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1.
Urology ; 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39313005

RESUMEN

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the effectiveness and safety of PCNL performed as a day-case surgery in comparison to inpatient PCNL. METHODS: Databases were searched up to January 27, 2024, for randomized and non-randomized studies comparing outcomes between day case PCNL and inpatient PCNL. Pooled data were analyzed using a Random-Effects (RE) model when Higgins I2% heterogeneity values were >50%; otherwise, a Fixed-Effects model was employed. The results were reported as odds ratios (OR), mean difference (MD) or standardized MD (SMD) with 95% confidence intervals (CI). Statistical significance was set at p < 0.05. RESULTS: One randomized controlled trial (RCT) and fourteen observational studies totaling 1574 patients were included. Pooled results revealed that patients in the day-case PCNL group experienced reduced blood loss (SMD -0.71 95% CI: [-1.31, -0.12] p 0.02) and transfusion rates (OR 0.10 95% CI: [0.03, 0.39], p 0.0008), lower overall and minor complications (OR 0.56, 95% CI: [0.42, 0.76], p 0.0002, and OR 0.52, 95% CI: [0.37, 0-73], p 0.0002, respectively), shorter operative time (MD -11.46, 95% CI: [-17.41, -5-50], p < 0.00001), and reduced total costs (MD -1597.18, 95% CI [-2436.42, -757.93], p 0.0002). Major complications, stone-free rate (SFR), emergency department (ED) visits, and readmission rates were similar between the groups. CONCLUSION: Day-case PCNL is a feasible and safe alternative to inpatient PCNL surgery in carefully selected patients, without increasing the risk of complications or readmission rates, and is likely to reduce total costs.

2.
Materials (Basel) ; 17(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39274816

RESUMEN

The construction sector is presently among the most resource-intensive industries, driving a substantial body of research dedicated to the development of more sustainable materials to address these demands. A particularly promising approach within the framework of the circular economy is the repurposing of waste as a principal raw material for the creation of new construction products. Within this context, the primary aim of this study is to engineer ceramic materials for brick production using 100% waste-derived inputs, specifically aggregate washing sludge and manganese mining by-products. To evaluate the potential of these sustainable ceramic materials, an extensive investigation was conducted, encompassing both physical and mechanical testing, as well as a thorough characterisation of the waste inputs. For this purpose, a series of ceramic specimens were fabricated with varying proportions of mining residues and aggregate washing sludge, adhering to the conventional protocols employed in the manufacture of ceramic bricks. The results demonstrate that these sustainable ceramics exhibit a linear shrinkage reduction of up to 5% compared to traditional clay-based ceramics. Furthermore, they show water absorption levels-whether via capillarity, cold water, or hot water absorption-that are up to twice those observed in conventional clay ceramics, while maintaining comparable density values. This increased absorption, however, correlates with a reduction in mechanical strength at higher concentrations of manganese waste, yet the material continues to meet the minimum strength requirements as specified by industry standards for such products. In conclusion, this research introduces a novel, sustainable ceramic material that not only reduces economic and environmental costs but also adheres to the required performance criteria for construction applications.

3.
Lab Chip ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291871

RESUMEN

Point-of-care (POC) platelet function analysis can enable timely and precise management of bleeding and clotting in emergency rooms, operation rooms and intensive care units. However, POC platelet testing is currently not commonly performed, due to the complexity of sample preparation and limitations of existing technologies. Here, we report the development of an integrated microfluidic multiple electrode aggregometry (µMEA) sensor which uses multi-frequency impedance measurement of an embedded microelectrode array to perform platelet aggregometry directly from whole blood, sensing and measuring platelet activation in a label-free manner and without requiring any additional sample preparation. Additionally, the sensor incorporates blood flow during the assay to account for physiological flow and shear conditions. We show that the impedance signal from the sensor can be used to accurately detect and quantify platelet aggregation in a label-free manner, which was further validated by simultaneous fluorometric measurement and visualization of platelet aggregation. Further, we optimized the sensitivity and repeatability of the sensor using its frequency response and demonstrated that the sensor could be used to characterize drug dose-response in antiplatelet therapy with a frequency-tunable dynamic range. We also demonstrate that the sensor provides high sensitivity to perform platelet aggregometry under thrombocytopenic or low platelet count conditions. The µMEA sensor could thus enable POC platelet function analysis across several clinical applications.

4.
Liver Transpl ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39172015

RESUMEN

Hypothermic oxygenated machine perfusion (HOPE) is an organ preservation strategy shown to reduce ischemia-reperfusion-injury (IRI)-related complications following liver transplantation (LT). In animal models HOPE can also decrease alloimmune responses post-transplantation, but this remains to be evaluated in humans. Our study, involving 27 LT patients enrolled in 2 randomised controlled trials comparing static cold storage (SCS) with HOPE (14 HOPE- and 13 SCS-treated), delves into the impact of HOPE on the molecular profile of liver allografts and on the immune responses elicited post-transplantation. Following HOPE treatment, fewer intra-hepatic immune cells were observed in liver perfusates compared to SCS. Analysis of liver tissue transcriptome at reperfusion revealed an effect of HOPE on the reactive oxygen species pathway. Two weeks post-transplantation, HOPE recipients exhibited increased circulating CD4+FOXP3+CD127lo regulatory T cells (Tregs) (p<0.01), which corresponded to a higher frequency of donor specific Tregs (p<0.01) and was followed by reduced alloreactivity index of CD8+ T cells 3 months post-transplant. Our study provides novel mechanistic insight into the capacity of HOPE to influence liver IRI and to modulate effector and regulatory donor-specific T cell responses post-transplantation. These findings, which confirm observations made in animal models, help explain the decreased rejection rates reported in patients receiving HOPE-treated allografts.

5.
Cureus ; 16(6): e63100, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39055432

RESUMEN

Introduction and objective Interstitial lung disease (ILD) is a subject with which preclinical medical students often struggle. Because case-based learning (CBL) engages students in discussions centered around complex clinical scenarios, it may be effective for teaching ILD to preclinical medical students by fostering the development of critical thinking and clinical reasoning skills. Methods Lecture-based learning on ILD in the second-year Respiratory System course was replaced with a large group CBL session. Students worked in a large group team-based CBL (TB-CBL) to answer questions about the etiology, presentation, diagnostic radiology images, pathophysiology, and management of various ILDs. Performance on ILD-related final exam questions from Cohort A (Class of 2023, lecture) was compared with Cohort B (Class of 2025, TB-CBL). Student satisfaction was assessed through an anonymous end-of-course survey (5-point Likert). Results Mean performance on ILD-related final exam questions was 85.4 (SD: 16.5) for Cohort B (TB-CBL) vs. 80.0 (SD: 17.6) for Cohort A (lecture). Mean overall satisfaction was 3.31 (SD: 1.37), with 87.6%, 88.4%, and 87.6% agreeing or strongly agreeing with the statements "The session was well organized," "The session contributed to my learning," and "The session was a valuable use of my time," respectively. Conclusion Students participating in TB-CBL scored higher on ILD-related final exam questions compared with those who received lecture-based learning of the same material. Student satisfaction was acceptable but lower than expected. This TB-CBL session may be adapted at other institutions aiming to utilize active learning methods to teach the principles of diagnosis and management of ILD to preclinical medical students.

6.
Plant Cell Environ ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965812

RESUMEN

This study aims to elucidate if the regulation of plant aquaporins by the arbuscular mycorrhizal (AM) symbiosis occurs only in roots or cells colonized by the fungus or at whole root system. Maize plants were cultivated in a split-root system, with half of the root system inoculated with the AM fungus and the other half uninoculated. Plant growth and hydraulic parameters were measured and aquaporin gene expression was determined in each root fraction and in microdissected cells. Under well-watered conditions, the non-colonized root fractions of AM plants grew more than the colonized root fraction. Total osmotic and hydrostatic root hydraulic conductivities (Lo and Lpr) were higher in AM plants than in non-mycorrhizal plants. The expression of most maize aquaporin genes analysed was different in the mycorrhizal root fraction than in the non-mycorrhizal root fraction of AM plants. At the cellular level, differential aquaporin expression in AM-colonized cells and in uncolonized cells was also observed. Results indicate the existence of both, local and systemic regulation of plant aquaporins by the AM symbiosis and suggest that such regulation is related to the availability of water taken up by fungal hyphae in each root fraction and to the plant need of water mobilization.

7.
J Med Virol ; 96(7): e29752, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38949191

RESUMEN

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.


Asunto(s)
COVID-19 , Mitocondrias , SARS-CoV-2 , Proteínas Virales , Humanos , Células A549 , COVID-19/metabolismo , COVID-19/virología , COVID-19/patología , Mitocondrias/metabolismo , Sistemas de Lectura Abierta , SARS-CoV-2/genética , Transcriptoma , Proteínas Virales/genética , Proteínas Virales/metabolismo , Proteínas Reguladoras y Accesorias Virales/metabolismo , Proteínas Reguladoras y Accesorias Virales/genética , Proteínas Viroporinas/metabolismo
8.
Artículo en Inglés | MEDLINE | ID: mdl-38794880

RESUMEN

BACKGROUND: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies. METHODS: SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD. RESULTS: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by TNF-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term. CONCLUSIONS: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.

9.
Pediatr Emerg Care ; 40(7): 536-540, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38718820

RESUMEN

OBJECTIVE: Patients with multisystem inflammatory syndrome in children (MIS-C) often require hospital admission. Treatment of MIS-C has included intravenous immunoglobulin, systemic corticosteroids, and/or immunomodulators. There is no standardized approach to when steroids should be initiated during treatment. The study objective was to determine whether early initiation of steroids in patients with MIS-C is associated with the duration of hospital length of stay (LOS). METHODS: This is a single-center retrospective cohort study of patients younger than 21 years who were hospitalized with MIS-C between March 2020 and September 2021 and received steroids. Cases were obtained from an institutional MIS-C log. Patients with culture proven sepsis and/or those who received intravenous immunoglobulin or steroids within the previous 30 days were excluded. We used a multivariable linear regression model, controlling for potential confounders, to assess the association between early steroids and LOS. RESULTS: A total of 56 patients hospitalized with MIS-C were identified; 38 received systemic corticosteroids and were included in the study. The mean time from admission to steroid administration was 9.8 hours (SD = 7.7) in the early group and 44.6 hours (SD = 14.2) in the late group. There was a statistically significant difference in baseline characteristics of patients receiving early versus late steroids in initial C-reactive peptide, procalcitonin, brain natriuretic peptide, and cardiac dysfunction. After controlling for confounders, initiating steroids within 24 hours of admission for MIS-C was associated with a decreased hospital LOS: in patients treated with early steroids, LOS was 58.3 hours less (95% confidence interval, -100.0 to -16.6; P = 0.007) than in those who received late steroids. CONCLUSIONS: Among patients with MIS-C, initiating systemic corticosteroids within 24 hours of admission was associated with decreased hospital LOS.


Asunto(s)
Corticoesteroides , Tiempo de Internación , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Estudios Retrospectivos , Femenino , Masculino , Tiempo de Internación/estadística & datos numéricos , Niño , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Preescolar , Adolescente , Lactante , COVID-19/complicaciones
10.
Pediatr Emerg Care ; 40(8): e169-e173, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38718751

RESUMEN

OBJECTIVES: The objectives are to determine whether diphenhydramine coadministered with prochlorperazine versus prochlorperazine only is associated with a difference in the risk of migraine treatment failure, as measured by the need for additional therapy, hospitalization rates, and 72-hour return rates, and to compare extrapyramidal adverse effects between groups. METHODS: Retrospective cohort of patients aged 7 to 18 years treated in the emergency department for migraines using prochlorperazine with or without diphenhydramine between 2013 and 2019. Patients were included if they had International Classification of Diseases, Ninth or Tenth Revision, codes for migraine or unspecified headache and were treated with prochlorperazine as part of their initial migraine therapy. Data collected included demographics, medications administered, pain scores, neuroimaging, disposition, return visits, and documentation of extrapyramidal adverse effects. Multivariable logistic regression was used to estimate the association between diphenhydramine coadministration and each of the outcomes. RESULTS: A total of 1683 patients were included. Overall, 13% required additional therapy with a 16.7% admission rate and a 72-hour return rate of 5.3%. There was no association between initial treatment with diphenhydramine and the odds of additional therapy (adjusted odds ratio [aOR], 0.74 [95% confidence interval {CI}, 0.53-1.03]), admission rates (aOR, 1.22 [95% CI, 0.89-1.67]), or return visit rates (aOR, 0.91 [95% CI, 0.55-1.51]). Extrapyramidal adverse effects occurred in 2.4% of patients in the prochlorperazine group and 0% in the prochlorperazine with diphenhydramine group. CONCLUSIONS: There was no association between diphenhydramine coadministration and the need for additional therapy, 72-hour return visit rates or admission rates. Extrapyramidal effects did not occur in patients treated with diphenhydramine.


Asunto(s)
Difenhidramina , Servicio de Urgencia en Hospital , Trastornos Migrañosos , Proclorperazina , Insuficiencia del Tratamiento , Humanos , Proclorperazina/uso terapéutico , Proclorperazina/efectos adversos , Proclorperazina/administración & dosificación , Difenhidramina/uso terapéutico , Difenhidramina/administración & dosificación , Difenhidramina/efectos adversos , Niño , Femenino , Masculino , Estudios Retrospectivos , Adolescente , Trastornos Migrañosos/tratamiento farmacológico , Quimioterapia Combinada , Hospitalización/estadística & datos numéricos , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Antagonistas de los Receptores Histamínicos H1/administración & dosificación
11.
Eur J Hosp Pharm ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697803

RESUMEN

OBJECTIVES: This study aimed to assess and compare the occurrence of 3-HIT in people living with HIV (PLWH) and seronegative patients. Additionally, the study investigated whether HIV infection could serve as a predictor of the presence of 3-HIT. METHODS: A cross-sectional study was conducted between December 2022 and January 2023 to compare PLWH with a group of seronegative patients with chronic diseases attending an outpatient hospital pharmacy service. The 3-HIT concept encompasses the simultaneous presence of non-adherence to concomitant treatment (NAC), drug-drug interactions (DDIs), and high pharmacotherapeutic complexity in polymedicated patients. The assessment of 3-HIT compliance included NAC, evaluated using both the Morisky-Green questionnaire and electronic pharmacy dispensing records. DDIs were analysed using the Liverpool University and Micromedex databases. Pharmacotherapeutic complexity was measured using the Medication Regimen Complexity Index (MRCI) tool. Logistic regression analysis was performed to identify independent factors related to 3-HIT. Additionally, an explanatory logistic model was created to investigate whether HIV infection, along with other adjustment variables, could predict compliance with the 3-HIT concept. RESULTS: The study included 145 patients: 75 PLWH and 70 seronegative patients. The median age was 40 versus 39 years, respectively (p=0.22). Seronegative patients exhibited a higher prevalence of NAC (p<0.01). HIV infection was identified as a protective factor in the context of DDIs (p<0.01). Male sex (p<0.01) and age (p=0.01) were identified as being associated with an MRCI ≥11.25 points. A higher prevalence of 3-HIT was observed in seronegative patients (18.7% vs 48.6%, p<0.01). However, the developed regression model identified HIV infection as a risk factor associated with an increased likelihood of 3-HIT (OR 4.00, 95% CI 1.88 to 8.52, p<0.01). CONCLUSIONS: The 3-HIT concept exhibited a high prevalence among seronegative patients with chronic diseases, with HIV infection identified as a predicted risk factor for NAC and the development of 3-HIT.

12.
J Sch Health ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711264

RESUMEN

BACKGROUND: Pediatric lower urinary tract symptoms (LUTS) are a set of common childhood problems. Community-level interventions that target behavioral change among children with LUTS can improve symptoms outside of the clinic environment. Parents, navigating the home and school environments, are key in supporting healthy bladder behaviors. Thus, we asked parents about their perceptions and barriers related to pediatric bladder health. METHODS: English-speaking parents (n = 30) of children ages 5-10 years with and without LUTS were interviewed. Transcripts were coded iteratively by two independent coders using deductive and inductive approaches that emphasized consensus coding and peer debriefing. RESULTS: Ninety-three percent of participants were women, 50% were 30-39 years old, and 60% held a graduate degree. Parents identified school-, classroom-, and child-based barriers to bladder health. These included the bathroom environment, restrictive policies for bathroom use, and anxiety on how and when to use the bathroom. CONCLUSIONS: Addressing school-, classroom-, and child-based barriers is necessary to promote healthy bladder habits among children in the school environment and beyond. Recommended school-based interventions include bathroom use and sanitation policies that support students' voiding needs, teachers' professional development, and school readiness initiatives. Limitations include participation of English-speaking parents only.

13.
Sci Adv ; 10(15): eadm7600, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38608019

RESUMEN

Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves. Our data indicate that neddylation exerts a global influence on the complex transcriptional and posttranscriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2 and the negative regulators c-Jun and Sox2, and inducing global secondary changes in downstream pathways, including the mTOR and YAP/TAZ signaling pathways. This places neddylation as a critical regulator of myelination and delineates the potential pathogenic mechanisms involved in CMT mutations related to neddylation.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth , Células de Schwann , Animales , Ratones , Vaina de Mielina/genética , Enfermedad de Charcot-Marie-Tooth/genética , Mutación , Procesamiento Proteico-Postraduccional
14.
Plants (Basel) ; 13(6)2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38592857

RESUMEN

Under stress or in optimum conditions, plants foster a specific guild of symbiotic microbes to strengthen pivotal functions including metabolic regulation. Despite that the role of the plant genotype in microbial selection is well documented, the potential of this genotype-specific microbial assembly in maintaining the host homeostasis remains insufficiently investigated. In this study, we aimed to assess the specificity of the foliar metabolic response of contrasting olive genotypes to microbial inoculation with wet-adapted consortia of plant-growth-promoting rhizobacteria (PGPR), to see if previously inoculated plants with indigenous or exogenous microbes would display any change in their leaf metabolome once being subjected to drought stress. Two Tunisian elite varieties, Chetoui (drought-sensitive) and Chemleli (drought-tolerant), were tested under controlled and stressed conditions. Leaf samples were analyzed by gas chromatography-mass spectrometry (GC-TOFMS) to identify untargeted metabolites. Root and soil samples were used to extract microbial genomic DNA destined for bacterial community profiling using 16S rRNA amplicon sequencing. Respectively, the score plot analysis, cluster analysis, heat map, Venn diagrams, and Krona charts were applied to metabolic and microbial data. Results demonstrated dynamic changes in the leaf metabolome of the Chetoui variety in both stress and inoculation conditions. Under the optimum state, the PGPR consortia induced noteworthy alterations in metabolic patterns of the sensitive variety, aligning with the phytochemistry observed in drought-tolerant cultivars. These variations involved fatty acids, tocopherols, phenols, methoxyphenols, stilbenoids, triterpenes, and sugars. On the other hand, the Chemleli variety displaying comparable metabolic profiles appeared unaffected by stress and inoculation probably owing to its tolerance capacity. The distribution of microbial species among treatments was distinctly uneven. The tested seedlings followed variety-specific strategies in selecting beneficial soil bacteria to alleviate stress. A highly abundant species of the wet-adapted inoculum was detected only under optimum conditions for both cultivars, which makes the moisture history of the plant genotype a selective driver shaping microbial community and thereby a useful tool to predict microbial activity in large ecosystems.

15.
J Cell Physiol ; 239(5): e31198, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38451745

RESUMEN

Liver sinusoidal endothelial cells (LSECs) dysfunction is a key process in the development of chronic liver disease (CLD). Progressive scarring increases liver stiffness in a winch-like loop stimulating a dysfunctional liver cell phenotype. Cellular stretching is supported by biomechanically modulated molecular factors (BMMFs) that can translocate into the cytoplasm to support mechanotransduction through cytoskeleton remodeling and gene transcription. Currently, the molecular mechanisms of stiffness-induced LSECs dysfunction remain largely unclear. Here we propose calcium- and integrin-binding protein 1 (CIB1) as BMMF with crucial role in LSECs mechanobiology in CLD. CIB1 expression and translocation was characterized in healthy and cirrhotic human livers and in LSECs cultured on polyacrylamide gels with healthy and cirrhotic-like stiffnesses. Following the modulation of CIB1 with siRNA, the transcriptome was scrutinized to understand downstream effects of CIB1 downregulation. CIB1 expression is increased in LSECs in human cirrhosis. In vitro, CIB1 emerges as an endothelial BMMF. In human umbilical vein endothelial cells and LSECs, CIB1 expression and localization are modulated by stiffness-induced trafficking across the nuclear membrane. LSECs from cirrhotic liver tissue both in animal model and human disease exhibit an increased amount of CIB1 in cytoplasm. Knockdown of CIB1 in LSECs exposed to high stiffness improves LSECs phenotype by regulating the intracellular tension as well as the inflammatory response. Our results demonstrate that CIB1 is a key factor in sustaining cellular tension and stretching in response to high stiffness. CIB1 downregulation ameliorates LSECs dysfunction, enhancing their redifferentiation, and reducing the inflammatory response.


Asunto(s)
Proteínas de Unión al Calcio , Células Endoteliales , Cirrosis Hepática , Hígado , Mecanotransducción Celular , Animales , Humanos , Masculino , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/genética , Femenino , Ratas , Ratas Sprague-Dawley
16.
iScience ; 27(3): 109283, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38450150

RESUMEN

Small nucleolar RNAs (snoRNAs) have been identified dysregulated in several pathologies, and these alterations can be detected in tissues and in circulation. The main aim of this study was to analyze the whole snoRNome in advanced colorectal neoplasms and to identify new potential non-invasive snoRNA-based biomarkers in fecal samples by different analytical approaches. SNORA51, SNORD15B, SNORA54, SNORD12B, SNORD12C, SNORD72, SNORD89, and several members of SNORD115 and SNORD116 clusters were consistently deregulated in both tissue sets. After technical validation, SNORA51 and SNORD15B were detected in FIT+ samples. SNORA51 was significantly upregulated in FIT+ samples from CRC patients compared to healthy controls. This upregulation, together with the fecal hemoglobin concentration, was sufficient to identify, among FIT+ individuals, patients with CRC (AUC = 0.86) and individuals with advanced adenomas (AUC = 0.68). These findings portray snoRNAs as an alternative source of candidates for further studies and SNORA51 appears as a potential non-invasive biomarker for CRC detection.

17.
Inflamm Bowel Dis ; 30(2): 167-182, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37536268

RESUMEN

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Colitis Ulcerosa/diagnóstico , Enfermedad de Crohn/diagnóstico , Metabolómica , Intestinos
18.
Pediatr Emerg Care ; 40(1): 38-44, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36972489

RESUMEN

STUDY OBJECTIVE: This study aimed to determine the association between opioid prescriptions given after tonsillectomy with adenoidectomy (T + A) and pain-related return visit rates in pediatric patients. Determine association between Food and Drug Administration (FDA) black box warning against opioid use in this population and pain-related return visit rates. METHODS: This was a single-institution retrospective cohort study of pediatric patients who underwent T + A between April 2012 and December 2015 and had return visits to the emergency department or urgent care center. Data were obtained from the hospital electronic warehouse using International Classification of Diseases-9/10 procedure codes. Odds ratios (ORs) with 95% confidence intervals (CIs) for return visits were calculated. Multivariate logistic regression analysis was used to measure association between opioid prescriptions and return visit rates as well as FDA warning and return visit rates adjusting for confounders. RESULTS: There were 4778 patients who underwent T + A, median age, 5 years. Of these, 752 (15.7%) had return visits. Pain-related return visits were higher in patients who received opioid prescriptions (adjusted OR, 1.31; 95% CI, 1.09-1.57). After FDA warning, opioids were prescribed at a lower rate (47.9%) compared with previous (98.6%) (OR, 0.01; 95% CI, 0.008-0.02). Pain-related return visits were lower after FDA warning (OR, 0.73; 95% CI, 0.61-0.87). Steroid prescription rate increased after FDA warning (OR, 415; 95% CI, 197-874). CONCLUSIONS: Opioid prescriptions were associated with higher pain-related return visits after T + A, whereas issuance of FDA black box warning against codeine use was associated with lower pain-related return visits. Our data suggest that the black box warning potentially had unintended benefits in pain management and health care usage.


Asunto(s)
Trastornos Relacionados con Opioides , Tonsilectomía , Estados Unidos/epidemiología , Niño , Humanos , Preescolar , Analgésicos Opioides/efectos adversos , Adenoidectomía/efectos adversos , Tonsilectomía/efectos adversos , Estudios Retrospectivos , United States Food and Drug Administration , Dolor/tratamiento farmacológico , Servicio de Urgencia en Hospital , Trastornos Relacionados con Opioides/tratamiento farmacológico , Prescripciones de Medicamentos
20.
Artículo en Español | LILACS | ID: biblio-1535461

RESUMEN

Introducción: La lesión pulmonar aguda (TRALI) y la sobrecarga circulatoria (TACO) son las principales causas de morbilidad y mortalidad relacionadas con la transfusión. La TRALI se presenta durante o después de las transfusiones de plasma y sus derivados, o por inmunoglobulinas en alta concentración intravenosa; se asocia a procesos sépticos, cirugías y transfusiones masivas. La TACO es la exacerbación de manifestaciones respiratorias en las primeras 6 horas postransfusión. Reporte caso: Paciente de sexo masculino de 38 días de vida, ingresó al servicio de urgencias con un cuadro clínico de 8 días de evolución, caracterizado por dificultad respiratoria dado por retracciones subcostales y aleteo nasal sin otro síntoma asociado, con antecedentes de importancia de prematuridad y bajo peso al nacer. El reporte de hemograma arrojó cifras compatibles con anemia severa, por lo que requirió transfusión de glóbulos rojos empaquetados desleucocitados. El paciente presentó un cuadro respiratorio alterado en un periodo menor a 6 horas, por lo que se descartaron causas infecciosas y finalmente se consideró cuadro compatible con TRALI. Conclusiones: Se debe considerar una lesión pulmonar aguda relacionada con una transfusión de sangre si se produce una insuficiencia respiratoria aguda durante o inmediatamente después de la infusión de hemoderivados que contienen plasma.


Introduction: Acute lung injury (TRALI) and circulatory overload (TACO) are the main causes of transfusion-related morbidity and mortality. TRALI occurs during or after transfusions of plasma or its derivatives, or by immunoglobulins in high intravenous concentration; it is associated with septic processes, surgeries, and massive transfusions. TACO is the exacerbation of respiratory manifestations in the first 6 hours post transfusion. Case report: A 38-day-old male was admitted to the emergency department with clinical symptoms experienced over the course of 8 days and characterized by respiratory distress due to subcostal retractions and nasal flaring with no other associated symptoms. Important antecedents included prematurity and low birth weight. The hemogram report showed figures compatible with anemia, which benefited from transfusion of packed red blood cells without leukocytes. In a period of less than 6 hours, the patient presented altered respiratory symptoms, practitioners ruled out infectious causes and finally considered clinical signs compatible with TRALI. Conclusion: Acute lung injury related to blood transfusion should be considered if acute respiratory failure occurs during or immediately after infusion of plasma-containing blood products.


Asunto(s)
Humanos , Masculino , Lactante , Recien Nacido Prematuro , Reacción a la Transfusión , Lesión Pulmonar Aguda Postransfusional , Síndrome de Dificultad Respiratoria del Recién Nacido , Signos y Síntomas , Anemia
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