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Abstract Background Vasculogenic mimicry (VM) is an alternative intratumoral microcirculation system that depends on the capacity of tumor cells to reorganize and grow in three-dimensional (3D) channel architectures like the capillaries formed by endothelial cells. Both VM and angiogenesis may coordinately function to feed cancer cells, allowing tumor growth. Long noncoding RNAs (lncRNAs) regulate critical cellular functions in cancer cells, including cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. The lncRNA, known as actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), has been described as an oncogene in diverse types of cancers. However, its role in VM and metastasis in triple-negative breast cancer (TNBC) is unknown. Methods Reverse transcription and quantitative polymerase chain reaction (RT‒qPCR) experiments were performed to evaluate the expression of 10 selected lncRNAs from literature in metastatic and nonmetastatic biopsies from TNBC patients. The expression of AFAP1-AS1 was analyzed in Genotype-Tissue Expression Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. The AFAP1-AS1 expression was knocked in TNBC Hs578T cells by transfection of specific siRNAs. Channel-like formation assays were performed using 3D cultures over Matrigel in hypoxia-treated Hs578T cancer cells with diminished expression of AFAP1-AS1. The angiogenesis tests were conducted using human umbilical vein endothelial cells (HUVECs) and AFAP1-AS1- silenced Hs578T cells on 3D cell cultures. The presence of VM (CD31-/PAS+) in tumor tissues from TNBC patients with and without metastasis was assessed through immunohistochemistry using endothelial marker CD31 antibodies and periodic acid-Schiff (PAS) staining. Results Compared with normal mammary tissues, AFAP1-AS1 expression was higher in breast cancer tissues. Moreover, AFAP1-AS1 expression was upregulated in the TNBC subtype compared to receptor-positive breast tumors. In addition, the expression of AFAP1-AS1 was correlated with the expression of the thirteen genes characteristic of a previously reported hypoxia signature. Interestingly, AFAP1-AS1 was upregulated in primary TNBC tumors from patients who developed metastasis compared with the nonmetastatic group. Functional analysis revealed that the knockdown of AFAP1-AS1 in Hs578T cells significantly impaired the hypoxia-induced VM, accompanied by a decrease in the development of 3D channel networks. Similarly, AFAP1-AS1 knockdown counteracts the angiogenic potential of cancer cells, as indicated by a reduction in the number of polygons, sprouting cells, and nodes in HUVEC cells. Remarkably, an increase in CD31-/PAS + staining of 3D channel networks in primary breast tumors from metastatic patients was found compared with the nonmetastatic group. Finally, we found that the number of blood vessels increased in the nonmetastatic group more than in the metastatic cohort. Conclusions Our data suggested that AFAP1-AS1 controls both VM and angiogenesis in Hs578T breast cancer cells and that increased metastasis is associated with VM in TNBC patients.

Persistent infection with high-risk human papillomavirus remains the primary factor associated with the progression of cervical squamous intraepithelial lesions and the development of cervical cancer. Nevertheless, a combination of factors, including genetic predisposition, immune response, hormonal influences, and nutritional status, contribute synergistically to the development of cervical cancer. Among the various factors involved in the pathogenesis and therapy of cervical cancer, retinoids have gained considerable attention due to their multifaceted roles in different cellular processes. This review investigates defects within the vitamin A metabolism pathway and their correlation with cervical cancer. Additionally, it integrates epidemiological and experimental findings to discuss the potential utility of retinoid-based therapies, either alone or combined with other therapies, as agents against premalignant lesions and cervical cancer.

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn’s disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.

Tumor cells grow in three-dimensional (3D) channels-like structures denoted as vasculogenic mimicry (VM), which provides a route for nutrients and oxygen acquisition. VM is activated by hypoxia and associated with metastasis and poor prognosis. MetastamiRs are microRNAs regulating metastasis, however, if they control VM in breast cancer remains poorly understood. The aim of this study was to evaluate the expression of VM-associated microRNAs in tumors of metastatic breast cancer patients. Firstly, we constructed microRNAs/mRNAs coregulation networks using expression data from TCGA databases. Dozens of microRNAs regulating genes involved in VM and metastasis were found. Of these, we selected 10 microRNAs for further characterization. The presence of VM in histological samples from patients with or without metastasis was evaluated using CD31-/PAS+ immunophenotyping. Remarkably, data showed that VM was significantly increased in tumors from patients with metastasis in comparison with no-metastatic group. Gene expression analysis indicated that miR-145, miR-142-3p, miR-31, miR-148a, miR-200b-3p and miR-526b were downregulated in primary tumors from patients with metastatic disease and positive for VM. Moreover, modulated microRNAs showed a predictive clinical value in overall survival in a cohort (n=1262) of breast cancer patients. Of these, we evaluated the role of miR-145 in formation of hypoxia-induced 3D channels-like using an in vitro model that recapitulates the early stages of VM. Data showed that miR-145 mimics was able to abolish the VM development in both metastatic Hs578t and MDA-MB-231 breast cancer cells. In conclusion, manipulation of miR-145 levels may represent a therapeutic approach in metastatic breast cancer patients that developed VM.

Brachybacterium conglomeratum, traditionally considered an environmental bacterium, has recently garnered attention for its potential involvement in human health. While prior research hinted at its pathogenic role in humans, our study aims to determine its prevalence and associations in diverse clinical contexts. We examined vaginal swabs from three distinct patient groups: patients with low-grade squamous intraepithelial lesions (LSIL), patients with cervicovaginal infections, and patients with a history of precancerous lesions undergoing follow-up. B. conglomeratum was present in all three patient groups, with the highest prevalence observed in the LSIL group. Statistically significant associations were primarily identified in the LSIL group, where B. conglomeratum was present in 60% of cases. Notably, the LSIL group exhibited coinfections with multiple high-risk oncogenotypes of human papillomavirus (HPV), suggesting potential synergistic effects, and understanding these microbial relationships and their influence on viral persistence, particularly with HPV, holds promise for mitigating HPV-related carcinogenesis. Furthermore, Gardnerella vaginalis and Atopobium vaginae were frequently detected in this group, along with Ureaplasma parvum as the predominant sexually transmitted bacterium. In all cases, B. conglomeratum was found in association with these microorganisms rather than as a sole pathogen. This coexistence underscores the intricate microbial interactions within cervicovaginal infections and precancerous lesions. This study marks the first report of B. conglomeratum prevalence in women with these clinical conditions.

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain.MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients.ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92–2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0–1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses.ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Persistent infection with Helicobacter pylori (H. pylori) is an important factor in gastric diseases. The vacA and cagA virulence factors of H. pylori contribute to the development of these diseases. Triple therapy containing clarithromycin has been used to eradicate this infection. Unfortunately, resistance to this antibiotic is the primary cause of treatment failure. This study aimed to determine the prevalence of clarithromycin resistance-associated mutations and to assess the relationship between virulence factors and Mexican patients infected with H. pylori. The cagA and vacA genotypes were determined by multiplex PCR. Furthermore, a qPCR was used to identify mutations of the 23S rRNA gene. This study reported a prevalence of 84.3% of H. pylori among patients with gastric diseases, and the vacA s1m1/cagA+ genotype was the most frequent (44.8%) in antrum and corpus. Analysis of the 23S rRNA gene revealed a 19.8% prevalence of clarithromycin resistance-associated mutations. The most prevalent mutations were A2143G (56%) and A2142C (25%). A significant association (p < 0.05) between the A2142G and the vacA s1m1/cagA+ genotype was detected. In conclusion, we report a high prevalence (>15%) of clarithromycin resistance-associated mutations, and we found an association between the genotypes of virulence factors and a mutation in the 23S rRNA gene.

The COVID-19 pandemic has been a main concern over the last two years and has become one of the most important crises in the history of human health. Today, there is still a need for affordable and reliable diagnostic tests for massive disease monitoring. Previously, a set of highly specific DNA-aptamers (C7/C9) binding to the SARS-CoV-2 Spike (S) protein were isolated but its performance in clinical samples remained to be tested. Here, 242 samples were collected through three different methods and subjected to florescence-linked aptamer assays (FLAA) based on C7/C9 aptamers through two readout protocols. Then, a step-by-step statistical approach which included agreement tests, proportion comparisons and binomial and multinomial logistic regressions was used to predict optimal conditions for the novel C7/C9 FLAA test. RTqPCR threshold cycles, symptoms onset and processing time were influential factors on FLAA test results. Naturally occurring mutations on S were also detected and analyzed. Aminoacidic substitutions D614G and T732A appeared relevant for aptamer recognition although further studies are necessary. The methodology presented here is the first step to determine the performance and diagnosis across a range of clinical contexts and it might serve as a base for a complete analysis applicable to other designs of new diagnostic tests.

Gestational diabetes (GD), pre-gestational diabetes (PD), and pre-eclampsia (PE) are morbidities affecting gestational health which have been associated with dysbiosis of the mother’s gut microbiota. This study aimed to assess the extent of change in the gut microbiota diversity, short-chain fatty acids (SCFA) production, and fecal metabolites profile in a sample of Mexican women affected by these disorders. Fecal samples were collected from women with GD, PD, or PE in the third trimester of pregnancy, along with clinical and biochemical data. Gut microbiota was characterized by high-throughput DNA sequencing of V3-16S rRNA gene libraries; SCFA and metabolites were measured by High-Pressure Liquid Chromatography (HPLC) and (Fourier Transform Ion Cyclotron Mass Spectrometry (FT-ICR MS), respectively, in extracts prepared from feces. Although the results for fecal microbiota did not show statistically significant differences in alfa diversity for GD, PD, and PE concerning controls, there was a difference in beta diversity for GD versus CO, and a high abundance of Proteobacteria, followed by Firmicutes and Bacteroidota among gestational health conditions. DESeq2 analysis revealed bacterial genera associated with each health condition; the Spearman’s correlation analyses showed selected anthropometric, biochemical, dietary, and SCFA metadata associated with specific bacterial abundances, and although the HPLC did not show relevant differences in SCFA content among the studied groups, FT-ICR MS disclosed the presence of interesting metabolites of complex phenolic, valeric, arachidic, and caprylic acid nature. The major conclusion of our work is that GD, PD, and PE are associated with fecal bacterial microbiota profiles, with distinct predictive metagenomes.

As a result of the COVID-19 pandemic, various joint efforts have been made to support the creation of vaccines. Different projects have been under development, of which some are in the clinical evaluation stage and others in are in phase III with positive results. The aim of this paper was to describe the current situation of the development and production of vaccines available to the population to facilitate future research and continue developing and proposing ideas for the benefit of the population. So, we carried out a systematic review using databases such as PubMed, ScienceDirect, SciELO, and MEDLINE, including keywords such as “vaccines,” “COVID-19,” and “SARS-CoV-2”. We reviewed the development and production of the anti-COVID vaccine and its different platforms, the background leading to the massive development of these substances, and the most basic immune aspects for a better understanding of their physiological activity and the immune response in those who receive the vaccine. We also analyzed immunization effects in populations with any medical or physiological conditions (such as immunosuppression, people with comorbidities, and pregnancy), as well as the response to immunization with heterologous vaccines and the hybrid immunity (the combination of natural immunity to SARS-CoV-2 with immunity generated by the vaccine). Likewise, we address the current situation in Mexico and its role in managing the vaccination process against SARS-CoV-2 at the national and international levels. There are still many clinical and molecular aspects to be described, such as the duration of active immunity and the development of immunological memory, to mention some of the most important ones. However, due to the short time since the global vaccination roll-out and that it has been progressive (not counting children and people with medical conditions), it is premature to say whether a second vaccination schedule will be necessary for the near future. Thus, it is essential to continue with health measures.

Background and study aims Chromoendoscopy with targeted biopsy is the technique of choice for colorectal cancer screening in longstanding inflammatory bowel disease. We aimed to analyze results of a chromoendoscopy screening program and to assess the possibility of identifying low-risk dysplastic lesions by their endoscopic appearance in order to avoid histological analysis. Materials and methods We retrospectively reviewed chromoendoscopies performed between February 2011 and June 2017 in seven Spanish hospitals in a standardized fashion. We analyzed the findings and the diagnostic yield of the Kudo pit pattern for predicting dysplasia. Results A total of 709 chromoendoscopies (569 patients) were reviewed. Median duration of disease was 16.7 years (SD 8.1); 80.4 % had ulcerative colitis. A total of 2025 lesions (3.56 lesions per patient) were found; two hundred and thirty-two lesions were neoplastic (11.5 %) (223 were LGD (96.1 %), eight were HGD (3.4 %), and one was colorectal cancer (0.5 %). The correlation between dysplasia and Kudo pit patterns predictors of dysplasia (≥ III) was low, with an area under the curve of 0.649. Kudo I and II lesions were correctly identified with a high negative predictive value (92 %), even by non-experts. Endoscopic activity, Paris 0-Is classification, and right colon localization were risk factors for dysplasia detection, while rectum or sigmoid localization were protective against dysplasia. Conclusions Chromoendoscopy in the real-life setting detected 11 % of dysplastic lesions with a low correlation with Kudo pit pattern. A high negative predictive value would prevent Kudo I and, probably, Kudo II biopsies in the left colon, reducing procedure time and avoiding complications.

Many amateur sportsmen in the West, have today started undertaking long and intensive ordeals where their personal capacity to withstand increasing suffering is the prime objective. Running, jogging, triathlon and trekking, etc., are the sorts of ordeal where people without any particular ability are not pitting themselves against others, but are committed to testing their own capacity to withstand increasing pain. Constantly called upon to prove themselves in a society where reference points are both countless and contradictory and where values are in crisis, people are now seeking a one-to-one relationship by radical means, testing their strength of character, their courage and their personal resources. Going right on to the end of a self-imposed ordeal gives a legitimacy to life and provides a symbolic plank that supports them. Performance itself is of secondary significance; it is has a value only to the individual. There is no struggle against a third party, only a method for reinforcing personal will-power and overcoming suffering by going right to the limit of a personally-imposed demand. The physical limit has come to replace the moral limit that present-day society is failing to provide. Overcoming suffering tempers the individual, providing a renewed significance and value to his life

La artritis séptica no gonocóccica es una urgencia en reumatología. Su diagnóstico y tratamiento tempranos evitan deformidades e incapacidades articulares. Se realizó un estudio retrospectivo de esta forma de artritis, en pacientes del Hospital Universitario San Vicente de Paúl, de MedeIlín, entre 1984 y 1992, para evaluar su forma de presentación, los factores predisponentes, el agente causal, las articulaciones comprometIdas y las complicaciones. De una revisión de 302 historias clínicas de pacientes mayores de 12 años con presunción diagnóstica de artritis séptica se hallaron 54 con aislamiento de la bacteria causal a partir del líquido articular, los hemocultivos O ambos; dichos pacientes con etiología comprobada motivan este informe. El grupo estuvo formado por 38 hombres (70.4%) y 16 mujeres (29.6%) cuya edad promedio era 27 años. Predominó Staphylococcus aureus (43 pacientes; 79.6%) seguido por bacilos Gram negativos (9 pacientes; 16.7%); hubo dos casos debidos a estreptococos (3.7%). La enfermedad fue monoarticular en 49 casos (90.7%) y biarticular en 5. Comprometió, en su orden, la rodilla (30 casos; 55.6%), la cadera (19; 35.2%), el tobillo y el hombro (tres casos cada uno), la articulación sacrollíaca (2 casos), la metacarpofalánglca y la esternoclavicular (un caso de cada una). Como complicaciones se hallaron 13 casos de sepsis, 13 de osteomielitis, 6 de bronconeumonía, 3 de insuficiencia renal aguda, 1 de coagulación intravascular diseminada y 1 de pericarditis. Este total de 37 complicaciones afectó a 23 pacientes. Ningún paciente falleció. En cuanto a los factores predisponentes y las enfermedades subyacentes se detectaron los siguientes: infección de tejidos blandos en 9 pacientes, endometritis en 3, LES o linfomano Hodgkin en 2 pacientes cada uno, artritis reumatoidea O inyección intraarticular en un paciente cada una. La consulta tuvo lugar después de la primera semana de evolución en 43 pacientes (79.6%). Non-gonococcal septic arthritis is a rheumatological emergency; early diagnosis and treatment prevent deformities and disabilities. A retrospective study of this disease was carried out for the period 1984-1992, at Hospital Universitario San Vicente de Paúl, Medellín, Colombia; 54 patients older than 12 years were found that presented clinical manifestations of septic arthritis and in whom etiologic diagnosis was established by either joint fluid or blood culture. The following aspects were Included in the survey: form of presentation, predisposing factors, etiology and complications. There were 38 males (70.4%) and 16 females (29.6%); average age was 27 years. The disease was monoarticular In 49 cases (90.7%) and affected 2 joints In 5; In decreasing order of frequency the following joints were Involved: knee (30 cases; 55.6%); hip (19 cases; 35.2%), ankle and shoulder (3 cases each), sacroiliac joint (2 cases), metacarpophalangic and sterno clavicular joints (1 case each). The infection was due to Staphylococcus aureus in 43 cases (79.6%) followed by Gram-negative bacilli (9 cases; 16.7%); the remaining 2 cases were streptococcal. Complications were sepsis (13 cases), ostomyelitis (13 cases), bronchopneumonia (6 cases), renal insufficiency (3 cases), Intravascular disseminated coagulation (1 case) and pericarditis (1 case); these 37 complicating events occurred In 23 patients. Predisposing factors and underlying diseases were as follows: soft tissue infection (9 , patients), endometritis (3 patients), systemic erythematous lupus (2 patients), non-Hodgkin Iymphoma (2 patients), rheumatoid arthritis and intra-articular Injection (1 patient each). Evolution had been longer than one week In 43 patients (79.6%) when they first attended the Hospital; despite the delay there were no fatalities.

Muchos deportistas aficionados en occidente, están emprendiendo hoy en dí­a, largas e intensas ordalí­as donde la capacidad personal de resistir al sufrimiento en aumento constituye el objetivo principal. La carrera, el footing, el triatlón, el trekking, etc., son tipos de ordalí­as en las que la gente, sin apoyarse en una habilidad especí­fica, no compite contra otros, sino que somete a prueba su propia capacidad para soportar el dolor creciente. El individuo se evalúa constantemente a sí­ mismo en una sociedad donde los puntos de referencia son incontables y contradictorios, donde los valores están en crisis, y busca entonces una relación cercana con significados profundos, probando su fuerza de carácter, su coraje y sus recursos personales. Seguir adelante hasta final de las ordalí­as autoimpuestas da una legitimidad a la vida y provee un umbral simbólico en el cual apoyarse. El funcionamiento en sí­ mismo tiene una importancia secundaria; sólo cuenta para el individuo. No se trata de luchar contra un tercero, es sólo un método para reforzar la voluntad personal y vencer el sufrimiento, justo al lí­mite de una demanda personalmente impuesta. El lí­mite fí­sico ha venido a sustituir el lí­mite moral que la sociedad actual no logra proporcionar. Sobreponiéndose al sufrimiento se templa el carácter del individuo, proporcionando así­ una importancia renovada y valiosa a su vida