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BACKGROUND: Alzheimer's disease (AD) is the most prevalent dementia, showing higher incidence in women. Besides, lipids play an essential role in brain, and they could be dysregulated in neurodegeneration. Specifically, impaired plasma lipid levels could predict early AD diagnosis. This work aims to identify the main plasma lipids altered in early AD female mouse model and evaluate their relationship with brain lipidome. Also, the possible involvement of the estrous cycle in lipid metabolism has been evaluated. METHODS: Plasma samples of wild-type (n = 10) and APP/PS1 (n = 10) female mice of 5 months of age were collected, processed, and analysed using a lipidomic mass spectrometry-based method. A statistical analysis involving univariate and multivariate approaches was performed to identify significant lipid differences related to AD between groups. Also, cytology tests were conducted to confirm estrous cycle phases. RESULTS: Three hundred thirty lipids were detected in plasma, 18 of them showed significant differences between groups; specifically, some triacylglycerols, cholesteryl esters, lysophosphatidylcholines, phosphatidylcholines, and ether-linked phosphatidylcholines, increased in early AD; while other phosphatidylcholines, phosphatidylethanolamines, ceramides, and ether-linked phosphatidylethanolamines decreased in early AD. A multivariate approach was developed from some lipid variables, showing high diagnostic indexes (70% sensitivity, 90% specificity, 80% accuracy). From brain and plasma lipidome, some significant correlations were observed, mainly in the glycerophospholipid family. Also, some differences were found in both plasma and brain lipids, according to the estrous cycle phase. CONCLUSIONS: Therefore, lipid alterations can be identified in plasma at early AD stages in mice females, with a relationship with brain lipid metabolism for most of the lipid subfamilies, suggesting some lipids as potential AD biomarkers. In addition, the estrous cycle monitoring could be relevant in female studies.
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Enfermedad de Alzheimer , Precursor de Proteína beta-Amiloide , Encéfalo , Modelos Animales de Enfermedad , Ciclo Estral , Lipidómica , Lípidos , Ratones Transgénicos , Animales , Femenino , Ciclo Estral/fisiología , Ciclo Estral/sangre , Lipidómica/métodos , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/sangre , Precursor de Proteína beta-Amiloide/genética , Lípidos/sangre , Presenilina-1/genética , Ratones , Metabolismo de los Lípidos/fisiología , Ratones Endogámicos C57BLRESUMEN
The crystallographic structure of the FolB enzyme from Mycobacterium tuberculosis (MtFolB), complexed with its inhibitor 8-mercaptoguanine (8-MG), was elucidated at a resolution of 1.95 Å. A novel series of S8-functionalized 8-MG derivatives were synthesised and evaluated as in vitro inhibitors of dihydroneopterin aldolase (DHNA, EC 4.1.2.25) activity of MtFolB. These compounds exhibited IC50 values in the submicromolar range. Evaluation of the activity for five compounds indicated their inhibition mode and inhibition constants. Molecular docking analyses were performed to determine the enzyme-inhibitor intermolecular interactions and ligand conformations upon complex formation. The inhibitory activities of all compounds against the M. tuberculosis H37Rv strain were evaluated. Compound 3e exhibited a minimum inhibitory concentration in the micromolar range. Finally, Compound 3e showed no apparent toxicity in both HepG2 and Vero cells. The findings presented herein will advance the quest for novel, specific inhibitors targeting MtFolB, an attractive molecular target for TB drug development.
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Aldehído-Liasas , Antituberculosos , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/enzimología , Antituberculosos/farmacología , Antituberculosos/síntesis química , Antituberculosos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Relación Estructura-Actividad , Aldehído-Liasas/antagonistas & inhibidores , Aldehído-Liasas/metabolismo , Aldehído-Liasas/química , Células Vero , Estructura Molecular , Cristalografía por Rayos X , Chlorocebus aethiops , Animales , Guanina/farmacología , Guanina/química , Guanina/análogos & derivados , Guanina/síntesis química , Simulación del Acoplamiento Molecular , Células Hep G2 , Modelos MolecularesRESUMEN
Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100 mg/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-α. Moreover, using UPLC-MS/MS we found that maternal supplementation with Ole during pregnancy and/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. Overall, our results indicate that pretreatment with Ole confers neuroprotection and can prevent HI-induced brain damage by modulating apoptosis and neuroinflammation.
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BACKGROUND: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.
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Aquaporin-4 (AQP4) expression is associated with the development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed a modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells was overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect. Here, we verified the location of this CD11c+ expression in the corpus callosum (CC) and cerebellum of AQP4-KO mice and analysed its time course. Immunofluorescence labelling of the CD11c protein in the CC and cerebellum of WT and KO animals at P3, P5, P7 and P11 confirmed an expanded presence of these cells in both tissues of the KO animal; CD11c+ cells appeared at P3 and reached a peak at P11, whereas in the WT animal, they appeared at P5, reached their peak at P7 and were undetectable by P11. The gene expression analysis in the CC samples at P11 confirmed the presence of CD11c+ microglial cells in this tissue. Among the more than 4000 overexpressed genes, Spp1 stood out with the highest differential gene expression (â 600), with other genes, such as Gpnmb, Itgax, Cd68 and Atp6v0d2, also identified as overexpressed. Therefore, CD11c+ cells appear to be necessary for normal corpus callosum development during postnatal life, and the absence of AQP4 prolonged its expression in this tissue.
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Acuaporina 4 , Cuerpo Calloso , Ratones Noqueados , Microglía , Animales , Acuaporina 4/metabolismo , Acuaporina 4/genética , Microglía/metabolismo , Ratones , Cuerpo Calloso/metabolismo , Antígeno CD11c/metabolismo , Antígeno CD11c/genética , Ratones Endogámicos C57BLRESUMEN
Melanopsin is a photopigment belonging to the G Protein-Coupled Receptor (GPCR) family expressed in a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) and responsible for a variety of processes. The bistability and, thus, the possibility to function under low retinal availability would make melanopsin a powerful optogenetic tool. Here, we aim to utilize mouse melanopsin to trigger macrophage migration by its subcellular optical activation with localized blue light, while simultaneously imaging the migration with red light. To reduce melanopsin's red light sensitivity, we employ a combination of in silico structure prediction and automated quantum mechanics/molecular mechanics modeling to predict minimally invasive mutations to shift its absorption spectrum towards the shorter wavelength region of the visible spectrum without compromising the signaling efficiency. The results demonstrate that it is possible to achieve melanopsin mutants that resist red light-induced activation but are activated by blue light and display properties indicating preserved bistability. Using the A333T mutant, we show that the blue light-induced subcellular melanopsin activation triggers localized PIP3 generation and macrophage migration, which we imaged using red light, demonstrating the optogenetic utility of minimally engineered melanopsins.
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Opsinas de Bastones , Transducción de Señal , Animales , Opsinas de Bastones/metabolismo , Opsinas de Bastones/genética , Opsinas de Bastones/química , Ratones , Movimiento Celular , Simulación por Computador , Macrófagos/metabolismo , Optogenética/métodos , Luz , MutaciónRESUMEN
INTRODUCTION: Poststroke hyperglycaemia is an independent risk factor for poorer outcomes in patients treated with mechanical thrombectomy (MT) and is associated with a lower probability of functional recovery and higher mortality at 3 months. This study aims to evaluate the association between glucose levels during cerebral reperfusion with MT and functional recovery at 3 months, measured by subcutaneous continuous glucose monitoring (CGM) devices. METHODS: This prospective observational study aims to recruit 100 patients with ischaemic stroke and large anterior circulation vessel occlusion, in whom MT is indicated. CGM will be performed using a Freestyle Libre ProIQ device (FSL-CGM, Abbott Diabetes Care, Alameda, California, USA), which will be implanted on admission to the emergency department, to monitor glucose levels before, during and after reperfusion. The study's primary endpoint will be the functional status at 3 months, as measured by the dichotomised modified Rankin Scale (0-2 indicating good recovery and 3-6 indicating dependency or death). We will analyse expression profiles of microRNA (miRNA) at the time of reperfusion and 24 hours later, as potential biomarkers of ischaemic-reperfusion injury. The most promising miRNAs include miR-100, miR-29b, miR-339, miR-15a and miR-424. All patients will undergo treatment according to current international recommendations and local protocols for the treatment of stroke, including intravenous thrombolysis if indicated. ETHICS AND DISSEMINATION: This study (protocol V.1.1, dated 29 October 2021, code 6017) has been approved by the Clinical Research Ethics Committee of La Paz University Hospital (Madrid, Spain) and has been registered in ClinicalTrials.gov (NCT05871502). Study results will be disseminated through peer-reviewed publications in Open Access format and at conference presentations. TRIAL REGISTRATION NUMBER: NCT05871502.
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Glucemia , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Trombectomía , Humanos , Estudios Prospectivos , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/cirugía , Trombectomía/métodos , Daño por Reperfusión/terapia , Glucemia/metabolismo , Glucemia/análisis , Hiperglucemia/complicaciones , Estudios Observacionales como Asunto , Masculino , MicroARNs , Recuperación de la Función , FemeninoRESUMEN
One third of all emerging infectious diseases are vector-borne, with no licensed antiviral therapies available against any vector-borne viruses. Zika virus and Usutu virus are two emerging flaviviruses transmitted primarily by mosquitoes. These viruses modulate different host pathways, including the PI3K/AKT/mTOR pathway. Here, we report the effect on ZIKV and USUV replication of two AKT inhibitors, Miransertib (ARQ-092, allosteric inhibitor) and Capivasertib (AZD5363, competitive inhibitor) in different mammalian and mosquito cell lines. Miransertib showed a stronger inhibitory effect against ZIKV and USUV than Capivasertib in mammalian cells, while Capivasertib showed a stronger effect in mosquito cells. These findings indicate that AKT plays a conserved role in flavivirus infection, in both the vertebrate host and invertebrate vector. Nevertheless, the specific function of AKT may vary depending on the host species. These findings indicate that AKT may be playing a conserved role in flavivirus infection in both, the vertebrate host and the invertebrate vector. However, the specific function of AKT may vary depending on the host species. A better understanding of virus-host interactions is therefore required to develop new treatments to prevent human disease and new approaches to control transmission by insect vectors.
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Tuberculosis is a disease caused by a single pathogen that leads to a death toll estimated to be more than a million per year. Mycobacterium tuberculosis (Mtb), which affects mainly the lungs, spreads by airborne transmission when infectious respiratory particles from an infected human enter the respiratory tract of another person. Despite diagnosis and treatment being well established, the rise of cases of patients infected with Mtb strains with multidrug resistance to the antibiotics used in the regimen against the disease is alarming. Indole used as a core molecule has been described as a promising structure to treat several diseases. 5-Fluoroindole (5-FI) compound, evaluated in the free base and in the hydrochloride (5-FI.HCl) forms, inhibited the growth of pan-sensitive Mtb H37Rv strain in the same range (4.7-29.1 µM) of clinical isolates that have resistance to at least two first-line drugs. Although 5-FI showed no cytotoxicity in Vero and HepG2 cells, high permeability (2.4.10-6 cm/s) in the PAMPA assay, and high metabolic stability (Clint 9.0 mL/min/kg) in rat liver microsomes, limited solubility at plasmatic and intestinal pH values prompted formation and employment of its salt form (5-FI.HCl). Although the 5-FI.HCl compound showed increased solubility at pH values of 7.4 and 9.1 and increased stability in aqueous solutions, data for intrinsic clearance (Clint = 48 mL/min/kg) and a half-life (t 1/2 = 12 min) showed decreased metabolic stability. As 5-FI.HCl showed both good absorption and ability to reach the systemic circulation of animals without the need to use vehicles containing cosolvents or surfactants, it was chosen to evaluate its effectiveness in the model of tuberculosis in mice. The in vivo results showed the concentration of the compound in plasma increasing within 30 min in the systemic circulation and the capacity of reducing the Mtb burden in the lungs at the concentration of 200 µmol/kg after 21 days of infection, with no toxicity in mice.
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BackgroundRecent migration trends have shown a notable entry of Latin American asylum seekers to Madrid, Spain.AimTo characterise the profile of asylum-seeking Latin American migrants who are living with HIV in Spain and to outline the barriers they face in accessing HIV treatment.MethodsA prospective cohort study was conducted between 2022 and 2023 with a 6-month follow-up period. Latin American asylum seekers living with HIV were recruited mainly from non-governmental organisations and received care at an HIV clinic in a public hospital in Madrid.ResultsWe included 631 asylum seekers. The primary countries of origin were Colombia (30%), Venezuela (30%) and Peru (18%). The median age was 32â¯years (interquartile range (IQR):â¯28-37), and 553 (88%) were cis men of which 94% were men who have sex with men. Upon their arrival, 49% (nâ¯=â¯309) lacked social support, and 74% (nâ¯=â¯464) faced barriers when attempting to access the healthcare system. Upon entry in Europe, 500 (77%) participants were taking antiretroviral therapy (ART). At their first evaluation at the HIV clinic, only 386 (61%) had continued taking ART and 33% (nâ¯=â¯209) had detectable plasma HIV-1 RNA levels. Six months later, 99% took ART and 98% had achieved an undetectable viral load.ConclusionsLatin American asylum seekers living with HIV in Madrid, Spain encountered barriers to healthcare and to ART. One-third of these individuals presented detectable HIV viral load when assessed in the HIV clinic, highlighting this as an important public health issue.
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Infecciones por VIH , Refugiados , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/etnología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Refugiados/estadística & datos numéricos , Estudios Prospectivos , Masculino , Adulto , España/epidemiología , Femenino , América Latina/etnología , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Migrantes/estadística & datos numéricosRESUMEN
AQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4-/- mice (KO) due to stenosis of Silvio's aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice. We compared periaqueductal samples from wild-type and KO mice. The microarray-based transcriptome analysis reflected a large number of genes with differential expression (809). Gene sets (GS) associated with ependymal development, ciliary function and the immune system were specially modified qPCR confirmed reduced expression in the KO mice genes: (i) coding for transcription factors for ependymal differentiation (Rfx4 and FoxJ1), (ii) involved in the constitution of the central apparatus of the axoneme (Spag16 and Hydin), (iii) associated with ciliary assembly (Cfap43, Cfap69 and Ccdc170), and (iv) involved in intercellular junction complexes of the ependyma (Cdhr4). By contrast, genes such as Spp1, Gpnmb, Itgax, and Cd68, associated with a Cd11c-positive microglial population, were overexpressed in the KO mice. Electron microscopy and Immunofluorescence of vimentin and γ-tubulin revealed a disorganized ependyma in the KO mice, with changes in the intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane. These structural alterations translate into reduced cilia beat frequency, which might alter cerebrospinal fluid movement. The presence of CD11c + microglia cells in the periaqueductal zone of mice during the first postnatal week is a novel finding. In AQP4-/- mice, these cells remain present around the aqueduct for an extended period, showing peak expression at P11. We propose that these cells play an important role in the normal development of the ependyma and that their overexpression in KO mice is crucial to reduce ependyma abnormalities that could otherwise contribute to the development of obstructive hydrocephalus.
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Acuaporina 4 , Epéndimo , Hidrocefalia , Ratones Noqueados , Microglía , Animales , Epéndimo/metabolismo , Epéndimo/patología , Hidrocefalia/metabolismo , Hidrocefalia/genética , Hidrocefalia/patología , Microglía/metabolismo , Acuaporina 4/metabolismo , Acuaporina 4/genética , Ratones , Acueducto del Mesencéfalo/metabolismo , Acueducto del Mesencéfalo/patología , Antígenos CD11/metabolismo , Antígenos CD11/genética , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Patients with COVID-19 often experience severe long-term sequelae. This study aimed to assess resilience and Quality of Life (QoL) of patients who underwent mechanical ventilation due to COVID-19, one year after discharge. METHODS: This cross-sectional study enrolled patients who received mechanical ventilation for severe COVID-19 and were assessed one-year post-discharge. Participants completed a structured questionnaire via telephone comprising the Connor-Davidson Resilience Scale (CD-RISC) and the Post-COVID-19 Functional Status scale (PCFS). To establish the association between QoL and resilience, Spearman correlations were calculated between the PCFS and the CD-RISC. Linear regression models were adjusted to evaluate which factors were associated with QoL, with the total score of PCFS as the dependent variable. RESULTS: A total of 225 patients were included in the analysis. The CD-RISC had a median score of 83 (IQR 74-91). The PCFS results showed that 61.3% (n = 138) of the patients were able to resume their daily activities without limitations. Among them, 37.3% (n = 84) were classified as Grade 0 and 24% (n = 54) as Grade 1. Mild and moderate functional limitations were found in 33.7% of the patients, with 24.8% (n = 56) classified as Grade 2 and 8.8% (n = 20) as Grade 3. Severe functional limitations (Grade 4) were observed in 4.8% (n = 11) of the patients. High CD-RISC scores were associated with lower levels of PCFS score (p < 0.001). CONCLUSIONS: In this cohort of critically ill patients who underwent mechanical ventilation due to COVID-19, 38% of patients experienced a significant decline in their QoL one year after hospital discharge. Finally, a high level of resilience was strongly associated with better QoL one year after discharge.
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COVID-19 , Alta del Paciente , Calidad de Vida , Resiliencia Psicológica , Respiración Artificial , Humanos , COVID-19/psicología , Calidad de Vida/psicología , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Anciano , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
In the Mexican Caribbean, environmental changes, hydrometeorological events, and anthropogenic activities promote dynamism in the coastal vegetation cover associated with the dune; however, their pace and magnitude remain uncertain. Using Landsat 7 imagery, spatial and temporal changes in coastal dune vegetation were estimated for the 2011-2020 period in the Sian Ka'an Biosphere Reserve. The SAVI index revealed cover changes at different magnitudes and paces at the biannual, seasonal, and monthly timeframes. Climatic seasons had a significant influence on vegetation cover, with increases in cover during northerlies (SAVI: p = 0.000), while the topographic profile of the dune was relevant for structure. Distance-based multiple regressions and redundancy analysis showed that temperature had a significant effect (p < 0.05) on SAVI patterns, whereas precipitation showed little influence (p > 0.05). The Mann-Kendall tendency test indicated high dynamism in vegetation loss and recovery with no defined patterns, mostly associated with anthropogenic disturbance. High-density vegetation such as mangroves, palm trees, and shrubs was the most drastically affected, although a reduction in bare soil was also recorded. This study demonstrated that hydrometeorological events and climate variability in the long term have little influence on vegetation dynamism. Lastly, it was observed that anthropogenic activities promoted vegetation loss and transitions; however, the latter were also linked to recoveries in areas with pristine environments, relevant for tourism.
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Introducción. El manejo perioperatorio de las urgencias hepatobiliares por parte del cirujano general es una competencia esperada y se considera un reto por su relativa frecuencia, impacto en la salud del individuo y la economía, así como las implicaciones en el ejercicio clínico confiable y de alta calidad. Se desconocen los aspectos formales de la educación en cirugía hepatobiliar para el cirujano general en Colombia. El objetivo del presente estudio fue explorar la perspectiva de los cirujanos hepatobiliares sobre esta problemática. Métodos. Se realizó un estudio cualitativo, mediante entrevistas semiestructuradas con 14 especialistas en cirugía hepatobiliar colombianos, en donde se exploraron los desafíos del entrenamiento, el tiempo y las características de una rotación, la evaluación de la confiabilidad, el número de procedimientos y el rol de la simulación. Se hizo un análisis temático de la información. Resultados. Los expertos mencionaron la importancia de la rotación obligatoria por cirugía hepatobiliar para los cirujanos en formación. El tiempo ideal es de tres meses, en el último año de residencia, en centros especializados, con exposición activa y bajo supervisión. Conclusiones. Por las características epidemiológicas del país y la frecuencia de enfermedades hepatobiliares que requieren tratamiento quirúrgico, es necesario que el cirujano general cuente con una formación sólida en este campo durante la residencia. El presente estudio informa sobre las características ideales del entrenamiento en este campo desde la visión de los expertos colombianos.
Introduction. The perioperative management of hepatobiliary emergencies by the general surgeon is an expected competence and is considered a challenge due to its relative frequency, impact on the individual health and the economy, as well as the implications for reliable and high-quality clinical practice. The formal aspects of education in hepatobiliary surgery for the general surgeon in Colombia are unknown. The objective of the present study was to explore the perspective of hepatobiliary surgeons on this problem. Methods. A qualitative study was carried out through semi-structured interviews with 14 Colombian hepatobiliary surgery specialists, where the challenges of training, time and characteristics of the rotation, evaluation of reliability, number of procedures and role of simulation. A thematic analysis of the information was carried out. Results. The experts mentioned the importance of mandatory rotation for hepatobiliary surgery for surgeons in training. The ideal duration was three months, during the last year of residency, in specialized centers with active exposure and under supervision. Conclusions. Due to the epidemiological characteristics of the country and the frequency of hepatobiliary diseases that require surgical treatment, it is necessary for the general surgeon to have solid training in this field during residency. The present study reports on the ideal characteristics of training in this field from the perspective of Colombian experts.
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Humanos , Procedimientos Quirúrgicos del Sistema Biliar , Educación de Postgrado en Medicina , Cirugía General , Enfermedades de las Vías Biliares , Tratamiento de Urgencia , Entrenamiento SimuladoRESUMEN
Bone defects are due to trauma, infections, tumors, or aging, including bone fractures, bone metastases, osteoporosis, or osteoarthritis. The global burden of these demands research into innovative strategies that overcome the limitations of conventional autografts. In this sense, the development of three-dimensional (3D) bioprinting has emerged as a promising approach in the field of tissue engineering and regenerative medicine (TERM) for the on-demand generation and transplantation of tissues and organs, including bone. It combines biological materials and living cells, which are precisely positioned layer by layer. Despite obtaining some promising results, 3D bioprinting of bone tissue still faces several challenges, such as generating an effective vascular network to increase tissue viability. In this review, we aim to collect the main knowledge on methods and techniques of 3D bioprinting. Then, we will review the main biomaterials, their composition, and the rationale for their application in 3D bioprinting for the TERM of bone.
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The pericardiocentesis procedure is common, often performed via the subxiphoid approach, although other transthoracic approaches have been described. This short communication describes an off-plane technique ultrasound-guided pericardiocentesis using an anterior approach, performed using a linear transducer and guided in real-time by ultrasound, offering the advantage of continuous needle tracking to reduce complications associated with this approach such as pneumothorax, inadvertent cardiac puncture, and injury to the left internal mammary artery (LIMA).
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Nanoliposomes are nano-sized vesicles that can be used as drug delivery carriers with the ability to encapsulate both hydrophobic and hydrophilic compounds. Moreover, their lipid compositions facilitate their internalization by cells. However, the interaction between nanoliposomes and the membrane barrier of the human body is not well-known. If cellular tests and animal testing offer a solution, their lack of physiological relevance and ethical concerns make them unsuitable to properly mimic human body complexity. Microfluidics, which allows the environment of the human body to be imitated in a controlled way, can fulfil this role. However, existing models are missing the presence of something that would mimic a basal membrane, often consisting of a simple cell layer on a polymer membrane. In this study, we investigated the diffusion of nanoliposomes in a microfluidic system and found the optimal parameters to maximize their diffusion. Then, we incorporated a custom made GelMA with a controlled degree of substitution and studied the passage of fluorescently labeled nanoliposomes through this barrier. Our results show that highly substituted GelMA was more porous than lower substitution GelMA. Overall, our work lays the foundation for the incorporation of a hydrogel mimicking a basal membrane on a drug delivery microfluidic platform.
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Insuficiencia Cardíaca , Defectos del Tabique Interatrial , Corazón Auxiliar , Dispositivo Oclusor Septal , Humanos , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/diagnóstico por imagen , Insuficiencia Cardíaca/cirugía , Cateterismo Cardíaco/métodos , Cateterismo Cardíaco/instrumentación , Implantación de Prótesis/métodos , Implantación de Prótesis/instrumentaciónRESUMEN
BACKGROUND: The growing incidence of lower gastrointestinal bleeding (LGIB) is leading to a rise in-hospital admissions even though most LGIB episodes are self-limiting. The Oakland and SHA2PE scores were designed to identify patients best suited to outpatient care. Our aim is explore the validity of the SHA2PE score and compare both of these scores in terms of predictiveness of safe discharge. METHODS: Retrospective observational study of LGIB patients admitted to a tertiary hospital between June 2014 and June 2019. Safe discharge was defined as the absence of all the following: blood transfusion, haemostatic intervention, re-bleeding, in-hospital death, and re-admission due to LGIB within 28 days after discharge. RESULTS: From 595 hospital admissions for LGIB, 398 episodes were included. Fifty-four per cent met safe discharge criteria, with these cases being younger, with a lower score in the Charlson's index and significantly higher haemoglobin concentration upon arrival. The performance of both scores was good, with an AUC for the Oakland score of 0.85 (95% CI 0.82-0.89) and of 0.797 (95% CI 0.75-0.84) for the SHA2PE score. The Oakland score performed better in terms of prediction of safe discharge, with a positive predictive value and specificity of 100% when a cut-off value of ≤ 8 points was used; however, only a minority of patients might benefit from its implementation given its low sensitivity. CONCLUSIONS: Almost half of the patients admitted for LGIB met criteria for safe discharge. However, the available indexes only allow for the identification of a small proportion of those patients candidates for outpatient care.