RESUMEN
Living at high altitudes impose physiological and ecological challenges to which species may respond altering their body size, body proportions, and the shape of their body parts. Despite the importance of this topic for understanding the origin of species diversity, little attention has been invested in this phenomenon at the populational level. This paper study the relationship between altitude and body size, body proportions, and forewing shape venation of two populations of the parasitoid wasp Cotesia flavipes. Wasps were collected from Diatraea spp. larvae from sugarcane crops in two Colombian mountain ranges that cover between 600â¯m and 2143â¯m of altitude. Linear measurements of different body regions and geometric morphometrics of the forewing were subject to multivariate comparisons and allometric analyses to assess variation and to compare trends between ranges. Central (600â¯m to 1704â¯m) and Eastern Cordillera (877â¯m to 2143â¯m) populations showed different trends between body size and altitude. Allometric trends were not uniform within or between populations nor between structures. The allometric slopes of five body measurements from a single altitude differed from these from its own mountain range suggesting that body size trends along the cordilleras are a consequence of altitude and not of intrinsic body resource allocation processes. Wing shape between populations differed; however, these changes were poorly related to altitude. In agreement with recent studies in other groups, the observed allometric and wing shape differences between the two C. flavipes populations could be a plasticity response to altitude with interesting implications for posterior genetic differentiation.
RESUMEN
Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic ß cells, leading to a disruption in glucose homeostasis. Therapeutic intervention for T1DM requires a complex regimen of glycaemic monitoring and the administration of exogenous insulin to regulate blood glucose levels. Advances in continuous glucose monitoring and algorithm-driven insulin delivery devices have improved the quality of life of patients. Despite this, mimicking islet function and complex physiological feedback remains challenging. Pancreatic islet transplantation represents a potential functional cure for T1DM but is hindered by donor scarcity, variability in harvested cells, aggressive immunosuppressive regimens and suboptimal clinical outcomes. Current research is directed towards generating alternative cell sources, improving transplantation methods, and enhancing cell survival without chronic immunosuppression. This Review maps the progress in cell replacement therapies for T1DM and outlines the remaining challenges and future directions. We explore the state-of-the-art strategies for generating replenishable ß cells, cell delivery technologies and local targeted immune modulation. Finally, we highlight relevant animal models and the regulatory aspects for advancing these technologies towards clinical deployment.
RESUMEN
Mitrofanova et al.1 engineer a human colonic in vitro model capable of producing an intestinal mucus barrier, with potential applications for predicting drug-induced gastrointestinal toxicity. This improved system paves the way for more accurate and efficient drug development processes.
Asunto(s)
Colon , Humanos , Colon/efectos de los fármacos , Colon/patología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Modelos Biológicos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismoRESUMEN
Nanoparticle exsolution has emerged as a versatile method to functionalize oxides with robust metallic nanoparticles for catalytic and energy applications. By modifying certain external parameters during thermal reduction (temperature, time, reducing gas), some morphological and/or compositional properties of the exsolved nanoparticles can be tuned. Here, it is shown how the application of high pressure (<100 bar H2) enables the control of the exsolution of ternary FeCoNi alloyed nanoparticles from a double perovskite. H2 pressure affects the lattice expansion and the nanoparticle characteristics (size, population, and composition). The composition of the alloyed nanoparticles could be controlled, showing a reversal of the expected thermodynamic trend at 10 and 50 bar, where Fe becomes the main component instead of Ni. In addition, pressure drastically lowers the exsolution temperature to 300 °C, resulting in unprecedented highly-dispersed and small-sized nanoparticles with a similar composition to those obtained at 600 °C and 10 bar. The mechanisms behind the effects of pressure on exsolution are discussed, involving kinetic, surface thermodynamics, and lattice-strain factors. A volcano-like trend of the exsolution extent suggests that competing pressure-dependent mechanisms govern the process. Pressure emerges as a new design tool for metallic nanoparticle exsolution enabling novel nanocatalysts and surface-functionalized materials.
RESUMEN
The focus of dermatology has increasingly shifted towards exploring new and innovative approaches [...].
Asunto(s)
Dermatología , Enfermedades de la Piel , Humanos , Dermatología/tendencias , Enfermedades de la Piel/terapia , Enfermedades de la Piel/tratamiento farmacológico , Terapia Molecular Dirigida/métodosRESUMEN
ß3-Adrenergic receptor (ß3AR) agonists have been shown to protect against ischemia-reperfusion injury (IRI). Since ß3ARs are present both in cardiomyocytes and in endothelial cells, the cellular compartment responsible for this protection has remained unknown. Using transgenic mice constitutively expressing the human ß3AR (hß3AR) in cardiomyocytes or in the endothelium on a genetic background of null endogenous ß3AR expression, we show that only cardiomyocyte expression protects against IRI (45 min ischemia followed by reperfusion over 24 h). Infarct size was also limited after ischemia-reperfusion in mice with cardiomyocyte hß3AR overexpression on top of endogenous ß3AR expression. hß3AR overexpression in these mice reduced IRI-induced cardiac fibrosis and improved long-term left ventricular systolic function. Cardiomyocyte-specific ß3AR overexpression resulted in a baseline remodeling of the mitochondrial network, characterized by upregulated mitochondrial biogenesis and a downregulation of mitochondrial quality control (mitophagy), resulting in elevated numbers of small mitochondria with a depressed capacity for the generation of reactive oxygen species but improved capacity for ATP generation. These processes precondition cardiomyocyte mitochondria to be more resistant to IRI. Upon reperfusion, hearts with hß3AR overexpression display a restoration in the mitochondrial quality control and a rapid activation of antioxidant responses. Strong protection against IRI was also observed in mice infected with an adeno-associated virus (AAV) encoding hß3AR under a cardiomyocyte-specific promoter. These results confirm the translational potential of increased cardiomyocyte ß3AR expression, achieved either naturally through exercise or artificially through gene therapy approaches, to precondition the cardiomyocyte mitochondrial network to withstand future insults.
RESUMEN
BACKGROUND AND AIMS: The association of inflammatory bowel disease (IBD) with other immune-mediated inflammatory diseases (IMIDs) in the same patient is well known. We aimed to evaluate the degree of knowledge that patients with IBD have regarding the coexistence of other IMIDs and to analyze the factors associated with the concordance between self-reported and confirmed medical information. METHODS: Patients with IBD at a tertiary hospital answered a questionnaire on the presence of 54 IMIDs (self-reported diagnosis), and their IMID diagnosis was confirmed in their medical records (reference diagnosis). Agreement between the self-reported IMID and the IMID according to medical records was evaluated. The association between concordance and different predictors was evaluated using logistic regression models. RESULTS: A total of 1,620 patients were included. Six hundred and twenty-six (39%) patients were diagnosed with at least one IMID, and 177 (11%) with two or more. Overall agreement between patients´ self-report and medical records was k:0.61. When we grouped IMIDs according to affected organs or systems, agreement on rheumatic IMIDs was moderate (k:0.58), whereas agreement on cutaneous (k:0.66), endocrine (k: 0.74) and ocular (k:0.73) IMIDs was substantial. Among patients who had IMIDs, the factor associated with greater concordance was female gender, while lower concordance was associated with a lower educational level and the fact that the IMID had been diagnosed at the same time or later than IBD. CONCLUSION: The knowledge that patients with IBD have regarding the coexistence of other IMIDs is poor, especially in rheumatic IMIDs.
RESUMEN
INTRODUCTION: Intragastric balloon (IGB) is a minimally invasive and reversible option for obesity treatment. There is a worldwide growing number of different IGB models. The efficacy and safety profile for each model must be demonstrated. We aim to evaluate IGB safety profile according to the experience of the Spanish Bariatric Endoscopy Group (GETTEMO). METHODS: A survey of 37 IGBs safety-related questions was sent to all GETTEMO members, to retrospectively collect a multicenter Spanish registry. Incidence, causes, and resolution of both major and minor complications and adverse events (AEs), including legal consequences, differentiated for each balloon model were evaluated. Secondary outcome was weight loss data to confirm efficacy. RESULTS: Twenty-one Spanish hospitals experienced in IGBs responded. The overall data encompassed 20,680 IGBs, including 12 different models. Mean %TBWL of 17.66 ± 2.5% was observed. Early removal rate due to intolerance was 3.62%. Mean major complications rate was 0.70% (> 1% in Spatz2, HB, and Spatz3 models), mainly complicated gastric ulcer. Minor AEs rate was 6.37%, mainly esophagitis. Nine cases (0.04%) required surgery. A single case of mortality (0.0048%) occurred. Seven lawsuits (0.0034%) were received, all with favorable resolution. CONCLUSIONS: In the Spanish experience accumulating 20,680 IGBs and including 12 different balloon models, a low incidence rate of major complications and minor AEs are observed (0.70% and 6.37%, respectively), mostly resolved with medical/endoscopic management. IGB shows good tolerance and efficacy profile. These safety data are within the accepted quality standards.
Asunto(s)
Balón Gástrico , Obesidad Mórbida , Pérdida de Peso , Humanos , España/epidemiología , Estudios Retrospectivos , Femenino , Obesidad Mórbida/cirugía , Masculino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Sistema de RegistrosRESUMEN
Adherens junction-associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed significantly decreased presynaptic GBR levels in Ajap1-/- and Ajap1W183C/+ mice. Consequently, these mice exhibited reduced GBR-mediated presynaptic inhibition at excitatory and inhibitory synapses, along with impaired synaptic plasticity. Our study reveals that AJAP1 enables the postsynaptic neuron to regulate the level of presynaptic GBR-mediated inhibition, supporting the clinical relevance of loss-of-function AJAP1 variants.
Asunto(s)
Neurotransmisores , Sinapsis , Transmisión Sináptica , Animales , Femenino , Humanos , Masculino , Ratones , Alelos , Epilepsia/metabolismo , Epilepsia/genética , Epilepsia/patología , Mutación con Pérdida de Función , Ratones Noqueados , Trastornos del Neurodesarrollo/metabolismo , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/patología , Plasticidad Neuronal , Neuronas/metabolismo , Neurotransmisores/metabolismo , Sinapsis/metabolismo , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismoRESUMEN
PURPOSE: To investigate the phenotype of sarcoidosis according to the time when a malignancy is diagnosed (preexisting to the diagnosis of sarcoidosis, concomitant, or sequential) and to identify prognostic factors associated with malignancies in a large cohort of patients with sarcoidosis. METHODS: We searched for malignancies in the SARCOGEAS cohort, a multicenter nationwide database of consecutive patients diagnosed with sarcoidosis according to the ATS/ESC/WASOG criteria. Solid malignancies were classified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) nomenclature, and hematological malignancies using the 2016 WHO classification. We excluded patients with a biopsy-proven diagnosis of sarcoidosis based exclusively on demonstrating granulomas in tissues also involved by malignant cells. RESULTS: Out of 1942 patients with sarcoidosis, 233 (12%) developed 250 malignancies, including solid (n = 173), hematological (n = 57), and both types of malignancies (n = 3). Concerning the time interval between the diagnoses of both conditions, 83 (36%) patients were diagnosed with malignancy at least 1 year before sarcoidosis diagnosis, 22 (9%) had s synchronous diagnosis of both diseases, and 118 (51%) developed malignancies at least 1 year after the diagnosis of sarcoidosis (the remaining cases developed malignancies in different time intervals). The multivariate-adjusted model showed that individuals with sarcoidosis who developed a malignancy had an hazard ratio (HR) of 2.27 [95% confidence interval (CI), 1.62-3.17] for having an asymptomatic clinical phenotype at diagnosis of sarcoidosis and that spleen (presence vs. absence: HR = 2.06; 95% CI, 1.21-3.51) and bone marrow (presence vs. absence: HR = 3.04; 95% CI, 1.77-5.24) involvements were independent predictors for the development of all-type malignancies. No predictive factors were identified when the analysis was restricted to the development of solid malignancies. The analysis limited to the development of hematological malignancies confirmed the presence of involvement in the spleen (HR = 3.73; 95% CI, 1.38-10.06) and bone marrow (presence vs. absence: HR = 8.00; 95% CI, 3.15-20.35) at the time of sarcoidosis diagnosis as predictive factors. CONCLUSION: It is essential to consider the synchronous or metachronous timing of the diagnosis of malignancies in people with sarcoidosis. We found that half of the malignancies were diagnosed after a diagnosis of sarcoidosis, with spleen and bone marrow involvement associated with a four to eight times higher risk of developing hematological malignancies. Key messages What is already known on this topic Malignancies are one of the comorbidities more frequently encountered in people with sarcoidosis What this study adds Malignancies occur in 12% of patients with sarcoidosis Malignancy may precede, coincide with, or follow the diagnosis of sarcoidosis One-third were identified before sarcoidosis, and half were diagnosed after Spleen and bone marrow involvement are risk factors for developing hematological malignancies How this study might affect research, practice or policy Patients with sarcoidosis should be regularly monitored for neoplasms, informed of the increased risk, and educated on early detection. Those with spleen or bone marrow involvement must be closely followed.
RESUMEN
Many relevant high-temperature chemical processes require the use of oxide-supported metallic nanocatalysts. The harsh conditions under which these processes operate can trigger catalyst degradation via nanoparticle sintering, carbon depositions or poisoning, among others. This primarily affects metallic nanoparticles created via deposition methods with low metal-support interaction. In this respect, nanoparticle exsolution has emerged as a promising method for fabricating oxide-supported nanocatalysts with high interaction between the metal and the oxide support. This is due to the mechanism involved in nanoparticle exsolution, which is based on the migration of metal cations in the oxide support to its surface, where they nucleate and grow as metallic nanoparticles partially embedded in the oxide. This anchorage confers high robustness against sintering or coking-related problems. For these reasons, exsolution has attracted great interest in the last few years. Multiple works have been devoted to proving the high catalytic stability of exsolved metallic nanoparticles in several applications for high-temperature energy storage and conversion. Additionally, considerable attention has been directed towards understanding the underlying mechanism of metallic nanoparticle exsolution. However, this growing field has not been limited to these types of studies and recent discoveries at the forefront of materials design have opened new research avenues. In this work, we define six new trends in nanoparticle exsolution, taking a tour through the most important advances that have been recently reported.
RESUMEN
Sirtuin 7 (SIRT7) is a member of the mammalian family of nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases, known as sirtuins. It acts as a potent oncogene in numerous malignancies, but the molecular mechanisms employed by SIRT7 to sustain lung cancer progression remain largely uncharacterized. We demonstrate that SIRT7 exerts oncogenic functions in lung cancer cells by destabilizing the tumor suppressor alternative reading frame (ARF). SIRT7 directly interacts with ARF and prevents binding of ARF to nucleophosmin, thereby promoting proteasomal-dependent degradation of ARF. We show that SIRT7-mediated degradation of ARF increases expression of protumorigenic genes and stimulates proliferation of non-small-cell lung cancer (NSCLC) cells both in vitro and in vivo in a mouse xenograft model. Bioinformatics analysis of transcriptome data from human lung adenocarcinomas revealed a correlation between SIRT7 expression and increased activity of genes normally repressed by ARF. We propose that disruption of SIRT7-ARF signaling stabilizes ARF and thus attenuates cancer cell proliferation, offering a strategy to mitigate NSCLC progression.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Proliferación Celular , Progresión de la Enfermedad , Neoplasias Pulmonares , Sirtuinas , Humanos , Sirtuinas/metabolismo , Sirtuinas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Regulación Neoplásica de la Expresión Génica , Línea Celular TumoralRESUMEN
Hematopoietic stem cells (HSCs) are the apical cells of the hematopoietic system, giving rise to cells of the blood and lymph lineages. HSCs reside primarily within bone marrow niches that contain matrix and cell-derived signals that help inform stem cell fate. Aspects of the bone marrow microenvironment have been captured in vitro by encapsulating cells within hydrogel matrices that mimic native mechanical and biochemical properties. Hydrogel microparticles, or microgels, are increasingly being used to assemble granular biomaterials for cell culture and noninvasive delivery applications. Here, we report the optimization of a gelatin maleimide hydrogel system to create monodisperse gelatin microgels via a flow-focusing microfluidic process. We report characteristic hydrogel stiffness, stability, and swelling characteristics as well as encapsulation of murine hematopoietic stem and progenitor cells, and mesenchymal stem cells within microgels. Microgels support cell viability, confirming compatibility of the microfluidic encapsulation process with these sensitive bone marrow cell populations. Overall, this work presents a microgel-based gelatin maleimide hydrogel as a foundation for future development of a multicellular artificial bone marrow culture system.
RESUMEN
OBJECTIVE: Systematic review of current evidence to analyze the prevalence of extracranial large vessel vasculitis (LVV) using 18F-FDG PET/CT in patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA). MATERIALS AND METHODS: PubMed and EMBASE were searched and the results were screened by two reviewers. Study quality was assessed using a modified version of the Newcastle-Ottawa scale. Heterogeneity between studies was assessed using the I2 statistic and the Q test. Further subgroup analyses were performed by disease type, study quality, and 18F-FDG PET/CT uptake criteria. Publication bias was assessed by funnel plot and Egger's test. RESULTS: 268 publications were identified, of which 17 met the selection criteria and were included in the meta-analysis. The overall pooled prevalence of extracranial LVV by 18F-FDG PET/CT was 54.5% [95% CI: 42.6%-66.1%]. In patients with GCA the prevalence was significantly higher than in patients with PMR (60.1% vs. 41.8%, Pâ¯=â¯0.006). Likewise, studies with a lower risk of bias reported a higher prevalence of extracranial LVV (61.1% vs. 46.9%; Pâ¯=â¯0.010). No publication bias was observed. CONCLUSIONS: The 18F-FDG PET/CT test may be useful in the detection of extracranial LVV, both in patients with PMR or GCA. Such involvement is more frequent in patients with GCA, and may vary depending on the quality of the studies.
Asunto(s)
Fluorodesoxiglucosa F18 , Arteritis de Células Gigantes , Polimialgia Reumática , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Humanos , Arteritis de Células Gigantes/diagnóstico por imagen , Polimialgia Reumática/diagnóstico por imagen , Vasculitis/diagnóstico por imagenRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0255555.].
RESUMEN
PURPOSE: To analyze changes in tear levels of inflammatory mediators in symptomatic contact lens (CL) wearers after refitting with daily disposable CLs and to identify potential biomarkers of success in CL discomfort (CLD) management. METHODS: Symptomatic CL wearers (CLDEQ-8 ≥ 12) were refitted (V1) with daily disposable CLs (Delefilcon A). After one month (V2), participants were classified into the post-fitting non-symptomatic (CLDEQ <12) and symptomatic (CLDEQ ≥12) groups. At each visit, the participants were clinically evaluated, tears were collected, and 20 inflammatory mediators and substance P (SP) were measured using multiplex immunobead analysis and ELISA, respectively. The detection rates and concentrations were compared between visits and groups, and logistic regression models were performed. RESULTS: Forty-three subjects (32 women/11 men; mean age: 23.2 ± 4.9 years) were enrolled. The IL-1ß and IL-9 detection rates were higher at V2 (p ≤ 0.044). The detection rates of IL-1ß, IL-9, MIP-1α/CCL3, and MMP-9 at V1 (p ≤ 0.045) and IL-17A at V2 (p ≤ 0.014) were higher in the post-fitting symptomatic group. The tear IL-9 concentration was increased at V2 (p = 0.018). The tear concentrations of fractalkine/CX3CL1, IL-2, IL-6, IL-10, MCP-3/CCL7, MIP-1ß, NGF, RANTES/CCL5, and TNF-α were higher in the post-fitting symptomatic group (p ≤ 0.044). Additionally, levels of fractalkine/CX3CL1, IL-2, IL-6, IL-10, RANTES/CCL5, and TNF-α at V1 were significantly associated with the post-fitting grouping (p ≤ 0.044). CONCLUSIONS: Low tear concentrations of specific inflammatory mediators may be used as a predictive biomarker of success for refitting symptomatic CL wearers with daily disposable CLs. However, complementary treatments might be required for symptomatic CL wearers with higher levels of these inflammatory molecules.
RESUMEN
Immune cell therapy (ICT) is a transformative approach used to treat a wide range of diseases including type 1 diabetes, sickle cell disease, disorders of the hematopoietic system, and certain forms of cancers. Despite excellent clinical successes, the scope of adoptively transferred immune cells is limited because of toxicities like cytokine release syndrome and immune effector cell-associated neurotoxicity in patients. Furthermore, reports suggest that such treatment can impact major organ systems including cardiac, renal, pulmonary, and hepatic systems in the long term. Additionally, adoptively transferred immune cells cannot achieve significant penetration into solid tissues, thus limiting their therapeutic potential. Recent studies suggest that biomaterial-assisted delivery of immune cells can address these challenges by reducing toxicity, improving localization, and maintaining desired phenotypes to eventually regain tissue function. In this review, recent efforts in the field of biomaterial-based immune cell delivery for the treatment of diseases, their pros and cons, and where these approaches stand in terms of clinical treatment are highlighted.
RESUMEN
Deer antlers are the fastest growing tissue. Because they are based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus their extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound by testing the direct effects in cells of different tumours: glioblastoma (GBM; lines U87MG and U251), colorectal (CRC; lines DLD-1, HT-29, SW480, and SW620), breast cancer (BRCA; lines MCF7, SKBR3, and PA00), and leukaemia (THP-1). DVA reduced the viability of tumours but not healthy cells (NHC; lines 293T and HaCaT). Mobility decreased at least for the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight by 66.3% and 61.4% respectively, and it also reduced spleen weight (43.8%). In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related to tumour fighting and down-regulated those related to inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system. DVA may contain a future anticancer medicine without secondary effects.
RESUMEN
Activation of O2 by subnanometer metal clusters is a fundamental step in the reactivity and oxidation processes of single-cluster catalysts. In this work, we examine the adsorption and dissociation of O2 on RenPtm (n + m = 5) clusters supported on rutile TiO2(110) using DFT calculations. The adhesion energies of RenPtm clusters on the support are high, indicating significant stability of the supported clusters. Furthermore, the bimetallic Re-Pt clusters attach to the surface through the Re atoms. The oxygen molecule was adsorbed on three sites of the supported systems: the metal cluster, the surface, and the interface. At the metal cluster site, the O2 molecule binds strongly to RenPtm clusters, especially on the Re-rich clusters. O2 activation occurs by charge transfer from the metal atoms to the molecule. The dissociation of O2 on the RenPtm clusters is an exothermic process with low barriers. As a result, sub-nanometer Re-Pt clusters can be susceptible to oxidation. Similar results are obtained at the metal-support interface, where both the surface and cluster transfer charge to O2. To surface sites, molecular oxygen is adsorbed onto the Ti5c atoms with moderate adsorption energies. The polarons, which are produced by the interaction between the metal cluster and the surface, participate in the activation of the molecule. However, dissociating O2 in these sites is challenging due to the endothermic nature of the process and the high energy barriers involved. Our findings provide novel insights into the reactivity of supported clusters, specifically regarding the O2 activation by Re-Pt clusters on rutile TiO2(110).
RESUMEN
INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.