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Background: The consensus in scientific literature is that each child undergoes a unique linguistic development path, albeit with shared developmental stages. Some children excel or lag behind their peers in language skills. Consequently, a key challenge in language acquisition research is pinpointing factors influencing individual differences in language development. Methods: We observed children longitudinally from 3 to 24 months of life to explore early predictors of vocabulary size. Based on the productive vocabulary size of children at 24 months, 30 children met our sample selection criteria: 10 late talkers and 10 early talkers, and we compared them with 10 typical talkers. We evaluated interactive behaviors at 3, 6, 9 and 12 months, considering vocal production, gaze at mother's face, and gestural production during mother-child interactions, and we considered mothers' report of children's actions and gestures and receptive-vocabulary size at 15 and 18 months. Results: Results indicated early precursors of language outcome at 24 months identifiable as early as 3 months in vocal productions, 6 months for gaze at mother's face and 12 months for gestural productions. Conclusions: Our research highlights both theoretical and practical implications. Theoretically, identifying the early indicators of belonging to the group of late or early talkers underscores the significant role of this developmental period for future studies. On a practical note, our findings emphasize the crucial need for early investigations to identify predictors of vocabulary development before the typical age at which lexical delay is identified.
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Desarrollo del Lenguaje , Humanos , Lactante , Femenino , Masculino , Preescolar , Vocabulario , Relaciones Madre-Hijo , Habla/fisiología , Estudios Longitudinales , GestosRESUMEN
Doxorubicin (DOX) is a highly effective chemotherapeutic agent whose clinical use is hindered by the onset of cardiotoxic effects, resulting in reduced ejection fraction within the first year from treatment initiation. Recently it has been demonstrated that DOX accumulates within mitochondria, leading to disruption of metabolic processes and energetic imbalance. We previously described that phosphoinositide 3-kinase γ (PI3Kγ) contributes to DOX-induced cardiotoxicity, causing autophagy inhibition and accumulation of damaged mitochondria. Here we intend to describe the maladaptive metabolic rewiring occurring in DOX-treated hearts and the contribution of PI3Kγ signalling to this process. Metabolomic analysis of DOX-treated WT hearts revealed an accumulation of TCA cycle metabolites due to a cycle slowdown, with reduced levels of pyruvate, unchanged abundance of lactate and increased Acetyl-CoA production. Moreover, the activity of glycolytic enzymes was upregulated, and fatty acid oxidation downregulated, after DOX, indicative of increased glucose oxidation. In agreement, oxygen consumption was increased in after pyruvate supplementation, with the formation of cytotoxic ROS rather than energy production. These metabolic changes were fully prevented in KD hearts. Interestingly, they failed to increase glucose oxidation in response to DOX even with autophagy inhibition, indicating that PI3Kγ likely controls the fuel preference after DOX through an autophagy-independent mechanism. In vitro experiments showed that inhibition of PI3Kγ inhibits pyruvate dehydrogenase (PDH), the key enzyme of Randle cycle regulating the switch from fatty acids to glucose usage, while decreasing DOX-induced mobilization of GLUT-4-carrying vesicles to the plasma membrane and limiting the ensuing glucose uptake. These results demonstrate that PI3Kγ promotes a maladaptive metabolic rewiring in DOX-treated hearts, through a two-pronged mechanism controlling PDH activation and GLUT-4-mediated glucose uptake.
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Cardiotoxicidad , Doxorrubicina , Metabolismo Energético , Ácidos Grasos , Glucosa , Oxidación-Reducción , Animales , Doxorrubicina/toxicidad , Glucosa/metabolismo , Ácidos Grasos/metabolismo , Metabolismo Energético/efectos de los fármacos , Fosfatidilinositol 3-Quinasa Clase Ib/metabolismo , Glucólisis/efectos de los fármacos , Autofagia/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Ciclo del Ácido Cítrico/efectos de los fármacos , Ratones Endogámicos C57BL , Cardiopatías/inducido químicamente , Cardiopatías/metabolismo , Cardiopatías/patología , Cardiopatías/prevención & control , Cardiopatías/fisiopatología , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/patología , Mitocondrias Cardíacas/enzimología , Ratones Noqueados , Modelos Animales de Enfermedad , Especies Reactivas de Oxígeno/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Antibióticos Antineoplásicos/toxicidad , Antibióticos Antineoplásicos/efectos adversosRESUMEN
OBJECTIVE: To describe the frequency and types of congenital anomalies and associated risk factors in Brazilian women with type 2 diabetes. METHODS: In this retrospective cohort study between 2005 and 2021, we included all pregnant participants with type 2 diabetes from the two major public hospitals in southern Brazil. We collected data from the electronic hospital records. Congenital anomalies were classified by the 10th revised International Classification of Diseases, Q chapter, enhanced by the EUROCAT registry classification, and categorized by type and gravity. We used multiple Poisson regression with robust estimates to estimate risks. RESULTS: Among 648 participants, we excluded 19, and 62 were lost to follow-up; therefore, we included 567 participants. Overt diabetes arose in 191 participants (33.7%, 95% CI 30.0% - 38.0%). Less than 20% of the participants supplemented folate. Congenital anomalies occurred in 78 neonates (13.8%, CI 11.0 - 16.9%), 73 babies (93.6%) presented major anomalies, and 20 (10.5%) cases occurred in participants with overt diabetes. Cardiac anomalies were the most frequent (43 isolated and 12 combined). Pre-eclampsia was associated with an increased risk in the analyses including all women (adjusted RR 1.87 (95% CI 1.23-2.85), p = 0.003), but not in analyses including only women with an HbA1c measured up to the 14th gestational age. HbA1c, either measured at any time in pregnancy (adjusted RR 1.21 (95% CI 1.10-1.33), p < 0.001) or up to the first 14 weeks (adjusted RR 1.22, 95% CI 1.10-1.35, p < 0.001) was the only sustained risk factor. Risk factors such as maternal age, obesity, diabetes diagnosis, or use of antidiabetic medications were not associated with congenital anomalies. CONCLUSION: We found a high frequency of congenital anomalies associated with poor maternal glycemic control and revealed an almost universal lack of preconception care. An urgent call to action is mandatory for the reversal of this gray scenario.
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Purpose: To study plasma levels, efficacy and tolerability of imatinib in a patient affected by metastatic GIST treated with oral Imatinib and undergoing hemodialysis. Patients and methods: The patient suffered from metastatic GIST to the liver having a mutation of exon 9 of KIT. He was on hemodialysis and received first-line treatment with imatinib 400 mg/day. Results: The overall mean plasma level of imatinib was 1875,4 ng/ml pre-dialysis, 1553,0 ng/ml post-dialysis and 1998,1 ng/ml post-24h. In red blood cells the overall mean level of imatinib was 619,5 ng/ml pre-dialysis, 484,9 ng/ml post-dialysis and 663,1 ng/ml post-24h. The plasma level of nor-imatinib/imatinib was 16,2% pre-dialysis, 15,6% post-dialysis and 16,4% post-24h. Comparing our findings regarding levels of imatinib in plasma and RBC, we found a statistically significant difference between pre-dialysis and post-dialysis (respectively p < 0,001 and p = 0,002), post-dialysis and post-24h (both p < 0,001), pre-dialysis and post-24h (respectively p = 0.035 and p = 0,042). Ultimately, regarding nor-imatinib/imatinib in plasma, we did not find any statistically significant difference between pre-dialysis and post-dialysis (p = 0,091), post-dialysis and post-24h (p = 0,091), pre-dialysis and post-24h (p = 0.903). Currently the patient is receiving oral imatinib 400 mg/day with radiological evidence of response. Conclusion: In this case, hemodialysis did not affect significantly imatinib plasma levels. The statistically significant difference between pre- and post-dialysis can be explained by the fact that dialysis may likely contribute to a small portion of the normal metabolism of imatinib. The evaluation of imatinib levels in RBC and of its main metabolite in plasma also suggests that hemodialysis did not affect other aspects of the elimination of the drug.
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Down syndrome is one of the most common genetic diseases, generally associated with an increased probability of congenital heart diseases. This increased risk contributes to escalated levels of morbidity and mortality. In this study, we sought to analyze nationwide data of pediatric and adult patients with Down syndrome and congenital heart disease over a 15-year period. Data obtained from the hospital discharge form between 2001 and 2016 of patients diagnosed with Down syndrome in Italy and at least one congenital heart disease were included. Information on 12362 admissions of 6527 patients were included. Age at first admission was 6.2 ± 12.8 years and was a predictor of mortality (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). 3923 (60.1%) patients underwent only one admission, while 2604 (39.9%) underwent multiple (> 1) admissions. There were 5846 (47.3%) admissions for cardiac related symptoms. Multiple admissions (SHR: 3.13; 95% CI: 2.99, 3.27; P < 0.01) and cardiac admissions (SHR: 2.00; 95% CI: 1.92, 2.09; P < 0.01) were associated with an increased risk of additional potential readmissions. There was an increased risk of mortality for patients who had cardiac admissions (HR = 1.45, 95% CI: 1.08-1.94, p = 0.012), and for those who underwent at least 1 cardiac surgical procedure (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). CONCLUSIONS: A younger age at first admission is a predictor for mortality in patients with Down syndrome and congenital heart disease. If patients undergo more than one admission, the risk of further readmissions increases. There is a pivotal role for heart disease in influencing the hospitalization rate and subsequent mortality. WHAT IS KNOWN: ⢠Down syndrome individuals often face an increased risk of congenital heart diseases. ⢠Congenital heart diseases contribute significantly to morbidity and mortality in Down syndrome patients. WHAT IS NEW: ⢠This study analyzes nationwide data covering a 15-year period of pediatric and adult patients in Italy with Down syndrome and congenital heart disease. ⢠It identifies a younger age at first admission as a predictor for mortality in these patients, emphasizing the criticality of early intervention. ⢠Demonstrates a correlation between multiple admissions, particularly those related to cardiac issues, and an increased risk of further readmissions, providing insights into the ongoing healthcare needs of these individuals.
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Síndrome de Down , Cardiopatías Congénitas , Hospitalización , Humanos , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/mortalidad , Femenino , Masculino , Italia/epidemiología , Hospitalización/estadística & datos numéricos , Niño , Adolescente , Preescolar , Lactante , Adulto , Adulto Joven , Estudios Retrospectivos , Recién Nacido , Readmisión del Paciente/estadística & datos numéricos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The present study aims to explore the forms of psychological parental control that are interconnected with dysfunctional emotional states (i.e., anxiety and depression), and how these internalizing problems may manifest as distorted behaviors (i.e., vigorexic and orthorexic behaviors) during adolescence. Participants included 403 Italian adolescent athletes (231 boys and 172 girls) aged 14 to 18 years. The participants completed self-report questionnaires designed to assess psychological parental control oriented towards dependence and achievement, anxiety and depression, and vigorexia and orthorexia. The results highlight how both forms of psychological parental control predict anxiety and depression. Furthermore, anxiety was found to be linked to both vigorexic and orthorexic behaviors, while depression is connected only to vigorexia. This study delves into the intricacies of parental influence on adolescents, revealing that both dependency-oriented and success-oriented psychological parental control have notable implications for the mental well-being of adolescents. The findings underscore the interconnectedness of these factors, demonstrating that anxiety can set off a chain reaction, leading to engagement in vigorexic and orthorexic behaviors. On the other hand, depression appears to be uniquely associated with vigorexia. These insights contribute to our understanding of the complex dynamics between parental control and adolescent mental health. The implications of this research extend to both theoretical frameworks and practical interventions, emphasizing the need for a nuanced approach to supporting adolescents in navigating these challenges.
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Background: Given the growing interest in studying the role of choline and phosphocholine in the development and progression of tumor pathology, in this study we describe the development and validation of a fast and robust method for the simultaneous analysis of choline and phosphocholine in human plasma. Methods: Choline and phosphocholine quantification in human plasma was obtained using a hydrophilic interaction liquid chromatography-tandem mass spectrometry technique. Assay performance parameters were evaluated using EMA guidelines. Results: Calibration curve ranged from 0.60 to 38.40 µmol/L (R2 = 0.999) and 0.08-5.43 µmol/L (R2 = 0.998) for choline and phosphocholine, respectively. The Limit Of Detection of the method was 0.06 µmol/L for choline and 0.04 µmol/L for phosphocholine. The coefficient of variation range for intra-assay precision is 2.2-4.1 % (choline) and 3.2-15 % (phosphocholine), and the inter-assay precision range is < 1-6.5 % (choline) and 6.2-20 % (phosphocholine). The accuracy of the method was below the ±20 % benchmarks at all the metabolites concentration levels. In-house plasma pool of apparently healthy adults was tested, and a mean concentration of 15.97 µmol/L for Choline and 0.34 µmol/L for Phosphocholine was quantified. Conclusions: The developed method shows good reliability in quantifying Choline and Phosphocholine in human plasma for clinical purposes.
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The COVID-19 pandemic caused many enduring changes in the everyday life of families, with negative effects on parents' and children's wellbeing. However, there is a lack of studies in the literature exploring the emotional reactions and coping strategies of both mothers and children of different ages. Furthermore, most studies used only self-reports. This study aimed to identify the emotions and coping strategies of children, adolescents and their mothers and to verify the association between maternal and child wellbeing. A mixed-method design using interviews and questionnaires was applied to collect information on wellbeing (emotional reactions, behavioral/emotional problems) and coping strategies of both mothers (n = 65; M age = 42.17; SD = 4.40; M age = 41.63; SD = 4.48), and their children (n = 35, 8-10 year; n = 30, 11-13 year) during the second wave of the pandemic (December 2020). No differences between the groups emerged concerning the emotional reactions reported. In contrast, mothers and children of different ages reported different self-regulation and other-regulation strategies. Moreover, maternal strategies had different effects on children's wellbeing. The integration of qualitative and quantitative results was informative to understand how families adapted to the radical changes of everyday life related to the pandemic. The implications for developing interventions in such similar stressful situations to promote family wellbeing are discussed.
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Objective: To evaluate whether there is an increase in vaccination rates of patients with diabetes mellitus who received guidance to update their vaccination schedules for influenza, hepatitis B, pneumonia, and tetanus. Methodology: A randomized controlled trial was conducted between December 2018 and November 2020. The sample consisted of 139 patients from the endocrinology service outpatient clinic of Santa Maria University Hospital was randomized into an intervention group (n = 68) and a control group (n = 71). The intervention consisted of a phone call to update the vaccination schedule for the diseases evaluated. Results: The mean age of the subjects was 59.17 ± 12.91 years and 62.6% were female. No age differences were observed between genders and randomization groups (p = 0.548, p = 0.791) and groups were homogeneous (p = 0.173, p = 0.443). The intervention group showed a significant increase in vaccination rates after the intervention. For influenza, 79.4-89.7% (p = 0.016); hepatitis B, 29.4-48.5% (p = 0.002); tetanus, 51.5-72.1% (p = 0.007); and pneumonia, 22.1-29.4% (p = 0.049). No significant increase was observed in control group. Conclusion: The orientation to update the vaccination schedule through telephone contact was effective in increasing vaccination rates for influenza, hepatitis B, pneumonia, and tetanus. Trial registry: RBR-92z99d2 https://ensaiosclinicos.gov.br/rg/RBR-92z99d2.
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OBJECTIVES: The aim of this study was to elucidate predictors of death and reintervention after mitral valve (MV) surgery in children. METHODS: A single-centre retrospective study was performed enrolling 142 patients younger than 18 years who underwent primary index surgical mitral repair or replacement at Bambino Gesù Children's Hospital in Rome from July 1982 to April 2020. Patients with complete, transitional or partial atrioventricular septal defect and patients with single ventricle physiology were excluded. Patients were stratified according to the age group: group 1 (<1 year old), group 2 (1-5 years old) and group 3 (>5 years old). The composite primary outcome was freedom from death or transplant. The secondary outcome was freedom from redo MV surgery. RESULTS: Transplant-free survival was 89% at 5 years and 88% at 10 years. Stratified by age, group 1 had poorer outcome in comparison with other groups (log-rank test P = 0.105). Both univariate and multivariate analyses showed that age <1 year was a significant risk factor for death or transplant (P = 0.044). Age <1 year was associated with increased risk of reoperation (aHR = 3.38, P = 0.009), while the presence of genetic syndrome (aHR = 0.22) and preoperative EF% (aHR = 0.97) were protective factors for reoperation. CONCLUSIONS: The overall survival and freedom from reoperation in children undergoing MV surgery still need improvements. Younger age was a significant risk factor for death and reintervention both after repair and replacement of the MV. In particular, infants and neonates have a three-fold risk for death compared to children.
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Procedimientos Quirúrgicos Cardíacos , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Niño , Preescolar , Estudios de Seguimiento , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Lactante , Recién Nacido , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Reoperación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A simple not solvent and time consuming Fe3O4@MIL-100(Fe), synthesized in the presence of a small amount of magnetite (Fe3O4) nanoparticles (27.3 wt%), is here presented and discussed. Layer-by-layer alone (20 shell), and combined layer-by-layer (5 shell)/reflux or /hydrothermal synthetic procedures were compared. The last approach (Fe3O4@MIL-100_H sample) is suitable (i) to obtain rounded-shaped nanoparticles (200-400 nm diameter) of magnetite core and MIL-100(Fe) shell; (ii) to reduce the solvent and time consumption (the layer-by-layer procedure is applied only 5 times); (iii) to give the highest MIL-100(Fe) amount in the composite (72.7 vs. 18.5 wt% in the layer-by-layer alone); (iv) to obtain a high surface area of 3546 m2 g-1. The MIL-100(Fe) sample was also synthesized and both materials were tested for the absorption of Ofloxacin antibiotic (OFL). Langmuir model well describes OFL adsorption on Fe3O4@MIL-100_H, indicating an even higher adsorption capacity (218 ± 7 mg g-1) with respect to MIL-100 (123 ± 5 mg g-1). Chemisorption regulates the kinetic process on both the composite materials. Fe3O4@MIL-100_H performance was then verified for OFL removal at µg per liter in tap and river waters, and compared with MIL-100. Its relevant and higher adsorption efficiency and the magnetic behavior make it an excellent candidate for environmental depollution.
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Contingent negative variation (CNV) is an informative electrophysiological measure of pain anticipation showing higher amplitudes when highly painful stimulation is expected while presenting lower amplitudes when low painful stimulation is expected. Two groups of participants were recruited: one group expected and received an electrical stimulation of different intensities while being alone in the room (i.e. without social context), while a second group performed the same experiment with an observer in the room (i.e. with social context). Lower pain ratings and slower reaction times were observed in the group with social context and these results were accompanied in this group by a lower amplitude in the early component of the CNV as well as a lower amplitude of the later component of the wave. These results show that CNV can be considered a precise measure of central elaboration of pain anticipation explaining both its perceptual and motor components.
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Variación Contingente Negativa , Motivación , Estimulación Eléctrica , Humanos , Dolor , Tiempo de ReacciónRESUMEN
In order to render potent, but toxic antibiotics more selective, we have explored a novel conjugation strategy that includes drug accumulation followed by infection-triggered release of the drug. Bacterial targeting was achieved using a modified fragment of the human antimicrobial peptide ubiquicidin, as demonstrated by fluorophore-tagged variants. To limit the release of the effector colistin only to infection-related situations, we introduced a linker that was cleaved by neutrophil elastase (NE), an enzyme secreted by neutrophil granulocytes at infection sites. The linker carried an optimized sequence of amino acids that was required to assure sufficient cleavage efficiency. The antibacterial activity of five regioisomeric conjugates prepared by total synthesis was masked, but was released upon exposure to recombinant NE when the linker was attached to amino acids at the 1- or the 3-position of colistin. A proof-of-concept was achieved in co-cultures of primary human neutrophils and Escherichia coli that induced the secretion of NE, the release of free colistin, and an antibacterial efficacy that was equal to that of free colistin.
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Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Colistina/farmacología , Escherichia coli/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Células Cultivadas , Técnicas de Cocultivo , Colistina/síntesis química , Colistina/química , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de Sensibilidad Microbiana , Conformación MolecularRESUMEN
Two different zinc-based metal-organic frameworks (MOFs) were investigated to remove one of the most used fluoroquinolone antibiotic, Ofloxacin (OFL), from polluted water. The most common zeolitic imidazolate framework-8 (ZIF-8) and the green Zn(II) and benzene-1,3,5-tri-carboxylate (Zn3(BTC)2) were prepared through a facile synthetic route and characterized by means of Fourier-Transform Infrared (FT-IR) Spectroscopy, X-ray Powder Diffraction (XRPD), and Scanning Electron Microscopy (SEM) analyses. The two MOFs were compared in terms of both adsorption and kinetic aspects under real conditions (tap water, natural pH). Results showed that OFL was adsorbed in remarkable amounts, 95 ± 10 and 25.3 ± 0.8 mg g-1 on ZIF-8 and Zn3(BTC)2, respectively, following different mechanisms. Specifically, a Langmuir model well described the ZIF-8 profile, while for Zn3(BTC)2, cooperative adsorption occurred. Moreover the kinetic results were quite different, pseudo-second-order and sigmoidal, respectively. The suitability of ZIF-8 and Zn3(BTC)2 as adsorbent phases for water depollution was tested on tap water samples spiked with OFL 10 µg L-1. The obtained removal efficiencies, of 88% for ZIF-8 and 72% for Zn3(BTC)2, make these materials promising candidates for removing fluoroquinolone antibiotics (FQs) from polluted waters, notwithstanding their limited reusability in tap water, as demonstrated by in-depth characterization of the two MOFs after usage.
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Estructuras Metalorgánicas , Contaminantes Químicos del Agua , Zeolitas , Adsorción , Ofloxacino , Espectroscopía Infrarroja por Transformada de Fourier , Contaminantes Químicos del Agua/análisis , ZincRESUMEN
Tumor immunosuppression is a major cause for treatment failure and disease relapse, both in solid tumors and leukemia. Local hypoxia is among the conditions that cause immunosuppression, acting at least in part through the upregulation of extracellular adenosine levels, which potently suppress T cell responses and skew macrophages towards an M2 phenotype. Hence, there is intense investigation to identify drugs that target this axis. By using the TCL1 adoptive transfer CLL mouse model, we show that adenosine production and signaling are upregulated in the hypoxic lymphoid niches, where intense colonization of leukemic cells occurs. This leads to a progressive remodeling of the immune system towards tolerance, with expansion of T regulatory cells (Tregs), loss of CD8+ T cell cytotoxicity and differentiation of murine macrophages towards the patrolling (M2-like) subset. In vivo administration of SCH58261, an inhibitor the A2A adenosine receptor, re-awakens T cell responses, while limiting Tregs expansion, and re-polarizes monocytes towards the inflammatory (M1-like) phenotype. These results show for the first time the in vivo contribution of adenosine signaling to immune tolerance in CLL, and the translational implication of drugs interrupting this pathway. Although the effects of SCH58261 on leukemic cells are limited, interfering with adenosine signaling may represent an appealing strategy for combination-based therapeutic approaches.
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Leucemia Linfocítica Crónica de Células B , Animales , Modelos Animales de Enfermedad , Tolerancia Inmunológica , Terapia de Inmunosupresión , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Ratones , Receptores Purinérgicos P1RESUMEN
Expectations and motor reactions related to pain are mainly acquired through personal experiences. Contingent negative variation (CNV) has been shown to be an informative electrophysiological measure of this pain anticipation. Expectations can also arise while observing others in painful conditions. However, it still remains unclear what are the neural correlates of this phenomenon and how the observation of others in pain can subsequently change our personal pain perception as well as our motor reaction to pain. Using CNV as a measure of expectation, this study aims to assess whether expectations formed through observation change the observer's own experience of pain and reaction to pain. A new cooperative task was designed where one participant, the model, received an electrical stimulation while another, the observer, watched the experiment and both were asked to stop the stimulation as fast as possible. Crucially, in a successive session, participants inverted their roles so that models became observers and vice versa. CNV was recorded in both participants simultaneously by means of two synchronized electroencephalograms. Results showed that CNV area did not differ between models and observers and reaction times were significantly faster in observers compared to models. Moreover, observers' pain perception was correlated to models' pain perception as well as to observers' empathy scores. These data show how expectations, perceptions as well as reactions related to pain are crucially affected not only by observation but by personal attitudes toward others and all these changes can be clearly described through CNV.
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Anticipación Psicológica/fisiología , Variación Contingente Negativa/fisiología , Empatía/fisiología , Percepción del Dolor/fisiología , Percepción Social , Adulto , Estimulación Eléctrica , Electroencefalografía , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Pursuing the search for a new class of structurally simple mimics of antimicrobial peptides, we optimized a short, cheap and high-yielding synthesis of mono-charged amphiphilic α-hydrazido acid derivatives. The most active derivatives furnished MICs that are among the best values reported in literature for synthetic amphiphilic membranolytic compounds. They exhibited a broad-spectrum in vitro activity against a variety of Gram-positive and Gram-negative bacteria, including two multidrug-resistant strains. In spite of the minimal cationic charge, the best compounds demonstrated to be selective toward bacterial cell membranes over mammalian cell membranes. The relationship between either the antibacterial or the hemolytic activity and the overall lipophilicity furnished an easy way to individuate the best dimensional range for the hydrophobic portions. The importance of a non-disrupted amphiphilicity was also demonstrated. Considering the bioactivity profile and the ease of synthesis, these chemically and proteolitically stable hydrochlorides are suitable for development of a new class of wide-spectrum antibiotics.
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Antibacterianos/síntesis química , Antibacterianos/farmacología , Membrana Celular/efectos de los fármacos , Diseño de Fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Hidrazinas/química , Cationes/química , Interacciones Hidrofóbicas e Hidrofílicas , Pruebas de Sensibilidad Microbiana , Relación Estructura-ActividadRESUMEN
Leukemia develops as the result of intrinsic features of the transformed cell, such as gene mutations and derived oncogenic signaling, and extrinsic factors, such as a tumor-friendly, immunosuppressed microenvironment, predominantly in the lymph nodes and the bone marrow. There, high extracellular levels of nucleotides, mainly NAD+ and ATP, are catabolized by different ectonucleotidases, which can be divided in two families according to substrate specificity: on one side those that metabolize NAD+, including CD38, CD157, and CD203a; on the other, those that convert ATP, namely CD39 (and other ENTPDases) and CD73. They generate products that modulate intracellular calcium levels and that activate purinergic receptors. They can also converge on adenosine generation with profound effects, both on leukemic cells, enhancing chemoresistance and homing, and on non-malignant immune cells, polarizing them toward tolerance. This review will first provide an overview of ectonucleotidases expression within the immune system, in physiological and pathological conditions. We will then focus on different hematological malignancies, discussing their role as disease markers and possibly pathogenic agents. Lastly, we will describe current efforts aimed at therapeutic targeting of this family of enzymes.
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Adenosina Trifosfato/metabolismo , Neoplasias Hematológicas/enzimología , NAD/metabolismo , Nucleotidasas/fisiología , 5'-Nucleotidasa/química , 5'-Nucleotidasa/fisiología , ADP-Ribosil Ciclasa/química , ADP-Ribosil Ciclasa/fisiología , ADP-Ribosil Ciclasa 1/química , ADP-Ribosil Ciclasa 1/fisiología , Animales , Antígenos CD/química , Antígenos CD/fisiología , Apirasa/química , Apirasa/fisiología , Proteínas Ligadas a GPI/química , Proteínas Ligadas a GPI/fisiología , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Nucleotidasas/antagonistas & inhibidoresRESUMEN
INTRODUCTION: Changing drug dosage is common in clinical practice. Recent evidence showed that psychological factors may affect the therapeutic outcome. The aim of this study is to test whether verbal communication about drug dosage changes motor performance and fatigue in Parkinson's Disease (PD) patients. METHODS: We performed clinical (Unified PD Rating Scale), motor (number of finger flexions and perceived fatigue), and electrophysiological measurements (readiness potential, RP) in PD patients during medication-off and medication-on conditions in three groups. The first group got a full dose of l-dopa and was told it was a full dose. The second group got half dose and was told it was half dose. The third group got half dose, but it was told it was a full standard dose. RESULTS: We found that overt half dose was less effective than the full dose for clinical improvement, motor performance, and readiness potential. However, if half dose was given along with verbal instructions that it was a full dose, clinical improvement, motor performance and readiness potential were not significantly different from the full dose. CONCLUSIONS: Our findings indicate that verbal communication about dose reduction is as effective as the 50% dose reduction itself, demonstrating that deceptive information about the dose may have an important impact on the therapeutic outcome. Moreover, the supplementary motor area, source of the RP, seems to be involved in this psychological effect.