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Abstract Background The course of kidney function and outcomes of severe malaria infection in pregnant women is poorly understood. The indications for renal replacement therapy in pregnant patients with AKI are similar to the general population. This is the case of a pregnant patient with severe Plasmodium falciparum infection that caused cerebral malaria, acute kidney injury (AKI) who required renal replacement therapy and kidney biopsy during her hospitalization. Case presentation A 29-year-old pregnant woman from Equatorial Guinea was admitted to the hospital with haemolytic anaemia, hyperbilirubinaemia and thrombocytopenia. During hospitalization, a thick blood smear was performed where parasitaemia by P. falciparum were observed and confirmed by real-time PCR assay. The patient developed cerebral malaria secondary to an ischaemic-type cerebral vascular event, hypotension and severe. After confirming diagnosis of P. falciparum infection, artesunate, artemether/lumefantrine and primaquine were started. Kidney biopsy revealed an active tubulointerstitial nephritis with acute tubular lesion and pigment tubulopathy with negative immunofluorescence. After CVVHDF, the patient received intermittent haemodialysis until the recovery of kidney function. After discharge, follow-up was carried until the successful resolution of the pregnancy by cesarean delivery and not shown deterioration in kidney function or proteinuria. Conclusion In this case, intensive dialysis was started and dialysis intensity progressively reduced when kidney function improved. Due to the evolution of kidney function, a kidney biopsy was performed which showed tubulointerstitial nephritis as a manifestation of the infection. While the kidney biopsy was of interest for discriminating between tubular and glomerular involvement, the availability of placental biomarkers (sflt1-PlGF) would have been of help for ruling out preeclampsia and placental damage. The multidisciplinary approach to AKI during pregnancy should be the rule, with diligent care of maternal–fetal well-being during pregnancy and monitoring of kidney function after delivery.

Background: As the migratory flow to the USA has intensified in recent months, health problems associated have been identified. The aim of this work was the identification of malaria cases imported into Mexican territory. Methods: Operational definitions of suspected and confirmed cases were used for investigation of malaria cases. Detection of parasitic entities by thick blood smear and molecular biology served as a confirmatory test. With the characteristics of the cases, a heat map was made to determine common clinical pictures. Finally, epidemiological analysis of cases was performed for the construction of timelines of imported malaria and the tracing of migratory routes. Results: Twelve migrants from four countries were treated for presenting clinical symptoms with suspected dengue or malaria. Malaria was confirmed and two Plasmodium species were identified. From the epidemiological dates of arrival in Mexico, onset of symptoms and migratory routes, we speculate that ten cases acquired P. vivax during their crossing through Honduras, El Salvador or Guatemala. For the Guinea cases, we conclude that there was African importation of P. falciparum. Conclusion: The epidemiological panorama of malaria cases imported into Mexico show the need to join efforts to ensure universal access to health services, with the objective of timely detection of imported cases.

In the SARS-CoV-2 lineage, RNA elements essential for its viral life cycle, including genome replication and gene expression, have been identified. Still, the precise structures and functions of these RNA regions in coronaviruses remain poorly understood. This lack of knowledge points out the need for further research to better understand these crucial aspects of viral biology and, in time, prepare for future outbreaks. In this research, the in silico analysis of the cis RNA structures that act in the alpha-, beta-, gamma-, and deltacoronavirus genera has provided a detailed view of the presence and adaptation of the structures of these elements in coronaviruses. The results emphasize the importance of these cis elements in viral biology and their variability between different viral variants. Some coronavirus variants in some groups, depending on the cis element (stem-loop1 and -2; pseudoknot stem-loop1 and -2, and s2m), exhibited functional adaptation. Additionally, the conformation flexibility of the s2m element in the SARS variants was determined, suggesting a coevolution of this element in this viral group. The variability in secondary structures suggests genomic adaptations that may be related to replication processes, genetic regulation, as well as the specific pathogenicity of each variant. The results suggest that RNA structures in coronaviruses can adapt and evolve toward different viral variants, which has important implications for viral adaptation, pathogenicity, and future therapeutic strategies.

Existen diversos factores que pueden modificar la productividad en los hatos ovinos, uno de ellos es la parasitosis gastrointestinal (GI) por nematodos, la cual puede generar pérdida de peso, retrasos en el crecimiento y en situaciones extremas la muerte. Las infecciones de parásitos involucran al sistema inmune para la resistencia o susceptibilidad, por lo que actualmente se buscan estrategias que sean eficientes a largo plazo para disminuir esta afectación. Una de estas estrategias es la ganadería de precisión, la cual consiste en la identificación y selección de animales genéticamente más resistentes, empleando para ello marcadores moleculares. El objetivo de esta revisión es reunir información novedosa en rasgos cuantitativos (QTL) y estudios de asociación del genoma completo (GWAS), que confirman la relevancia de algunas regiones o genes en la resistencia a la parasitosis gastrointestinal ovina. Así mismo, se analizó la posible relevancia de nuevas regiones para realizar mapeos más finos y encontrar conjuntos de polimorfismos que permitan una selección más eficiente, considerando al mismo tiempo, las condiciones particulares de los hatos ovinos.

Infections pose a risk for patients undergoing hematopoietic stem cell (HSC) transplants due to their immunosuppression, making them susceptible to opportunistic infections. Therefore, understanding the composition of the aerobiome in this area is vital. The aim of this study was to characterize the aerobiome in an HSC transplant area, evaluating the impact of infrastructure and health personnel operations on air contamination. The environmental parameters and aerobiome of the HSC transplant area at Hospital Juárez de México were quantified over one year. Finally, a double-entry Vester matrix was constructed to classify problems according to their degree of causality. The abundance and taxonomic diversity of the aerobiome were dependent on seasonality, environmental factors, and high-efficiency filtration. Gram-positive bacteria predominated, followed by fungi and Gram-negative bacteria. ANOVA revealed significant differences in the bacterial aerobiome but not in the fungal aerobiome among the transplant rooms. Clinically, fungi such as Aspergillus fumigatus, Alternaria spp., Cladosporium spp., and Penicillium spp. were identified. ESKAPE bacteria typing revealed clonal dispersion. Finally, the Vester matrix highlighted critical problems associated with contamination due to the absence of HEPA filtration and non-adherence in patient management practices. HEPA filtration and positive pressure are essential to improve the air quality and reduce the microbiological load. However, the control areas will depend on patient management and routine activities, such as entry protocols in controlled areas.

Acinetobacter pittii has increasingly been associated with several types of hospital-acquired severe infections. Genes implicated in carbapenem resistance, tigecycline resistance, or genes encoding extended spectrum cephalosporinases, such as blaADC, are commonly found in isolates implicated in these infections. A. pittii strains that are pandrug resistant have occasionally been identified. Food for human consumption, animals and plants are environmental sources of this pathogen. An alarming situation is that A. pitti has been identified as responsible for outbreaks in different regions worldwide. In this study, 384 genomes of A. pittii were analyzed, comprising sequences from clinical and non-clinical origins from 32 countries. The objective was to investigate if clinical strains possess genetic traits facilitating hospital adaptation. Results indicate significant genomic variability in terms of size and gene content among A. pittii isolates. The core genome represents a small portion (25–36%) of each isolate’s genome, while genes associated with antibiotic resistance and virulence predominantly belong to the accessory genome. Notably, antibiotic resistance genes are encoded by a diverse array of plasmids. As the core genome between environmental and hospital isolates is the same, we can assume that hospital isolates acquired ARGs due to a high selective pressure in these settings. The strain’s phylogeographic distribution indicates that there is no geographical bias in the isolate distribution; isolates from different geographic regions are dispersed throughout a core genome phylogenetic tree. A single clade may include isolates from extremely distant geographical areas. Furthermore, strains isolated from the environment or animal, or plant sources frequently share the same clade as hospital isolates. Our analysis showed that the clinical isolates do not already possess specific genes, other than antibiotic-resistant genes, to thrive in the hospital setting.

ABSTRACT Acinetobacter junii is an opportunistic human and animal pathogen severely understudied. Here, we conducted the largest genomic epidemiological study on this pathogen to date. Our data show that this bacterium has spread globally. Also, we found that some human and non-human isolates are not well differentiated from one another, implying transmission between clinical and non-clinical, non-human settings. Remarkably, human but also some non-human isolates have clinically important antibiotic resistance genes, and some of these genes are located in plasmids. Given these results, we put forward that A. junii should be considered an emerging One Health problem. In this regard, future molecular epidemiological studies about this species will go beyond human isolates and will consider animal-, plant-, and water-associated environments.IMPORTANCEAcinetobacter baumannii is the most well-known species from the genus Acinetobacter. However, other much less studied Acinetobacter species could be important opportunistic pathogens of animals, plants and humans. Here, we conducted the largest genomic epidemiological study of A. junii, which has been described as a source not only of human but also of animal infections. Our analyses show that this bacterium has spread globally and that, in some instances, human and non-human isolates are not well differentiated. Remarkably, some non-human isolates have important antibiotic resistance genes against important antibiotics used in human medicine. Based on our results, we propose that this pathogen must be considered an issue not only for humans but also for veterinary medicine.

The presence of skin bacteria capable of forming biofilm, exhibiting antibiotic resistance, and displaying virulence represents a significant challenge in the field of transfusion medicine. This underscores the necessity of enhancing the microbiological safety of blood and blood components against pathogens with virulent characteristics. The aim of this work was to demonstrate bacterial inactivation in plasma by using a photoinactivation method against virulent bacteria and to evaluate coagulation factors before and after treatment. Logarithmic loads of biofilm-producing, antibiotic-resistant, and virulent bacteria isolated from skin (Enterobacter cloacae, Klebsiella ozaenae, and Staphylococcus epidermidis) were used in artificial contamination assays of fresh frozen plasma bags and subjected to photoreduction. FVIII and FI activity were evaluated before and after photoinactivation. The photoinactivation of plasma was demonstrated to be an effective method for the elimination of these bacteria. However, the efficiency of this method was found to be dependent on the bacterial load and the type of test microorganism. Conversely, decay of coagulation factors was observed with net residual activities of 61 and 69% for FVIII and FI, respectively. The photoinactivation system could have a bias in its effectiveness that is dependent on the test pathogen. These findings highlight the importance of employing technologies that increase the safety of the recipient of blood and/or blood components, especially against virulent bacteria, and show the relevance of the role of photoinactivation systems as an option in transfusion practice.

The blaNDM-1 gene and its variants encode metallo-beta-lactamases that confer resistance to almost all beta-lactam antibiotics. Genes encoding blaNDM-1 and its variants can be found in several Acinetobacter species, and they are usually linked to two different plasmid clades. The plasmids in one of these clades contain a gene encoding a Rep protein of the Rep_3 superfamily. The other clade consists of medium-sized plasmids in which the gene (s) involved in plasmid replication initiation (rep)have not yet been identified. In the present study, we identified the minimal replication region of a blaNDM-1-carrying plasmid of Acinetobacter haemolyticus AN54 (pAhaeAN54e), a member of this second clade. This region of 834 paired bases encodes three small peptides, all of which have roles in plasmid maintenance. The plasmids containing this minimal replication region are closely related; almost all contain blaNDM genes, and they are found in multiple Acinetobacter species, including A. baumannii. None of these plasmids contain an annotated Rep gene, suggesting that their replication relies on the minimal replication region that they share with the plasmid pAhaeAN54e. These observations suggest that this plasmid lineage plays a crucial role in the dissemination of the blaNDM-1 gene and its variants.

The issue of counting independent sets of a graph, G, represented as i(G), is a significant challenge within combinatorial mathematics. This problem finds practical applications across various fields, including mathematics, computer science, physics, and chemistry. In chemistry, i(G) is recognized as the Merrifield–Simmons (M-S) index for molecular graphs, which is one of the most relevant topological indices related to the boiling point in chemical compounds. This article introduces an innovative algorithm designed for tallying independent sets within grid-like structures. The proposed algorithm is based on the ‘branch-and-bound’ technique and is applied to compute i(Gm,n) for a square grid formed by m rows and n columns. The proposed approach incorporates the widely recognized vertex reduction rule as the basis for splitting the current subgraph. The methodology involves breaking down the initial grid iteratively until outerplanar graphs are achieved, serving as the ’basic cases’ linked to the leaf nodes of the computation tree or when no neighborhood is incident to a minimum of five rectangular internal faces. The time complexity of the branch-and-bound algorithm speeds up the computation of i(Gm,n) compared to traditional methods, like the transfer matrix method. Furthermore, the scope of the proposed algorithm is more general than the algorithms focused on grids since it could be applied to process general mesh graphs.

The interruption of bacteriological surveillance due to the COVID-19 pandemic brought serious consequences, such as the collapse of health systems and the possible increase in antimicrobial resistance. Therefore, it is necessary to know the rate of resistance and its associated mechanisms in bacteria causing hospital infections during the pandemic. The aim of this work was to show the phenotypic and molecular characteristics of antimicrobial resistance in ESKAPE bacteria in a Mexican tertiary care hospital in the second and third years of the pandemic. For this purpose, during 2021 and 2022, two hundred unduplicated strains of the ESKAPE group (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) were collected from various clinical sources and categorized by resistance according to the CLSI. An analysis of variance (ANOVA) complemented by the Tukey test was performed to search for changes in antimicrobial susceptibility profiles during the study period. Finally, the mechanisms of resistance involved in carbapenem resistance were analyzed, and the search for efflux pumps and high-risk sequence types in A. baumannii was performed by multilocus analysis (MLST). The results showed no changes in K. pneumoniae resistance during the period analyzed. Decreases in quinolone resistance were identified in E. coli (p = 0.039) and P. aeruginosa (p = 0.03). Interestingly, A. baumannii showed increases in resistance to penicillins (p = 0.004), aminoglycosides (p < 0.001, p = 0.027), carbapenems (p = 0.027), and folate inhibitors (p = 0.001). Several genes involved in carbapenem resistance were identified (blaNDM, blaVIM, blaOXA, blaKPC, blaOXA-40, and blaOXA-48) with a predominance of blaOXA-40 and the adeABCRS efflux pump in A. baumannii. Finally, MLST analysis revealed the presence of globally distributed sequence types (ST369 and ST758) related to hospital outbreaks in other parts of the world. The results presented demonstrate that the ESKAPE group has played an important role during the COVID-19 pandemic as nosocomial antibiotic-resistant pathogens and in particular A. baumannii MDR as a potential reservoir of resistance genes. The implications of the increases in antimicrobial resistance in pathogens of the ESKAPE group and mainly in A. baumannii during the COVID-19 pandemic are analyzed and discussed.

Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of aggressive lymphoma. Approximately 60% of fit patients achieve curation with immunochemotherapy, but the remaining patients relapse or have refractory disease, which predicts a short survival. Traditionally, risk stratification in DLBCL has been based on scores that combine clinical variables. Other methodologies have been developed based on the identification of novel molecular features, such as mutational profiles and gene expression signatures. Recently, we developed the LymForest-25 profile, which provides a personalized survival risk prediction based on the integration of transcriptomic and clinical features using an artificial intelligence system. In the present report, we studied the relationship between the molecular variables included in LymForest-25 in the context of the data released by the REMoDL-B trial, which evaluated the addition of bortezomib to the standard treatment (R-CHOP) in the upfront setting of DLBCL. For this, we retrained the machine learning model of survival on the group of patients treated with R-CHOP (N=469) and then made survival predictions for those patients treated with bortezomib plus R-CHOP (N=459). According to these results, the RB-CHOP scheme achieved a 30% reduction in the risk of progression or death for the 50% of DLBCL patients at higher molecular risk (p-value 0.03), potentially expanding the effectiveness of this treatment to a wider patient population as compared with other previously defined risk groups.

Infections pose a risk for patients undergoing hematopoietic stem cell (HSC) transplants due to their immunosuppression, making them susceptible to opportunistic infections. Therefore, understanding the composition of the aerobiome in this area is vital. The aim of this study was to characterize the aerobiome in an HSC transplant area, evaluating the impact of infrastructure and health personnel operations on air contamination. The environmental parameters and aerobiome of the HSC transplant area at Hospital Juárez de México were quantified over one year. Finally, a double-entry Vester matrix was constructed to classify problems according to their degree of causality. The abundance and taxonomic diversity of the aerobiome were dependent on seasonality, environmental factors, and high-efficiency filtration. Gram-positive bacteria predominated, followed by fungi and Gram-negative bacteria. ANOVA revealed significant differences in the bacterial aerobiome but not in the fungal aerobiome among the transplant rooms. Clinically, fungi such as Aspergillus fumigatus, Alternaria spp., Cladosporium spp., and Penicillium spp. were identified. ESKAPE bacteria typing revealed clonal dispersion. Finally, the Vester matrix highlighted critical problems associated with contamination due to the absence of HEPA filtration and non-adherence in patient management practices. HEPA filtration and positive pressure are essential to improve the air quality and reduce the microbiological load. However, the control areas will depend on patient management and routine activities, such as entry protocols in controlled areas. [ABSTRACT FROM AUTHOR]

One of the priority lines of action to contain the SARS-CoV-2 pandemic was vaccination programs for healthcare workers. However, with the emergence of highly contagious strains, such as the Omicron variant, it was necessary to know the serological status of health personnel to make decisions for the application of reinforcements. The aim of this work was to determine the seroprevalence against SARS-CoV-2 in healthcare workers in a Mexican hospital after six months of the administration of the Pfizer-BioNTech vaccine (two doses, 4 weeks apart) and to investigate the association between comorbidities, response to the vaccine, and reinfections. Neutralizing antibodies against SARS-CoV-2 were determined using ELISA assays for 262 employees of Hospital Juárez de México with and without a history of COVID-19. A beta regression analysis was performed to study the associated comorbidities and their relationship with the levels of antibodies against SARS-CoV-2. Finally, an epidemiological follow-up was carried out to detect reinfections in this population. A significant difference in SARS-CoV-2 seroprevalence was observed in workers with a history of COVID-19 prior to vaccination compared to those without a history of the disease (MD: 0.961 and SD: 0.049;

Empirical use of antibiotics in the treatment of eye infections leads to bacterial pathogens becoming resistant to antibiotics; consequently, treatment failure and eye health complications occur. The aim of this study was to describe the phenotype and genotype of the resistance and adherence of bacterial agents causing eye infections in patients at Hospital Juárez de México. An observational, prospective, cross-sectional, and descriptive study was carried out in patients with signs and symptoms of ocular infection. Bacterial agents were isolated and identified by classical microbiology and mass spectrometry. Antibiotic resistance and adherence profiles were determined. Finally, resistance (mecA/SCCmec) and virulence (icaA and icaD) genes were detected in the Gram-positive population. The results showed that blepharitis was the most prevalent condition in the study population. A MALDI-TOF analysis revealed that Staphylococcus and Pseudomonas genus were the most prevalent as causal agents of infection. Resistances to β-lactams were detected of 44 to 100%, followed by clindamycins, aminoglycosides, folate inhibitors, and nitrofurans. A multiple correspondence analysis showed a relationship between mecA genotype and β-lactams resistance. The identification of SCCmecIII and SCCmecIV elements suggested community and hospital sources of infection. Finally, the coexistence of icaA+/icaD+/mecA(SCCmecIII) and icaA+/icaD+/mecA(SCCmecIV) genotypes was detected in S. aureus. The identification of resistant and virulent isolates highlights the importance of developing protocols that address the timely diagnosis of ocular infections. Herein, implications for the failure of antimicrobial therapy in the treatment of ocular infections in susceptible patients are analysed and discussed.

The effectiveness of trabeculoplasmy in lowering intraocular pressure (IOP) in glaucoma patients was determined. A longitudinal study was carried out in 10 patients with open-angle glaucoma that underwent trabeculoplasmy. The postoperative results Of IOP, visual acuity (VA) and the occurrence of complications were evaluated at 24 hours, one week, 3, 6, 9 and 12 months. 10 surgeries were performed (10 eyes, 10 patients). Preoperative average IOP was 32.5mmHg and preoperative VA was 0.5. At one year the average IOP was 10.10 mmHg and the average VA was 0.7, both values were significant (p

Los sistemas inteligentes siempre han sido motivo de culto considerando desde películas, avances científicos y tendencias tecnológicas. Construir este tipo de aplicaciones es sumamente complejo porque se requieren elementos como: bases de conocimiento, mecanismos de inferencia para la toma de decisiones, generación de acciones y respuestas por parte de los agentes inteligentes. El insumo principal para el funcionamiento del agente es contar con una base de conocimiento lo suficientemente amplia, que esté sustentada en el dominio del cual se quiere trabajar, del conocimiento de expertos, esto implica que los ingenieros de conocimiento deben ser capaces de extraer cada elemento del dominio, sus relaciones y sus estructuras, para generar cuestionamientos y respuestas eficientes que no sean descartados por los humanos como acciones incorrectas o poco creíbles del agente. En este trabajo se presenta una metodología de apoyo a los estudiantes de la materia de ingeniería del conocimiento a construir sus dominios a partir de un ejemplo al alcance de sus manos como es la elaboración de platillos. Se consideró para el diseño de esta metodología la empatía considerando los momentos que vive la sociedad ante la pandemia, generar una experiencia significativa que sea difícil de olvidar, que sea lo suficientemente asociativa para establecer un proceso cognitivo de manera que ellos sean capaces de desarrollar una representación de conocimiento fuera del contexto escolar. Los resultados de esta metodología aportan información importante sobre los procesos de aprendizaje de los estudiantes, así como el proceso de retroalimentación que tuvieron entre los equipos de trabajo para poder generar estrategias para la identificación de términos del dominio muy diversas y efectivas de acuerdo con un modelo situacional generado a partir de la experiencia que han tenido en otras materias con distintas herramientas y técnicas para obtener información.

Introducción y objetivo: Este trabajo describe la importancia de adoptar métodos efectivos de muestreo de endoscopios reprocesados para la detección de microorganismos adheridos a las paredes internas de estos dispositivos. El objetivo de este trabajo es comparar la tasa de contaminación bacteriana de los canales de endoscopios reprocesados, mediante cultivo del agua de irrigación y la obtenida posterior a un cepillado de los canales. Un objetivo secundario fue determinar la sensibilidad antimicrobiana de los patógenos aislados en ambos métodos. Método: Un total de 26 endoscopios (duodenoscopios, gastroscopios, colonoscopios, broncoscopios y ecoendoscopios) fueron sometidos a limpieza y reprocesamiento automático antes de su uso en pacientes del Hospital Juárez de México. Los endoscopios limpios y reprocesados se sometieron simultáneamente a dos métodos de prueba bacteriológica basados en ausencia de cepillado (método A) y cepillado (método B) de los canales. Las cepas bacterianas aisladas después del cultivo de canales se identificaron a nivel de género y especie y se sometieron a pruebas de resistencia antimicrobiana. Resultados: El método A reveló cero tasa de contaminación bacteriana residual en ambos canales (succión y trabajo). Los resultados microbiológicos obtenidos por el método B revelaron tasas de contaminación bacteriana del 30.7%. Se identificaron cepas bacterianas pertenecientes a las familias Enterobacteriaceae, Bacillaceae, Pseudomonadaceae, Micrococcaceae y Staphylococcaceae. Se detectaron altas tasas de resistencia antimicrobiana contra 12 antibióticos probados de ocho familias diferentes. Conclusión: La implementación de la vigilancia microbiológica del reprocesamiento de endoscopios con métodos modificados de muestreo es necesaria para prevenir infecciones asociadas a la atención de la salud por procedimientos endoscópicos.

Advances in the knowledge of the pathogenesis of SARS-CoV-2 allowed the survival of COVID-19 patients in intensive care units. However, due to the clinical characteristics of severe patients, they resulted in the appearance of colonization events. Therefore, we speculate that strains of Candida spp. isolated from COVID-19 patients have virulent genetic and phenotypic backgrounds involved in clinical worsening of patients. The aim of this work was to virutype Candida spp. strains isolated from colonized COVID-19 patients, analyze their genomic diversity, and establish clonal dispersion in care areas. The virulent potential of Candida spp. strains isolated from colonized COVID-19 patients was determined through adhesion tests and the search for genes involved with adherence and invasion. Clonal association was done by analysis of intergenic spacer regions. Six species of Candida were involved as colonizing pathogens in COVID-19 patients. The genotype analysis revealed the presence of adherent and invasive backgrounds. The distribution of clones was identified in the COVID-19 care areas, where C. albicans was the predominant species. Evidence shows that Candida spp. have the necessary genetic tools to be able colonize the lungs, and could be a possible causal agent of coinfections in COVID-19 patients. The detection of dispersion of opportunistic pathogens can be unnoticed by classical epidemiology. Epidemiological surveillance against opportunistic fungal pathogens in COVID-19 patients is an immediate need, since the findings presented demonstrate the potential virulence of Candida spp.

SARS-CoV-2 was the cause of the global pandemic that caused a total of 14.9 million deaths during the years 2020 and 2021, according to the WHO. The virus presents a mutation rate between 10−5 and 10−3 substitutions per nucleotide site per cell infection (s/n/c). Due to this, studies aimed at knowing the evolution of this virus could help us to foresee (through the future development of new detection strategies and vaccines that prevent the infection of this virus in human hosts) that a pandemic caused by this virus will be generated again. In this research, we performed a functional annotation and identification of changes in Nsp (non-structural proteins) domains in the coronavirus genome. The comparison of the 13 selected coronavirus pangenomes demonstrated a total of 69 protein families and 57 functions associated with the structural domain’s differentials between genomes. A marked evolutionary conservation of non-structural proteins was observed. This allowed us to identify and classify highly pathogenic human coronaviruses into alpha, beta, gamma, and delta groups. The designed Nsp cluster provides insight into the trajectory of SARS-CoV-2, demonstrating that it continues to evolve rapidly. An evolutionary marker allows us to discriminate between phylogenetically divergent groups, viral genotypes, and variants between the alpha and betacoronavirus genera. These types of evolutionary studies provide a window of opportunity to use these Nsp as targets of viral therapies.

Pharmaceutical drugs in the aquatic medium may pose significant risk to non-target organisms. In this study, the potential toxicity of a mixture of three compounds commonly detected in marine waters (ibuprofen, ciprofloxacin and flumequine) was assessed, by studying bioaccumulation, oxidative stress and neurotoxicity parameters (catalase CAT, superoxide dismutase SOD, glutathione reductase GR, glutathione S-transferase GST, lipid peroxidation LPO, glutathione peroxidase GPX, metallothionein MT and acetylcholinesterase AChE) in the clam Scrobicularia plana. Temporal evolution of selected endpoints was evaluated throughout an exposure period (1, 7 and 21 days) followed by a depuration phase. The accumulation of all drugs was fast, however clams showed the ability to control the internal content of drugs, keeping their concentration constant throughout the exposure and reducing their content after 7 days of depuration. The induction of biochemical alterations (SOD, CAT, LPO, MT, AChE) was observed in gills and digestive gland probably related to an imbalance in the redox state of clams as a consequence of the exposure to the drug mixture. These alterations were also maintained at the end of the depuration week when the high levels of SOD, CAT, GST and LPO indicated the persistence of oxidative stress and damage to lipids despite the fact that clams were no longer exposed to the mixture.

The ESKAPE group constitute a threat to public health, since these microorganisms are associated with severe infections in hospitals and have a direct relationship with high mortality rates. The presence of these bacteria in hospitals had a direct impact on the incidence of healthcare-associated coinfections in the SARS-CoV-2 pandemic. In recent years, these pathogens have shown resistance to multiple antibiotic families. The presence of high-risk clones within this group of bacteria contributes to the spread of resistance mechanisms worldwide. In the pandemic, these pathogens were implicated in coinfections in severely ill COVID-19 patients. The aim of this review is to describe the main microorganisms of the ESKAPE group involved in coinfections in COVID-19 patients, addressing mainly antimicrobial resistance mechanisms, epidemiology, and high-risk clones.

The Pseudomonas aeruginosa genome can change to adapt to different ecological niches. We compared four genomes from a Mexican hospital and 59 genomes from GenBank from different niches, such as urine, sputum, and environmental. The ST analysis showed that high-risk STs (ST235, ST773, and ST27) were present in the genomes of the three niches from GenBank, and the STs of Mexican genomes (ST167, ST2731, and ST549) differed from the GenBank genomes. Phylogenetic analysis showed that the genomes were clustering according to their ST and not their niche. When analyzing the genomic content, we observed that environmental genomes had genes involved in adapting to the environment not found in the clinics and that their mechanisms of resistance were mutations in antibiotic resistance-related genes. In contrast, clinical genomes from GenBank had resistance genes, in mobile/mobilizable genetic elements in the chromosome, except for the Mexican genomes that carried them mostly in plasmids. This was related to the presence of CRISPR-Cas and anti-CRISPR; however, Mexican strains only had plasmids and CRISPR-Cas. blaOXA-488 (a variant of blaOXA50) with higher activity against carbapenems was more prevalent in sputum genomes. The virulome analysis showed that exoS was most prevalent in the genomes of urinary samples and exoU and pldA in sputum samples. This study provides evidence regarding the genetic variability among P. aeruginosa isolated from different niches.

Acinetobacter pittii has increasingly been associated with several types of hospital-acquired severe infections. Genes implicated in carbapenem resistance, tigecycline resistance, or genes encoding extended spectrum cephalosporinases, such as blaADC, are commonly found in isolates implicated in these infections. A. pittii strains that are pandrug resistant have occasionally been identified. Food for human consumption, animals and plants are environmental sources of this pathogen. An alarming situation is that A. pitti has been identified as responsible for outbreaks in different regions worldwide. In this study, 384 genomes of A. pittii were analyzed, comprising sequences from clinical and non-clinical origins from 32 countries. The objective was to investigate if clinical strains possess genetic traits facilitating hospital adaptation. Results indicate significant genomic variability in terms of size and gene content among A. pittii isolates. The core genome represents a small portion (25-36%) of each isolate's genome, while genes associated with antibiotic resistance and virulence predominantly belong to the accessory genome. Notably, antibiotic resistance genes are encoded by a diverse array of plasmids. As the core genome between environmental and hospital isolates is the same, we can assume that hospital isolates acquired ARGs due to a high selective pressure in these settings. The strain's phylogeographic distribution indicates that there is no geographical bias in the isolate distribution; isolates from different geographic regions are dispersed throughout a core genome phylogenetic tree. A single clade may include isolates from extremely distant geographical areas. Furthermore, strains isolated from the environment or animal, or plant sources frequently share the same clade as hospital isolates. Our analysis showed that the clinical isolates do not already possess specific genes, other than antibiotic-resistant genes, to thrive in the hospital setting. [ABSTRACT FROM AUTHOR]

Background and Purpose: Organisms, including humans, are subjected to the simultaneous action of a wide variety of pollutants, the effects of which should not be considered in isolation, as many synergies and antagonisms have been found between many of them. Therefore, this work proposes an in vivo study to evaluate the effect of certain metal contaminants on the bioavailability and metabolism of pharmacologically active compounds. Because the most frequent entry vector is through ingestion, the influence of the gut microbiota and the possible protective effects of selenium has been additionally evaluated. Experimental Approach: A controlled exposure experiment in mammals (Mus musculus) to a "chemical cocktail" consisting of metals and pharmaceuticals (diclofenac and flumequine). The presence of selenium has also been evaluated as an antagonist. Mouse plasma samples were measured by UPLC‐QTOF. A targeted search of 48 metabolites was also performed. Key Results: Metals significantly affected the FMQ plasma levels when the gut microbiota was depleted. Hydroxy FMQ decreased if metals were present. Selenium minimized this decrease. The 3‐hydroxy DCF metabolite was not found in any case. Changes in some metabolic pathways are discussed. Conclusions and Implications: The presence of metals in the mouse diet as well as the prior treatment of mice with an antibiotic mixture (Abxs), which deplete the gut microbiota, has a decisive effect on the bioavailability and metabolism of the tested pharmaceuticals and dietary selenium minimize some of their effects. [ABSTRACT FROM AUTHOR]

The presence of skin bacteria capable of forming biofilm, exhibiting antibiotic resistance, and displaying virulence represents a significant challenge in the field of transfusion medicine. This underscores the necessity of enhancing the microbiological safety of blood and blood components against pathogens with virulent characteristics. The aim of this work was to demonstrate bacterial inactivation in plasma by using a photoinactivation method against virulent bacteria and to evaluate coagulation factors before and after treatment. Logarithmic loads of biofilm-producing, antibiotic-resistant, and virulent bacteria isolated from skin (Enterobacter cloacae, Klebsiella ozaenae, and Staphylococcus epidermidis) were used in artificial contamination assays of fresh frozen plasma bags and subjected to photoreduction. FVIII and FI activity were evaluated before and after photoinactivation. The photoinactivation of plasma was demonstrated to be an effective method for the elimination of these bacteria. However, the efficiency of this method was found to be dependent on the bacterial load and the type of test microorganism. Conversely, decay of coagulation factors was observed with net residual activities of 61 and 69% for FVIII and FI, respectively. The photoinactivation system could have a bias in its effectiveness that is dependent on the test pathogen. These findings highlight the importance of employing technologies that increase the safety of the recipient of blood and/or blood components, especially against virulent bacteria, and show the relevance of the role of photoinactivation systems as an option in transfusion practice. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Despite notable therapeutic advances in the last decades, 30%–40% of affected patients develop relapsed or refractory disease that frequently precludes an infamous outcome. With the advent of new therapeutic options, it becomes necessary to predict responses to the standard treatment based on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). In a recent communication, we presented a new machine learning model (LymForest-25) that was based on 25 clinical, biochemical, and gene expression variables. LymForest-25 achieved high survival prediction accuracy in patients with DLBCL treated with upfront immunochemotherapy. In this study, we aimed to evaluate the performance of the different features that compose LymForest-25 in a new UK-based cohort, which contained 481 patients treated with upfront R-CHOP for whom clinical, biochemical and gene expression information for 17 out of 19 transcripts were available. Additionally, we explored potential improvements based on the integration of other gene expression signatures and mutational clusters. The validity of the LymForest-25 gene expression signature was confirmed, and indeed it achieved a substantially greater precision in the estimation of mortality at 6 months and 1, 2, and 5 years compared with the cell-of-origin (COO) plus molecular high-grade (MHG) classification. Indeed, this signature was predictive of survival within the MHG and all COO subgroups, with a particularly high accuracy in the “unclassified” group. Integration of this signature with the International Prognostic Index (IPI) score provided the best survival predictions. However, the increased performance of molecular models with the IPI score was almost exclusively restricted to younger patients (