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Breast cancer survivorship is a recognized risk factor for sexual dysfunction, with various clinical, sociocultural, and psychological factors potentially interacting differently across populations. This study compared sexual dysfunction, anxiety, and depression between females with breast cancer and those without, aiming to identify associated factors. A total of 362 females participated, including 227 with sexual dysfunction and 135 controls. Among them, 195 are breast cancer survivors, while 167 have no personal history of cancer. Key variables were analyzed using Student’s t-test for quantitative data and Fisher’s exact test for categorical data, while logistic regression models were used to assess the association between sexual dysfunction and various factors. Multivariate analysis revealed that, in sexually active females, breast cancer survivorship increased the odds of sexual dysfunction 2.7-fold (95% CI: 1.17–6.49; p = 0.020). Anxiety was significantly associated with sexual dysfunction, regardless of cancer status (AdOR 6.00; 95% CI: 2.50–14.43; p < 0.001). The interaction between cancer survival and anxiety further increased the odds of sexual dysfunction by more than 11-fold (AdOR 11.55; 95% CI: 3.81–35.04; p < 0.001). Additionally, obesity was found to be a protective factor among cancer survivors (AdOR 0.149; 95% CI: 0.027–0.819; p = 0.029). In conclusion, breast cancer has a significant impact on sexual function, with psychological factors like anxiety playing a crucial role. Addressing these issues requires a holistic, patient-centered approach that considers the complex interplay of physical, emotional, and sociocultural factors.

Abstract Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation. First, we found that CTH is induced in the colon mucosa in mice with dextran sulfate sodium-induced colitis. Expression of CTH was completely absent in the colon of Cth –/– mice. We observed that clinical and histological parameters are ameliorated in Cth-deficient mice compared to wild-type animals. However, Cth deletion had no effect on tumorigenesis and the level of dysplasia in mice treated with azoxymethane-DSS, as a reliable model of colitis-associated carcinogenesis. Mechanistically, we determined that the deletion of the gene Slc7a11 encoding for solute carrier family 7 member 11, the transporter of the anionic form of cysteine, does not affect DSS colitis. Lastly, we found that the richness and diversity of the fecal microbiota were significantly increased in Cth –/– mice compared to both WT and Slc7a11 –/– mice. In conclusion, our data suggest that the enzyme CTH represents a target for clinical intervention in patients with inflammatory bowel disease, potentially by beneficially reshaping the composition of the gut microbiota.

Enteropathogenic Escherichia coli (EPEC) is a bacterium that causes attaching/effacing (A/E) lesions and serious diarrheal disease, a major health issue in developing countries. EPEC pathogenicity results from the effect of virulence factors and dysregulation of host responses. Polyamines, including spermidine, play a major role in intestinal homeostasis. Spermidine is the substrate for deoxyhypusine synthase (DHPS), which catalyzes the conjugation of the amino acid hypusine to eukaryotic translation initiation factor 5A (EIF5A); hypusinated EIF5A (EIF5AHyp) binds specific mRNAs and initiates translation. Our aim was to determine the role of hypusination during infection with A/E pathogens. We found that DHPS and EIF5AHyp levels are induced in i) a colonic epithelial cell line and human-derived colon organoids infected with EPEC, and ii) the colon of mice infected with Citrobacter rodentium, the rodent equivalent of EPEC. Specific deletion of Dhps in intestinal epithelial cells worsened clinical, histological, and pro-inflammatory parameters in C. rodentium-infected mice. These animals also exhibited an exacerbated pathogenic transcriptome in their colon. Furthermore, infected mice with specific Dhps deletion exhibited reduced levels of proteins involved in detoxification of tissue-damaging reactive aldehydes and consequently increased electrophile adducts in the colon. Thus, hypusination in intestinal epithelial cells protects from infectious colitis mediated by A/E pathogens.

Gas hydrate formation poses a significant challenge in offshore oil and gas production, particularly during cold restarts after extended shut–ins, which can lead to pipeline blockages. Although steady–state models have traditionally been used to predict hydrate formation under continuous production conditions, these models are often inadequate for transient operations due to issues like near–zero fluid flow shear affecting the viscosity calculations of hydrate slurries. This study introduces novel conceptual models for dispersed water–in–crude oil systems specifically designed for cold restart scenarios. The models are supported by direct observations and various experimental approaches, including bottle tests, rheometer measurements, micromechanical force apparatus, and rocking cell studies, which elucidate the underlying mechanisms of hydrate formation. Additionally, this work introduces a modeling approach to represent conceptual pictures, incorporating particle settling and yield stress, to determine whether the system will plug or not upon restart. Validation is provided through transient large–scale flowloop tests, confirming the plugging mechanisms outlined. This comprehensive approach offers insights into conditions that may safely prevent or potentially lead to blockages in the fully dispersed system during field restarts, thereby enhancing the understanding and management of gas hydrate risks in offshore oil and gas operations.

Background: Annona muricata L. (guanabana) leaves are rich in bioactive compounds with potential antioxidant properties. In the state of Colima, both ethanolic extracts and infusions are traditionally used in folk medicine to address various ailments. This study aimed to evaluate and compare the phytochemical composition and antioxidant activities of ethanolic extracts and infusions of A. muricata leaves from three geographic regions in Colima, Mexico, with a focus on how geographic origin affects their bioactive properties. Methods: Ethanolic extracts and infusions were prepared from A. muricata leaves and analyzed using phytochemical screening; DPPH, total antioxidant capacity (TAC), and total phenolic content (TPC) measurements; and HPLC. TLC was also conducted to examine the presence of specific compounds, such as flavonoids and phenols. Results: Both the ethanolic extracts and infusions contained significant levels of alkaloids, flavonoids, tannins, and phenolic compounds. The infusions demonstrated superior antioxidant capacity, with DPPH inhibition values of 72.5%, 68.3%, and 65.1% in the northern, central, and southern regions, respectively, compared to the ethanolic extracts’ values of 50.3%, 48.9%, and 45.0%. HPLC identified quercetin as a major compound across all samples. Geographically, the northern region exhibited higher concentrations of bioactive compounds, particularly total flavonoid content (TFC) and iron-reducing power (FRPA). Conclusions: Both the ethanolic extracts and infusions of A. muricata leaves exhibited significant antioxidant properties, with the infusions showing superior performance. The results suggest that A. muricata infusions may have potential applications in managing oxidative stress-related diseases such as cancer and diabetes. Exploring their use in traditional medicine and employing this type of approach can help discern the metabolite profile responsible for these bioactivities. Geographic factors influence the bioactive profile of the plant, and further research is needed to isolate specific bioactive compounds and elucidate their therapeutic mechanisms.

Background: The COVID-19 pandemic significantly impacted mental health and substance use patterns, particularly among young adults. Objective: This study aimed to assess changes in anxiety, depression, self-esteem, and substance use among university students in Mexico before, during, and after the pandemic. Methods: Using a repeated cross-sectional design, this study was conducted with university students in Mexico across three periods: pre-pandemic (2017 and 2019); during the pandemic (2021); and post-pandemic (2023). A total of 2167 students were interviewed during one of the three periods. Standardized scales measured anxiety, depression, self-esteem, Erotic Response and Sexual Orientation Scale (EROS), and substance use. Results: showed a marked and significant increase in the proportion of students with anxiety (40.0%, 71.7%, and 79.6%) and depression (14.4%, 61.9%, and 62.6%) during the pre-pandemic, pandemic, and post-pandemic periods, respectively. Self-esteem significantly decreased during and after the pandemic, compared to pre-pandemic, particularly among females. The proportion of students categorized as moderate/high-risk for their substance use changed over time, showing a reduction in alcohol use (from 29.9% to 20.2%) and tobacco use (from 26.0% to 18.2%) but an increase in sedative use (from 7.1% to 11.7%), before vs after the pandemic, respectively. Multivariate analysis revealed that anxiety, low self-esteem, and increased sedative use were consistently linked to a heightened risk of depression during and after the pandemic. Notably, anxiety and depression levels remained in a proportion significantly elevated even in the post-pandemic period. Conclusions: These findings underscore the enduring impact of the COVID-19 pandemic on the mental health of university students, highlighting the urgent need for targeted interventions, early detection strategies, and customized educational programs to effectively support students’ mental well-being in the ongoing post-pandemic era.

Background/Objectives: Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain unclear. This study aimed to assess the association between diabetes and specific shoulder injuries, as well as the degree of functional impairment in affected patients. Methods: A case–control study was conducted involving 136 patients with shoulder functional impairment (UCLA Shoulder Scale ≤ 27). The study included 38 patients with diabetes and 98 non-diabetic controls. Shoulder injuries were diagnosed using ultrasonography, focusing on the supraspinatus tendon, long head of the biceps tendon, subscapularis tendon, and the presence of adhesive capsulitis or rotator cuff tears. Results: Diabetic patients had significantly higher rates of poor shoulder function compared to non-diabetic controls (89.47% vs. 63.26%, adjusted OR [adOR] 5.22, 95% CI 1.57–17.32, p = 0.007). While both groups had high rates of supraspinatus and long head of the biceps tendon injuries (~80%), no significant differences were found between them (p > 0.300). However, diabetic patients were more than three times as likely to have subscapularis tendon injuries (adOR 3.15, 95% CI 1.26–7.90, p = 0.014) and massive rotator cuff tears (adOR 3.76, 95% CI 1.16–12.15, p = 0.027). Additionally, diabetes was associated with a fourfold increased risk of adhesive capsulitis (adOR 4.16, 95% CI 1.20–14.47, p = 0.025). Conclusions: Diabetes mellitus is linked to greater functional and structural deterioration of the shoulder, highlighting the importance of considering diabetes as a risk factor for specific shoulder injuries. Early diagnosis and treatment may improve outcomes for diabetic patients with shoulder disorders.

Low crop diversification in highly productive areas has led to declines in total organic carbon (TOC) in soil, essential nutrients for plant’s growth and microbial diversity/activity. This could have an impact on the movement of water in the soil profile and, consequently, on the production of crops. To address these challenges there is growing support for crops intensification, which involves increasing the number/variety of crops throughout the year. The purpose of this study was to assess the influence of crop intensification on the initial infiltration of water in the upper layer of the soil profile and the activity/abundance of soil microorganisms involved in the turnover of TOC and phosphorus (P). Three crop regimes were assessed in a long-term experiment established in the southeast of the Argentinean Pampas: without intensification (Monocrop: soybean), intensified (Cover crop: CC [oat]/soybean) and Rotation (CC [oat]/soybean-corn-wheat). Soil in the Monocrop regime exhibited the highest sorptivity values and a lower TOC, suggesting a higher initial rate of water entry into the profile, which could break down soil aggregates. Under rotation, the highest infiltration rate was recorded, which would guarantee more water flow into the profile. Intensified soils showed the highest total glomalin content and root colonization with arbuscular mycorrhizal fungi (AMF), which are known to contribute to plant nutrient uptake and growth and soil aggregate stability. Trichoderma abundance and their P-solubilizing capacity were also higher under Rotation, which could favor AMF activity. Correlation analysis revealed a significant positive correlation between sorptivity and glomalin under Rotation. Our study suggests that soils from the Argentinean south-eastern Humid Pampas under crop intensification promote soil water storage and maintenance of soil structure in the upper layers compared to Monocrop, which could be attributed —at least in part— to a greater microbiological activity and TOC content.

Abstract The intestinal immune response is crucial in maintaining a healthy gut, but the enhanced migration of macrophages in response to pathogens is a major contributor to disease pathogenesis. Integrins are ubiquitously expressed cellular receptors that are highly involved in immune cell adhesion to endothelial cells while in the circulation and help facilitate extravasation into tissues. Here we show that specific deletion of the Tln1 gene encoding the protein talin-1, an integrin-activating scaffold protein, from cells of the myeloid lineage using the Lyz2-cre driver mouse reduces epithelial damage, attenuates colitis, downregulates the expression of macrophage markers, decreases the number of differentiated colonic mucosal macrophages, and diminishes the presence of CD68-positive cells in the colonic mucosa of mice infected with the enteric pathogen Citrobacter rodentium. Bone marrow-derived macrophages lacking expression of Tln1 did not exhibit a cell-autonomous phenotype; there was no impaired proinflammatory gene expression, nitric oxide production, phagocytic ability, or surface expression of CD11b, CD86, or major histocompatibility complex II in response to C. rodentium. Thus, we demonstrate that talin-1 plays a role in the manifestation of infectious colitis by increasing mucosal macrophages, with an effect that is independent of macrophage activation.

An increased fertilizer application for agricultural purposes has resulted in increased nitrate (NO3−) levels in surface water and groundwater around the globe, highlighting demand for a low-maintenance NO3− treatment technology that can be applied to nonpoint sources. Ion exchange (IEX) is an effective NO3− treatment technology and research has shown that bioregeneration of NO3− laden resins has the potential to minimize operational requirements and brine waste production that often prevents IEX application for decentralized treatment. In this work, batch denitrification experiments were conducted using solutions with low IEX selectivity capable of supporting the growth of denitrifying bacteria, while minimizing NO3− desorption from resins, encouraging resin-phase denitrification. Although only 15% of NO3− was desorbed by the low selectivity solution, this initial desorption started a cycle in which desorbed NO3− was biologically transformed to NO2−, which further desorbed NO3− that could be biotransformed. Denitrification experiments resulted in a 43% conversion rate of initially adsorbed NO3−, but biotransformations stopped at NO2− due to pH limitations. The balance between adsorption equilibria and biotransformation observed in this work was used to propose a continuous-flow reactor configuration where gradual NO3− desorption might allow for complete denitrification in the short retention times used for IEX systems. HIGHLIGHTS Microorganisms preferentially transformed aqueous-phase NO3−, and no indicators of resin-phase NO3− transformation were observed.; Aqueous- and resin-phase ion concentrations are driven toward an equilibrium state that is dependent on ion selectivities.; The balance between adsorption equilibria and biotransformations is relevant to the implementation of a continuous-flow BIEX reactor.;

Antecedentes: La progresión de la enfermedad venosa crónica (EVC) suele estar ligada a factores de riesgo que son motivo de investigación aun sin asociación clara. Objetivo: Identificar si los factores de riesgo cardiovascular (FRC) impactan la progresión de la EVC. Método: Análisis retrospectivo observacional de datos clínicos y epidemiológicos de 314 pacientes atendidos por el Servicio de Angiología y Cirugía Vascular del Hospital Central del Estado de Chihuahua de enero de 2021 a mayo de 2023. Resultados: El grupo de edad más afectado por la EVC fue de los 52 a 61 años (27.1%), el 68.2% de los pacientes fueron mujeres, el 53.2% se identificó en estadio de insuficiencia venosa crónica (IVC), en una relación hombre-mujer de 28.7-71.3%. La presentación más frecuente fue C3 (30.6%). En el análisis de riesgo de los FRC, la ausencia de dislipidemia y tabaquismo representaron una reducción en la probabilidad de progresión de la EVC a IVC en un 35 y 34% respectivamente. Conclusión: Esta revisión propone que algunos FRC podrían impactar en la progresión de la EVC hacia IVC.

In the ongoing fight against Coronavirus Disease 2019 (COVID-19), researchers are exploring potential treatments to improve outcomes, especially in severe cases. This includes investigating the repurposing of existing medications, such as furosemide, which is widely available. This study aimed to evaluate the impact of furosemide on mortality rates among COVID-19 patients with severe or critical illness. We assessed a cohort of 515 hospitalized adults who experienced a high mortality rate of 43.9%. Using a multivariate analysis with adjusted risk ratios (AdRRs), factors like smoking (AdRR 2.48, 95% CI 1.53–4.01, p < 0.001), a high Pneumonia Severity Index (PSI) score (AdRR 7.89, 95% CI 5.82–10.70, p < 0.001), mechanical ventilation (AdRR 23.12, 95% CI 17.28–30.92, p < 0.001), neutrophilia (AdRR 2.12, 95% CI 1.52–2.95, p < 0.001), and an elevated neutrophil-to-lymphocyte ratio (NLR) (AdRR 2.39, 95% CI 1.72–3.32, p < 0.001) were found to increase mortality risk. In contrast, vaccination and furosemide use were associated with reduced mortality risk (AdRR 0.58, p = 0.001 and 0.60, p = 0.008; respectively). Furosemide showed a pronounced survival benefit in patients with less severe disease (PSI < 120) and those not on hemodialysis, with mortality rates significantly lower in furosemide users (3.7% vs. 25.7%). A Kaplan–Meier analysis confirmed longer survival and better oxygenation levels in patients treated with furosemide. Furthermore, a Structure–Activity Relationship analysis revealed that furosemide’s sulfonamide groups may interact with cytokine sites such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), potentially explaining its beneficial effects in COVID-19 management. These findings suggest that furosemide could be a beneficial treatment option in certain COVID-19 patient groups, enhancing survival and improving oxygenation.

PCR and its variants (RT-PCR and qRT-PCR) are valuable and innovative molecular techniques for studying nucleic acids. qPCR has proven to be highly sensitive, efficient, and reproducible, generating reliable results that are easy to analyze. During the COVID-19 pandemic, qPCR became the gold standard technique for detecting the SARS-CoV-2 virus that allowed to confirm the infection event, and those asymptomatic ones, and thus save millions of lives. In-house multiplex qPCR tests were developed worldwide to detect different viral targets and ensure results, follow the infections, and favor the containment of a pandemic. Here, we present the detailed fundamentals of the qPCR technique based on fluorogenic probes and processes to develop and optimize a successful multiplex RT-qPCR test for detecting SARS-CoV-2 that could be used to diagnose COVID-19 accurately.

ABSTRACTPathogenic enteric Escherichia coli present a significant burden to global health. Food-borne enteropathogenic E. coli (EPEC) and Shiga toxin-producing E. coli (STEC) utilize attaching and effacing (A/E) lesions and actin-dense pedestal formation to colonize the gastrointestinal tract. Talin-1 is a large structural protein that links the actin cytoskeleton to the extracellular matrix though direct influence on integrins. Here we show that mice lacking talin-1 in intestinal epithelial cells (Tln1Δepi) have heightened susceptibility to colonic disease caused by the A/E murine pathogen Citrobacter rodentium. Tln1Δepi mice exhibit decreased survival, and increased colonization, colon weight, and histologic colitis compared to littermate Tln1fl/fl controls. These findings were associated with decreased actin polymerization and increased infiltration of innate myeloperoxidase-expressing immune cells, confirmed as neutrophils by flow cytometry, but more bacterial dissemination deep into colonic crypts. Further evaluation of the immune population recruited to the mucosa in response to C. rodentium revealed that loss of Tln1 in colonic epithelial cells (CECs) results in impaired recruitment and activation of T cells. C. rodentium infection-induced colonic mucosal hyperplasia was exacerbated in Tln1Δepi mice compared to littermate controls. We demonstrate that this is associated with decreased CEC apoptosis and crowding of proliferating cells in the base of the glands. Taken together, talin-1 expression by CECs is important in the regulation of both epithelial renewal and the inflammatory T cell response in the setting of colitis caused by C. rodentium, suggesting that this protein functions in CECs to limit, rather than contribute to the pathogenesis of this enteric infection.

ABSTRACTHelicobacter pylori-induced inflammation is the strongest known risk factor for gastric adenocarcinoma. Hypoxia-inducible factor-1 (HIF-1α) is a key transcriptional regulator of immunity and carcinogenesis. To examine the role of this mediator within the context of H. pylori-induced injury, we first demonstrated that HIF-1α levels were significantly increased in parallel with the severity of gastric lesions in humans. In interventional studies targeting HIF-1α, H. pylori-infected mice were treated ± dimethyloxalylglycine (DMOG), a prolyl hydroxylase inhibitor that stabilizes HIF-1α. H. pylori significantly increased proinflammatory chemokines/cytokines and inflammation in vehicle-treated mice; however, this was significantly attenuated in DMOG-treated mice. DMOG treatment also significantly decreased function of the H. pylori type IV secretion system (T4SS) in vivo and significantly reduced T4SS-mediated NF-κB activation and IL-8 induction in vitro. These results suggest that prolyl hydroxylase inhibition protects against H. pylori-mediated pathologic responses, and is mediated, in part, via attenuation of H. pylori cag-mediated virulence and suppression of host proinflammatory responses.

Abstract Background Whipple’s disease is a chronic multisystemic infectious disease that rarely presents as culture-negative endocarditis. Most patients reported with Tropheryma whipplei endocarditis involve a native valve and few describe prosthetic valve disease. Case presentation A patient with chronic polyarthritis and previous mitral valve replacement developed decompensated heart failure without fever. Transesophageal echocardiography revealed a prosthetic mitral valve vegetation and he underwent prosthetic mitral valve replacement. Blood and prosthetic mitral valve cultures were unrevealing. Broad-range polymerase chain reaction (PCR) of the extracted valve and subsequent Periodic-acid-Schiff (PAS) staining established the diagnosis of T. whipplei prosthetic valve endocarditis. Conclusion Whipple’s disease may present as culture-negative infective endocarditis and affect prosthetic valves. Histopathology with PAS staining and broad-range PCR of excised valves are essential for the diagnosis. Greater clinical awareness and implementation of these diagnostic procedures should result in an increased reported incidence of this rare disease.

Abstract Using past material and spiritual remains, cultural heritage examines communities’ identity formation across time. Cultural heritage requires public and private institutions to care about its restoration, maintenance, conservation, and promotion. Through a bibliometric perspective, this study has analyzed, quantified, and mapped the scientific production of the fourth industrial revolution applied to heritage studies from 2016 to 2021 in the Scopus and Web of Science databases. Biblioshiny software from RStudio was employed to categorize and evaluate the contribution of authors, countries, institutions, and journals. In addition, VOSviewer was used to visualize their collaboration networks. As a main result, we found that augmented reality and remote sensing represent the research hotspot concerning heritage studies. Those techniques have become common in archaeology, as well as museums, leading to an increase in their activity. Perhaps, more recent tools, such as machine learning and deep learning, will provide future pathways in cultural heritage from data collected in social networks. This bibliometric analysis, therefore, provides an updated perspective of the implementations of technologies from industry 4.0 in heritage science as a possible guideline for future worldwide research.

Antecedentes: En los pseudoaneurismas infectados de arteria femoral asociados al uso de drogas intravenosas, la ligadura primaria para el tratamiento causa controversia, sin embargo, el territorio comprometido puede continuar irrigado por vías colaterales. Objetivo: Reportar la experiencia del manejo de pseudoaneurismas en un servicio de angiología y cirugía vascular. Métodos: Estudio observacional, descriptivo de una serie de casos. Resultados: Se reportan 15 pacientes, relación hombre: mujer 14:1, promedio de edad de 42 años. Siete (46.6%) con presentación de pseudoaneurisma femoral izquierdo, 5 (33.3%) de ellos con presentación de pseudoaneurisma femoral derecho, 2 (13.3%) con pseudoaneurisma humeral derecho y uno (6.6%) con pseudoaneurisma humeral izquierdo. En 12 se realizó exclusión del pseudoaneurisma con triple ligadura; y 3 pacientes fueron sometidos a revascularización. Conclusiones: En nuestra experiencia, la ligadura primaria sin revascularización tuvo incidencia de amputación baja y supervivencia alta de los pacientes afectados, siendo la claudicación la secuela más frecuente.

Chain elongation is a relevant bioprocess in support of a circular economy as it can use a variety of organic feedstocks for production of valuable short and medium chain carboxylates, such as butyrate (C4), caproate (C6), and caprylate (C8). Alcohols, including the biofuel, butanol (C4), can also be generated in chain elongation but the bioreactor conditions that favor butanol production are mainly unknown. In this study we investigated production of butanol (and its precursor butyrate) during ethanol and acetate chain elongation. We used semi-batch bioreactors (0.16 L serum bottles) fed with a range of ethanol concentrations (100–800 mM C), a constant concentration of acetate (50 mM C), and an initial total gas pressure of ∼112 kPa. We showed that the butanol concentration was positively correlated with the ethanol concentration provided (up to 400 mM C ethanol) and to chain elongation activity, which produced H2 and further increased the total gas pressure. In bioreactors fed with 400 mM C ethanol and 50 mM C acetate, a concentration of 114.96 ± 9.26 mM C butanol (∼2.13 g L−1) was achieved after five semi-batch cycles at a total pressure of ∼170 kPa and H2 partial pressure of ∼67 kPa. Bioreactors with 400 mM C ethanol and 50 mM C acetate also yielded a butanol to butyrate molar ratio of 1:1. At the beginning of cycle 8, the total gas pressure was intentionally decreased to ∼112 kPa to test the dependency of butanol production on total pressure and H2 partial pressure. The reduction in total pressure decreased the molar ratio of butanol to butyrate to 1:2 and jolted H2 production out of an apparent stall. Clostridium kluyveri (previously shown to produce butyrate and butanol) and Alistipes (previously linked with butyrate production) were abundant amplicon sequence variants in the bioreactors during the experimental phases, suggesting the microbiome was resilient against changes in bioreactor conditions. The results from this study clearly demonstrate the potential of ethanol and acetate-based chain elongation to yield butanol as a major product. This study also supports the dependency of butanol production on limiting acetate and on high total gas and H2 partial pressures.

COVID-19 vaccines primarily prevent severe illnesses or hospitalization, but there is limited data on their impact during hospitalization for seriously ill patients. In a Mexican cohort with high COVID-19 mortality, a study assessed vaccination’s effects. From 2021 to 2022, 462 patients with 4455 hospital days were analyzed. The generalized multivariate linear mixed model (GENLINMIXED) with binary logistic regression link, survival analysis and ROC curves were used to identify risk factors for death. The results showed that the vaccinated individuals were almost half as likely to die (adRR = 0.54, 95% CI = 0.30–0.97, p = 0.041). When stratifying by vaccine, the Pfizer group (BNT162b2) had a 2.4-times lower risk of death (adRR = 0.41, 95% CI = 0.2–0.8, p = 0.008), while the AstraZeneca group (ChAdOx1-S) group did not significantly differ from the non-vaccinated (adRR = 1.04, 95% CI = 0.5–2.3, p = 0.915). The Pfizer group exhibited a higher survival, the unvaccinated showed increasing mortality, and the AstraZeneca group remained intermediate (p = 0.003, multigroup log-rank test). Additionally, BNT162b2-vaccinated individuals had lower values for markers, such as ferritin and D-dimer. Biochemical and hematological indicators suggested a protective effect of both types of vaccines, possibly linked to higher lymphocyte counts and lower platelet-to-lymphocyte ratio (PLR). It is imperative to highlight that these results reinforce the efficacy of COVID-19 vaccines. However, further studies are warranted for a comprehensive understanding of these findings.

Background & Aims: Metaplasia in the stomach is highly associated with development of intestinal-type gastric cancer. Two types of metaplasias, spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia (IM), are considered precancerous lesions. However, it remains unclear how SPEM and IM are related. Here we investigated a new lineage-specific marker for SPEM cells, aquaporin 5 (AQP5), to assist in the identification of these 2 metaplasias. Methods: Drug- or Helicobacter felis (H felis) infection-induced mouse models were used to identify the expression pattern of AQP5 in acute or chronic SPEM. Gene-manipulated mice treated with or without drug were used to investigate how AQP5 expression is regulated in metaplastic lesions. Metaplastic samples from transgenic mice and human gastric cancer patients were evaluated for AQP5 expression. Immunostaining with lineage-specific markers was used to differentiate metaplastic gland characteristics. Results: Our results revealed that AQP5 is a novel lineage-specific marker for SPEM cells that are localized at the base of metaplastic glands initially and expand to dominate glands after chronic H felis infection. In addition, AQP5 expression was up-regulated early in chief cell reprogramming and was promoted by interleukin 13. In humans, metaplastic corpus showed highly branched structures with AQP5-positive SPEM. Human SPEM cells strongly expressing AQP5 were present at the bases of incomplete IM glands marked by TROP2 but were absent from complete IM glands. Conclusions: AQP5-expressing SPEM cells are present in pyloric metaplasia and TROP2-positive incomplete IM and may be an important component of metaplasia that can predict a higher risk for gastric cancer development.

Chronic mucosal pathogens have evolved multiple strategies to manipulate the host immune response; consequently, microbes contribute to the development of >2 million cases of cancer/year. Gastric adenocarcinoma is the fourth leading cause of cancer-related death and Helicobacter pylori confers the highest risk for this disease. Gastric innate immune effectors can either eliminate bacteria or mobilize adaptive immune responses including Toll-like receptors (TLRs), and cytosolic DNA sensor/adaptor proteins (e.g., stimulator of interferon genes, STING). The H. pylori strain-specific cag type IV secretion system (T4SS) augments gastric cancer risk and translocates DNA into epithelial cells where it activates the microbial DNA sensor TLR9 and suppresses injury in vivo; however, the ability of H. pylori to suppress additional nucleic acid PRRs within the context of chronic gastric inflammation and injury remains undefined. In this study, in vitro and ex vivo experiments identified a novel mechanism through which H. pylori actively suppresses STING and RIG-I signaling via downregulation of IRF3 activation. In vivo, the use of genetically deficient mice revealed that Th17 inflammatory responses are heightened following H. pylori infection within the context of Sting deficiency in conjunction with increased expression of a known host immune regulator, Trim30a. This novel mechanism of immune suppression by H. pylori is likely a critical component of a finely tuned rheostat that not only regulates the initial innate immune response, but also drives chronic gastric inflammation and injury.

Macrophages play a crucial role in the inflammatory response to the human stomach pathogen Helicobacter pylori, which infects half of the world’s population and causes gastric cancer. Recent studies have highlighted the importance of macrophage immunometabolism in their activation state and function. We have demonstrated that the cysteine-producing enzyme cystathionine γ-lyase (CTH) is upregulated in humans and mice with H. pylori infection. Here, we show that induction of CTH in macrophages by H. pylori promoted persistent inflammation. Cth–/– mice had reduced macrophage and T cell activation in H. pylori–infected tissues, an altered metabolome, and decreased enrichment of immune-associated gene networks, culminating in decreased H. pylori–induced gastritis. CTH is downstream of the proposed antiinflammatory molecule, S-adenosylmethionine (SAM). Whereas Cth–/– mice exhibited gastric SAM accumulation, WT mice treated with SAM did not display protection against H. pylori–induced inflammation. Instead, we demonstrated that Cth-deficient macrophages exhibited alterations in the proteome, decreased NF-κB activation, diminished expression of macrophage activation markers, and impaired oxidative phosphorylation and glycolysis. Thus, through altering cellular respiration, CTH is a key enhancer of macrophage activation, contributing to a pathogenic inflammatory response that is the universal precursor for the development of H. pylori–induced gastric disease.

Gastric carcinogenesis is mediated by complex interactions among Helicobacter pylori, host, and environmental factors. Here, we demonstrate that H. pylori augmented gastric injury in INS-GAS mice under iron-deficient conditions. Mechanistically, these phenotypes were not driven by alterations in the gastric microbiota; however, discovery-based and targeted metabolomics revealed that bile acids were significantly altered in H. pylori–infected mice with iron deficiency, with significant upregulation of deoxycholic acid (DCA), a carcinogenic bile acid. The severity of gastric injury was further augmented when H. pylori–infected mice were treated with DCA, and, in vitro, DCA increased translocation of the H. pylori oncoprotein CagA into host cells. Conversely, bile acid sequestration attenuated H. pylori–induced injury under conditions of iron deficiency. To translate these findings to human populations, we evaluated the association between bile acid sequestrant use and gastric cancer risk in a large human cohort. Among 416,885 individuals, a significant dose-dependent reduction in risk was associated with cumulative bile acid sequestrant use. Further, expression of the bile acid receptor transmembrane G protein–coupled bile acid receptor 5 (TGR5) paralleled the severity of carcinogenic lesions in humans. These data demonstrate that increased H. pylori–induced injury within the context of iron deficiency is tightly linked to altered bile acid metabolism, which may promote gastric carcinogenesis.

Background and Objectives: Gentamicin (GM) is a nephrotoxic aminoglycoside. Neutral electrolyzed saline (SES) is a compound with anti-inflammatory, antioxidant, and immunomodulatory properties. The objective of the present study was to evaluate whether kidney damage by GM can be prevented and/or reversed through the administration of SES. Materials and Methods: The study was carried out as a prospective, single-blind, five-arm, parallel-group, randomized, preclinical trial. The nephrotoxicity model was established in male BALB/c mice by administering GM at a dose of 100 mg/kg/day intraperitoneally for 30 days, concomitantly administering (+) SES or placebo (physiologic saline solution), and then administering SES for another 30 days after the initial 30 days of GM plus SES or placebo. At the end of the test, the mice were euthanized, and renal tissues were evaluated histopathologically. Results: The GM + placebo group showed significant tubular injury, interstitial fibrosis, and increased interstitial infiltrate of inflammatory cells compared with the group without GM. Tubular injury and interstitial fibrosis were lower in the groups that received concomitant GM + SES compared with the GM + placebo group. SES administration for 30 days after the GM administration periods (GM + placebo and GM + SES for 30 days) did not reduce nephrotoxicity. Conclusions: Intraperitoneal administration of SES prevents gentamicin-induced histologic nephrotoxicity when administered concomitantly, but it cannot reverse the damage when administered later.

Doxycycline (Doxy) is an antibiotic, which has exhibited anti-inflammatory activity and glucose metabolism improvement. The present study was proposed to evaluate its effects on glucose metabolism and other associated processes, such as lipemia and adipogenesis, as well as, to evaluate its effects on the liver, pancreas, and aorta in subjects fed with an occidental high-fat diet (HFD). The trial followed three groups of BALB/c mice for 6 months: (1) Standard diet (SD); (2) HFD-placebo (saline solution); and (3) HFD-Doxy (10 mg/kg/day). Intrahepatic fat accumulation (steatohepatosis) and the epididymal fat pad, as well as the hepatic inflammatory infiltrate and ALT serum levels were higher in both groups with the HFD (with/without doxycycline) in comparison with the SD group. The thickness of the aorta (preclinic atherosclerosis) was significantly elevated in the HFD group with respect to the HFD + Doxy and SD group, these two being similar groups to each other. The HFD-Doxy group had pancreatic morphological parameters very similar to those of the SD group; on the contrary, the HFD group reduced the number of pancreatic islets and the number of β cells per mm2, in addition to losing large islets. The index of β cell function (∆Insulin0–30/∆Glucose0–30 ratio) was significantly higher in the HFD + Doxy group, compared to the rest of the groups.

El documento plantea un acercamiento crítico a las tendencias políticas que demarcan la realidad docente en Colombia, integrado a la perspectiva del quehacer docente bajo las teorías de la resistencia. Ello permite visibilizar las estrategias de participación política de los maestros y la necesaria discusión sobre la formación docente dentro de un marco socioeconómico y cultural más dialógico entre las comunidades. Finalmente, propone las condiciones para ejercer la docencia desde cierta política integral como una estrategia de mejoramiento que vincula al ser docente dentro de las prioridades del campo político.

La lesión renal aguda se produce en el 4-23% de los casos en pacientes con coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2). La gravedad de la pandemia ha provocado una escasez significativa de suministros médicos, entre ellos la hemodiálisis, sin embargo, el manejo de diálisis peritoneal en esta entidad por enfermedad por coronavirus 2019 (COVID-19) no ha recibido mucha atención, pudiendo ser una solución práctica para los pacientes con lesión renal aguda y enfermedad renal crónica en etapa terminal. Este artículo describimos nuestra experiencia con la implementación de diálisis peritoneal urgente para lesión renal aguda en pacientes con COVID-19.

ABSTRACT The Helicobacter pylori Cag type IV secretion system (T4SS) translocates the effector protein CagA and nonprotein bacterial constituents into host cells. In this study, we infected Mongolian gerbils with an H. pylori strain in which expression of the cagUT operon (required for Cag T4SS activity) is controlled by a TetR/tetO system. Transcript levels of cagU were significantly higher in gastric tissue from H. pylori-infected animals receiving doxycycline-containing chow (to derepress Cag T4SS activity) than in tissue from infected control animals receiving drug-free chow. At 3 months postinfection, infected animals receiving doxycycline had significantly increased gastric inflammation compared to infected control animals. Dysplasia (a premalignant histologic lesion) and/or invasive gastric adenocarcinoma were detected only in infected gerbils receiving doxycycline, not in infected control animals. We then conducted experiments in which Cag T4SS activity was derepressed during defined stages of infection. Continuous Cag T4SS activity throughout a 3-month time period resulted in higher rates of dysplasia and/or gastric cancer than observed when Cag T4SS activity was limited to early or late stages of infection. Cag T4SS activity for the initial 6 weeks of infection was sufficient for the development of gastric inflammation at the 3-month time point, with gastric cancer detected in a small proportion of animals. These experimental results, together with previous studies of cag mutant strains, provide strong evidence that Cag T4SS activity contributes to gastric carcinogenesis and help to define the stages of H. pylori infection during which Cag T4SS activity causes gastric alterations relevant for cancer pathogenesis. IMPORTANCE The “hit-and-run model” of carcinogenesis proposes that an infectious agent triggers carcinogenesis during initial stages of infection and that the ongoing presence of the infectious agent is not required for development of cancer. H. pylori infection and actions of CagA (an effector protein designated a bacterial oncoprotein, secreted by the Cag T4SS) are proposed to constitute a paradigm for hit-and-run carcinogenesis. In this study, we report the development of methods for controlling H. pylori Cag T4SS activity in vivo and demonstrate that Cag T4SS activity contributes to gastric carcinogenesis. We also show that Cag T4SS activity during an early stage of infection is sufficient to initiate a cascade of cellular alterations leading to gastric inflammation and gastric cancer at later time points.