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This current study aimed to investigate the impact of drum training on behavior and brain function in autistic adolescents with no prior drumming experience. Thirty-six autistic adolescents were recruited and randomly assigned to one of two groups. The drum group received individual drum tuition (two lessons per week over an 8-wk period), while the control group did not. All participants attended a testing session before and after the 8-wk period. Each session included a drumming assessment, an MRI scan, and a parent completing questionnaires relating to the participants' behavioral difficulties. Results showed that improvements in drumming performance were associated with a significant reduction in hyperactivity and inattention difficulties in drummers compared to controls. The fMRI results demonstrated increased functional connectivity in brain areas responsible for inhibitory control, action outcomes monitoring, and self-regulation. In particular, seed-to-voxel analyses revealed an increased functional connectivity in the right inferior frontal gyrus and the right dorsolateral prefrontal cortex. A multivariate pattern analysis demonstrated significant changes in the medial frontal cortex, the left and right paracingulate cortex, the subcallosal cortex, the left frontal pole, the caudate, and the left nucleus accumbens. In conclusion, this study investigates the impact of a drum-based intervention on neural and behavioral outcomes in autistic adolescents. We hope that these findings will inform further research and trials into the potential use of drum-based interventions in benefitting clinical populations with inhibition-related disorders and emotional and behavioral difficulties.
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Trastorno Autístico , Música , Fenómenos Fisiológicos del Sistema Nervioso , Adolescente , Trastorno Autístico/terapia , Encéfalo , Niño , Emociones , Humanos , Aprendizaje , Musicoterapia , Agitación PsicomotoraRESUMEN
Thyroid hormone action is involved in virtually all physiological processes. It is well known that the liver and thyroid are intimately linked, with thyroid hormone playing important roles in de novo lipogenesis, beta-oxidation (fatty acid oxidation), cholesterol metabolism, and carbohydrate metabolism. Clinical and mechanistic research studies have shown that thyroid hormone can be involved in chronic liver diseases, including alcohol-associated or NAFLD and HCC. Thyroid hormone action and synthetic thyroid hormone analogs can exert beneficial actions in terms of lowering lipids, preventing chronic liver disease and as liver anticancer agents. More recently, preclinical and clinical studies have indicated that some analogs of thyroid hormone could also play a role in the treatment of liver disease. These synthetic molecules, thyromimetics, can modulate lipid metabolism, particularly in NAFLD/NASH. In this review, we first summarize the thyroid hormone signaling axis in the context of liver biology, then we describe the changes in thyroid hormone signaling in liver disease and how liver diseases affect the thyroid hormone homeostasis, and finally we discuss the use of thyroid hormone-analog for the treatment of liver disease.
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BACKGROUND: Outcomes of catheter ablation (CA) among patients with nonparoxysmal atrial fibrillation (AF) are largely disappointing. OBJECTIVE: We sought to evaluate the feasibility, effectiveness, and safety of a single-stage stepwise endo-/epicardial approach in patients with persistent/longstanding-persistent AF. METHODS: We enrolled 25 consecutive patients with symptomatic persistent (n = 4) or longstanding-persistent (n = 21) AF and at least one prior endocardial procedure, who underwent CA using an endo-/epicardial approach. Our anatomical stepwise protocol included multiple endocardial as well as epicardial (Bachmann's bundle [BB] and ligament of Marshall ablations) components, and entailed ablation of atrial tachycardias emerging during the procedure. The primary outcome was freedom from any AF/atrial tachycardia episode after a 3-month blanking period. The secondary outcome was patients' symptom status during follow-up. RESULTS: The stepwise endo-/epicardial approach allowed sinus rhythm restoration in 72% of patients, either directly (n = 6, 24%) or after AF organization into atrial tachycardia (n = 12, 48%). BB's ablation was commonly implicated in arrhythmia termination. After a median follow-up of 266 days (interquartile range, 96 days), survival free from AF/atrial tachycardia was 88%. Antiarrhythmic drugs could be discontinued in 22 patients (88%). As compared to baseline, more patients were asymptomatic at 9-month follow-up (0% vs. 56%, p = .02). Five patients (20%) developed mild medical complications, whereas one subject (4%) had severe kidney injury requiring dialysis. CONCLUSION: A single-stage endo-/epicardial CA resulted in favorable rhythm and symptom outcomes in a cohort of patients with symptomatic persistent/longstanding-persistent AF and one or more prior endocardial procedures. Epicardial ablation of BB was commonly implicated in procedural success.
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Fibrilación Atrial , Ablación por Catéter , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Humanos , Mediterranea , Recurrencia , Resultado del TratamientoRESUMEN
This study evaluated the ability of T2 mapping magnetic resonance imaging at 3 T, in addition to morphological sequences, to assess efficacy of platelet-rich plasma (PRP) injections, characterizing qualitatively and quantitatively the grade of knee cartilage repair in patients with patellofemoral chondropathy. We retrospectively studied 34 patients (22 men, 12 women, mean age 41.8 years, including 22 men) with patellofemoral knee chondropathy, who underwent intra-articular PRP injections and completed a clinical and instrumental follow-up. As control group, we evaluated 34 patients who underwent non-operative therapy. All patients were submitted to clinical (using VAS and WOMAC index) and imaging studies with 3 T magnetic resonance with cartilage analysis with T2 mapping sequences for cartilage analysis before and after treatment. In the study group, mean pre-treatment T2 relaxation time values were 44.2 ± 2.5 ms, considering all articular cartilage compartments, with significant reduction at the follow-up (p < 0.001). At the index compartment, mean pre-treatment T2 relaxation times values were 47.8 ± 3.6 ms, with statistically significant reduction at the follow-up (p < 0.001). Evaluation of focal cartilage lesions reported pre-treatment mean T2 value of 70.1 ± 13.0 ms and post-treatment mean value of 59.9 ± 4.6 ms (p < 0.001). From a clinical point of view, the pre-treatment WOMAC and VAS scores were 18.3 ± 4.5 and 7 (IQR:6-7.2), respectively; the post-treatment values were 7.3 ± 3.2 and 2 (IQR: 1.7-3.0), respectively (p < 0.001). In the control group, despite clinical improvement, we didn't find significant T2 values change during the follow-up period. In conclusion, T2 mapping is a valuable indicator for chondropathy and treatment-related changes over time.
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Cartílago Articular/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/terapia , Plasma Rico en Plaquetas , Adulto , Femenino , Fémur , Humanos , Inyecciones Intraarticulares , Masculino , Persona de Mediana Edad , Rótula , Estudios Retrospectivos , Adulto JovenRESUMEN
Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton's Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1ß) and anti-inflammatory (IL-10, TGF-ß1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1ß (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols.
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Células de la Médula Ósea/metabolismo , Factor 5 de Diferenciación de Crecimiento/farmacología , Células Madre Mesenquimatosas/metabolismo , Tenocitos/metabolismo , Adulto , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Diferenciación Celular , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Decorina/genética , Decorina/metabolismo , Femenino , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Tenascina/genética , Tenascina/metabolismo , Tenocitos/citología , Cordón Umbilical/citologíaRESUMEN
OBJECTIVES: The aim of our study was to assess the role of videofluorography (VFG) in the evaluation of swallowing and oesophageal peristalsis in patients with systemic sclerosis (SSc). METHODS: From June 2014 to September 2017, 55 consecutive SSc patients, defined according to the 2013 ACR/EULAR classification criteria, underwent VFG study using a remote-controlled digital device. In order to evaluate possible abnormalities, 18 dynamic parameters were chosen, dividing the act of swallowing into three phases: oral, pharyngeal and oesophageal phases. The following dynamic radiological findings were considered: veil motility in phonation, leakage, drooling, salivation and presence of residues in the oral cavity, pharyngeal residues, penetration, aspiration, altered motility of the upper oesophageal sphincter, efficacy of primary peristaltic contractions, oesophageal clearance capacity, reflux, oesophagitis and motility of the lower oesophageal sphincter. RESULTS: The VFG study was well tolerated in all patients. Dysfunctions of oesophageal motility were common and included abnormal motility of UES (12.7%) and LES (76.4%), inadequate primary peristalsis (52.7%), abnormal secondary peristalsis (29.1%) and non-peristaltic contractions (40%). A defective oesophageal clearance was observed in 69.4% of patients. Moreover, most patients presented signs of oesophageal reflux (63.6%), oesophagitis (81.8%) and hiatal hernia (80%). Pharyngeal abnormalities were less common and involved up to 50% of patients. Oesophageal dysfunction and defective clearance were associated with dcSSc and pulmonary involvement. CONCLUSIONS: The VFG study is a useful technique for the morphological and functional evaluation of swallowing in SSc patients.
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Cinerradiografía/métodos , Trastornos de Deglución , Fluoroscopía/métodos , Esclerodermia Sistémica , Trastornos de Deglución/diagnóstico por imagen , Trastornos de Deglución/etiología , Femenino , Reflujo Gastroesofágico , Humanos , Masculino , Manometría , Persona de Mediana Edad , Peristaltismo , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico por imagenRESUMEN
The incidence of multifocal (MF) and multicentric (MC) breast cancer has a wide variation among different clinical studies, mostly due to the lack of a standardized classification and definition of these two separate entities. The optimal surgical treatment for multiple ipsilateral breast cancer remains a long debated subject. Multifocal and multicentric breast cancer is usually considered a relative contraindication for breast conserving therapy (BCT). In this narrative review we analyzed differences between MC and MF early breast cancer, the role of magnetic resonance imaging (MRI) in detection of multiple breast lesions, and its role in the surgical approach. We evaluate data from the literature about feasibility of breast conservative surgery and loco-regional treatment modalities. Recent studies brought evidence that treatment of patients with MC/MF breast cancer with BCT plus radiotherapy and adjuvant systemic therapy can have low-rates for in-breast recurrence. Prospective studies are needed to confirm these findings.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Imagen por Resonancia Magnética , Mastectomía , Quimioterapia Adyuvante/métodos , Medicina Basada en la Evidencia , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Mastectomía/métodos , Mastectomía Segmentaria , Estadificación de Neoplasias , Radioterapia Adyuvante/métodos , Resultado del TratamientoRESUMEN
Management of patient with concomitant severe coronary and carotid artery disease is challenging. The combined or staged surgical revascularization is burdened by a high risk of morbidity and mortality. Carotid artery stenting (CAS) has been recently introduced as an alternative revascularization approach. We describe a case of simultaneous hybrid revascularization by CAS followed by immediate coronary artery bypass graft in a patient with a severe coronary artery disease and bilateral carotid artery stenosis.
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Angioplastia de Balón/instrumentación , Estenosis Carotídea/terapia , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/cirugía , Stents , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Background: Hormone receptor-positive tumors are unlikely to exhibit a complete pathological tumor response. The association of CDK 4/6 inhibitor plus hormone therapy has changed this perspective. Case presentation: In this study, we retrospectively reviewed the charts of patients with a diagnosis of luminal A/B advanced/metastatic tumors treated with a CDK 4/6 inhibitor-based therapy. In this part of the study, we present clinical and ultrasound evaluation. Eight female patients were considered eligible for the study aims. Three complete and five partial responses were reported, including a clinical tumor response of 50% or more in five out of nine assessed lesions (55%). All patients showed a response on ultrasound. The mean lesion size measured by ultrasound was 27.1 ± 15.02 mm (range, 6-47 mm) at the baseline; 16.08 ± 14.6 mm (range, 0-40 mm) after 4 months (T1); and 11.7 ± 12.9 mm (range, 0-30 mm) at the 6 months follow-up (T2). Two patients underwent surgery. The radiological complete response found confirmation in a pathological complete response, while the partial response matched a moderate residual disease. Conclusion: The evaluation of breast cancer by ultrasound is basically informative of response and may be an easy and practical tool to monitor advanced tumors, especially in advanced/unfit patients who are reluctant to invasive exams.
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A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10), is involved in several metabolic and inflammatory pathways. We speculated that ADAM10 plays a modulatory role in adipose tissue inflammation and metabolism. To this end, we studied adipose tissue-specific ADAM10 knock-out mice (aKO). While young, regular chow diet-fed aKO mice showed increased insulin sensitivity, following prolonged (33 weeks) high-fat diet (HFD) exposure, aKO mice developed obesity and insulin resistance. Compared to controls, aKO mice showed less inflammatory adipokine profile despite the significant increase in adiposity. In brown adipose tissue, aKO mice on HFD had changes in CD8+ T cell populations indicating a lesser inflammatory pattern. Following HFD, both aKO and control littermates demonstrated decreased adipose tissue pro-inflammatory macrophages, and increased anti-inflammatory accumulation, without differences between the genotypes. Collectively, our observations indicate that selective deletion of ADAM10 in adipocytes results in a mitigated inflammatory response, leading to increased insulin sensitivity in young mice fed with regular diet. This state of insulin sensitivity, following prolonged HFD, facilitates energy storage resulting in increased fat accumulation which ultimately leads to the development of a phenotype of obesity and insulin resistance. In conclusion, the data indicate that ADAM10 has a modulatory effect of inflammation and whole-body energy metabolism.
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Proteína ADAM10 , Tejido Adiposo , Dieta Alta en Grasa , Ratones Noqueados , Animales , Masculino , Ratones , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Dieta Alta en Grasa/efectos adversos , Inflamación/metabolismo , Resistencia a la Insulina , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Obesidad/metabolismo , Obesidad/etiología , FenotipoRESUMEN
SARS-CoV-2 vaccination is strongly recommended, particularly for fragile patients such as those undergoing active oncological treatments. It is crucial to conduct post-marketing surveillance in this patient population. In our study, we conducted a retrospective analysis of real-world data, including 136 patients who received SARS-CoV-2 vaccines and were undergoing anticancer treatments between March 1st and June 30th, 2021. All patients received mRNA vaccines, namely Pfizer-BioNTech's COMIRNATY (BNT162b2 mRNA) and Moderna's mRNA-1273 COVID-19 vaccines. We collected blood samples from the patients one week to 10 days before and after vaccine administration to assess full blood count with white cell differentials. Additionally, we monitored serology titers to detect any previous SARS-CoV-2 infection before hospital admission and tracked changes over time. Our findings revealed a significant occurrence of leukopenia following both the first and second vaccine doses among patients receiving chemotherapy and chemo-immunotherapy. Importantly, this effect was independent of demographic factors such as sex, age, and Body Mass Index. In the chemo-immunotherapy treated group, we observed that concomitant immune-mediated diseases were significantly associated with leukopenia following the second vaccine dose. Notably, in healthy subjects, transient neutropenia was recognized as an adverse event following vaccination. The observed lymphocytopenia during SARS-CoV-2 infection, combined with the impact on leukocyte counts observed in our study, underscores the need for larger post-marketing surveillance studies. Despite a treatment delay occurring in 6.6% of patients, the administration of mRNA vaccines did not have a significant impact on the treatment schedule in our series. These findings from a real-world setting provide valuable insights and suggest avenues for further prospective studies to explore potential complex interactions specific to this patient population.
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Thermogenic fat differentiation and function can be promoted through multiple pathways, resulting in a common cell phenotype characterized by the expression of Uncoupling Protein-1 and the ability to dissipate energy, but local and systemic stimuli are necessary to promote adequate thermogenic fat vascularization, which is a precondition for the transport of substrate and the dissipation of heat. Angiopoietin-2 is an important driver of vascularization, and its transcription is in part promoted by estrogen signaling. In this study we demonstrate that adipose tissue-specific knock out of Angiopoietin-2 causes a female-specific reduced thermogenic fat differentiation and function, resulting in obesity and impaired glucose tolerance with end-organ features consistent with metabolic syndrome. In humans, angiopoietin-2 levels are higher in females than in males, and are inversely correlated with adiposity and age more strongly in pre-menopause when compared to post-menopause. Collectively, these data indicate a novel and important role for estrogen-mediated Angiopoietin-2 adipose tissue production in the protection against calorie overload in females, and potentially in the development of postmenopausal weight gain.
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Tejido Adiposo Pardo , Síndrome Metabólico , Adipocitos/metabolismo , Tejido Adiposo Pardo/metabolismo , Angiopoyetina 2/genética , Angiopoyetina 2/metabolismo , Estrógenos/metabolismo , Femenino , Humanos , Masculino , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Proteína Desacopladora 1/metabolismoRESUMEN
We developed a (three-dimensional) 3D scaffold, we named HY-FIB, incorporating a force-transmission band of braided hyaluronate embedded in a cell localizing fibrin hydrogel and poly-lactic-co-glycolic acid (PLGA) nanocarriers as transient components for growth factor controlled delivery. The tenogenic supporting capacity of HY-FIB on human-Bone Marrow Mesenchymal Stem Cells (hBM-MSCs) was explored under static conditions and under bioreactor-induced cyclic strain conditions. HY-FIB elasticity enabled to deliver a mean shear stress of 0.09 Pa for 4 h/day. Tendon and cytokine marker expression by hBM-MSCs were studied. Results: hBM-MSCs embedded in HY-FIB and subjected to mechanical stimulation, resulted in a typical tenogenic phenotype, as indicated by type 1 Collagen fiber immunofluorescence. RT-qPCR showed an increase of type 1 Collagen, scleraxis, and decorin gene expression (3-fold, 1600-fold, and 3-fold, respectively, at day 11) in dynamic conditions. Cells also showed pro-inflammatory (IL-6, TNF, IL-12A, IL-1ß) and anti-inflammatory (IL-10, TGF-ß1) cytokine gene expressions, with a significant increase of anti-inflammatory cytokines in dynamic conditions (IL-10 and TGF-ß1 300-fold and 4-fold, respectively, at day 11). Mechanical signaling, conveyed by HY-FIB to hBM-MSCs, promoted tenogenic gene markers expression and a pro-repair cytokine balance. The results provide strong evidence in support of the HY-FIB system and its interaction with cells and its potential for use as a predictive in vitro model.
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Biomarcadores/metabolismo , Citocinas/metabolismo , Fibrina/química , Ácido Hialurónico/química , Células Madre Mesenquimatosas/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Tendones/metabolismo , Andamios del Tejido/química , Adulto , Reactores Biológicos , Células Cultivadas , Microambiente Celular , Colágeno/metabolismo , Portadores de Fármacos/química , Regulación de la Expresión Génica , Factor 5 de Diferenciación de Crecimiento/metabolismo , Humanos , Nanopartículas/químicaRESUMEN
Neuroblastoma, one of the most common extracranial solid malignancies in children, is often localized in the adrenal glands (49%). The staging system for prognostic purpose was one of the first points of disagreement, which led to the International Neuroblastoma Staging System (INSS) of 1986, revised in 1989, which relies on surgical staging. The limit of this classification was the different surgical resection, also done at interval times from diagnosis. To overcome this difficulty, a new staging system was made based on preoperative imaging by the International Neuroblastoma Risk Group (INRG) in 2009. This new staging system uses 20 Image-Defined Risk Factors (IDRFs) across multiple organ systems. The scope of this IDRFs is to predict surgical outcomes and, in addition with clinical data, to provide risk stratification. The INRG Staging System (INRGSS) relies on Imaging-Defined Risk Factors (IDRFs) that are determined before surgery or other therapy. With the application of the INRGSS the radiologist's role in staging children with neuroblastoma increased. The review provides an overview of the INRGSS and the IDRFs in adrenal neuroblastoma.
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Wharton's jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiative potential, an immuno-privileged status and easy access for collection, which raise no legal or ethical issues. WJ-MSCs exhibit several features of embryonic stem cells, both in the phenotypic and genetic aspects, with only a few differences, such as a shorter doubling time and a more extensive ex vivo expansion capacity. WJ-MSCs have immunomodulatory properties, involving both innate and adaptive immune responses. This review focuses on the role of WJ-MSCs in the management of graft-versus-host disease (GvHD), a life-threatening complication of the allogenic transplantation of hematopoietic stem cells. Different studies documented the beneficial effect of the infusion of WJ-MSCs, even when not fully HLA identical, in patients with severe GvHD, refractory to standard treatment. Finally, we summarized current ongoing clinical trials with WJ-MSCs and their potential in regenerative medicine.
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The prevalence of reactive nasal inflammatory conditions, for example, allergic rhinitis and chronic rhinosinusitis, is steadily increasing in parallel with significant environmental changes worldwide. Allergens and as yet undefined environmental agents may trigger these conditions via the involvement of host intrinsic factors, including the innate and adaptive immune system, the nasal epithelium, and the nasal nervous system. The critical role of the nasal microbiota in coordinating these components has emerged in recent studies documenting a significant association between microbial composition and the onset and progression of allergic or nonallergic inflammation. It is now clear that the local microbiota is a major player in the development of the mucosa-associated lymphoid tissue and in the regulation of such adaptive responses as IgA production and the function of effector and regulatory T cells. Microbial components also play a major role in the regulation of epithelial barrier functions, including mucus production and the control of paracellular transport across tight junctions. Bacterial components, including lipopolysaccharide, have also been shown to induce or amplify neuroinflammatory responses by engaging specific nociceptors. Finally, bacterial products may promote tissue remodeling processes, including nasal polyp formation, by interacting with formyl peptide receptors and inducing the expression of angiogenic factors and matrix-degrading enzymes.
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Microbiota , Rinitis/metabolismo , Rinitis/microbiología , Transducción de Señal , Animales , Biodiversidad , Interacciones Huésped-Patógeno/inmunología , Humanos , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Inmunomodulación , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Mucosa Nasal/microbiología , Mucosa Nasal/patología , Neuroinmunomodulación , Rinitis/inmunologíaRESUMEN
BACKGROUND: Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD). Expression of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease. METHODS: We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS). RESULTS: The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS > HS > COPD). TOS levels were significantly lower in HnS than in smoke-associated subjects (COPD and HS), while TEAC levels were progressively lower according (HnS > HS > COPD). In COPD patients, SIRT1 activity, but not protein levels, correlated significantly with both lung function parameters (FEV1/FVC and FEV1) and TEAC. CONCLUSIONS: These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD.
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Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/patología , Sirtuina 1/metabolismo , Anciano , Antioxidantes/metabolismo , Estudios de Casos y Controles , Femenino , Volumen Espiratorio Forzado , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , FumarRESUMEN
AIMS: We aimed to assess whether the RenalGuard™ System is effective in preventing acute kidney injury (AKI) following transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Forty-eight consecutive patients with chronic kidney disease (CKD) scheduled for TAVI were assigned to: 1) hydration with sodium bicarbonate solution (Control group), or 2) hydration with RenalGuard Therapy (RenalGuard group). Hypotension was defined as periprocedural mean blood pressure <55 mmHg. The primary endpoint was the occurrence of AKI (i.e., an increase of ≥0.3 mg/dL in the serum creatinine concentration at seven days). AKI occurred in 10/26 (38.5%) patients in the Control group and in 1/22 (4.5%) patients in the RenalGuard group (p=0.005, odds ratio [OR] 0.076, 95% confidence interval [CI]: 0.009-0.66). RenalGuard Therapy protected against AKI (OR 0.71, 95% CI: 0.07-0.775, p=0.026), whereas post-procedural hypotension (OR 3.88, 95% CI: 1.06-14.24, p=0.040), and contrast media volume (OR 3.65, 95% CI: 1.15-5.75, p=0.043) increased the risk of AKI. CONCLUSIONS: This non-randomised pilot study suggests that RenalGuard Therapy may be effective in preventing AKI in CKD patients undergoing TAVI.
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Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/cirugía , Estenosis de la Válvula Aórtica/terapia , Implantación de Prótesis de Válvulas Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Lesión Renal Aguda/fisiopatología , Cateterismo Cardíaco/métodos , Creatinina/sangre , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Humanos , Masculino , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Resultado del TratamientoRESUMEN
In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population. The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs. Their manufacture requires the same pharmaceutical framework as for conventional drugs and this means that industrial, large-scale manufacturing process has to be adapted to the peculiar characteristics of cell-containing products. Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product.