/ghrelin hormone ratio scores observed in MetS 2-3 group, along with their correlation with insulin levels and HOMA-IR, highlight the role of leptin and ghrelin on insulin sensitivity and metabolic regulation. An increased ratio of anti-leptin/anti-ghrelin immune complexes suggests affinity changes in these antibodies that may lead to alterations in hormone function.

Association Between Baseline Macular Morphologic Features on Optical Coherence Tomography and Visual Outcomes in Patients with Vogt-Koyanagi-Harada Disease.

PURPOSE: The choroidal thickening and serous retinal detachments that characterize Vogt-Koyanagi-Harada (VKH) disease can be imaged in detail using spectral domain optical coherence tomography (SD-OCT). Whether specific qualitative and quantitative SD-OCT features at presentation were associated with visual outcomes in a randomized controlled trial comparing methotrexate to mycophenolate for steroid-sparing control of uveitis were evaluated. METHODS: An exploratory subanalysis of data from the FAST trial in which SD-OCT images from VKH participants were analyzed for presence/absence of bacillary detachments, retinal pigment epithelium (RPE) folds, and internal limiting membrane (ILM) fluctuations was performed. A modified RPE undulation index was calculated to provide a quantifiable surrogate marker for choroidal folds. RESULTS: SD-OCT images were available from 158 eyes with VKH. At baseline, bacillary detachments were present in 23.5% of eyes, RPE folds in 22.8% of eyes, and ILM fluctuations in 35.2% of eyes. For each 0.1 unit increase in modified RPE undulation index, there was an associated 0.13 increase in mean logMAR BSCVA at baseline. None of the SD-OCT features were associated with BSCVA at the 6-month primary endpoint. Indeed, mean final BSCVA was similar in those with and without the SD-OCT features of interest at baseline, and was between 0.1 and 0.2 logMAR (Snellen visual acuity 20/25 to 20/30). CONCLUSIONS: While eyes with VKH may present with a variety of SD-OCT imaging pathology prior to starting immunosuppression with methotrexate or mycophenolate mofetil, final visual outcome in our study was excellent. With appropriate immunosuppression, good visual outcomes are possible in VKH.ClinicalTrials.gov Identifier NCT01829295Date of Registration: April 11, 2013.

Swine farm environmental microbiome: exploring microbial ecology and functionality across farms with high and low sanitary status.

Introduction: Stringent regulations in pig farming, such as antibiotic control and the ban on certain additives and disinfectants, complicate disease control efforts. Despite the evolution of microbial communities inside the house environment, they maintain stability over the years, exhibiting characteristics specific to each type of production and, in some cases, unique to a particular company or farm production type. In addition, some infectious diseases are recurrent in specific farms, while other farms never present these diseases, suggesting a connection between the presence of these microorganisms in animals or their environment. Therefore, the aim of this study was to characterise environmental microbiomes of farms with high and low sanitary status, establishing the relationships between both, health status, environmental microbial ecology and its functionality. Methods: For this purpose, 6 pig farms were environmentally sampled. Farms were affiliated with a production company that handle the majority of the pigs slaughtered in Spain. This study investigated the relationship among high health and low health status farms using high throughput 16S rRNA gene sequencing. In addition, to identify ecologically relevant functions and potential pathogens based on the 16S rRNA gene sequences obtained, functional Annotation with PROkaryotic TAXa (FAPROTAX) was performed. Results and Discussion: This study reveals notable differences in microbial communities between farms with persistent health issues and those with good health outcomes, suggesting a need for protocols tailored to address specific challenges. The variation in microbial populations among farms underscores the need for specific and eco-friendly cleaning and disinfection protocols. These measures are key to enhancing the sustainability of livestock farming, ensuring safer products and boosting competitive edge in the market.

An investigation of the transmission of Actinobacillus pleuropneumoniae within vertically integrated systems using whole genome sequencing.

Actinobacillus pleuropneumoniae (APP) causes significant economic losses to the swine industry. Antibiotic treatment can be challenging due to its clinical urgency and the turnover of antimicrobial susceptibility results from the diagnostic laboratory. The aim of this study was to evaluate the vertical transmission of APP within integrated systems as a criterion for optimising antimicrobial treatment in the field, using whole genome sequencing (WGS). Additionally, the genetic variability of Spanish APP isolates has been assessed to decipher antimicrobial resistance (AMR) determinants, toxin presence, serotype, and phenotype/genotype concordance of AMR. A total of 169 isolates from clinical cases of porcine pleuropneumonia with known antimicrobial susceptibility profiles were sequenced. Additionally, 48 NCBI assemblies were included to perform a phylogenetic analysis. Phylogenetic analysis revealed high association between phylogenetic clusters, serotypes, and presence of toxins that are associated within vertically integrated systems by its epidemiological link. Concordance between presence of AMR determinants (genotype) vs in-vitro antimicrobial susceptibility pattern (phenotype) was acceptable for amoxicillin, florfenicol, oxytetracycline, and enrofloxacin using epidemiological cut-off values (ECOFFs), but low concordance was observed for doxycycline and trimethoprim-sulfamethoxazole (T/S). On the other hand, using CLSI clinical breakpoints (CBPs), concordance was acceptable for florfenicol and enrofloxacin and not evaluated for doxycycline, oxytetracycline, trimethoprim-sulfamethoxazole (T/S), and amoxicillin because no CBP are available for them. Finally, WGS has demonstrated the clonality between isolates that shared a common origin (grandmother's farm) and resistance phenotype, suggesting vertical transmission of this pathogen and supporting the use of the epidemiological approach as a good criterion to optimise the antimicrobial use.

Outcomes in Patients With Vogt-Koyanagi-Harada Disease From the First-Line Antimetabolites for Steroid-Sparing Treatment Uveitis Trial.

PURPOSE: To compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: A subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX vs MMF) and disease stage (acute vs chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25 mg weekly oral MTX or 1.5 g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). RESULTS: Ninety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P = .12) or in BSCVA improvement (P = .78). MTX was superior to MMF in reducing CST (P = .003) and resolving SRD (P = .02). There was no significant difference in treatment success by disease stage (P = .25), but patients with acute VKH had greater improvement in BSCVA (P < .001) and reduction of CST (P = .02) than chronic VKH patients. CONCLUSIONS: MTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. NOTE: Publication of this article is sponsored by the American Ophthalmological Society TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182929.

Differences in enteric pathogens and intestinal microbiota between diarrheic weaned piglets and healthy penmates.

Postweaning diarrhea (PWD) is a multifactorial disease caused by different aetiological agents, like viruses or bacteria and where the role of the microbiota remains unclear. The aim of this study was to assess differences between healthy and diarrheic weaned pigs concerning the prevalence of pathogens and changes in the intestinal microbiota. Eighteen farms with PWD were selected and 277 fecal samples were collected (152 diarrheic vs 125 healthy). Presence of Rotavirus A (RVA), B (RVB), C (RVC) and Porcine Epidemic Diarrhea Virus (PEDV), virulence factors of Escherichia coli and Clostridioides difficile were analyzed by PCR. Finally, the microbiota composition was also study by 16 S rRNA sequencing on 148 samples (102 diarrheic vs 46 healthy). RVA (53.95 % vs 36 %, p=0.04) and RVB (49.67 % vs 28.8 %, p<0.001) were more frequent in diarrheic animals. Furthermore, RVA viral load was higher in diseased animals. VT2 toxin was significantly associated with diarrhea, whereas other virulence factors were not. Presence of C. difficile and PEDV was almost negligible. Regarding microbiota changes, Fusobacteriota phylum was more frequent in diarrheic samples and Ruminococcaceae family in healthy penmates. During the first week postweaning, Enterobacteriace and Campylobacteria were enriched in animals presenting diarrhea. Furthermore, Lactobacillus was detected in those individuals with no RVA infection. In conclusion, RVA seems to play a primary role in PWD. Classic E. coli virulence factors were not associated with diarrhea, indicating the need for revising their implication in disease. Moreover, Lactobacillus was found frequently in animals negative for RVA, suggesting some protective effect.

Gut microbiome and resistome characterization of pigs treated with commonly used post-weaning diarrhea treatments.

BACKGROUND: The global burden of antimicrobial resistance demands additional measures to ensure the sustainable and conscious use of antimicrobials. For the swine industry, the post-weaning period is critical and for many years, antimicrobials have been the most effective strategy to control and treat post-weaning related infections. Among them, post-weaning diarrhea causes vast economic losses, as it severely compromises piglets' health and growth performance. In this study, 210 piglets were transferred from a farm with recurrent cases of post-weaning diarrhea to an experimental farm and divided into six different treatment groups to determine the effect of the different treatments on the growth performance and survival, the microbiome, and the resistome in a cross-sectional and longitudinal study. The different treatments included antimicrobials trimethoprim/sulfamethoxazole, colistin, and gentamicin, an oral commercial vaccine, a control with water acidification, and an untreated control. An extra group remained at the farm of origin following the implemented amoxicillin routine treatment. A total of 280 fecal samples from pigs at four different sampling times were selected for metagenomics: before weaning-treatment at the farm of origin, and three days, two weeks, and four weeks post-treatment. RESULTS: The control group with water acidification showed a reduced death risk in the survival analyses and non-significant differences in average daily weight gain in comparison to the antibiotic-treated groups. However, the growth-promoting effect among antibiotic-treated groups was demonstrated when comparing against the untreated control group at the experimental farm. After four weeks of treatment, diversity indexes revealed significantly decreased diversity for the untreated control and the group that remained at the farm of origin treated with amoxicillin. For this last group, impaired microbial diversity could be related to the continuous amoxicillin treatment carried out at the farm. Analysis of the resistome showed that both gentamicin and amoxicillin treatments significantly contributed to the emergence of resistance, while trimethoprim/sulphonamide and colistin did not, suggesting that different treatments contribute differently to the emergence of resistance. CONCLUSIONS: Overall, this shotgun longitudinal metagenomics analysis demonstrates that non-antibiotic alternatives, such as water acidification, can contribute to reducing the emergence of antimicrobial resistance without compromising pig growth performance and gut microbiome.

Transcriptional Inflammatory Signature in Healthy Donors and Different Radiotherapy Cancer Patients.

Cancer and ionizing radiation exposure are associated with inflammation. To identify a set of radiation-specific signatures of inflammation-associated genes in the blood of partially exposed radiotherapy patients, differential expression of 249 inflammatory genes was analyzed in blood samples from cancer patients and healthy individuals. The gene expression analysis on a cohort of 63 cancer patients (endometrial, head and neck, and prostate cancer) before and during radiotherapy (24 h, 48 h, ~1 week, ~4-8 weeks, and 1 month after the last fraction) identified 31 genes and 15 up- and 16 down-regulated genes. Transcription variability under normal conditions was determined using blood drawn on three separate occasions from four healthy donors. No difference in inflammatory expression between healthy donors and cancer patients could be detected prior to radiotherapy. Remarkably, repeated sampling of healthy donors revealed an individual endogenous inflammatory signature. Next, the potential confounding effect of concomitant inflammation was studied in the blood of seven healthy donors taken before and 24 h after a flu vaccine or ex vivo LPS (lipopolysaccharide) treatment; flu vaccination was not detected at the transcriptional level and LPS did not have any effect on the radiation-induced signature identified. Finally, we identified a radiation-specific signature of 31 genes in the blood of radiotherapy patients that were common for all cancers, regardless of the immune status of patients. Confirmation via MQRT-PCR was obtained for BCL6, MYD88, MYC, IL7, CCR4 and CCR7. This study offers the foundation for future research on biomarkers of radiation exposure, radiation sensitivity, and radiation toxicity for personalized radiotherapy treatment.

Case-control study assessing the impact of COVID19 in advanced kidney cancer patients treated with antiangiogenics or immunotherapy: the COVID-REN study.

BACKGROUND: Cancer is a risk factor for developing severe COVID19. Additionally, SARS-CoV2 has a special tropism for renal cells and complications like thrombosis or cytokine storm could be enhanced by standard treatments in kidney cancer (i.e., antiangiogenics or immunotherapy). Thus, understanding the impact of COVID19 in patients with this tumor is key for their correct management. METHODS: We designed a retrospective case-control study comparing the outcome of three groups of advanced kidney cancer patients on systemic treatment: cohort A (developed COVID19 while on antiangiogenics), cohort B (developed COVID19 while on immunotherapy) and cohort C (non-infected). Matching factors were age, gender, and treatment. RESULTS: 95 patients were recruited in 16 centers in Spain from September 2020 to May 2021. Finally, 85 were deemed as eligible (23 cohort A, 21 cohort B, 41 cohort C). Patients with COVID required more dose interruptions (25 vs. six) and hospitalizations (10 vs. none) than those without COVID (both p = 0.001). No difference between cohorts A and B was observed regarding hospitalization or length of stay. No ICU admission was registered and one patient in cohort B died due to COVID19. Regarding cancer evolution, three patients in cohort A presented progressive disease after COVID19 compared to two in cohort B. One case in cohort B, initially deemed as stable disease, achieved a partial response after COVID19. CONCLUSIONS: Kidney cancer patients who developed COVID19 while on systemic therapy required more treatment interruptions and hospitalizations than those non-infected. However, no significant impact on cancer outcome was observed. Also, no difference was seen between cases on antiangiogenics or immunotherapy.

Caracterización del bienestar en hogares mexicanos de niñas y niños con diarrea, Ensanut Continua 2022.

OBJETIVO: Analizar el nivel de bienestar en los hogares mexicanos de niñas y niños menores de cinco años que presentaron enfermedad diarreica aguda (EDA) en las últimas dos semanas en México, según la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. La encuesta se realizó entre julio y diciembre de 2022. Variable dependiente: ocurrencia de EDA. Variable independiente: nivel de bienestar de los hogares. Se realizó análisis bivariado y regresiones logísticas crudas y ajustadas. RESULTADOS: Se estima que 9.4% de los menores de cinco años presentaron EDA, de quienes 76.4% (IC95%: 69.0,82.5) pertenecía a hogares con nivel de bienestar bajo-medio. La EDA fue más frecuente en los niños y niñas de un año de edad (razón de momios ajustada [RMa] 3.00; IC95%: 1.76,5.11), en comparación con quienes tenían menor edad y en los hogares donde el agua para beber no es tratada (RMa 2.13; IC95%: 1.11,4.08). CONCLUSIONES: Se requiere fortalecer las medidas sanitarias preventivas de EDA en niñas y niños de un año de edad, principalmente implementar acciones para asegurar la disponibilidad de agua potable o el tratamiento adecuado para beberla, y planear, ejecutar y evaluar acciones de política pública integrales y multisectoriales para coadyuvar en garantizar el derecho humano a la salud durante la niñez.

Cobertura de vacunación en niños, niñas y adolescentes en México.

OBJETIVO: Describir las coberturas de vacunación en 2022 en niñas, niños y en adolescentes, así como comparar las prevalencias observadas con los datos de la Encuesta Nacional de Salud y Nutrición 2021 (Ensanut 2021). Material y métodos. Análisis de datos obtenidos de la Ensanut 2022. RESULTADOS: En los niños menores de cinco años, las coberturas de vacuna con Bacilo de Calmette y Guérin (BCG), hepatitis B, pentavalente o hexavalente, neumocócica, antirotavirus y triple viral (SRP) fueron de 78.5% (IC95%: 70.8,84.6), 65.1% (IC95%: 58.4,71.2), 69.0% (IC95%: 61.8,75.4), 88.0% (IC95%: 83.0,91.7), 81.6% (IC95%: 75.7,86.2) y 61.8% (IC95%: 55.6,67.6), respectivamente. Al primer y segundo año de vida, 42.6% (IC95%: 34.3,51.4) y 26.6% (IC95%: 22.1,31.5) habían recibido el esquema correspondiente. Se redujo la cobertura estimada para primera dosis de SRP 72.6% (IC95%: 67.5,77.1) vs. 61.8% (IC95%: 55.6,67.5). En adolescentes, el antecedente de vacunación contra VPH, hepatitis B, tétanos y doble viral (SR) lo refirieron en 43.7% (IC95%: 39.9,47.6), 31.8% (IC95%: 29.8,34.0), 38.5% (IC95%: 35.9,41.2) y 32.6% (IC95%: 30.15,35.1). Conclusión. No se alcanza la meta de cobertura de 90% para ningún inmunógeno investigado. La cobertura para primera dosis de SRP se ha reducido.

Porcentaje de infección respiratoria aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de infección respiratoria aguda (IRA) en menores de cinco años en las últimas dos semanas en México, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. Se analizaron datos de la Ensanut Continua 2022. RESULTADOS: El porcentaje de IRA fue de 27.6% (IC95%: 25.2,30.1). La prevalencia fue mayor en el primer tercil socioeconómico (44.1% [IC95%: 38.0,50.4]). El signo de alarma IRA más identificado fue "verse más enfermo" 33.0% (IC95%: 30.1,36.0) y el menos identificado fue "salir pus del oído" (1.5% [IC95%: 0.9,2.7]). CONCLUSIONES: Las IRA afectan cerca de una tercera parte de los niños y las niñas menores de cinco años en México, particularmente de los hogares con menores capacidades económicas. Es necesario fortalecer las estrategias de prevención, entre ellas la vacunación, el control y la promoción de la salud.

Porcentaje de enfermedad diarreica aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de enfermedad diarreica aguda (EDA) en menores de cinco años en las últimas dos semanas, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022. Material y métodos. Se analizaron los datos de menores de cinco años incluidos en la Encuesta Nacional de Salud y Nutrición Continua 2022 respecto a la EDA en las últimas dos semanas. Se compararon los datos con los de ediciones previas de la encuesta. RESULTADOS: El porcentaje de EDA en México fue de 9.4% (IC95%: 7.9,11.2), similar al de 2000, con diferencias por grupo etario. Durante el episodio de EDA, 38.7% (IC95%: 27.7,51.0) de las personas cuidadoras ofrecen menor cantidad de alimentos a la habitual. CONCLUSIONES: El elevado porcentaje de EDA en menores de cinco años en México en el 2022 evidencia la necesidad de fortalecer estrategias de prevención y promoción de la salud.

Vacunación en adultos y adultos mayores en México.

OBJETIVO: Estimar la prevalencia del antecedente de vacunación en adultos de 20 a 59 años y mayores de 60 años mediante autorreporte. Material y métodos. Análisis de datos obtenidos de la Encuesta Nacional de Salud y Nutrición 2022 (Ensanut 2022). RESULTADOS: El 27.4% de los adultos de 20-39 años refirió haber recibido vacuna doble viral (sarampión y rubeola [SR]) y 57.3% de adultos de 20-59 años cualquier vacuna con toxoide tetánico (Td) en los últimos diez años. En mujeres de 29 a 49 años, 18.7% (IC95%: 17.0,20.5) y 58.46% (IC95%: 56.2,60.7) habían sido vacunadas con vacuna SR y Td, respectivamente. En mayores de 60 años, 48.8% (IC95%: 45.9,51.7), 24.4% (IC95%: 22.2,26.8) y 49.1% (IC95%: 46.1,52.2) informaron haber recibido cualquier vacuna conteniendo Td, vacuna antineumococo y vacuna antiinfluenza estacional desde septiembre del año anterior a la encuesta, respectivamente. Conclusión. Los resultados de este estudio muestran que una proporción considerable de adultos, mujeres en edad fértil y adultos mayores no estaban protegidos contra enfermedades prevenibles por vacunación en 2022.

The Susceptibility Trends of Respiratory and Enteric Porcine Pathogens to Last-Resource Antimicrobials.

Monitoring the antimicrobial susceptibility of last-resource antimicrobials for veterinary pathogens is urgently needed from a one-health perspective. The objective of this study was to analyze the antimicrobial susceptibility trends of Spanish porcine bacteria to quinolones, cephalosporins, and polymyxins. Isolates of Actinobacillus pleuropneumoniae, Pasteurella multocida, and Escherichia coli were isolated from sick pigs from 2019 to 2022. An antimicrobial susceptibility test was determined based on the minimal inhibitory concentration (MIC) following an internationally accepted methodology. The MIC categorization was based on distributing the range of MIC values in four categories, with category one being the most susceptible (lowest MIC value) and category four the least susceptible (highest MIC value). Moreover, clinical susceptibility (susceptible/non-susceptible) was also determined according to the CLSI and EUCAST clinical breakpoints. A logistic and multinomial logistic regression model was used to analyze the susceptibility data for dichotomized and categorized MIC data, respectively, for any pair of antimicrobial/microorganism. In general terms, the antimicrobial susceptibility of pig bacteria to these antimicrobials remained stable or increased in the last four years in Spain. In the case of A. pleuropneumoniae and quinolones, a significant temporal trend was observed where isolates from 2020 had significantly increased odds of being more susceptible than isolates from 2019. In the case of E. coli and polymyxins, a significant temporal trend was observed where isolates from 2020 and 2021 had significantly increased odds of being more susceptible than isolates from 2019 and 2020, respectively. Finally, significant odds of being less susceptible were only observed for cephalosporins and E. coli for 2020 versus 2019, stagnating for the rest of study period. These results provide sound data on critically important antimicrobials in swine medicine.

HEALTH ASSESSMENT OF CAPTIVE BEARDED VULTURES (GYPAETUS BARBATUS) IN CATALONIA (SPAIN).

Bearded vulture (Gypaetus barbatus) populations are declining worldwide primarily due to anthropogenic factors. A captive breeding program has been established in Spain, a country with one of the largest free-living populations in Europe, to further enhance the conservation efforts of this emblematic species. However, captive vulture populations can be exposed to different risks through food, such as drug residues and antimicrobial-resistant (AMR) bacteria. Health surveillance of species involved in captive breeding programs is important to face introduction of healthy animals in situ and to obtain baseline clinical data. The objective of this study was to assess the general health status of bearded vultures held in captivity in Catalonia (northeastern Spain) by carrying out hematologic, biochemical, toxicologic, and bacteriologic analyses. A total of 16 bearded vultures were sampled; the data obtained from one vulture, with a chronic tibiotarsal fracture, were excluded from the statistical analysis. Hematologic and biochemical parameters of the bearded vultures were mostly within the range of standard values as stated in previous studies. Basal feather and serum corticosterone levels were analyzed and described for the first time in this species. A total of 15 Escherichia coli isolates were obtained that were resistant to fluoroquinolones (80%), tetracycline (60%), trimethoprim and ampicillin (40%), sulfamethoxazole (33%), and colistin (20%), with 40% of them being multidrug resistant. Three of 15 isolates were carriers of the mcr-1 gene. Only the injured bird previously treated with enrofloxacin was positive for fluoroquinolone residues. Periodic monitoring for the presence of AMR bacteria would be recommended in captive breeding programs as a preventive action to establish future therapies.

Mexican Biobank advances population and medical genomics of diverse ancestries.

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution and inference of identity-by-descent segments, we inferred ancestral population sizes across Mesoamerican regions over time, unravelling Indigenous, colonial and postcolonial demographic dynamics2-6. We observed variation in runs of homozygosity among genomic regions with different ancestries reflecting distinct demographic histories and, in turn, different distributions of rare deleterious variants. We conducted genome-wide association studies (GWAS) for 22 complex traits and found that several traits are better predicted using the Mexican Biobank GWAS compared to the UK Biobank GWAS7,8. We identified genetic and environmental factors associating with trait variation, such as the length of the genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into the genetic histories of individuals in Mexico and dissects their complex trait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.

Spi1 R235C point mutation confers hypersensitivity to radiation-induced acute myeloid leukemia in mice.

Ionizing radiation (IR) is a risk factor for acute myeloid leukemia (rAML). Murine rAMLs feature both hemizygous chromosome 2 deletions (Del2) and point mutations (R235) within the hematopoietic regulatory gene Spi1. We generated a heterozygous CBA Spi1 R235 mouse (CBASpm/+) which develops de novo AML with 100% incidence by ∼12 months old and shows a dose-dependent reduction in latency following X-irradiation. These effects are reduced on an AML-resistant C57Bl6 genetic background. CBASpm/Gfp reporter mice show increased Gfp expression, indicating compensation for Spm-induced Spi1 haploinsufficiency. Del2 is always detected in both de novo and rAMLs, indicating that biallelic Spi1 mutation is required for AML. CBASpm/+ mice show that a single Spm modification is sufficient for initiating AML development with complete penetrance, via the "two-hit" mechanism and this is accelerated by IR exposure. Similar SPI1/PU.1 polymorphisms in humans could potentially lead to enhanced susceptibility to IR following medical or environmental exposure.