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Abstract Objective Neurofilament heavy‐chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk. Methods Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta‐analyses of published case–control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole‐genome sequencing data. Results Fixed‐effects meta‐analysis found that rare (MAF

The ecology of macrofauna on the sandy bottom of oceanic islands in the tropics has rarely been studied. The present study was conducted at Isla del Coco, Costa Rica, a tropical oceanic island, to determine how the soft-bottom macrofauna assemblages vary along different levels of ocean exposure and their associated environmental conditions. The macrofauna was collected from five grabs at each of the 27 stations (between 3 and 75 m deep) in April 2010. The broad-scale pattern consists of a gradual increase in the complexity of assemblages (taxonomical or feeding guilds in the sediment) from the inner part to the outside of the bays. The leading determinant of this pattern was the interplay between ocean exposure and sediment variation with depth that produces habitat heterogeneity. The main taxa responsible for differences between ocean exposure zones were the polychaetes Westheidesyllis heterocirrata and Magelona californica, the filter-feeding bivalve Gouldia californica, and the predatory isopod Eurydice caudata. Coarse bottoms had more mobile predators and suspension feeders, whereas passive suspension feeders or subsurface deposit feeders dominated fine sands. The deeper stations were dominated by organisms feeding actively on particles from the water or on the sediment surface. Moreover, more feeding guilds were found in deeper waters. Additionally, at the small-scale view (grabs within each station), macrofauna composition evidences a mosaic pattern, mainly at the inner and middle of the bays, caused by biological or environmental disturbances.

Fire plays a critical role in nutrient cycling and species diversity but also causes severe disturbances to ecosystems. Despite remote sensing has emerged as a valuable tool to study wildfires, a lack of information regarding post-fire dynamics still remains for certain regions. This study investigated the post-fire dynamics of four burned sites in the temperate forest of Chihuahua, northern Mexico from 2009 to 2017, based on the variability of spectral indices under varied topographic conditions of aspects and slopes. The Normalized Difference Vegetation index (NDVI), Soil Adjusted Vegetation Index (SAVI), Normalized Burn Ratio (NBR), and Normalized Difference Water index (NDWI) were utilized to assess vegetation recovery on the burned sites. One-way ANOVAs and Tukey´s tests were performed to evaluate separately the effects of aspect and slope on the indices’ variability (p < 0.05). In general, the NDVI measured the highest values of the burned sites along the evaluated lapse while the NDWI indicated the lowest measures. Results indicated significant effects of aspect on NDVI and SAVI (p < 0.05), while slope significantly influenced the four evaluated indices (p < 0.05).That in turn showed northern aspects and steeper slopes to have the highest post-fire vegetation recoveries. Furthermore, aspect only affected the bi-annual variability of SAVI (p < 0.05). However, the NBR and NDWI showed higher magnitudes of change among periods than the SAVI (i. e., recovery and non-recovery). Besides registering a continuous recovery of the burned sites from the wildfire events to 2015, this study revealed the NDVI and SAVI as the most useful spectral indices for assessing post-fire vegetation dynamics in the region. Besides aspect and slope, future studies could focus on the inclusion of additional indicators to more effectively assess post-fire ecosystem dynamics in northern Mexico.

Abstract The evaluation of diagnostic systems is pivotal for ensuring the deployment of high-quality solutions, especially given the pronounced context-sensitivity of certain systems, particularly in fields such as biomedicine. Of notable importance are predictive models where the target variable can encompass multiple values (multiclass), especially when these classes exhibit substantial frequency disparities (imbalance). In this study, we introduce the Imbalanced Multiclass Classification Performance (IMCP) curve, specifically designed for multiclass datasets (unlike the ROC curve), and characterized by its resilience to class distribution variations (in contrast to accuracy or F $$_\beta$$ β -score). Moreover, the IMCP curve facilitates individual performance assessment for each class within the diagnostic system, shedding light on the confidence associated with each prediction—an aspect of particular significance in medical diagnosis. Empirical experiments conducted with real-world data in a multiclass context (involving 35 types of tumors) featuring a high level of imbalance demonstrate that both the IMCP curve and the area under the IMCP curve serve as excellent indicators of classification quality.

Hemiurid digeneans conspecific with Stomachicola muraenesocis Yamaguti, 1934 (the type species of the genus Stomachicola Yamaguti, 1934) were collected from the stomach of the daggertooth pike conger Muraenesox cinereus (Forsskål) off the Persian Gulf of Iran. This study aimed to provide a detailed characterization of Stom. muraenesocis, including measurements, illustrations and scanning electron microscopy (s.e.m.) representations. Comparisons with the original and previous descriptions revealed morphological and metrical variations in several features (i.e. body size and shape, arrangement of reproductive organs, soma to ecsoma length ratio, position of genital opening, number of vitelline tubules and extension of uterine coils) between Stom. muraenesocis from different hosts and localities. This study presents the first molecular sequence data associated with the small (18S) and large (28S) subunit nuclear ribosomal RNA genes (rDNA) for Stom. muraenesocis. Phylogenetic analyses of the 18S dataset placed Stom. muraenesocis as sister lineage to a clade formed of a group of species of Lecithaster Lühe, 1901 (Lecithasteridae Odhner, 1905). In contrast, phylogenetic analyses based on the 28S consistently recovered a sister relationship between Stom. muraenesocis and representatives of the Hemiuridae Looss, 1899. Further comprehensive phylogenetically based classification in light of morphology and taxonomic history of the Hemiuridae and Lecithasteridae is required to infer phylogenetic affinities and historical biogeography of Stomachicola. A comprehensive list of previously reported species of Stomachicola together with their associated hosts, localities and morphometric data is provided.

Antecedentes: El COVID persistente se define como la persistencia de síntomas de COVID-19 después de cuatro semanas de cursar con un cuadro agudo, según la definición más reciente de los Centers for Disease Control and Prevention. Se estima que existen 65 millones de personas afectadas por esta entidad, aunque algunos reportes indican 200 millones. Objetivo: Caracterizar a la población afectada por COVID persistente en México. Material y métodos: Se incluyeron pacientes mayores de 18 años que consintieron responder a una encuesta en línea y que cumplían los criterios de COVID persistente. Resultados: Se incluyeron los datos de 203 sujetos. Se identificó que 138 (68.0 %) contestaron ser del sexo femenino, con una media de edad de 41.8 años; 29.6 % presentó enfermedad grave y 70.4 %, enfermedad leve a moderada; 89.7 % había recibido vacunas previas para COVID-19: 6.9 %, una dosis; 31.5 %, dos dosis; y 51.2 %, tres o más dosis. Los principales factores de riesgo fueron diabetes, sobrepeso u obesidad e hipertensión arterial sistémica. El principal síntoma reportado fue fatiga, seguido de otras manifestaciones neuropsiquiátricas. Conclusión: Es importante caracterizar a la población para generar protocolos de diagnóstico y tratamiento.

Abstract Background Alactic base excess (ABE) is a novel biomarker that estimates the renal capability of handling acid–base alterations during the sepsis. Hence, the aim of this study was to evaluate the use of ABE to predict the renal replacement therapy (RRT) in patients with septic shock. Methods A total of 164 patients admitted to the intensive care units with a diagnosis of septic shock according to the third international consensus on sepsis and septic shock (Sepsis-3) were included. This study was retrospective, single center, and conducted between January 1, 2016, and December 31, 2020. The individuals were stratified in patients who did [n = 68] or did not [n = 96] receive the RRT. The diagnostic performed of the variables for the classification into patients who required RRT was evaluated by receiver operating characteristic (ROC) analysis and area under curve (AUC) was calculated. Univariate and multivariate logistic regression models were used to identify risk factors for RRT. Results The median age of the patients was 59 years and female sex (51.8%) predominated. ABE (odds ratio [OR] 1.2270, [95% confidence interval [CI] 1.0453–1.4403], p = 0.0124) and urea (OR 1.0114, [95% CI 1.0053–1.0176], p = 0.0002) were associated with risk of RRT. HCO3− (OR 0.6967, [95% CI 0.5771–0.8410], p = 0.0002) was a protective factor of RRT. ABE (AUC = 0.649, p 75 mg/dL, respectively. Conclusion Although HCO3− is associated with low risk, ABE and urea are independent risk factors for RRT in the patients with septic shock.

Abstract Myxozoans are a unique group of microscopic parasites that infect mainly fishes. These extremely reduced cnidarians are highly diverse and globally distributed in freshwater and marine habitats. Myxozoan diversity dimension is unknown in Mexico, a territory of an extraordinary biological diversity. This study aimed to explore, for the first time, myxozoan parasite diversity from fishes of the Neotropical region of Mexico. We performed a large morphological and molecular screening using host tissues of 22 ornamental and food fish species captured from different localities of Veracruz, Oaxaca and Chiapas. Myxozoan infections were detected in 90% of the fish species, 65% of them had 1 or 2 and 35% had 3 and up to 8 myxozoan species. Forty-one putative new species were identified using SSU rDNA phylogenetic analyses, belonging to two main lineages: polychaete-infecting (5 species) and oligochaete-infecting (36 species) myxozoans; from those we describe 4 new species: Myxidium zapotecus sp. n., Zschokkella guelaguetza sp. n., Ellipsomyxa papantla sp. n. and Myxobolus zoqueus sp. n. Myxozoan detection increased up to 6 × using molecular screening, which represents 3.7 × more species detected than by microscopy. This study demonstrated that Neotropical fishes from Mexico are hosts of a multitude of myxozoans, representing a source of emerging diseases with large implications for economic and conservation reasons.

Black gobies (Gobius niger) from the Finnish Archipelago, Baltic Sea, were screened for helminth infections in summer 2020. Helminths were identified morphologically and/or molecularly. Altogether 26 novel sequences were generated and analysed using maximum likelihood estimation. Morphological and phylogenetic analyses based on mitochondrial genes revealed the presence of 8 species belonging to the Digenea (Diplostomum mergi Lineage 3), Cestoda (Bothriocephalus scorpii), Nematoda (Contracaecum rudolphii A, Cucullanus sp. and Hysterothylacium aduncum), and Acanthocephala (a putative new species of Corynosoma, Corynosoma semerme and Neoechinorhynchus sp.). Phylogenetic and comparative sequence analyses revealed that the putative new acanthocephalan species is closely related to C. neostrumosum described from the Caspian seal, Pusa caspica, in the Caspian Sea. The black goby represents a new host record for four parasite species (Diplostomum mergi Lineage 3, Contracaecum rudolphii A, Corynosoma semerme and Corynosoma sp.). The Finnish Archipelago is a novel locality record for three species (Corynosoma sp., Diplostomum mergi Lineage 3 and Bothriocephalus scorpii).

Membrane proteins are the main targets of therapeutic drugs and most of them are glycosylated. Glycans play pivotal roles in several biological processes, and glycosylation changes are a well-established hallmark of several types of cancer, including pancreatic cancer, that contribute to tumor growth. Mucin-4 (MUC-4) is a membrane glycoprotein which is associated with pancreatic cancer and metastasis, and it has been targeted as a promising vaccine candidate. In this study, Surface Plasmon Resonance Microscopy (SPRM) was implemented to study complex influences of the native N-glycan cellular environment on binding interactions to the MUC-4 receptor as this is currently the only commercially available label-free technique with high enough sensitivity and resolution to measure binding kinetics and heterogeneity on single cells. Such unique capability enables for a more accurate understanding of the "true" binding interactions on human cancer cells without disrupting the native environment of the target MUC-4 receptor. Removal of N-linked glycans in pancreatic cancer cells using PNGase F exposed heterogeneity in Concanavalin (Con A) binding by revealing three new binding populations with higher affinities than the glycosylated control cells. Anti-MUC-4 binding interactions of enzymatically N-linked deglycosylated pancreatic cancer cells produced a 25x faster association and 37x higher affinity relative to the glycosylated control cells. Lastly, four interaction modes were observed for Helix Pomatia Agglutinin (HPA) binding to the glycosylated control cells, but shifted and increased in activity upon removal of N-linked glycans. These results identified predominant interaction modes of glycan and MUC-4 in pancreatic cancer cells, the kinetics of their binding interactions were quantified, and the influence of N-linked glycans in MUC-4 binding interactions was revealed.

Introducción: Los factores reproductivos se asocian con cáncer de mama. Actualmente se estudia el comportamiento según subtipos moleculares. Objetivo: Establecer la prevalencia de estos subtipos y su asociación con factores reproductivos en mujeres atendidas en centros del nororiente colombiano. Método: Estudio observacional de corte transversal, en mujeres con cáncer de mama subtipos luminales y HER2 durante 2012-2021. Se indagaron variables sociodemográficas, factores reproductivos y estadio tumoral. Resultados: En total, 347 pacientes cumplieron criterios de elegibilidad, correspondiendo a luminal A el 49,8% (intervalo de confianza del 95% [IC95%]: 44,5-55,1), a luminal B el 29,1% (IC95%: 24,3-33,9) y a HER2 el 15,5% (IC95%: 11,7-19,4). Las mujeres con tumores de mama luminal B tenían más riesgo de tener estadios localmente avanzados (odds ratio [OR]: 1,83; IC95%: 1,11-3,01; p = 0,02). Agrupando los subtipos luminales frente a HER2 se encontró que el 40,72% de las pacientes con subtipos luminales no habían lactado, frente al 69,71% con HER2 (diferencia estadísticamente significativa a favor de luminal A; OR: 1,91; IC95%: 1,02-3,53; p = 0,041). Conclusiones: La prevalencia de tumores luminales es del 84,5%. Existe asociación diferencial entre el antecedente de lactancia materna y la aparición de subtipos luminales, es decir, las mujeres que no lactaron se corresponden con mayor frecuencia con HER2. No se estableció asociación con otros factores estudiados.

Statistical measures of complexity hold significant potential for applications in D-dimensional finite fermion systems, spanning from the quantification of the internal disorder of atoms and molecules to the information–theoretical analysis of chemical reactions. This potential will be shown in hydrogenic systems by means of the monotone complexity measures of Cramér–Rao, Fisher–Shannon and LMC(Lopez-Ruiz, Mancini, Calbet)–Rényi types. These quantities are shown to be analytically determined from first principles, i.e., explicitly in terms of the space dimensionality D, the nuclear charge and the hyperquantum numbers, which characterize the system’ states. Then, they are applied to several relevant classes of particular states with emphasis on the quasi-spherical and the highly excited Rydberg states, obtaining compact and physically transparent expressions. This is possible because of the use of powerful techniques of approximation theory and orthogonal polynomials, asymptotics and generalized hypergeometric functions.

Abstract Background Endometrioid Stromal Sarcomas are an infrequent group of mesenchymal tumors that we must take into account in the differential diagnosis despite representing only 0.2% of tumors of the female genital tract, as they can go unnoticed until advanced stages. Case presentation Fifty-fourth year-old woman referred from the Urology department due to incidental finding of adnexal mass in MRI during examination after renoureteral colic, in the case of a 50 mm solid cystic mass in LE. MT were within the normal range, and the CT scan observed this mass in contact with the left ureter. The surgery was completed with hysterectomy and contralateral adnexectomy without incident and chemotherapy treatment was not added. The pathological result was ovarian tissue with low-grade endometrial sarcoma. Currently, after two years of follow-up, the patient remains stable without any recurrence of disease. Conclusions Endometrioid stromal sarcomas are rare tumors that originate in the endometrial stroma, the ovarian location being rare. Management lies in surgical treatment, and adjuvant therapy is sometimes necessary in advanced stages.

Nowadays, cardiac transplant is considered the most efficient treatment to better the prognosis in patients with last stage cardiac insufficiency that is impossible to obtain through regular medical and/or surgical treatments. We report the case of the first cardiac transplant performed at the General Hospital of Mexico “Dr. Eduardo Liceaga,” we describe the patient’s and donor’s characteristics, pre- and post-surgical management, immunosuppressive therapy, cardiac rehabilitation, and patient follow-up. As well as the multidisciplinary approach necessary to achieve a successful result.

There are several goals of the two-dimensional data analysis: one may be interested in searching for groups of similar objects (clustering), another one may be focused on searching for some dependencies between a specified one and other variables (classification, regression, associate rules induction), and finally, some may be interested in serching for well-defined patterns in the data called biclusters. It was already proved that there exists a mathematically proven symmetry between some patterns in the matrix and implicants of data-defined Boolean function. This paper provides the new look for a specific pattern search—the pattern named the δ-shifting pattern. The shifting pattern is interesting, as it accounts for constant fluctuations in data, i.e., it captures situations in which all the values in the pattern move up or down for one dimension, maintaining the range amplitude for all the dimensions. Such a behavior is very common in real data, e.g., in the analysis of gene expression data. In such a domain, a subset of genes might go up or down for a subset of patients or experimental conditions, identifying functionally coherent categories. A δ-shifting pattern meets the necessity of shifting pattern induction together with the bias of the real values acquisition where the original shifts may be disturbed with some outer conditions. Experiments with a real dataset show the potential of our approach at finding biclusters with δ-shifting patterns, providing excellent performance. It was possible to find the 12×9 pattern in the 112×9 input data with MSR=0.00653. The experiments also revealed that δ-shifting patterns are quite difficult to be found by some well-known methods of biclustering, as these are not designed to focus on shifting patterns—results comparable due to MSR had much more variability (in terms of δ) than patterns found with Boolean reasoning.

The antibody-binding Fc γ receptors (FcγRs) trigger life-saving immune responses and many therapeutic monoclonal antibodies require FcγR engagement for full effect. One proven strategy to improve the efficacy of antibody therapies is to increase receptor binding affinity, in particular binding to FcγRIIIa/CD16a. Currently, affinities are measured using recombinantly-expressed soluble extracellular FcγR domains and CD16a-mediated antibody-dependent immune responses are characterized using cultured cells. It is notable that CD16a is highly processed with multiple N-glycosylation sites, and preventing individual N-glycan modifications affects affinity. Furthermore, multiple groups have demonstrated that CD16a N-glycan composition is variable and composition impacts antibody binding affinity. The level of N-glycosylation at each site is not known though computational prediction indicates low to moderate potential at each site based on primary sequence (40–70%). Here we quantify occupancy of the extracellular domains using complementary mass spectrometry-based methods. All five sites of the tighter-binding CD16a V158 allotype showed 65–100% N-glycan occupancy in proteomics-based experiments. These observations were confirmed using intact protein mass spectrometry that demonstrated the predominant species corresponded to CD16a V158 with five N-glycans, with a smaller contribution from CD16a with four N-glycans. Occupancy was likewise high for the membrane-bound receptor at all detected N-glycosylation sites using CD16a purified from cultured human natural killer cells. Occupancy of the N162 site, critical for antibody binding, appeared independent of N169 occupancy based on analysis of the T171A mutant protein. The weaker-binding CD16a F158 allotype showed higher occupancy of >93% at each site.

Abstract Background Multimodal rehabilitation allows optimization of functional recovery in surgery patients by reducing the postoperative stress and hospital stay duration, without increasing the morbidity and mortality. It is reportedly successful in other surgical disciplines, and guidelines for its application to gynecological surgery are available; however, most evidence for these guidelines is derived from observational and/or retrospective studies. Therefore, this study aimed to investigate the applicability of an enhanced recovery after surgery (ERAS) protocol in laparoscopic gynecological surgery and its influence on the postoperative stay, morbidity, mortality, and readmission, through a prospective approach. Methods This prospective cohort study was performed on 90 patients who underwent laparoscopic hysterectomy for benign causes from October 2017 to October 2019. Patients in whom the ERAS (ERAS group, n = 30) and traditional (control group, n = 60) protocols were implemented were compared. All patients were followed for 6 months. Results The groups were homogeneous and did not differ significantly with respect to the demographic characteristics (age, ASA score, body mass index), surgical indications, and surgery types. Adherence to the ERAS protocol was over 99%. The postoperative hospital-stay durations were 1.73 days (r = 1–3) and 2.97 days (r = 2–6) in the ERAS and control groups, respectively (p = 0.000). No significant intergroup differences were observed in the rates of complications and readmissions. Conclusions The ERAS protocol is applicable in laparoscopic gynecological surgery and can be implemented with good adherence. This can allow optimization of patient recovery by reducing the hospital stay duration, without increasing the rates of morbidity, mortality, or readmission.

Land-Use/Land-Cover (LULC) change is one of the main factors contributing to ecosystem degradation and to the global climate change. The Markov Chains (MC) model is a widely used technique for the spatio-temporal evaluation of LULC changes, allowing the projection of the landscape variability based on the multidirectional potential of LULC changes. This study assessed the LULC changes in a disturbed temperate forest basin of northern México during the period 1990–2019. In addition, three LULC scenarios, employing the MC model, were projected for 2048. Supervised classification techniques were performed on data from Landsat sensors to generate LULC maps. Results from the Kappa Index showed a precision of 85 and 85.8% for the classifications of 1990 and 2019, respectively. During the evaluated period, degradation and deforestation processes in the basin were the main factors of disturbance, causing the pine-oak forest to show the biggest loss of coverage (190.81 km2). Conversely, open lands showed the biggest increase in its coverage, which indicates anthropogenic activities as the main driver causing changes on the ecosystem. Projections for 2048 indicate processes of degradation and deforestation will continue, expecting increases in coverage for open lands, deciduous forest, and secondary forest. The current and projected conditions of the landscape highlight the importance of the implementation of conservation and restoration strategies, as well as responsible public policies in the study area to mitigate the impacts on these ecosystems.

DNA metabarcoding has great potential to improve marine biomonitoring programs by providing a rapid and accurate assessment of species composition in zoobenthic communities. However, some methodological improvements are still required, especially regarding failed detections, primers efficiency and incompleteness of databases. Here we assessed the efficiency of two different marker loci (COI and 18S) and three primer pairs in marine species detection through DNA metabarcoding of the macrozoobenthic communities colonizing three types of artificial substrates (slate, PVC and granite), sampled between 3 and 15 months of deployment. To accurately compare detection success between markers, we also compared the representativeness of the detected species in public databases and revised the reliability of the taxonomic assignments. Globally, we recorded extensive complementarity in the species detected by each marker, with 69% of the species exclusively detected by either 18S or COI. Individually, each of the three primer pairs recovered, at most, 52% of all species detected on the samples, showing also different abilities to amplify specific taxonomic groups. Most of the detected species have reliable reference sequences in their respective databases (82% for COI and 72% for 18S), meaning that when a species was detected by one marker and not by the other, it was most likely due to faulty amplification, and not by lack of matching sequences in the database. Overall, results showed the impact of marker and primer applied on species detection ability and indicated that, currently, if only a single marker or primer pair is employed in marine zoobenthos metabarcoding, a fair portion of the diversity may be overlooked.

The pulmonary valve’s anomalies can lead to the obstruction of the right ventricle’s outflow tract. This leads to the right ventricle’s pressure overload, dilation, hypertrophy and eventually his malfunction. Balloon angioplasty or valve replacement surgery is indicated in cases of severe pulmonary stenosis. Often, the insertion of bioprosthetic pulmonary valves is required; however, after several years these patients often require a second surgery due to the valve’s malcfunction. We report the case of a pregnant patient with a bioprosthetic pulmonary valve who required a ballon angioplasty due to this valve’s stenosis.

La coartación aórtica representa el 5-8% de todas las cardiopatías congénitas y se define como un estrechamiento de la luz aórtica a nivel del ligamento arterioso o debajo de este, clasificándose en preductal o posductal, y existen varias teorías que tratan de explicar su etiología, que aún sigue siendo poco clara. Puede diagnosticarse desde la infancia o en la edad adulta, debe sospecharse en todo paciente antes de los 30 años de edad que presente hipertensión arterial sistémica para poder brindar un tratamiento quirúrgico oportuno.

Canine mammary carcinomas (CMC) are associated with major aggressive clinical behavior and high mortality. The current standard of care is based on surgical resection, without an established effective treatment scheme, highlighting the urgent need to develop novel effective therapies. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis and progression in the majority of solid cancers, including human and canine mammary carcinomas. The first therapy developed to target VEGF was bevacizumab, a recombinant humanized monoclonal antibody, which has already been approved as an anticancer agent in several human cancers. The goal of this work was to establish the therapeutic value of MB02 bevacizumab biosimilar in CMC. First, through different in silico approaches using the MUSCLE multiple-sequence alignment tool and the FoldX protein design algorithm, we were able to predict that canine VEGF is recognized by bevacizumab, after showing an extremely high sequence similarity between canine and human VEGF. Further, by using an ELISA-based in vitro binding assay, we confirmed that MB02 biosimilar was able to recognize canine VEGF. Additionally, canine VEGF-induced microvascular endothelial cell proliferation was inhibited in a concentration-dependent manner by MB02 biosimilar. These encouraging results show a high potential for MB02 as a promising therapeutic agent for the management of CMC.

Abstract Background The systematic of several marine diphyllobothriid tapeworms of pinnipeds has been revised in recent years. However, 20 species of Diphyllobothrium from phocids and otariids are still recognized as incertae sedis. We describe a new species of Diphyllobothrium from the intestine of California sea lions Zalophus californianus (Lesson) (type-host) and South American sea lions Otaria flavescens (Shaw). Methods Zalophus californianus from the Pacific coast of the USA and O. flavescens from Peru and Argentina were screened for parasites. Partial fragments of the large ribosomal subunit gene (lsrDNA) and the cytochrome c oxidase subunit 1 (cox1) mitochondrial gene were amplified for 22 isolates. Properly fixed material from California sea lions was examined using light and scanning electron microscopy. Results A total of four lsrDNA and 21 cox1 sequences were generated and aligned with published sequences of other diphyllobothriid taxa. Based on cox1 sequences, four diphyllobothriid tapeworms from O. flavescens in Peru were found to be conspecific with Adenocephalus pacificus Nybelin, 1931. The other newly generated sequences fall into a well-supported clade with sequences of a putative new species previously identified as Diphyllobothrium sp. 1. from Z. californianus and O. flavescens. A new species, Diphyllobothrium sprakeri n. sp., is proposed for tapeworms of this clade. Conclusions Diphyllobothrium sprakeri n. sp. is the first diphyllobothriid species described from Z. californianus from the Pacific coast of North America, but O. flavescens from Argentina, Chile and Peru was confirmed as an additional host. The present study molecularly confirmed the first coinfection of two diphyllobothriid species in sea lions from the Southern Hemisphere.

Abstract Sampling impediments and paucity of suitable material for molecular analyses have precluded the study of speciation and radiation of deep-sea species in Antarctica. We analyzed barcodes together with genome-wide single nucleotide polymorphisms obtained from double digestion restriction site-associated DNA sequencing (ddRADseq) for species in the family Antarctophilinidae. We also reevaluated the fossil record associated with this taxon to provide further insights into the origin of the group. Novel approaches to identify distinctive genetic lineages, including unsupervised machine learning variational autoencoder plots, were used to establish species hypothesis frameworks. In this sense, three undescribed species and a complex of cryptic species were identified, suggesting allopatric speciation connected to geographic or bathymetric isolation. We further observed that the shallow waters around the Scotia Arc and on the continental shelf in the Weddell Sea present high endemism and diversity. In contrast, likely due to the glacial pressure during the Cenozoic, a deep-sea group with fewer species emerged expanding over great areas in the South-Atlantic Antarctic Ridge. Our study agrees on how diachronic paleoclimatic and current environmental factors shaped Antarctic communities both at the shallow and deep-sea levels, promoting Antarctica as the center of origin for numerous taxa such as gastropod mollusks.

Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions.

We used DNA metabarcoding to compare macrozoobenthic species colonization between autonomous reef monitoring structures (ARMS) and artificial seaweed monitoring systems (ASMS). We deployed both substrates in two different locations (Ría de Vigo and Ría de Ferrol, NW Iberian coast) and collected them after 6, 9, and 12 months to assess species composition of the colonizing communities through high-throughput sequencing of amplicons within the barcode region of the mitochondrial cytochrome c oxidase I (COI-5P) and the V4 domain of the 18S rRNA genes. We observed a consistently low similarity in species composition between substrate types, independently of sampling times and sites. A large fraction of exclusive species was recorded for a given substrate (up to 72%), whereas only up to 32% of species were recorded in both substrates. The shape and structural complexity of the substrate strongly affected the colonization preferences, with ASMS detecting more exclusive crustacean and gastropod species and a broader diversity of taxonomic groups (e.g., Entoprocta and Pycnogonida were detected exclusively in ASMS). We demonstrate that despite the customary use of ARMS for macrozoobenthos monitoring, by using ASMS we complemented the recovery of species and enlarged the scope of the taxonomic diversity recorded.

In this paper, we study how many algebraic limit cycles have the discontinuous piecewise linear differential systems separated by a straight line, with polynomial first integrals on both sides. We assume that at least one of the systems is Hamiltonian. Under this assumption, piecewise differential systems have no more than one limit cycle. This study characterizes linear differential systems with polynomial first integrals.

Este artículo desarrolla un panorama histórico de las evaluaciones de logro académico, estandarizadas y a gran escala, aplicadas en la educación mexicana. Mediante una investigación documental, se analizan los inicios, expansión, consolidación y situación actual de este tipo de pruebas. Se concluye destacando la relevancia de contar con evaluaciones confiables del logro académico, que contribuyan al desarrollo educativo nacional. logro académico pruebas de aprovechamiento evaluación a gran escala política educativa historia de México

La pancreatitis aguda es una enfermedad grave y causa frecuente de ingreso a los servicios de emergencias en México y los Estado Unidos de América debido a los factores de riesgo de la población, como obesidad, alcoholismo y hábitos dietéticos. Presenta una alta morbilidad y mortalidad, con una incidencia global de 33.74 casos por cada 100,000 personas/ año y una mortalidad de 1.16 por 100,000 personas; afecta a personas de todas las edades y con mayor riesgo para el sexo masculino que para el femenino. En el 80% de los pacientes se presenta de forma leve, pero hasta un 20% de los casos son graves, con una mortalidad del 20%. La etiología más frecuente de la pancreatitis aguda es de tipo obstructivo, en general secundaria a litiasis biliar (40-70%). Entender la fisiopatología de la enfermedad, junto con su estratificación, han llevado a que a lo largo de los años se hayan producido grandes cambios con la finalidad de evitar complicaciones asociadas y disminuir la morbimortalidad.

Introducción: Hasta donde se tiene conocimiento, la investigación que se presenta constituye el primer trabajo multicéntrico en México que estudia el desarrollo de la aptitud clínica en unidades formadoras de cardiólogos. Objetivo: Determinar el grado de desarrollo de la aptitud clínica en residentes de cardiología en tres unidades médicas de alta especialidad. Métodos: Diseño transversal multicéntrico. Se analizaron todos los estudiantes del ciclo académico 2019-2020. Se construyó un instrumento que evaluó la aptitud clínica a partir de ocho indicadores y 170 ítems; la validez conceptual/de contenido y la confiabilidad fueron valoradas por cinco cardiólogos con experiencia docente y en investigación educativa. Resultados: Por indicador y año de residencia se observaron diferencias estadísticas significativas en la sede CMN20Nov; en HCSXXI e INCICh se observaron diferencias estadísticamente significativas en uno de ocho indicadores. Se estimaron diferencias entre residentes R1 (n = 41) de las tres sedes por indicador, con significación estadística en tres de ocho indicadores. El resultado fue semejante al comparar R2 (n = 35) y R3 (n = 43). Conclusiones. El grado de desarrollo de la aptitud clínica se puede considerar medio en las tres sedes académicas, probablemente debido a que el instrumento exploró situaciones clínicas problematizadas que exigieron del residente la reflexión crítica de su experiencia clínica.

Objective: The objective of this study was to assess the association and interaction of laboratory parameters, Simplified Acute Physiology Score II (SAPSII), Modified Shock Index (MSI), and Mannheim Peritonitis Index (MPI) with in-hospital mortality. Material and methods: We conducted a single-center case–control study. Adult patients with abdominal sepsis were included from May 2015 to May 2020. Baseline characteristics, laboratory parameters, SAPSII, MSI, and MPI scores at admission were collected. A principal component (PC) analysis was applied to evaluate variable interactions. In-hospital mortality risk was determined through logistic regression models. Results: One hundred and twenty-seven patients were identified, 60 of which were included for analyses. Non-survivors (48.4%) had a higher frequency of hypertension, lactate and MPI, and lower BE and alactic BE levels. Eight PCs were obtained, PC1 being a linear combination of pH, AG, cAG, alactic BE, bicarbonate, and BE. MPI (OR = 9.87, 95% CI: 3.07-36.61, p = 0.0002), SAPSII (OR = 1.07, 95%CI: 1.01-1.14, p = 0.01), and PC1 (OR = 2.13, 95%CI: 1.12-4.76, p = 0.04) were significantly associated with mortality in univariate analysis, while MPI (OR = 10.1, 95%CI: 3.03-40.06, p = 0.0003) and SAPSII (OR = 1.07, CI95%: 1.01–1.14, p = 0.02) remained significant after adjusting for age and sex. Conclusion: MPI and SAPSII were associated with mortality, although the interaction of laboratory parameters was not.

Biodiversity loss is considered one of the main threats to marine ecosystems. In this framework of biodiversity decline, organisms that provide biogenic habitat play a relevant role by their capacity to structure assemblages and influence ecological processes. The Mediterranean mussel Mytilus galloprovincialis is considered an ecosystem engineer because it alters local environmental conditions maintaining habitat suitability for other organisms, and enhancing local biodiversity. Although it is widely recognized that mussel beds increase diversity, the drivers shaping these assemblages are poorly explored. We investigate whether mussel size homogenisation shapes the abundance, richness and structure of macrobenthic assemblages associated with mussel beds in two shores of the Galician coast (NW Spain). At each shore, two sites, 10 m apart, were selected and at each site, faunal assemblages were compared between mussel clumps showing shells of various sizes (control), and mussel clumps with closely similar-sized mussels, considered as homogenised. Homogenised clumps showed, in general, higher values in total number of individuals and species than control clumps. Regarding the effect of mussel size homogenisation on the multivariate structure of the assemblages, significant differences between control and homogenised clumps were found in three out of the four sites. Most relevant associated species usually reached higher abundances in homogenised clumps than control ones. Therefore, mussel size homogenisation influenced the structure of the macrofaunal assemblages associated with mussel beds but, its effect was context dependent (i.e., varied with sites). Information about the species contribution to dissimilarities among homogenised and control clumps was provided and the potential influence of sediment and algae on mussel clumps was discussed.

The various facets of the internal disorder of quantum systems can be described by means of the Rényi entropies of their single-particle probability density according to modern density functional theory and quantum information techniques. In this work, we first show the lower and upper bounds for the Rényi entropies of general and central-potential quantum systems, as well as the associated entropic uncertainty relations. Then, the Rényi entropies of multidimensional oscillator and hydrogenic-like systems are reviewed and explicitly determined for all bound stationary position and momentum states from first principles (i.e., in terms of the potential strength, the space dimensionality and the states’s hyperquantum numbers). This is possible because the associated wavefunctions can be expressed by means of hypergeometric orthogonal polynomials. Emphasis is placed on the most extreme, non-trivial cases corresponding to the highly excited Rydberg states, where the Rényi entropies can be amazingly obtained in a simple, compact, and transparent form. Powerful asymptotic approaches of approximation theory have been used when the polynomial’s degree or the weight-function parameter(s) of the Hermite, Laguerre, and Gegenbauer polynomials have large values. At present, these special states are being shown of increasing potential interest in quantum information and the associated quantum technologies, such as e.g., quantum key distribution, quantum computation, and quantum metrology.

Abstract Background Müllerian adenosarcoma is a rare malignancy. These tumors occur mainly in the uterus, but also in extrauterine locations, usually related to endometriosis. Because of their rarity, there is limited data on optimal management strategies. Case presentation We present a 44-year-old woman with a history of endometriosis who consults for chronic pelvic pain. In the imaging tests, a heterogeneous mass is observed that impresses endometriosis, encompassing the uterus and left appendage. Surgery is performed by finding an extrauterine adenosarcoma that affected the uterus, ovary and bladder wall. Conclusion This is a rare case but should be considered in a patient with atypical clinical characteristics or preoperative pathology, so we show the diagnostic and therapeutic strategies carried out for the resolution of the case.

Two species of heterophyid trematodes were found in the Magellanic penguin, Spheniscus magellanicus (Forster), from Patagonia, Argentina. Ascocotyle (Ascocotyle) patagoniensis Hernández-Orts et al. (2012) is re-described based on new, properly fixed specimens (original material from South American sea lion, Otaria flavescens Shaw, was from frozen hosts). Metacercariae of this species are reported and described for the first time from the heart of the silversides, Odontesthes argentinensis (Valenciennes) and O. smitti (Lahille), from Patagonia. Ascocotyle (Phagicola) cameliae n. sp. is described from the intestine of S. magellanicus. The new species is placed into the subgenus Phagicola Faust, 1920 because of the presence of a single row of circumoral spines and uterine loops and vitelline follicles being confined posterior to the ventral sucker. However, it differs distinctly from other members of this subgenus by the number (19–24) and length (23–31 μm) of massive circumoral spines and by the morphology of the ventrogenital sac with a large, simple gonotyl devoid of refractile bodies. Molecular data (partial 28S rDNA sequences) for both species are also provided. Matching sequences from metacercarial and adult stages helped elucidate partially the life-cycle of A. (A.) patagoniensis. The interspecific relationships and phylogenetic position of Ascocotyle were further assessed on a broad phylogeny on the Opisthorchioidea Looss, 1899. Ascocotyle (P.) ornamentata Shalaby, Esposito, Riegler & Carratù (1993) described from decomposed worms (all circumoral spines were detached) found in a dog in Egypt, with no type-specimens of this species deposited in a repository collection, is considered to be species inquirenda. Keywords: Digenea, Taxonomy, Phylogenetic relationships, Life-cycle, Fish-eating birds, Marine mammals, Silversides, South-western atlantic

Neu–Laxova syndrome is a rare and lethal genetic disease with autosomal recessive inheritance involving abnormalities of multiple systems. It was first reported in 1971. Since then, just eighty-eight cases have been reported. The syndrome is characterized by early and severe growth restriction, and craniofacial anomalies, such as microcephaly, hypertelorism and other malformations, resulting in quite characteristic features. Additionally, it might appear as generalized edema, flexion contractures and other malformations of the extremities, abnormalities in the CNS (central nervous system), skin (severe ichthyosis), and genitourinary and cardiac abnormalities. We present the case of a patient who had her first pregnancy with a fetus with Neu–Laxova syndrome diagnosed in our center during the second-trimester ultrasound. The ultrasound findings suggested the diagnosis, which was confirmed with a genetic study of the amniotic fluid: the variant of the PSAT1 gene, associated with NLS (Neu–Laxova syndrome) 2 in homozygosis. Moreover, there was a second pregnancy with a fetus carrying the same mutation in heterozygosis. In addition, we have carried out a review of published literature about this disease up to the present time.

The poorly known Clymene dolphin (Stenella clymene) is a small oceanic cetacean distributed in tropical and subtropical waters of the Atlantic Ocean. In this study, we report, for the first time, a vagrant individual of Clymene dolphin in Argentina (Rada Tilly) that represents the current southern-most record for this cetacean species. We provide a molecular identification of the dolphin, based on partial sequences of the mitochondrial cytochrome b gene, generated from DNA extracted from its metazoan parasites. Three prey species, namely Argentine hake, Patagonian squid and lobster krill were identified from hard pieces collected in the stomach. Seven metazoan parasite taxa (three in adult stage, one immature stage and three in larval stage) were identified using morphological and molecular data, i.e., the digenean Pholeter gastrophilus (new host record), the cestodes Tetrabothrius (Tetrabothrius) forsteri, Clistobothrium grimaldii unidentified phyllobothriid plerocercoids, the nematodes Anisakis pegreffii (new host record), Halocercus delphini and the acanthocephalan Corynosoma australe (new host record). Our study provides the first molecular exploration of the metazoan parasite diversity in delphinids from the southwestern Atlantic, and contributes significantly to understand the poorly known parasite fauna of the Clymene dolphin.

El coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2, conocido previamente como nCoV-2019) es el agente causal de una nueva enfermedad denominada COVID-19 (COronaVIrus Disease 2019) por la Organización Mundial de la Salud. Su presentación es la insuficiencia respiratoria aguda caracterizada por una hiperinflación del pulmón que conduce a un incremento de los capilares y permeabilidad epitelial, con pérdida de la aireación de tejido pulmonar e incremento de la rigidez pulmonar. Estas alteraciones conducen a desequilibrios entre la ventilación y la relación de perfusión, que finalmente resultan en hipoxemia y deterioro de la depuración de dióxido de carbono. Para la presente revisión se realizó una búsqueda en PubMed y Trip Database. Debido a la escasez de publicaciones no se utilizó un algoritmo de búsqueda específico. El objetivo es dar a conocer, de acuerdo con la evidencia y las recomendaciones de expertos nacionales e internacionales, el manejo hemodinámico y ventilatorio de estos pacientes.

(1) Background: Little is known about the effects of SARS-CoV-2 on the placenta, and whether the maternal inflammatory response is transmitted vertically. This research aims to provide information about the effects of SARS-CoV-2 infection on maternal and fetal immunity. (2) Methods: We have studied placental changes and humoral and cellular immunity in maternal and umbilical cord blood (UCB) samples from a group of pregnant women delivering after the diagnosis of SARS-CoV-2 infection during pregnancy. IgG and IgM SARS-CoV-2 antibodies, Interleukin 1b (IL1b), Interleukin 6 (IL6), and gamma-Interferon (IFN-γ), have been studied in the UCB samples. Lymphocyte subsets were studied according to CD3, CD8, CD4, CD34, and invariant natural Killer T cells (iNKT) markers. We used in situ hybridization techniques for the detection of viral RNA in placentas. (3) Results: During the study period, 79 pregnant women and their corresponding newborns were recruited. The main gestational age at the time of delivery was 39.1 weeks (SD 1.3). We did not find traces of the SARS-CoV-2 virus RNA in any of the analyzed placental samples. Detectable concentrations of IgG anti-SARS-CoV-2 antibodies, IL1b, IL6, and IFN-γ, in UCB were found in all cases, but IgM antibodies anti-ARS-CoV-2 were systematically undetectable. We found significant correlations between fetal CD3+ mononuclear cells and UCB IgG concentrations. We also found significant correlations between UCB IgG concentrations and fetal CD3+/CD4+, as well as CD3+/CD8+ T cells subsets. We also discovered that fetal CD3+/CD8+ cell counts were significantly higher in those cases with placental infarctions. (4) Conclusion: we have not verified the placental transfer of SARS-CoV-2. However, we have discovered that a significant immune response is being transmitted to the fetus in cases of SARS-CoV-2 maternal infection.

Under ambient conditions, surfaces are rapidly modified and contaminated by absorbance of molecules and a variety of nanoparticles that drastically change their chemical and physical properties. The atomic force microscope tip–sample system can be considered a model system for investigating a variety of nanoscale phenomena. In the present work we use atomic force microscopy to directly image nanoscale contamination on surfaces, and to characterize this contamination by using multidimensional spectroscopy techniques. By acquisition of spectroscopy data as a function of tip–sample voltage and tip–sample distance, we are able to determine the contact potential, the Hamaker constant and the effective thickness of the dielectric layer within the tip–sample system. All these properties depend strongly on the contamination within the tip–sample system. We propose to access the state of contamination of real surfaces under ambient conditions using advanced atomic force microscopy techniques.

Abstract Background Biclustering algorithms search for groups of genes that share the same behavior under a subset of samples in gene expression data. Nowadays, the biological knowledge available in public repositories can be used to drive these algorithms to find biclusters composed of groups of genes functionally coherent. On the other hand, a distance among genes can be defined according to their information stored in Gene Ontology (GO). Gene pairwise GO semantic similarity measures report a value for each pair of genes which establishes their functional similarity. A scatter search-based algorithm that optimizes a merit function that integrates GO information is studied in this paper. This merit function uses a term that addresses the information through a GO measure. Results The effect of two possible different gene pairwise GO measures on the performance of the algorithm is analyzed. Firstly, three well known yeast datasets with approximately one thousand of genes are studied. Secondly, a group of human datasets related to clinical data of cancer is also explored by the algorithm. Most of these data are high-dimensional datasets composed of a huge number of genes. The resultant biclusters reveal groups of genes linked by a same functionality when the search procedure is driven by one of the proposed GO measures. Furthermore, a qualitative biological study of a group of biclusters show their relevance from a cancer disease perspective. Conclusions It can be concluded that the integration of biological information improves the performance of the biclustering process. The two different GO measures studied show an improvement in the results obtained for the yeast dataset. However, if datasets are composed of a huge number of genes, only one of them really improves the algorithm performance. This second case constitutes a clear option to explore interesting datasets from a clinical point of view.

High dimensional atomic states play a relevant role in a broad range of quantum fields, ranging from atomic and molecular physics to quantum technologies. The D-dimensional hydrogenic system (i.e., a negatively-charged particle moving around a positively charged core under a Coulomb-like potential) is the main prototype of the physics of multidimensional quantum systems. In this work, we review the leading terms of the Heisenberg-like (radial expectation values) and entropy-like (Rényi, Shannon) uncertainty measures of this system at the limit of high D. They are given in a simple compact way in terms of the space dimensionality, the Coulomb strength and the state’s hyperquantum numbers. The associated multidimensional position–momentum uncertainty relations are also revised and compared with those of other relevant systems.

The saline gradient present in river mouths can be exploited using ion-exchange membranes in reverse electrodialysis (RED) for energy generation. However, significant improvements in the fabrication processes of these IEMs are necessary to increase the overall performance of the RED technology. This work proposes an innovative technique for synthesizing anion exchange membranes (AEMs) via electrospinning. The AEM synthesis was carried out by applying a high voltage while ejecting a mixture of polyepichlorohydrin (PECH), 1,4-diazabicyclo [2.2.2] octane (DABCO® 33-LV) and polyacrylonitrile (PAN) at room temperature. Different ejection parameters were used, and the effects of various thermal treatments were tested on the resulting membranes. The AEMs presented crosslinking between the polymers and significant fiber homogeneity with diameters between 1400 and 1510 nm, with and without thermal treatment. Good chemical resistance was measured, and all synthesized membranes were of hydrophobic character. The thickness, roughness, swelling degree, specific fixed-charge density and ion-exchange capacity were improved over equivalent membranes produced by casting, and also when compared with commercial membranes. Finally, the results of the study of the electrospinning parameters indicate that a better performance in electrochemical properties was produced from fibers generated at ambient humidity conditions, with low flow velocity and voltage, and high collector rotation velocity.

In this work, the spread of hypergeometric orthogonal polynomials (HOPs) along their orthogonality interval is examined by means of the main entropy-like measures of their associated Rakhmanov’s probability density—so, far beyond the standard deviation and its generalizations, the ordinary moments. The Fisher information, the Rényi and Shannon entropies, and their corresponding spreading lengths are analytically expressed in terms of the degree and the parameter(s) of the orthogonality weight function. These entropic quantities are closely related to the gradient functional (Fisher) and the Lq-norms (Rényi, Shannon) of the polynomials. In addition, the degree asymptotics for these entropy-like functionals of the three canonical families of HPOs (i.e., Hermite, Laguerre, and Jacobi polynomials) are given and briefly discussed. Finally, a number of open related issues are identified whose solutions are both physico-mathematically and computationally relevant.

Abstract Background Uterine leiomyosarcomas are very rare and highly aggressive tumors that have a high rate of recurrence and poor prognosis, even when early diagnosed. Due to their relative rarity, there is limited research on optimal management strategies. Case presentation A 60-year-old woman with a history of an asymptomatic uterine leiomyoma presented in October 2015 with postmenopausal bleeding and a friable vaginal cyst that bled when palpated. A partial cystectomy was performed, and malignant-like cystic and solid components were identified. Histopathology diagnosed an unclassifiable malignant epithelioid tumor. Subsequent imaging studies identified a malignant uterine tumor, a metabolically active vaginal lesion, and two benign leiomyomas. An anterior pelvic exenteration (colpectomy, hysterectomy, bilateral adnexectomy, total cystectomy, and cutaneous ureteroileostomy ad modum Bricker) were performed by laparotomy in March 2016. Examination of the surgical specimens identified a 75 × 75-mm leiomyoma, an 80 × 30-mm infiltrating mesenchymal uterine lesion with vascular invasion and tumor emboli, and a 60 × 30-mm perivascular vaginal tumor. Immunohistochemistry indicated a phenotypic transition from a uterine leiomyosarcoma to a vaginal epithelioid lesion; marker expression changed from the uterine tumor actin+/desmin+/caldesmon+/CD10− phenotype, through the tumor emboli, to an actin−/desmin−/caldesmon−/CD10+ phenotype in the vaginal lesion. A high-grade uterine mesenchymal tumor and vaginal metastasis were diagnosed. Adjuvant chemotherapy with docetaxel, gemcitabine, and doxorubicin commenced in May 2016 and treatment has been well tolerated. Conclusions Differentiating leiomyosarcoma from leiomyoma is challenging and few tools other than microscopic evaluation are available. Vaginal compromise in leiomyosarcoma usually results from tumor extension, not hematogenous metastasis. A vaginal metastasis is a very rare initial presentation. We have found only two cases like this described on published literature. The atypical clinical and histological presentation in our case complicated diagnosis and delayed treatment. An early diagnosis and complete surgical clearance gives the best chance of survival, and imaging tools should be applied early in instances of new suspicious malignant lesions.

Microtubules (Mts) are dynamic cytoskeleton structures that play a key role in vesicular transport. The Mts-mediated transport depends on motor proteins named kinesins and the dynein/dynactin motor complex. The Rab7 adapter protein FYCO1 controls the anterograde transport of the endocytic compartments through the interaction with the kinesin KIF5. Rab7 and its partner RILP induce the recruitment of dynein/dynactin to late endosomes regulating its retrograde transport to the perinuclear area to fuse with lysosomes. The late endosomal-lysosomal fusion is regulated by the HOPS complex through its interaction with RILP and the GTPase Arl8. Coxiella burnetii (Cb), the causative agent of Q fever, is an obligate intracellular pathogen, which generates a large compartment with autophagolysosomal characteristics named Cb-containing vacuole (CCV). The CCV forms through homotypic fusion between small non-replicative CCVs (nrCCV) and through heterotypic fusion with other compartments, such as endosomes and lysosomes. In this work, we characterise the role of Mts, motor proteins, RILP/Rab7 and Arl8 on the CCV biogenesis. The formation of the CCV was affected when either the dynamics and/or the acetylation state of Mts were modified. Similarly, the overexpression of the dynactin subunit non-functional mutants p150Glued and RILP led to the formation of small nrCCVs. This phenomenon is not observed in cells overexpressing WT proteins, the motor KIF5 or its interacting protein FYCO1. The formation of the CCV was normal in infected cells that overexpressed Arl8 alone or together with hVps41 (a HOPS subunit) or in cells co-overexpressing hVps41 and RILP. The dominant negative mutant of Arl8 and the non-functional hVps41 inhibited the formation of the CCV. When the formation of CCV was affected, the bacterial multiplication diminished. Our results suggest that nrCCVs recruit the molecular machinery that regulate the Mts-dependent retrograde transport, Rab7/RILP and the dynein/dynactin system, as well as the tethering processes such as HOPS complex and Arl8 to finally originate the CCV where C. burnetii multiplies.