Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer.

While CD40 agonism is an attractive approach for activating antigen-presenting cells and initiating antitumor responses, previous attempts have encountered limited clinical efficacy coupled with toxicity. We previously demonstrated that interactions between the antibody Fc domain and the inhibitory receptor FcγRIIB are critical for enhanced antitumor activity. Here, we present the results of a phase 1 study on intratumoral administration of an anti-CD40 agonistic antibody (2141-V11) Fc-engineered to enhance FcγRIIB binding. Primary endpoints included safety, maximum tolerated dose (MTD), and recommended phase 2 dose. Secondary objectives included preliminary clinical activity and correlative studies from biospecimens. 2141-V11 was well-tolerated without dose-limiting toxicities and MTD was not reached. In ten evaluable patients with metastatic cancer, the overall response rate was 20%, with complete responses in two patients (melanoma and breast carcinoma) and stable disease in six patients. 2141-V11 induced tumor regression in injected and non-injected lesions, with increased leukocyte infiltration and tertiary lymphoid structures (TLS) formation in post-treatment biopsies. In a humanized mouse model for CD40 and FcγRs, 2141-V11 induced TLS formation in mice bearing orthotopic breast carcinoma, correlating with local and abscopal antitumor effects, systemic immune activation, and immune memory. These findings support the safety and efficacy of 2141-V11, warranting phase 2 studies and suggesting a unique mechanism of action for this Fc-enhanced immunotherapy (NCT04059588).

Sleeve Gastrectomy Reduces Oxidative Stress and Reverses Mitochondrial Dysfunction Associated with Metabolic Syndrome.

INTRODUCTION: Previous studies have detected mitochondrial alterations in tissues of individuals with obesity and type 2 diabetes mellitus (T2DM). Metabolic surgery could be an effective treatment to improve mitochondrial morphology and reduce oxidative stress (OS). METHODS: An experimental study was carried out using 48 male Wistar rats, divided into 6 groups (n = 8): control (C), induced Metabolic Syndrome (MS); intervention with sleeve gastrectomy (SG), MS + SG with 6 weeks postoperatively (MS + SG6), MS + SG with 12 weeks postoperatively (MS + SG12), and MS + SG with 24 weeks postoperatively (MS + SG24). Biochemical markers indicative of MS (glycemia, cholesterol, and triglyceride levels) and oxidative stress markers (nitric oxide levels, Superoxide dismutase and Myeloperoxidase activity) were determined. To study mitochondrial morphology, tissue sections of the thoracic aorta, stomach, liver, heart, and kidney were observed by electron microscopy. RESULTS: MS group exhibited elevated glycemic values and dyslipidemia. SG and MS + SG groups showed improvements in glycemia and lipid profiles compared to MS. OS biomarkers indicated reduced oxidative stress in SG and MS + SG groups compared to MS. Electron microscopy revealed mitochondrial alterations in MS. SG group showed no changes compared to the control. MS + SG6 and MS + SG12 groups showed a recovery of mitochondrial morphology until reaching images similar to the control in MS + SG24. CONCLUSION: Metabolic surgery could improve mitochondrial function by restoring mitochondrial morphology and architecture and, consequently, reducing systemic oxidative stress and remitting associated metabolic alterations.

FcγRIIB Is an Immune Checkpoint Limiting the Activity of Treg-Targeting Antibodies in the Tumor Microenvironment.

Preclinical murine data indicate that fragment crystallizable (Fc)-dependent depletion of intratumoral regulatory T cells (Treg) is a major mechanism of action of anti-CTLA-4. However, the two main antibodies administered to patients (ipilimumab and tremelimumab) do not recapitulate these effects. Here, we investigate the underlying mechanisms responsible for the limited Treg depletion observed with these therapies. Using an immunocompetent murine model humanized for CTLA-4 and Fcγ receptors (FcγR), we show that ipilimumab and tremelimumab exhibit limited Treg depletion in tumors. Immune profiling of the tumor microenvironment (TME) in both humanized mice and humans revealed high expression of the inhibitory Fc receptor, FcγRIIB, which limits antibody-dependent cellular cytotoxicity/phagocytosis. Blocking FcγRIIB in humanized mice rescued the Treg-depleting capacity and antitumor activity of ipilimumab. Furthermore, Fc engineering of antibodies targeting Treg-associated targets (CTLA-4 or CCR8) to minimize FcγRIIB binding significantly enhanced Treg depletion, resulting in increased antitumor activity across various tumor models. Our results define the inhibitory FcγRIIB as an immune checkpoint limiting antibody-mediated Treg depletion in the TME, and demonstrate Fc engineering as an effective strategy to overcome this limitation and improve the efficacy of Treg-targeting antibodies.

Reduced expression of GluN2A induces a delay in neuron maturation.

NMDA receptors (NMDARs) play an important role in synaptic plasticity both in physiological and pathological conditions. GluN2A and GluN2B are the most expressed NMDAR regulatory subunits, in the hippocampus and other cognitive-related brain structures. GluN2B is characteristic of immature structures and GluN2A of mature ones. Changes in GluN2A expression were associated with complex phenotypes that led to complex neurodevelopmental disorders, including the occurrence of seizures. However, little is known about the role of GluN2A in these phenotypes. In this work, we reduced GluN2A expression in mature neuronal cultures and observed an altered GluN2A/GluN2B ratio. Furthermore, those neurons exhibit an increase in immature dendritic spines and dendritic branching, as well as an increased response to glutamate stimulus. This phenotype (considering GluN2A/GluN2B ratio, index branching and glutamate response) resembles those observed at immature neuronal stages in vitro. We propose that this immature phenotype led to a higher response to glutamate stimulus which, in vivo, would be the basis of reduced threshold for seizure onset in GluN2A-pathological conditions.

Apnea or cyanosis as COVID-19 initial presentation in newborns.

INTRODUCTION: The clinical manifestation of coronavirus disease 2019 (COVID-19) infection in newborns varies from asymptomatic infection to severe illness. Apnea or cyanosis as the earliest symptoms is rarely mentioned. The aim of this study is to describe the characteristics of newborns with COVID-19 infection admitted to the neonatal intensive care unit considering cyanosis or apnea as a form of presentation. METHODOLOGY: This is a descriptive observational study with retrospectively collected data. All neonates under 30 days old and preterm infants with corrected gestational age of 44 weeks who had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with a positive antigen or reverse transcriptase polymerase chain reaction (RT-PCR) test and who were attended to between March 2020 and March 2022 were included. RESULTS: During the two years of the study, 410 patients were admitted to the neonatal unit. Twenty-six patients (6.3%) presented with confirmed SARS-CoV-2 infection. The main clinical characteristic at admission was apnea in 55% and cyanosis in 45%. Of the 11 patients admitted with this presentation, eight were diagnosed with COVID-19 acute upper respiratory disease, and three met the definition of COVID-19 bronchiolitis. A large proportion of the patients had a mild infection (65%, n = 17), 31% (n = 8) had a severe infection and only one patient had a critical infection, accounting for 4%. CONCLUSIONS: Apnea and cyanosis can be a manifestation of SARS-CoV-2 infection in newborns, which suggests the need to include it in the diagnostic workup as other viral respiratory infections.

Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia.

Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique expression of a variety of antigens, including the RNA helicase U5 snRNP200, on the surface of AML cells but not on normal hematopoietic precursors and skewed Fc receptor distribution in the AML immune microenvironment. Cell membrane localization of U5 snRNP200 was linked to surface expression of the Fcγ receptor IIIA (FcγIIIA, also known as CD32A) and correlated with expression of interferon-regulated immune response genes. Anti-U5 snRNP200 antibodies engaging activating Fcγ receptors were efficacious across immunocompetent AML models and were augmented by combination with azacitidine. These data provide a roadmap of AML-associated antigens with Fc receptor distribution in AML and highlight the potential for targeting the AML cell surface using Fc-optimized therapeutics.

Evaluation of the generation of reactive oxygen species and antibacterial activity of honey as a function of its phenolic and mineral composition.

The antibacterial activity (ABA) of honey is associated with the generation of reactive oxygen species (ROS), where polyphenols (PFs) play a key role due to their pro-oxidant action modulated by metallic cations. In this work, the contents of PFs, H2O2, OH radicals, Cu, Fe, Mn, Zn, and ABA against Staphylococcus epidermidis and Pseudomonas aeruginosa were determined in honeys from central Chile. Then, their relationships were evaluated through partial least squares regression. The average contents of phenolic acids, flavonoids and metals in honey ranged from 0.4 to 4 µg/g, 0.3-1.5 µg/g and 3-6 µg/g, respectively. All honeys showed accumulation of H2O2 (1-35 µg/g) and OH radicals. The PLS showed that gallic acid, p-coumaric acid, chrysin, kaempferol, Fe, and Mn stimulate the generation of ROS. Quercetin, Cu, and Zn showed marginal antioxidant effects. PFs favor the ABA of honey against both bacteria and H2O2 against S. epidermidis.

Effect of surfactants on the sorption-desorption, degradation, and transport of chlorothalonil and hydroxy-chlorothalonil in agricultural soils.

The fungicide chlorothalonil (CTL) and its metabolite hydroxy chlorothalonil (OH-CTL) constitute a risk of soil and water contamination, highlighting the need to find suitable soil remediation methods for these compounds. Surfactants can promote the bioavailability of organic compounds for enhanced microbial degradation, but the performance depends on soil and surfactant properties, sorption-desorption equilibria of contaminants and surfactants, and possible adverse effects of surfactants on microorganisms. This study investigated the influence of five surfactants [e.g., Triton X-100 (TX-100), sodium dodecyl sulphate (SDS), hexadecyltrimethylammonium bromide (HDTMA), Aerosol 22 and Tween 80] on the sorption-desorption, degradation, and mobility of CTL and OH-CTL in two volcanic and one non-volcanic soil. Sorption and desorption of fungicides depended on the sorption of surfactants on soils, surfactants' capacity to neutralize the net negative charge of soils, surfactants' critical micellar concentration, and pH of soils. HDTMA was strongly adsorbed on soils, which shifted the fungicide sorption equilibria by increasing the distribution coefficient (Kd) values. Contrarily, SDS and TX-100 lowered CTL and OH-CTL sorption on soils by decreasing the Kd values, which resulted in an efficient extraction of the fungicide compounds from soil. SDS increased the degradation of CTL, especially in the non-volcanic soil (DT50 values were 14 and 7 days in natural and amended soils, with final residues <7% of the initial dose), whereas TX-100 enabled an early start and sustenance of OH-CTL degradation in all soils. CTL and OH-CTL stimulated soil microbial activities without noticeable deleterious effects of the surfactants. SDS and TX-100 also reduced the vertical transport of OH-CTL in soils. Results of this study could be extended to soils in other regions of the world because the tested soils represent widely different physical, chemical, and biological properties.

Pharmacological Action of Atorvastatin and Metformin on Non-alcoholic Fatty Liver Disease on an Experimental Model of Metabolic Syndrome.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in the world. It is known that there is a pathogenic relation between liver damage and the inflammatory and oxidative environment present in Metabolic Syndrome (MS). OBJECTIVE: To study the pharmacological action of atorvastatin and metformin in an experimental model of MS. METHODS: We used 40 male rats (Wistar) divided into the following groups: Control (A) (n=8), induced MS (B) (n=8), MS + atorvastatin treatment (C)(n=8), MS + metformin treatment (D) (n=8) and MS + combined treatment (E) (n=8). MS was induced by administering 10% fructose in drinking water for 45 days. Atorvastatin 0.035 mg/day/rat, metformin 1.78 mg/day/rat, and a combination of both drugs were administered for 45 days. Metabolic, oxidative (nitric oxide, myeloperoxidase and superoxide dismutase) and inflammatory (fibrinogen) parameters were determined. Histological sections of liver were analyzed by light microscopy. RESULTS: The glycemia, lipid profile and TG/HDL-C index were altered in MS group. After pharmacological treatment, metabolic parameters improve significantly in all treated groups. Inflammatory and oxidative stress biomarkers increase in MS. Treated groups showed an increase in NO bioavailability, no difference in MPO activity and an increase in fibrinogen. Atorvastatin showed a decrease in SOD while Metformin and combination treatment showed an increase in SOD compared to MS. In MS, we observed histological lesions consistent with NAFLD. However, after a combined treatment, we observed total regression of these lesions. CONCLUSION: Our results showed that there is an important synergy between atorvastatin and metformin in improving liver involvement in MS.

FcyRIIB is a novel immune checkpoint in the tumor microenvironment limiting activity of Treg-targeting antibodies.

Despite pre-clinical murine data supporting T regulatory (Treg) cell depletion as a major mechanism by which anti-CTLA-4 antibodies function in vivo, the two main antibodies tested in patients (ipilimumab and tremelimumab) have failed to demonstrate similar effects. We report analogous findings in an immunocompetent murine model humanized for CTLA-4 and Fcy receptors (hCTLA-4/hFcyR mice), where both ipilimumab and tremelimumab fail to show appreciable Treg depletion. Immune profiling of the tumor microenvironment (TME) in both mice and human samples revealed upregulation of the inhibitory Fcy receptor, FcyRIIB, which limits the ability of the antibody Fc fragment of human anti-CTLA-4 antibodies to induce effective antibody dependent cellular cytotoxicty/phagocytosis (ADCC/ADCP). Blocking FcyRIIB in humanized mice rescues Treg depleting capacity and anti-tumor activity of ipilimumab. For another target, CC motif chemokine receptor 8 (CCR8), which is selectively expressed on tumor infiltrating Tregs, we show that Fc engineering to enhance binding to activating Fc receptors, while limiting binding to the inhibitory Fc receptor, leads to consistent Treg depletion and single-agent activity across multiple tumor models, including B16, MC38 and MB49. These data reveal the importance of reducing engagement to the inhibitory Fc receptor to optimize Treg depletion by TME targeting antibodies. Our results define the inhibitory FcyRIIB receptor as a novel immune checkpoint limiting antibody-mediated Treg depletion in tumors, and demonstrate Fc variant engineering as a means to overcome this limitation and augment efficacy for a repertoire of antibodies currently in use or under clinical evaluation in oncology.

Quemadura genital por producto químico: reporte de caso / Genital burn by chemical product: case report

Resumen ANTECEDENTES: Las quemaduras son la forma más severa de estrés que el cuerpo puede sufrir; pueden generarse por diferentes agentes térmicos y químicos. CASO CLÍNICO: Paciente de 25 años, con dolor intenso en la región genital de 12 horas de evolución, secundario a la introducción en la vagina de una piedra de alumbre. Se le hicieron múltiples irrigaciones con solución salina al 0.9% sin obtener el resto de la piedra de alumbre. Se le aplicó sulfadiazina de plata en la cavidad vaginal cada 12 horas, óvulos vaginales de ketanserina, miconazol y metronidazol cada 8 horas, ketorolaco por vía oral 10 mg cada 8 horas. Durante su estancia hospitalaria tuvo buena evolución, con disminución de la inflamación en la zona genital, epitelización adecuada. Al tercer día se dio de alta del hospital con cita para valoración a los siete días. CONCLUSIÓN: El tratamiento de las quemaduras en el área genital, por agentes químicos, tiene como piedra angular la identificación del agente causante de la lesión que permita actuar de forma inmediata y evitar las secuelas físicas, sexuales y psicológicas mediante el lavado exhaustivo con solución o agua estéril para remover el agente causal y disminuir que continúe actuando en el sitio afectado.

Abstract BACKGROUND: Burns are the most severe form of stress that the body can suffer; they can be caused by various thermal and chemical agents. CLINICAL CASE: A 25-year-old female patient presented with severe genital pain of 12 hours' duration, secondary to the introduction of an alum stone into the vagina. She underwent several irrigations with 0.9% saline without obtaining the rest of the alum stone. She was given vaginal silver sulfadiazine every 12 hours, vaginal ketanserin, miconazole and metronidazole every 8 hours and oral ketorolac 10 mg every 8 hours. During her stay in hospital, she progressed well, with a decrease in genital inflammation and adequate epithelialisation. She was discharged on the third day with an appointment for a seven-day follow-up. CONCLUSION: The management of genital burns caused by chemical agents is based on the identification of the agent causing the lesion, which allows immediate action and prevents physical, sexual and psychological sequelae by thorough washing with sterile solution or water to remove the causative agent and reduce its continued action in the affected area.

Reducing environmental exposure to PPPs in super-high density olive orchards using UAV sprayers.

The increasing demand for optimizing the use of agricultural resources will require the adoption of cutting-edge technologies and precision farming management. Unmanned Aerial Vehicle (UAV) sprayers seem promising due to their potential to perform precision or spot spraying, particularly in woody crop environments where total surface spraying is unnecessary. However, incorporating this technology is limited by the lack of scientific knowledge about the environmental risks associated with UAV sprayers and the strict legal framework. Nonetheless, these spraying systems' characteristic downwash airflow and the limited swath width can potentially mitigate drift in hedgerow crops. During our study we performed comparative studies aimed to compare the airborne drift, soil, and crop depositions between a conventional orchard sprayer and a UAV sprayer in a commercial superhigh-density orchard in the South Iberian Peninsula in 2022. Our findings reveal that, in superhigh-density olive orchards, the UAV sprayer presents a substantial reduction in airborne drift, while soil depositions showed no significant differences compared to those of a conventional terrestrial orchard sprayer. Crop depositions were significantly lower when utilizing the UAV sprayer. These results suggest that introducing UAV spraying technology in Mediterranean agricultural systems, under specific scenarios, can effectively reduce the environmental impact of crop spraying and encourage the responsible use of plant protection products (PPPs).

Digital Quality Resources Resulting from Standardized Program for Rubric Training in Medical Residents.

INTRODUCTION: In the health care area, tuition is an essential part to provide the instrument that proves the graduates have acquired the necessary skills in their specialties. OBJECTIVE: Evaluation of the improvement in quality of resources for residents after standardized digital training program with rubrics. METHODS: Prospective observational study of first year medical residents in seven medical specialties in four different training centers. Five dimensions were considered to scale the quality of medical resident research: Validation of rubric in investigation methodology topics for each block in b-learning mode; initial and ending evaluation; colloquium investigation rubric; results of final investigation; satisfaction survey of 360 degrees. The instruments were validated using the delphi method with a minimum agreement of 0.8. We considered global values greater than 80 points as good quality. RESULTS: 85 medical residents participated and obtained a final average of 80.62 (±9.59), and the satisfaction of the course was qualified as excellent/good in 82.5%. A positive relation was observed between the scope of the evaluation and the level of satisfaction. Mean quality score for the course was good. There is no relationship between the research experience of the students and the final average r = 0.123 (p = 0.291). CONCLUSIONS: The implementation of research seminars in b-learning mode results in improving the education program for health residents after a training program with a rubric system and their acquiring research skills, and, as a consequence, the final product also showed better quality, even when the student did not have any experience in a scientific publication.

[Epidemiological and clinical characteristics of the COVID-19 epidemic in Mexico: Quintana Roo case]. / Características epidemiológicas y clínicas de la epidemia COVID-19 en México: caso Quintana Roo.

Objective: Identify risk factors for severe outcome in Mexican patients with COVID-19 in the population of Quintana Roo. Material and methods: Study of 5,916 who met the criteria for suspected cases of COVID-19, 2,531 confirmed by qrTPCR-Sars-CoV-2 tests, of which 1,486 were positive, among which they were classified as hospitalized (severe COVID-19) and outpatients. Multivariate logistic regression analysis was performed to explore the factors associated with the severity of COVID-19 and death as clinical outcomes. The basic reproduction number (R0) was calculated Statistical analysis) Endorsement of the ethics committee 2301. Results: SARS-CoV-2 positive patients presented a high prevalence of hypertension 29.1%, diabetes 23.5%, obesity 24%, and 48.5% have at least one chronic disease. There is a high risk of severity for COVID-19 in patients with diabetes OR=3.14, hypertension OR=1.88, obesity OR=1.68, kidney disease OR=3.2, older than 65 years OR=13.6 and men OR=1.7. These factors also increase the risk of death up to 7.7 times. The maximum R0 during the epidemic was 2.4. Conclusion: Liver and kidney disease, diabetes, hypertension, and obesity are significantly associated with severe COVID-19 and death.

Objetivo: identificar factores de riesgo para desenlace a COVID-19 grave en pacientes mexicanos con de COVID-19 en población en Quintana Roo. Material y métodos: estudio de 5,916 quienes cumplieron criterios de casos sospechosos de COVID-19, 2,531 confirmados por pruebas qrTPCR-Sars-CoV-2 de los cuales 1,486 fueron positivos entre los cuales se clasifico en hosptializados (COVID-19 grave) y ambulatorios. Se realizó análisis de regresión logística multivariada para explorar los factores asociados con la gravedad de COVID-19 y defunción como desenlaces clínicos. Se calculó el número básico de reproducción (R0) Análisis estadístico) Aval del comité de ética 2301. Resultados: pacientes positivos a SARS-CoV-2 presentaron alta prevalencia de hipertensión 29.1%, diabetes 23.5%, obesidad 24%, y 48.5% tiene al menos una enfermedad crónica. Existe alto riesgo de severidad para COVID-19 en pacientes con diabetes OR=3.14; hipertensión OR=1.88, obesidad OR=1.68, enfermedad renal OR=3.2, mayores de 65 años OR=13.6 y hombres OR=1.7. Estos factores también incrementan el riesgo de defunción hasta 7.7 veces. El R0 máximo durante la epidemia fue de 2.4. Conclusión: la enfermedad hepática, renal, diabetes, hipertensión y obesidad se asocian significativamente a COVID-19 severo y defunción.

Impaired fasting glucose, oxidative distress, and cognitive impairment. Is this the starting point on DBT cognitive decline?

Different studies performed in human patients, animal models, and in vitro cell cultures, show a correlation between type 2 diabetes (DBT2) and certain neurodegenerative pathologies. Also, it was proposed that increased inflammation and- or oxidative distress are a possible cause of DBT2-accelerated cognitive decline. The onset of DBT2 is characterized by an increase in blood glucose levels due to (an inability of the body's cells to use insulin properly) called impaired fasting glucose (IFG). Genetic and/or molecular causes of IFG have not yet been established, but metabolic syndrome, obesity, unbalanced diets, and sedentary lifestyle would be responsible, at least in part, for the multiplication in the number of this disease. It has been proposed that hyperglycemia itself causes an imbalance in the redox state and could compromise blood-brain barrier (BBB) causing neurodegeneration. For this reason, we propose, in this review, to evaluate the available data about redox state and neurocognitive studies during the IFG period.

Variantes citogenéticas en pacientes con síndrome de Turner diagnosticadas en un hospital de tercer nivel de atención en Ecuador / Cytogenetic variants in patients with Turner syndrome diagnosed in a third level care hospital in Ecuador

Resumen Introducción: El Síndrome de Turner (ST) es una alteración cromosómica sexual causada por la ausencia parcial o completa del cromosoma X, además de mosaicismos y otras alteraciones estructurales del cromosoma X o Y; está presente en 1 de 2500 nacidas vivas. Objetivo: Describir las variantes citogenéticas de pacientes con síndrome de Turner y evaluar su asociación con el fenotipo de presentación y la edad del diagnóstico. Método: Estudio retrospectivo de corte transversal de una serie de 82 casos de síndrome de Turner. Los cariotipos fueron realizados utilizando el medio RPMI-1640; las preparaciones de cromosomas se obtuvieron utilizando técnicas estándar y se analizaron mediante bandas GTG con una resolución de 400-450 bandas, donde se contó con 20-50 metafases para reducir la probabilidad de no detección de mosaicismo. Resultados: 45 (55.6%) fueron diagnosticadas, con monosomía clásica del cromosoma X, mientras 29 (35,8%) mostraron anomalías estructurales del cromosoma X y 7 (8,6%) se asociaron a mosaicos numéricos del cromosoma X. Solo 21 (26%) pacientes fueron diagnosticadas por debajo de los 12 años, mientras el resto 60 (74%) se detectaron entre la adolescencia y la adultez. La baja estatura fue una característica universal en todos los grupos de estudio. Conclusiones: Las fórmulas cromosómicas en el síndrome de Turner pueden ser muy variadas y tener diversas implicaciones en el fenotipo; se destaca la baja talla como un criterio clínico relevante en la sospecha clínica.

Abstract Introduction: Turner Syndrome (TS) is a sexual chromosomal alteration caused by the partial or complete absence of the X chromosome, in addition to mosaicisms and other structural alterations of the X or Y chromosome; It is present in 1 in 2,500 live births. Objective: To describe the cytogenetic variants of Turner syndrome patients and to evaluate their association with the phenotype at presentation and age at diagnosis. Methods: Retrospective cross-sectional study of a series of 82 cases of Turner syndrome. Karyotypes were performed using RPMI-1640 medium; Chromosome preparations were obtained using standard techniques and analyzed by GTG banding with a resolution of 400-450 bands where 20-50 metaphases were counted to reduce the probability of missing mosaicism. Results: 45 (55.6%) were diagnosed with classic monosomy of the X chromosome, while 29 (35.8%) showed structural abnormalities of the X chromosome and 7 (8.6%) were associated with numerical mosaics of the X chromosome. Only 21 (26%) patients were diagnosed under 12 years of age, while the rest 60 (74%) were detected between adolescence and adulthood. Short stature was a universal characteristic in all study groups. Conclusions: The chromosomal formulas in Turner syndrome can be variable and have different implications in the phenotype; short stature stands out as a relevant clinical criterion in clinical suspicion.

Morphological Biomarkers in the Amygdala and Hippocampus of Children and Adults at High Familial Risk for Depression.

Major Depressive Disorder (MDD) is highly familial, and the hippocampus and amygdala are important in the pathophysiology of MDD. Whether morphological markers of risk for familial depression are present in the hippocampus or amygdala is unknown. We imaged the brains of 148 individuals, aged 6 to 54 years, who were members of a three-generation family cohort study and who were at either high or low familial risk for MDD. We compared surface morphological features of the hippocampus and amygdala across risk groups and assessed their associations with depression severity. High- compared with low-risk individuals had inward deformations of the head of both hippocampi and the medial surface of the left amygdala. The hippocampus findings persisted in analyses that included only those participants who had never had MDD, suggesting that these are true endophenotypic biomarkers for familial MDD. Posterior extension of the inward deformations was associated with more severe depressive symptoms, suggesting that a greater spatial extent of this biomarker may contribute to the transition from risk to the overt expression of symptoms. Significant associations of these biomarkers with corresponding biomarkers for cortical thickness suggest that these markers are components of a distributed cortico-limbic network of familial vulnerability to MDD.

Pueblos indígenas suramericanos e interculturalidad en la pandemia de COVID-19

RESUMEN La incertidumbre es la regla en el abordaje sanitario para mitigar la pandemia de COVID-19 en los pueblos indígenas en muchos países al sur del continente americano. Es aquí donde tiene cabida la pertinencia intercultural como herramienta necesaria para aproximar el mundo científico-tecnológico o biologicista a la cultura de cada pueblo, es decir, a la construcción dinámica de creencias, conocimientos, pensamientos y prácticas o conductas aprendidas en su relación con el medio ambiente e iguales, con el fin de lograr un acuerdo mínimo en el tratamiento de patologías emergentes, y por tanto, no incluidas en los programas sanitarios y que pueden resultar devastadoras para estos sectores debido a sus peores condiciones para enfrentarla. La pertinencia intercultural, tema de transcendental actualidad, se cree es la estrategia con la que los Estados pueden aplicar plenamente en material de salud su carta magna, toda vez que muchas reconocen la organización social, política y económica que rige a los pueblos indígenas, y particularmente sus costumbres culturales y religiosas, su lengua y hábitat.

ABSTRACT Uncertainty is the rule in the health approach to mitigate COVID-19 pandemic in indigenous peoples in many countries in the south of the American continent. This is where intercultural relevance has a place as a necessary tool to bring the scientific-technological or biological world closer together to the culture of each people, that is, to the dynamic construction of beliefs, knowledge, thoughts and practices or behaviors learned in their relationship with the environment and peers, in order to achieve a minimum agreement in the treatment of emerging pathologies, and therefore, not included in health programs and that can be devastating for these sectors due to their worse conditions to face it. Intercultural relevance, a transcendental issue today, is believed to be the strategy with which States can fully apply their Magna Carta in health matters, since many recognize the social, political and economic organization that governs indigenous peoples, and particularly their cultural and religious customs, their language and habitat.

RESUMO A incerteza é a regra na abordagem da saúde para mitigar a pandemia de COVID-19 em povos indígenas em muitos países do sul do continente americano, onde a relevância intercultural tem lugar como ferramenta necessária para aproximar o mundo científico-tecnológico ou biológico mais próximos da cultura de cada povo, ou seja, da construção dinâmica de crenças, conhecimentos, pensamentos e práticas ou comportamentos aprendidos em sua relação com o meio ambiente e com os pares, a fim de alcançar um acordo mínimo no tratamento de patologias emergentes , e, portanto, não incluídos nos programas de saúde e que podem ser devastadores para esses setores devido às suas piores condições de enfrentá-lo. A relevância intercultural, hoje uma questão transcendental, acredita-se ser a estratégia com a qual os Estados podem aplicar plenamente sua Carta Magna em matéria de saúde, já que muitos reconhecem a organização social, política e econômica que rege os povos indígenas e, particularmente, seus costumes culturais e religiosos, sua língua e habitat.

Degradation of high concentrations of azithromycin when present in a high organic content wastewater by using a continuously fed laboratory-scale UASB bioreactor.

As the presence of emergent contaminants in wastewater, such as antibiotics, has become a threat for public health, the evaluation of strategies to treat them has been gaining importance. A critical example of this situation can be found in wastewaters coming from the pharmaceutical industry, where high concentrations of antibiotics are sometimes accompanied by high organic contents. Even the agroindustry can be affected by a similar problem when cattle infections are treated with antibiotics and part of the antibiotic-contaminated milk has to be wasted. With these situations in mind, in the present study we evaluated a progressive acclimation strategy for a granular sludge in a UASB reactor treating a high organic-content synthetic wastewater contaminated with azithromycin. In parallel, we tested a previously reported low-cost method for azithromycin determination by spectrophotometry, obtaining results comparable with liquid chromatography coupled to mass spectrometry. Although azithromycin has been reported as recalcitrant and resistant to biological degradation, the antibiotic was removed with efficiencies over 50% for wastewater with 10 mg L-1 of azithromycin and a COD of more than 4000 mgO2 L-1. Furthermore, efficiencies over 40% were achieved for wastewater with higher azithromycin concentrations (80 mg L-1) and a COD of 20,000 mgO2 L-1. A careful acclimation strategy permitted the partial removal of azithromycin from wastewater when treating concentrations comparable and higher than what would be expected for domestic and hospital wastewaters, even when its chemical oxygen demand is considerably higher than the average maximum of around 1000 mgO2 L-1.