Abstract The development of living beings depends on the health and chemical quality of the available water. In recent years, the importance of the environment in the spread of resistant and multi-resistant bacteria to antibiotics has been observed, a situation that has placed the problem of antibiotic resistance on a broader level and which is being studied from the perspective “One Health”. The objective of this work was to determine the presence of multi-resistant bacteria to antibiotics in irrigation water samples from the Chibunga river. Fourteen water samples of 100 mL each were collected in sterile containers and aseptically, were kept under refrigeration until analysis in the laboratory. Each sample was seeded by the surface seeding method on blood, cystine electrolyte deficient, MacConkey, Salmonella-Shigella and thiosulfate citrate bile sucrose agars, incubating in all cases at a temperature of 37 °C for a maximum time of 48 hours. The identification of bacterial colonies was carried out through physiological and biochemical tests according to the identification schemes indicated by MacFaddin. The resistance/sensitivity to antibiotics of the identified colonies was carried out by the disk diffusion method of Kirby Bauer. Two species of multi-resistant bacteria were identified, including strains of Morganella morgani and Plesiomonas shigelloides resistant to antibiotics of clinical use such as ceftazidime, aztreonam, ciprofloxacin, nalidixic acid and trimethoprim-sulfamethoxazole. The results show that the waters of Chibunga river harbor bacteria with multi-resistance to antimicrobials, representing a contamination risk of agricultural products harvested in its vicinity, as well as for the people who use these waters.

Resumen El bienestar y desarrollo de los seres vivos depende de la calidad sanitaria y química del agua disponible. En los últimos años se ha venido observando la importancia del ambiente en la diseminación de bacterias resistentes y multirresistentes a los antibióticos, situación que ha colocado la problemática de la resistencia en un plano más amplio y que se está estudiando desde la perspectiva “One Health”. En este sentido, el objetivo del presente trabajo fue determinar la presencia de bacterias multirresistentes a los antibióticos en muestras de agua de riego provenientes del río Chibunga. Se recolectaron 14 muestras de agua de un volumen de 100 mL cada una, en envases estériles y de manera aséptica, las cuales fueron conservadas bajo refrigeración hasta su análisis en el laboratorio. Cada muestra fue sembrada por el método de siembra en superficie en los agares cistina electrolito deficiente, MacConkey, Salmonella-Shigella, tiosulfato citrato bilis sacarosa y agar sangre, incubándose en todos los casos a una temperatura de 37 °C durante un tiempo máximo de 48 horas. La identificación de las colonias bacterianas se realizó mediante pruebas fisiológicas y bioquímicas de acuerdo con los esquemas de identificación indicados por MacFaddin. El perfil de susceptibilidad a los antibióticos de las colonias identificadas se realizó por el método de difusión en disco de Kirby Bauer. Se lograron identificar 2 especies de bacterias multirresistentes, entre ellas, cepas de Morganella morganii y Plesiomonas shigelloides resistentes a antibióticos de uso clínico como ceftazidima, aztreonam, ciprofloxacino, ácido nalidíxico y trimetroprim-sulfametoxazol. Los resultados muestran que las aguas del río Chibunga albergan bacterias con multirresistencia a los antimicrobianos, representando un riesgo de contaminación de los productos agrícolas cosechados en sus inmediaciones, así como para las personas que utilizan estas aguas.

Abstract Background: Members of the genus Cupiennius Simon, 1891 are categorized as wandering spiders and are part of the family Trechaleidae. The genomics and proteomics of Cupiennius spiders from North America remain uncharacterized. The present study explores for the first time molecular data from the endemic species Cupiennius chiapanensis Medina, 2006, and also presents new data for Cupiennius salei (Keyserling, 1878), both collected in southern Mexico. Methods: In total, 88 Cupiennius specimens were collected from southern Mexico and morphologically identified. DNA was extracted and the mitochondrial COI fragment was amplified. COI sequences were analyzed, and a phylogenetic tree was inferred for species from the Americas. Genetic diversity was analyzed using haplotype networks and gene distances. Venom was obtained from C. chiapanensis and C. salei by electrostimulation. The venom was separated by HPLC, visualized using SDS-PAGE, and quantified for use in toxicity bioassays in mice and insects. Results: Analysis of COI sequences from C. chiapanensis showed 94% identity with C. salei, while C. salei exhibited 94-97% identity with sequences from Central and South American conspecifics. The venom from C. chiapanensis exhibited toxic activity against crickets. Venoms from C. chiapanensis and C. salei caused death in Anastrepha obliqua flies. Analysis of venom fractions from C. salei and C. chiapanensis revealed molecular masses of a similar size as some previously reported toxins and neurotoxic components. We determined the amino acid sequences of ChiaTx1 and ChiaTx2, toxins that are reported here for the first time and which showed toxicity against mice and insects. Conclusion: Our work is the first to report COI-based DNA barcoding sequences from southern Mexican Cupiennius spiders. Compounds with toxic activity were identified in venom from both species. Background Simon 189 Trechaleidae uncharacterized Medina 2006 Keyserling, Keyserling (Keyserling 1878, 1878 , 1878) Methods total 8 amplified Americas distances C electrostimulation HPLC SDSPAGE, SDSPAGE SDS PAGE, PAGE SDS-PAGE insects Results 94 9497% 9497 97% 97 94-97 conspecifics crickets flies components ChiaTx ChiaTx2 Conclusion COIbased based 18 200 187 9 949 94-9 1 20 94- 2

Summary: Maize is an important cereal in terms of human and animal nutrition worldwide. In our study, the bacterial microbiome composition of the soil rhizosphere was compared among three maize (Zea mays L.) races: forage (C1), dual-purpose (C2) and grain (C3). Additionally, the impact of the bacterial microbiome of the soil rhizosphere over yield was determined. Our study was conducted in plots located in the El Retiro Experimental Field at Universidad Autónoma Agraria Antonio Narro (UAAAN). Soil sampling was carried out in June 13, 2021, 51 days after sowing. DNA was extracted from three samples of each maize race. The V3-V4 region of the 16S rRNA gene was amplified and massive next-generation sequencing was performed with Illumina. The bioinformatic analysis was conducted in QIIME using the bacterial taxonomic reference of EzBioCloud. The phylum Proteobacteria, the class Phycisphaerae, the orders Shingomonadales, Micrococcales and Phycisphaerales, the families Moroxellaceae, Micrococcaceae, Chitinophagaceae, Shingobacteriaceae and Enterobacteriaceae, as well as the genera Acinetobacter, Shingobacterium and Cryseobacterium, were the bacterial taxa that differed in relative abundance among the three races (P < 0.05, Kruskal-Wallis test and an average dissimilarity > 0.10 in the SIMPER analysis). Among the taxa identified, plant growth promoting bacteria (PGPB) such as Acinetobacter and Sphingobacterium were detected. The race C2 showed the best yields of grain weight (15.56 Mg ha-1) and forage dry weight (10.61 Mg ha-1). Thus, we conclude that C2 represents a good option to preserve the seed and that further research should be developed for this race under different conditions.

Resumen: El maíz es un cereal de importancia en términos de nutrición humana y animal a nivel mundial. En el presente estudio se comparó el microbioma bacteriano de la rizosfera del suelo entre tres razas criollas de maíz (Zea mays L.), forrajero (C1), doble propósito (C2) y grano (C3); asimismo se determinó su impacto sobre el rendimiento. Se trabajó en parcelas ubicadas en el Campo Experimental El Retiro de la Universidad Autónoma Agraria Antonio Narro (UAAAN). El muestreo de suelo se efectuó el 13 de junio del 2021, 51 días después de la siembra. El DNA se extrajo a partir de tres muestras de cada tipo de raza de maíz. Se amplificó la región V3-V4 del gen 16S rRNA y se realizó secuenciación masiva de siguiente generación con Illumina; el análisis bioinformático se desarrolló en QIIME utilizando la referencia taxonómica bacteriana EzBioCloud. El phylum Proteobacteria, la clase Phycisphaerae, los órdenes Shingomonadales, Micrococcales y Phycisphaerales, las familias Moroxellaceae, Micrococcaceae, Chitinophagaceae, Shingobacteriaceae y Enterobacteriaceae, así como los géneros Acinetobacter, Shingobacterium y Cryseobacterium, fueron los taxa bacterianos que difirieron en abundancia relativa entre las tres razas (P < 0.05, prueba Kruskal-Wallis y una disimilitud promedio > 0.10 en el análisis SIMPER). Dentro de los taxa mencionados se detectaron bacterias promotoras de crecimiento vegetal (BPCV) como Acinetobacter y Sphingobacterium. Se concluye que, de las razas analizadas, la C2 mostró los mejores rendimientos de peso del grano (15.56 Mg ha-1) y peso seco en forraje (10.61 Mg ha-1), la cual representa una buena opción para preservar la semilla y realizar investigaciones posteriores bajo diferentes condiciones.

ABSTRACT Introduction: The identification of the wide tropism of SARS-CoV-2 can be critical for viral pathogenesis, and it is therefore relevant to determine the infection mechanisms and identify new therapeutic targets. This study consists of two experimental blocks: a) isolation and characterization of the SARS-CoV-2 virus, and b) pathogenesis, tropism, and targets, both molecular and therapeutic. Methods: The procedures used were the following: a) clinical samples were obtained from the nasopharyngeal cavity of COVID-19 positive patients, which were inoculated in Vero E6 cells and analyzed by Scanning Electron Microscopy 72 h after infection. b) They were obtained visceral organ samples (lung, liver, kidney and brain) from patients dyed from COVID-19. Cryocuts were prepared and evaluated by Masson's Trichrome Staining, Electron Microscopy and Confocal Microscopy. Results: Results show a) Extensive damage in infected Vero E6 cells where virus particles and extracellular virions are observed, displaying a cytopathic effect; b) They were identified Physio pathological processes using Masson's Trichrome Staining, detecting a predominance of the most advanced stages of Diffuse Alveolar Damage. Using Electron Microscopy, we found a profuse loss of alveolar epithelial cells in the lung. Confocal Microscopy was able to detect the presence of the SARS-CoV-2 nucleocapsid co-localized with key molecules such as Fibronectin, Vimentin, and PPARγ, together with NLRP3 Inflammasome in the brain cortical tissues. Conclusions. The isolation of the SARS-CoV-2 virus was performed for the first time in Cuba in nasopharyngeal exudates of patients with COVID-19 in the Vero E6 cell line. We identified for the first time novel cellular and pathophysiological processes involved in the infection of SARS-CoV-2, as well as potential therapeutic targets that reveal promising drugs to combat COVID-19 and its sequelae.

RESUMEN Introducción: La identificación del amplio tropismo del SARS-CoV-2 puede ser crítico para la patogénesis viral, por lo que es relevante conocer los mecanismos de infección e identificar nuevas dianas terapéuticas. Esta investigación consta de 2 bloques experimentales: aislamiento y caracterización del virus SARS-CoV-2 y patogénesis, tropismo, dianas moleculares y terapéuticas. Métodos: Se realizaron los siguientes procederes a) de la cavidad nasofaríngea de pacientes positivos al COVID-19, se obtuvo muestras clínicas que se inocularon en las células Vero E6 y se analizaron mediante microscopía electrónica de barrido a las 72 h postinfección; b) se obtuvo muestras de órganos viscerales de fallecidos por COVID-19: pulmón, hígado, riñón y cerebro. Los criocortes o cortes ultra finos se evaluaron mediante la tinción de tricrómica de masson, microscopía electrónica y la microscopia confocal. Resultados: Se obtuvo los siguientes resultados principales: a) se identificó un extenso daño en las células Vero E6 infectadas en las cuales se pudieron observar partículas de virus y viriones extracelulares, evidenciando un efecto citopático; b) se identificaron procesos fisiopatológicos: por tinción de tricrómica de Masson, se identificó un predominio de las etapas más avanzadas del daño alveolar difuso, al microscopio electrónico en pulmón, se evidenció la pérdida abundante de las células epiteliales alveolares. A través de microscopia confocal, se detectó la presencia de la nucleocápside del SARS-CoV-2 colocalizada con las moléculas claves tales como: fibronectina, vimentina, PPARγ conjuntamente con el inflamasoma NLRP3 en tejidos corticales cerebrales. Como conclusiones, en esta investigación: a) se realizó por primera vez el aislamiento del virus SARS-CoV-2 en Cuba en exudados nasofaríngeos de pacientes con COVID-19 en la línea celular Vero E6. b) Se identificó por primera vez; novedosos procesos celulares y fisiopatológicos involucrados en la infección del virus SARS-CoV-2 y potenciales dianas terapéuticas que revelan fármacos prometedores para combatir la COVID-19 y sus secuelas.

Resumen Objetivo: Comparar los resultados anatómicos en pacientes con desprendimiento de retina regmatógeno, vitreorretinopatía proliferativa a partir de grado B y aplicación de implante de dexametasona transquirúrgico frente a un grupo control. También se valoraron la disminución de la vitreorretinopatía proliferativa y la agudeza visual (AV) final. Método: Los pacientes se evaluaron clínicamente y con tomografía de coherencia óptica por 10 meses. Se realizaron análisis de regresión logística para evaluar el efecto del implante en el redesprendimiento de retina. Se exploraron análisis correlacionales dependiendo de la distribución de variables y se aplicó la prueba t de muestras independientes para comparar la AV en ambos grupos. Resultados: Se incluyeron 38 ojos de pacientes con vitreorretinopatía proliferativa: 18 con el implante y 20 del grupo control. La evaluación del objetivo principal mostró diferencias significativas (p < 0.05) en el éxito anatómico entre ambos grupos (61.1% en los ojos con tratamiento frente a 20% en el grupo control); razón de momios de 6.29; intervalo de confianza del 95%: 1.5- 26.8; p = 0.013; R2 de Nagelkerke = 0.225. La prueba t mostró una diferencia significativa entre la AV final de los pacientes (t = 2.047; gl = 36; p = 0.048; d de Cohen = 0.66). Conclusiones: Se observó menor redesprendimiento, así como mejor AV, en los pacientes con el implante de dexametasona en comparación con el grupo control.

Abstract Objective: To compare the anatomical results in patients with rhegmatogenous retinal detachment, at least grade B of proliferative vitreoretinopathy, and with a trans-surgical dexamethasone implant vs the control group. We also assessed the diminution of proliferative vitreoretinopathy and the final visual acuity (VA). Method: The patients were evaluated clinically and with optical coherence tomography for 10 months. Logistic regression analyses were performed to evaluate the effect of the dexamethasone implant on retinal detachment. Correlational analyses were explored depending on the variables' distribution, and an independent samples t-test was used to compare the VA in both groups. Results: The study included 38 eyes of patients with proliferative vitreoretinopathy: 18 with the implant and 20 for the control group. The evaluation of the main objective showed significant differences (p < 0.05) in the anatomical success between the two groups (61.1% vs. 20%, treatment vs. control); odds ratio of 6.29; 95% confidence interval: 1.5- 26.8; p = 0.013; Nagelkerke's R2 = 0.225. The t-test showed a significant difference in the final VA of the patients (t = 2.047; df = 36; p = 0.048; Cohen's d = 0.66). Conclusions: Retinal redetachment was less frequent, and better VA was observed, in patients with the dexamethasone implant in comparison with the control group.

Resumen Objetivo: Identificar los factores asociados a la sobrevida a un año en pacientes postoperados de glioblastoma en un hospital del noreste de México. Material y métodos: Estudio de casos y controles anidado en una cohorte. Se incluyeron pacientes operados de glioblastoma entre 2016 y 2019. Se obtuvo la información sobre factores clínicos y quirúrgicos, se calculó la sobrevida mediante análisis de Kaplan-Meier. El análisis descriptivo se realizó con medianas y rangos, y el inferencial con prueba de χ2, Fisher, t de Student, razón de momios e intervalo de confianza al 95%. Se consideró significativo un valor de p < 0.05. Resultados: Se incluyeron 62 pacientes con glioblastoma, 27 (43.5%) mujeres y 35 (56.5%) hombres, mediana de edad de 56 años (rango: 6-83). La mediana de sobrevida fue de 3.6 meses (1-52), 45 (72.6%) sobrevivieron menos de 12 meses. Los factores asociados a mayor sobrevida fueron: administración de tratamiento adyuvante (p < 0.001), mejor estado funcional (p = 0.001) y ausencia de complicaciones posquirúrgicas (p = 0.034). Conclusiones: La mayoría de los pacientes con glioblastoma sobreviven menos de 12 meses y los factores más fuertemente asociados a mayor sobrevida son administración de tratamiento adyuvante, mejor estado funcional del paciente y ausencia de complicaciones posquirúrgicas.

Abstract Objective: To identify factors associated with one-year survival in postoperative glioblastoma patients at a hospital in northeastern Mexico. Material and methods: Nested case-control study. Patients operated on for glioblastoma between 2016-2019 were included. Information about clinical and surgical factors was obtained, survival was calculated by Kaplan-Meier analysis. Descriptive analysis was performed with medians and ranges, and inferential analysis with χ2, Fisher and Student t test, odds ratio and 95% confidence interval. A value of p < 0.05 was considered significant. Results: Sixty-two patients with glioblastoma were included, 27 (43.5%) women and 35 (56.5%) men, median age 56 years (range: 6-83). Median survival was 3.6 months (1-52), 45 (72.6%) survived less than 12 months. The factors associated with a higher survival were administration of adjuvant treatment (p < 0.001), better functional status (p = 0.001), and absence of post-surgical complications (p = 0.034). Conclusions: Most patients with glioblastoma survive less than 12 months and the factors most strongly associated with longer survival are administration of adjuvant treatment, better functional status of the patient and absence of post-surgical complications.

ABSTRACT Introduction: Intralesional infiltration of epidermal growth factor (EGF) has emerged as a therapeutic alternative for diabetic foot ulcer (DFU) healing. The objectives of this research were: to determine the molecular profile of patients with DFU and to characterize the systemic effects of EGF intralesional treatment in such patients, taking into account redox balance markers, components of the advanced glycation end-product (AGE) pathway, factors related to the extracellular matrix (ECM) stability and pro-inflammatory markers. Methods: Thirteen patients with DFU were characterized in comparison with diabetic patients without ulcers (compensated and non-compensated) and non-diabetic subjects, attending to redox balance markers, components of the AGE pathway, and elements related to the stability of the ECM. The systemic response of patients with DFU to the intralesional treatment with EGF was evaluated according to the same parameters, in addition to other pro-inflammatory markers. Results: Patients with DFU exhibited the most disheveled biochemical profile, with elevated oxidative stress, low antioxidant reserves, increased glycoxidation products and matrix metalloproteases (MMP), with respect to non-ulcerated diabetic patients and to non-diabetic subjects. The intralesional administration of EGF was associated with a significant recovery of the parameters studied and with the systemic attenuation of several pro-inflammatory markers. Conclusions: These results indicate that intralesional infiltration of EGF translates into systemic antioxidant, anti-inflammatory, anti-degradative and anti-AGE effects, which contribute to restoring homeostasis in the diabetic patient.

RESUMEN Introducción: La infiltración intralesional con factor de crecimiento epidérmico (EGF) ha emergido como alternativa terapéutica para la cicatrización de las úlceras de pie diabético (UPD). Los objetivos de esta investigación fueron: determinar el perfil molecular de los pacientes con UPD y caracterizar los efectos sistémicos del tratamiento intralesional con EGF en tales pacientes atendiendo a marcadores de balance redox, componentes de la vía de los productos avanzados de glicación (AGE), factores relacionados con la estabilidad de la matriz extracelular (MEC) y marcadores pro-inflamatorios. Métodos: Se caracterizaron 13 pacientes con UPD en comparación con diabéticos sin úlceras (compensados y no compensados) e individuos no diabéticos, atendiendo a marcadores de balance redox, componentes de la vía de los AGE y elementos relacionados con la estabilidad de la MEC. La respuesta sistémica de los pacientes con UPD al tratamiento intralesional con EGF se evaluó atendiendo a los mismos parámetros, además de otros marcadores pro-inflamatorios. Resultados: Los pacientes con UPD exhibieron un perfil bioquímico muy alterado, con elevado estrés oxidativo, bajas reservas antioxidantes, aumento de los productos de glicoxidación y de las metaloproteasas de la matriz (MMP), con respecto a los diabéticos sin úlceras y a los no diabéticos. La administración intralesional de EGF estuvo asociada a una recuperación significativa de los parámetros estudiados y a la atenuación sistémica de varios marcadores pro-inflamatorios. Conclusiones: Los resultados indican que la infiltración intralesional con EGF se traduce en efectos sistémicos antioxidantes, anti-inflamatorios, anti-degradativos y anti-AGE, que contribuyen a restaurar la homeostasia del paciente diabético.

ABSTRACT Introduction: CIGB-258 is a peptide, whose mechanism of action has been associated with the inhibition of inflammation. This paper aims to demonstrate that CIGB-258 reduces hyperinflammation in COVID-19 patients. Methods: Pharmacokinetic and biodistribution profiles of the peptide labeled with iodine 125 [125I] were studied in Lewis rats. Thirteen critical COVID-19 patients and nine severe ones were included and treated, according to the protocol established (RPCEC00000313). Serum samples were obtained before and after treatment with CIGB-258, for the determination of biomarkers of inflammation. Results: Maximum concentration of peptide in blood from rats was at 0,5 to 1 h; and the half-life (t½) was calculated to be 6,3 to 6,9 hours. 48 h after the treatment with CIGB-258, clinical, radiological, and ventilation improvement was observed in all patients. C-reactive protein (CRP) levels significantly decreased after 72 h. CRP levels were inversely associated with oxygen uptake efficiency in the mechanical ventilation cohort in critical patients. Laboratory tests associated with hyperinflammation included white blood cell count with differential, ferritin, lactate dehydrogenase and calprotectin, which were gradually normalized. CIGB-258 led to a significant reduction of IL-6, TNF α and IL-10. Conclusion: CIGB-258 induced a clinical and radiological improvement in the patients, according with its pharmacokinetic and biodistribution profile. This improvement was associated with a decrease in biomarkers of systemic inflammation.

RESUMEN Introducción: El CIGB-258 es un péptido, cuyo mecanismo de acción se ha asociado con la inhibición de la inflamación. El presente trabajo tiene como objetivo demostrar que el CIGB-258 reduce la hiperinflamación en los pacientes con COVID-19. Métodos. Se estudió el perfil de farmacocinética y biodistribucion del péptido marcado con yodo 125 [125I], en ratas Lewis. Se analizaron 13 pacientes críticos y 9 pacientes graves con COVID-19 de acuerdo al protocolo establecido (RPCEC00000313). Se obtuvieron muestras de suero antes y después del tratamiento con el CIGB-258, para la determinación de los biomarcadores de la inflamación. Resultados: El péptido alcanzó la máxima concentración en sangre a la media hora y su aclaramiento ocurrió aproximadamente en 6 h. Después de 48 h de tratamiento con el CIGB-258, hubo una mejoría clínica, radiológica y ventilatoria (P/F) en los pacientes. La Proteína C Reactiva (PCR) disminuyó significativamente en los pacientes, a partir de las 72 h de tratamiento. Hubo una correlación inversamente significativa entre P/F y la PCR en los pacientes críticos. Otros biomarcadores de la inflamación como: ferritina, lactado deshirogenasa y calprotectina disminuyeron significativamente. La terapia con el CIGB-258 redujo el cociente neutrófilos/linfocitos a valores normales. Las interleucinas (IL)-6, IL-10 y el TNF-α disminuyeron significativamente a las 96 h del tratamiento. Conclusiones: El CIGB-258 indujo una mejoría clínica y radiológica en los pacientes, en correspondencia con su perfil de farmacocinética y biodistribución. Dicha mejoría estuvo asociada con la disminución de biomarcadores de la inflamación sistémica.

Abstract BACKGROUND Diabetic foot ulcers are a common diabetic complication leading to alarming figures of amputation, disability, and early mortality. The diabetic glucooxidative environment impairs the healing response, promoting the onset of a ‘wound chronicity phenotype’. In 50% of ulcers, these non-healing wounds act as an open door for developing infections, a process facilitated by diabetic patients’ dysimmunity. Infection can elicit biofilm formation that worsens wound prognosis. How this microorganism community is able to take advantage of underlying diabetic conditions and thrive both within the wound and the diabetic host is an expanding research field. OBJECTIVES 1) Offer an overview of the major cellular and molecular derangements of the diabetic healing process versus physiological cascades in a non-diabetic host. 2) Describe the main immunopathological aspects of diabetics’ immune response and explore how these contribute to wound infection susceptibility. 3) Conceptualize infection and biofilim in diabetic foot ulcers and analyze their dynamic interactions with wound bed cells and matrices, and their systemic effects at the organism level. 4) Offer an integrative conceptual framework of wound–dysimmunity–infection–organism damage. EVIDENCE AQUISITION We retrieved 683 articles indexed in Medline/PubMed, SciELO, Bioline International and Google Scholar. 280 articles were selected for discussion under four major subheadings: 1) normal healing processes, 2) impaired healing processes in the diabetic population, 3) diabetic dysimmunity and 4) diabetic foot infection and its interaction with the host. DEVELOPMENT The diabetic healing response is heterogeneous, torpid and asynchronous, leading to wound chronicity. The accumulation of senescent cells and a protracted inflammatory profile with a pro-catabolic balance hinder the proliferative response and delay re-epithelialization. Diabetes reduces the immune system’s abilities to orchestrate an appropriate antimicrobial response and offers ideal conditions for microbiota establishment and biofilm formation. Biofilm–microbial entrenchment hinders antimicrobial therapy effectiveness, amplifies the host's pre-existing immunodepression, arrests the wound’s proliferative phase, increases localized catabolism, prolongs pathogenic inflammation and perpetuates wound chronicity. In such circumstances the infected wound may act as a proinflammatory and pro-oxidant organ superimposed onto the host, which eventually intensifies peripheral insulin resistance and disrupts homeostasis. CONCLUSIONS The number of lower-limb amputations remains high worldwide despite continued research efforts on diabetic foot ulcers. Identifying and manipulating the molecular drivers underlying diabetic wound healing failure, and dysimmunity-driven susceptibility to infection will offer more effective therapeutic tools for the diabetic population.

Resumen Reporte de un caso: Femenino de 29 años de edad sin comorbilidades, con baja visual progresiva en ojo derecho de 1 mes de evolución. A la exploración oftalmológica agudeza visual de ese ojo en 20/80, conjuntiva bulbar superior con vaso centinela, masa retroiridiana color naranja vascularizada que subluxa el cristalino hacia inferior. Por ultrabiomicroscopía se evidencia una masa en domo dependiente del cuerpo ciliar de 4.87x5.74mm con reflectividad interna media y regular. Se realiza primeramente BAAF reportando melanoma, después se hace enucleación con resultado histopatológico de melanoma amelanótico. Posterior, se realiza implante de prótesis cosmética y se encuentra en seguimiento por oncología sin presentar datos de actividad tumoral después de 4 años. Discusión: Los melanomas uveales son la causa más común de tumores malignos intraoculares primarios en adultos, localizados principalmente en coroides (90%), siendo extremadamente rara su aparición en el cuerpo ciliar (6%) e iris (4%). El abordaje de un tumor del cuerpo ciliar debe incluir una anamnesis y exploración física completa con estudios paraclínicos adecuados para poder discernir entre los diagnósticos diferenciales. El ultrasonido ocular es el estudio auxiliar más importante ya que brinda características típicas propias del tumor. El tratamiento continúa basado en el COMS con un pronóstico sombrío. Los factores de mal pronóstico son presencia de metástasis, tamaño del tumor, extensión extraocular y estirpe epitelioide. Limitaciones: No se contaban con todas las alternativas de tratamiento. Originalidad: Caso inusual en pacientes jóvenes y por su sitio.

Abstract: Case report: 29-year-old female with no comorbidities, with progressive vision loss in the right eye of 1 month's evolution. On ophthalmological examination, visual acuity was 20/80, superior bulbar conjunctiva with sentinel vessel, vascularised orange retroiridian mass generating a lens subluxation inferiorly. Ultrabiomicroscopy revealed a dome-shaped mass dependent on the ciliary body measuring 4.87x5.74mm with medium and regular internal reflectivity. A FNA was done and melanoma was reported, then enucleation was performed with histopathological findings of amelanotic melanoma. Subsequently, a cosmetic prosthesis was implanted and the patient has been followed up by oncology with no evidence of tumour activity after 4 years. Discussion: Uveal melanomas are the most common cause of primary intraocular malignant tumours in adults, mainly located in the choroid (90%), being extremely rare in the ciliary body (6%) and iris (4%). The approach to a ciliary body tumour should include a complete anamnesis and physical examination with appropriate paraclinical studies to be able to discern between differential diagnoses. Ocular ultrasound is the most important ancillary study as it provides typical features of the tumour. Treatment is still based on COMS and the prognosis remains poor. Poor prognostic factors are the presence of metastases, tumour size, extraocular extension and epithelioid lineage. Limitations: Not all treatment alternatives were available. Originality: Unusual case in young patients and because of its site.

Abstract Purpose: To report the clinical case of a 26-year-old patient, who presented with unilateral vision loss, associated with intense photophobia and headache as the first manifestation of choroidal metastases secondary to pancreatic adenocarcinoma. Case report: Through a multidisciplinary approach, ophthalmological and oncological ancillary studies and the performance of a liver biopsy, a diagnosis of systemic and choroidal metastases secondary to pancreatic adenocarcinoma was made. Conclusions: This is the first documented case of a metastatic pancreatic adenocarcinoma presenting with unilateral vision loss in Mexico.

Resumen Objetivo: Reportar el caso de un paciente de 26 años que acudió por presentar baja visual súbita unilateral, asociada a fotofobia intensa y cefalea, como primera manifestación de metástasis coroideas secundarias a adenocarcinoma de páncreas. Caso clínico: Mediante un trabajo multidisciplinario, estudios auxiliares tanto oftalmológicos como oncológicos y la realización de una biopsia hepática se llegó al diagnóstico de metástasis sistémicas y coroideas secundarias a adenocarcinoma de páncreas. Conclusiones: Este es el primer caso documentado en México de un paciente que presenta como primera manifestación baja visual unilateral secundaria a metástasis coroideas por adenocarcinoma de páncreas.

ABSTRACT Introduction: Infection with SARS-CoV-2 induces a prothrombotic state in patients, by the combination of hyperinflammatory response and hypoxia. In Cuba, the drug called Jusvinza, based on an immunomodulatory peptide, is used for the treatment of patients with COVID-19, who present signs and symptoms of hyperinflammation. Objectives: To describe the clinical course and behavior of various biomarkers associated with the inflammation and coagulation, in a group of critically ill patients with COVID-19 treated with Jusvinza, compared to a group of patients who did not receive treatment with this peptide. Methods: 40 critically ill patients with COVID-19 were included. The patients were divided into 2 groups: 20 patients were treated with Jusvinza and 20 were not treated with this peptide (control group). Demographic characteristics, comorbidities, vital signs, respiratory parameters and inflammation and coagulation biomarkers were obtained from the medical records of each patient. Results: Treatment with Jusvinza induced a clinical improvement in the patients, associated with the decrease of several inflammation and coagulation biomarkers. Patients treated with Jusvinza had a significantly higher survival than patients not treated with this peptide. Conclusions: Jusvinza is able to control hyperinflammation and hypercoagulation in critical ill patients with COVID-19.

RESUMEN Introducción: La infección con el SARS-CoV-2 induce un estado protrombótico en los pacientes, atribuible a la combinación de la respuesta hiperinflamatoria y la hipoxia. En Cuba, se usa el fármaco Jusvinza, basado en un péptido inmunomodulador, para el tratamiento de los pacientes con la COVID-19, que presenten signos y síntomas de hiperinflamación. Objetivos: Describir la evolución clínica y las variaciones de biomarcadores asociados con la inflamación y la coagulación, en un grupo de pacientes críticos con la COVID-19, tratados con Jusvinza, en comparación con un grupo de pacientes que no recibieron tratamiento con este péptido. Métodos: Se incluyeron 40 pacientes críticos con la COVID-19; se dividieron en 2 grupos: 20 pacientes tratados con Jusvinza y 20 no fueron tratados con dicho péptido (grupo control). Las características demográficas, comorbilidades, signos vitales, parámetros respiratorios, biomarcadores de la inflamación y de la coagulación se obtuvieron a partir de las historias clínicas de cada paciente. Resultados: El tratamiento con Jusvinza indujo una mejoría clínica en los pacientes, asociada con la disminución de varios biomarcadores de la inflamación y la coagulación. La sobrevida de los pacientes tratados con Jusvinza fue significativamente superior a la sobrevida de los pacientes no tratados con este péptido. Conclusiones: Jusvinza es capaz de controlar la hiperinflamación y la hipercoagulación en pacientes críticos con la COVID-19.

ABSTRACT Introduction: Dengue is one of the most important emerging diseases transmitted by mosquitoes; only one vaccine has been approved and licensed in 20 countries against DENV. This vaccine cannot be administered to children younger than 9 years, due to the increased risk of hospitalization observed in this age group. For this reason, the development of new vaccine candidates and/or immunization strategies continue to be a priority to the World Health Organization and the scientific community. Objectives: This work describes the results in prime-boost immunization schedules combining two different vaccine candidates: recombinant proteins and live attenuated vaccines. Firstly, we evaluated the capacity of Tetra DIIIC vaccine candidate to boost a memory immune response generated in DENV-immune monkeys and as a second study, we also evaluated in monkeys the combination of Tetra DIIIC with the LATV vaccine developed by NIAID and licensed to the Vietnamese company Vabiotech under the codename TV005. Methods: Macaca mulatta non-human primates were used in the studies. The tetravalent vaccine candidate Tetra DIIIC consists of recombinant proteins DIIIC-1-DIIIC4, corresponding to the four dengue virus serotypes, in adjuvant aluminum oxide. Tetravalent formulation of attenuated live viruses TV005 by Vabiotech included the virus strains DENV-1 Nauru/74 (WP), DENV-2 Tonga/74, DENV-3 Sleman/78, and DENV-4 Dominica/81. Results: Our results demonstrate that administration of Tetra DIIIC eight months after the infection was able to recall DENV specific memory B- and T-cell response. In addition, we demonstrate that animals primed with Tetra DIIIC (one or two doses) and later immunized with TV005 develop a neutralizing, protective antibody response against the four DENV serotypes, and that the immune response generated by Tetra DIIIC reduces LATV viremia significantly, which might reduce the reactogenicity that has afflicted the latter during clinical trials. Results described here highlight the possibility to combine our vaccine candidate Tetra DIIIC with live-attenuated tetravalent vaccine in a prime/boost strategy for immunizations. The present study supports the prime-boost strategies as alternative and promissory approaches solving the troubles associated with each individual antigen included in the combination.

RESUMEN Introducción: El dengue es una de las enfermedades más importantes trasmitida por mosquitos; sin embargo, solo existe una vacuna licenciada, la cual está registrada en 20 países. Sin embargo, la vacuna no podrá ser administrada en niños menores de nueve años de edad, dado el elevado riesgo de hospitalización observado en este grupo etario. Por lo tanto, el desarrollo de nuevos candidatos vacunales y estrategias de inmunización continúan siendo una prioridad para la Organización Mundial de la Salud y la comunidad científica. Objetivos: el presente trabajo describe los resultados obtenidos de la combinación en esquemas complementarios de dos tipos de candidatos vacunales: las proteínas recombinantes y los virus vivos atenuados. En un primer acercamiento, el candidato vacunal tetravalente Tetra DIIIC se administró en primates no humanos previamente infectados con virus dengue. En un segundo estudio se evaluó la combinación de Tetra DIIIC y la formulación tetravalente de virus vivos atenuados por vía molecular TV005, desarrollada por el Instituto de Salud de los Estados Unidos y licenciada a la compañía vietnamita Vabiotech. Métodos: Se utilizaron en los estudios primates no humanos sanos de la especie Macaca mulatta. El candidato vacunal tetravalente Tetra DIIIC, consiste en las proteínas recombinantes DIIIC-1-DIIIC4, correspondientes a los cuatro serotipos del virus dengue, adyuvadas en alúmina. La formulación tetravalente de virus vivos atenuados TV005 por Vabiotech incluyó las cepas virales DENV-1 Nauru/74 (WP), DENV-2 Tonga/74, DENV-3 Sleman/78 y DENV-4 Dominica/81. Resultados: Los resultados demuestran que la administración de Tetra DIIIC ocho meses después de la infección pudo activar la respuesta específica de las células B y T contra el DENV. Además, se demostró que los animales inoculados con Tetra DIIIC (una o dos dosis) y luego inmunizados con TV005 desarrollan una respuesta de anticuerpos protectora contra los cuatro serotipos del DENV y que la respuesta inmunológica generada por la Tetra DIIIC reduce la viremia LATV significativamente, lo cual pudiera reducir la reactogenicidad que ha afectado a este último durante los ensayos clínicos. Los resultados aquí descritos resaltan la posibilidad de combinar nuestro candidato vacunal Tetra DIIIC con la vacuna tetravalente del virus vivo atenuado en una estrategia reforzada de inmunización. El presente estudio respalda las estrategias reforzadas como alternativa y enfoques promisorios que solucionan los problemas asociados a cada antígeno individual incluido en la combinación.

Abstract Loricariid catfish (Pterygoplichthys disjunctivus [Weber, 1991]) has invaded water catchments throughout the world, due to the lack of predators and high fecundity. An approach to control its population could be using its roe as food; however, more knowledge is needed. Thus, the present study aimed to evaluate the shelf-life of fresh loricariid catfish roe stored in ice, as an approach for possible food utilisation. Physicochemical characteristics (moisture content, aw, pH, hardness, and colour), protein electrophoresis (SDS-PAGE), amino and fatty acid contents, oxidative stability (TBARS) and microbiology of roe were analysed at 0, 2, 4, 6, 11, 15 and 21 days. Moisture content (58.5 ± 2.1 vs. 60.4 ± 1.2%), aw (0.89) and pH (5.87 ± 0.14 vs. 5.96 ± 0.03) were shelf-stable (initial vs. final day, respectively). SDS-PAGE showed minor hydrolysis of its protein. Ice storage increased roe free amino acid concentration, confirming proteolysis of its proteins/peptides with not impact on the fatty acid content and TBARS (2.4–3.3 mg malonadehyde/kg sample). Thus, ice storage of fresh loricariid catfish (P. disjunctivus [Weber, 1991]) roe, under the study conditions, proved to be an effective preservation method for its food utilisation, maintaining its physicochemical and microbiological characteristics for up to 20 days.