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Little is known about the characteristics of uropathogenic Escherichia coli (UPEC) associated with recurrent urinary tract infections (RUTIs). The present study aimed to analyze the phenotypic antimicrobial resistance of recurrent UPEC isolates attributable to either relapse or reinfection. A total of 140 E. coli strains were isolated from 70 outpatients with RUTIs. All isolates were analyzed by random amplified polymorphic DNA-polymerase chain reaction to evaluate genetic similarity between the first and second isolates. We found that 64.2% (45/70) of outpatients had a relapse with the primary infecting E. coli strain and 35.7% (25/70) had reinfection with a new E. coli strain. Compared with reinfecting strains, relapse UPEC isolates exhibited much higher antimicrobial resistance; 89% of these isolates were multidrug-resistant and 46.6% were extended-spectrum ß-lactamase producers. Our study provides evidence that RUTIs are mainly driven by the persistence of the original strain in the host (relapses) despite appropriate antibiotic treatments, and only RUTIs attributed to relapses seem to favor multidrug resistance in UPEC isolates.

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Argemone mexicana L. has been used in traditional Mexican medicine. Among its bioactive constituents, berberine (BER) has garnered attention for its cytotoxic properties against different tumor cell lines. This study investigates the in vitro toxicity against HEP-G2 (human hepatocellular carcinoma) and murine lymphoma (L5178Y-R) cells using the MTT assay of the methanol extract (AmexM), sub-partitions of A. mexicana, and BER. Selectivity indices (SIs) were determined by comparing their cytotoxic effects on VERO (monkey kidney epithelial) and PBMC (human peripheral blood mononuclear) non-tumoral cells. Additionally, the anti-hemolytic effect of these treatments was assessed using the AAPH method. The treatment with the most promising activity against tumor cells and anti-hemolytic efficacy underwent further evaluation for toxicity in Artemia salina and antioxidant activities using DPPH, ABTS, and FRAP assays. BER demonstrated an IC50 = 56.86 µg/mL in HEP-G2 cells and IC50 < 5.0 µg/mL in L5178Y-R cells, with SI values of 15.97 and >5.40 in VERO and PBMC cells, respectively. No significant hemolytic effects were observed, although AmexM and BER exhibited the highest anti-hemolytic activity. BER also demonstrated superior antioxidant efficacy, with lower toxicity in A. salina nauplii compared to the control. Additionally, BER significantly attenuated nitric oxide production. This study highlights the antiproliferative effects of A. mexicana, particularly BER, against HEP-G2 and L5178Y-R tumor cell lines, along with its selectivity towards normal cells. Furthermore, its anti-hemolytic and antioxidant potentials were demonstrated, suggesting that BER is a promising candidate for potent chemotherapeutic agents.

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Chondrosarcoma (CS) is a malignant bone tumor arising from cartilage-producing cells. The conventional subtype of CS typically develops within a dense cartilaginous matrix, creating an environment deficient in oxygen and nutrients, necessitating metabolic adaptation to ensure proliferation under stress conditions. Although ketone bodies (KBs) are oxidized by extrahepatic tissue cells such as the heart and brain, specific cancer cells, including CS cells, can undergo ketolysis. In this study, we found that KBs catabolism is activated in CS cells under nutrition-deprivation conditions. Interestingly, cytosolic ß-hydroxybutyrate dehydrogenase 2 (BDH2), rather than mitochondrial BDH1, is expressed in these cells, indicating a specific metabolic adaptation for ketolysis in this bone tumor. The addition of the KB, ß-Hydroxybutyrate (ß-HB) in serum-starved CS cells re-induced the expression of BDH2, along with the key ketolytic enzyme 3-oxoacid CoA-transferase 1 (OXCT1) and monocarboxylate transporter-1 (MCT1). Additionally, internal ß-HB production was quantified in supplied and starved cells, suggesting that CS cells are also capable of ketogenesis alongside ketolysis. These findings unveil a novel metabolic adaptation wherein nutrition-deprived CS cells utilize KBs for energy supply and proliferation.

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BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.

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Although the C-Hα functionalization of N-heterocycles is, in fact, an easy chemical transformation, the C-Hß functionalization is, on the contrary, a quite difficult chemical process. Here, we present a two-step protocol that allows the ready conversion of pyrrolidines, piperidines, and an azepane into their corresponding 3-exo-alkenyl lactams via the transient formation of 3-alkoxyamino lactams followed by a Wittig-like C(sp3)-O bond olefination with stabilized ylides from phosphonium salts mediated by t-BuOK. Additionally, as a proof of the synthetic effectiveness of this novel methodology, the first synthesis of the natural product callylactam A was achieved through a TiCl4-catalyzed double bond isomerization of a 3-exo-alkenyl 2-piperidone to its endo-isomer.

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Inorganic arsenic (iAs) and fluoride (iF) are ubiquitous elements whose coexistence is frequent in several regions of the world due to the natural contamination of water sources destined for human consumption. It has been reported that coexposure to these two elements in water can cause toxic effects on health, which are controversial since antagonistic and synergistic effects have been reported. However, there is little information on the possible toxicological interaction between concurrent exposure to iAs and iF on the iAs metabolism profile.The goal of this study was to determine the effect of iF exposure on iAs methylation patterns in the urine and the tissues of female mice of the C57BL/6 strain, which were divided into four groups and exposed daily for 10 days through drinking water as follows: purified water (control); arsenite 1 mg/L, fluoride 50 mg/L and arsenite & fluoride 1:50 mg/L.To characterize the iAs methylation pattern in concomitant iF exposure, iAs and its methylated metabolites (MAs and DMAs) were quantified in the tissues and the urine of mice was exposed to iAs alone or in combination. Our results showed a statistically significant decrease in the arsenic species concentrations and altered relative proportions of arsenic species in tissues and urine in the As-iF coexposure group compared to the iAs-exposed group. These findings show that iF exposure decreases arsenic disposition and alters methylation capacity.Nevertheless, additional studies are required to elucidate the mechanisms involved in the iAs-iF interaction through iF exposure affecting iAs disposition and metabolism.

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The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The intravenous infusion is well established in loading infusion and maintenance with an onset of action of 30 minutes until 2 hours or even more. Our aim is to report three patients with pulmonary atresia that presented hypercyanotic spell due to a ductal spasm during cardiac catheterisation in whom the administration of a bolus of alprostadil reversed the spasm and increased pulmonary flow, immediately stabilising the condition of the patients allowing subsequent successful stent placement with no serious complications or sequelae after the administration of the bolus. More studies are needed to make a recommendation regarding the use of alprostadil in bolus in cases where the ductal spasm might jeopardise the life of the patient.

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Acute myeloid leukaemia (AML) is a highly heterogeneous disease, however the therapeutic approaches have hardly changed in the last decades. Metabolism rewiring and the enhanced production of reactive oxygen species (ROS) are hallmarks of cancer. A deeper understanding of these features could be instrumental for the development of specific AML-subtypes treatments. NADPH oxidases (NOX), the only cellular system specialised in ROS production, are also involved in leukemic metabolism control. NOX2 shows a variable expression in AML patients, so patients can be classified based on such difference. Here we have analysed whether NOX2 levels are important for AML metabolism control. The lack of NOX2 in AML cells slowdowns basal glycolysis and oxidative phosphorylation (OXPHOS), along with the accumulation of metabolites that feed such routes, and a sharp decrease of glutathione. In addition, we found changes in the expression of 725 genes. Among them, we have discovered a panel of 30 differentially expressed metabolic genes, whose relevance was validated in patients. This panel can segregate AML patients according to CYBB expression, and it can predict patient prognosis and survival. In summary, our data strongly support the relevance of NOX2 for AML metabolism, and highlights the potential of our discoveries in AML prognosis.

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Introduction: Transvaginal radiofrequency ablation is a relatively noninvasive approach for the treatment of fibroids in patients who do not wish to undergo conventional surgery. Information on potential complications of this novel technique is very scarce. Methods: Retrospective, descriptive, epidemiological study of 115 patients who underwent transvaginal radiofrequency ablation of fibroids and for whom complications were recorded. Results: We performed 115 transvaginal radiofrequency ablation procedures, we recorded a total of 11 complications (9.6%; 95% CI, 3.8-14.8). Of these, 8 (7.0%) were classified as Clavien-Dindo type I, 1 (0.9%,) as type II, and 2 (1.7%) as type IIIb (severe). No other complications were recorded in a year follow-up. Conclusion: Transvaginal radiofrequency ablation is a treatment option that makes it possible to treat fibroids that are difficult to manage using other techniques. Few associated complications have been described, and most of them are mild.

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Ten-day-old neonate who underwent correction of interrupted aortic arch developed a giant early post-surgical aneurysm. To our knowledge, this unusual complication has been only reported as a late complication.

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People with Down syndrome have more visual problems than the general population. They experience premature ageing, and they are expected to also have an acceleration in worsening visual function. A prospective observational study which includes visual acuity, refractive error, accommodation, binocular and colour vision was performed on young adults with (n = 69) and without (n = 65) Down syndrome and on a senior group (n = 55) without Down syndrome. Results showed significant differences in visual acuity between groups (p < 0.001), and it can be improved with a new prescription in 40% of the participants with Down syndrome. Regarding the accommodative state, no significant differences were found between groups of young people. Concerning binocular vision, 64.7% of strabismus was observed in the group with Down syndrome (p < 0.001). Visual abnormalities are significant in young adults with Down syndrome and are different from those of older people without Down syndrome, some of which can be improved by providing the optimal prescription as well as regular eye examinations.

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Inorganic elements such as heavy metals and other potentially toxic elements are frequently detected in humans. The aim of the present study was to analyze the blood concentrations of 49 inorganic elements in a cohort of 401 subjects from Cape Verde. The study was performed in the frame of the Pesticide Residues in Vegetables of the Macaronesia project (PERVEMAC-II). Concentration of inorganic elements, including elements in the ATSDR's priority pollutant list and rare earth elements (RREs) were measured by ICP-MS in the whole blood of participants. A total of 20 out of 49 elements (40.8%) were detected in ≥20% of participants. Arsenic, copper, mercury, lead, selenium, strontium and zinc were detected in ≥99% of samples. Among the REEs, 7 showed detection frequencies above 20%. The median number of different elements detected was 15. In the present series, 77.0, 99.2 and 33.4% of the participants showed values of arsenic, mercury and lead higher than Reference Values 95%. These percentages were much higher than those reported in similar studies. Niobium and tantalum showed the highest median concentrations: 1.35 and 1.34 ng/mL, suggesting an environmental source of these valuable REEs in Cape Verde. Age appeared as the most important factor influencing the blood levels of inorganic elements. Lifestyle had an effect on the concentration of some of these elements. Those subjects whose water source was pond water had significantly higher arsenic levels. The concentration of ∑REEs was significantly higher among individuals who purchase their food in supermarkets (P = 0.013). These variables are of relevance since they can be controlled individually to reduce exposure to these contaminants. Our results may be useful for the implementation of public health measures by the competent authorities.

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Forty-seven elements in leafy green vegetables were studied to estimate the daily intakes from this food category in different scenarios (average and high consumers) and age groups of the Canary Islands population. The contribution of the consumption of each type of vegetable to the reference intakes of essential, toxic and potentially toxic elements was assessed and the risk-benefit ratio was evaluated. The leafy vegetables that provide the highest levels of elements are spinach, arugula, watercress and chard. While spinach, chard, arugula, lettuce sprouts and watercress were the leafy vegetables with the highest concentrations of essential elements (38,743 ng/g of Fe in spinach, 3733 ng/g of Zn in watercress), the high levels of Mn in chard, spinach and watercress are noteworthy. Among the toxic elements, Cd is the element with the highest concentration, followed by As and Pb. The vegetable with the highest concentration of potentially toxic elements (Al, Ag, Be, Cr, Ni, Sr and V) is spinach. In average adult consumers, while the greatest contribution of essential elements comes from arugula, spinach and watercress, insignificant dietary intakes of potentially toxic metals are observed. Toxic metal intakes from the consumption of leafy vegetables in the Canary Islands do not show significant values, so the consumption of these foods does not pose a health risk. In conclusion, the consumption of leafy vegetables provides significant levels of some essential elements (Fe, Mn, Mo, Co and Se), but also of some potentially toxic elements (Al, Cr and Tl). A high consumer of leafy vegetables would see their daily nutritional needs regarding Fe, Mn, Mo, and Co covered, although they are also exposed to moderately worrying levels of Tl. To monitor the safety of dietary exposure to these metals, total diet studies on those elements with dietary exposures above the reference values derived from the consumption of this food category, mainly Tl, are recommended.

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BACKGROUND: In recent years, chronic kidney disease has increased in the pediatric population and has been related to environmental factors. In the diagnosis of kidney damage, in addition to the traditional parameters, early kidney damage biomarkers, such as kidney injury molecule 1, cystatin C, and osteopontin, among others, have been implemented as predictors of early pathological processes. OBJECTIVE: This study aimed to evaluate the relationship between exposure to environmental pollutants and early kidney damage biomarkers. METHODS: A cross-sectional pilot study was conducted in February 2016 and involved 115 apparently healthy children aged 6-15 residing in Apizaco, Tlaxcala. Participant selection was carried out randomly from among 16,472 children from the municipality of Apizaco. A socio-demographic questionnaire included  age, sex, education, duration of residence in the area, occupation, water consumption and dietary habits, pathological history, and some non-specific symptoms. Physical examination included blood pressure, weight, and height. The urine concentrations of urinary aluminum, total arsenic, boron, calcium, chromium, copper, mercury, potassium, sodium, magnesium, manganese, molybdenum, lead, selenium, silicon, thallium, vanadium, uranium, and zinc, were measured. Four of the 115 participants selected for the study were excluded due to an incomplete questionnaire or lack of a medical examination, leaving a final sample population of 111 participants. RESULTS: The results showed a mean estimated glomerular filtration rate of 89.1 ± 9.98 mL/min/1.73m2 and a mean albumin/creatinine ratio of 12.9 ± 16.7 mg/g urinary creatinine. We observed a positive and significant correlation between estimated glomerular filtration rate with fluoride, total arsenic and lead, and a correlation of albumin/creatinine ratio with fluoride, vanadium, and total arsenic. There was also a significant correlation between the early kidney damage biomarkers and fluoride, vanadium, and total arsenic, except for cystatin C. CONCLUSION: In conclusion, our results show that four urinary biomarkers: α1-microglobulin, cystatin C, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin are related to environmental exposure to urinary fluoride, vanadium, and total arsenic in our pediatric population.

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The number of craft breweries and the volume of craft beer produced globally is growing exponentially. However, little is known about their differences with mainstream beers regarding mycotoxin profile, pesticide and pollutant residues and elemental composition. Given that beer is one of the most consumed beverages worldwide, it is important to shed light on its toxicological profile. In this study, samples of 23 craft beers and 19 mainstream Spanish beers were collected to perform a comparative analysis including 8 mycotoxins, 225 pesticide residues and 50 POPs, and 50 elements. Mycotoxins were not detected in craft beers, while 100% of mainstream beers presented at least one mycotoxin. In contrast, craft beers contained higher average pesticide residues than their mainstream counterparts, although significant differences were only found in Mepiquat and Metrafenone content. No persistent organic pollutants were detected in any sample. The elemental composition presented differences between the two groups both in the concentration of elements and their hierarchy. In conclusion, the toxicological profile of all beers was safe and is unlikely to constitute a hazard to consumer health. Craft beers present significant differences from their mainstream counterparts in all the dimensions explored.

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Benzene is a known human carcinogen and one of the ten chemicals of major public health concern identified by the World Health Organization. Our objective was to evaluate benzene's carcinogenic and non-carcinogenic health risks (current and projected) in highly exposed children in Yucatan, Mexico. Benzene exposure was estimated through a reverse-translation, four-compartment, physiologically based pharmacokinetic model (PBPK) based on previously performed urine trans, trans-muconic acid (benzene metabolite) determinations. Using a risk assessment methodology, the carcinogenic and non-carcinogenic risks of benzene were estimated for 6-12-year-old children from a family of shoemakers. The children's hazard quotients for decreased lymphocyte count were 27 and 53 for 4 and 8 h/day exposure, respectively, and 37 for the projected 8 h/day exposure in adults. The risks of developing leukemia were 2-6 cases in 1000 children exposed 4 h/day; 4-10 cases in 1000 children exposed 8 h/day, and 2-9 cases in 1000 adults with an 8 h/day lifetime exposure. Children in Yucatan working in shoe-manufacturing workshops, or living next to them, are exposed to benzene concentrations above the reference concentration and have unacceptably high risks of presenting with non-carcinogenic and carcinogenic hematologic symptoms, now and in the future. Interventions to prevent further exposure and mitigate health risks are necessary.

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