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1.
Science ; 385(6715): 1327-1331, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39298597

RESUMO

Quantum state teleportation is commonly used in designs for large-scale quantum computers. Using Quantinuum's H2 trapped-ion quantum processor, we demonstrate fault-tolerant state teleportation circuits for a quantum error correction code-specifically the Steane code. The circuits use up to 30 qubits at the physical level and employ real-time quantum error correction. We conducted experiments on several variations of logical teleportation circuits using both transversal gates and lattice surgery. We measured the logical process fidelity to be 0.975 ± 0.002 for the transversal teleportation implementation and 0.851 ± 0.009 for the lattice surgery teleportation implementation as well as 0.989 ± 0.002 for an implementation of Knill-style quantum error correction.

2.
Cell Mol Life Sci ; 78(9): 4259-4282, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33595669

RESUMO

Misuse and overuse of antibiotics have contributed in the last decades to a phenomenon known as antibiotic resistance which is currently considered one of the principal threats to global public health by the World Health Organization. The aim to find alternative drugs has been demonstrated as a real challenge. Thanks to their biodiversity, insects represent the largest class of organisms in the animal kingdom. The humoral immune response includes the production of antimicrobial peptides (AMPs) that are released into the insect hemolymph after microbial infection. In this review, we have focused on insect immune responses, particularly on AMP characteristics, their mechanism of action and applications, especially in the biomedical field. Furthermore, we discuss the Toll, Imd, and JAK-STAT pathways that activate genes encoding for the expression of AMPs. Moreover, we focused on strategies to improve insect peptides stability against proteolytic susceptibility such as D-amino acid substitutions, N-terminus modification, cyclization and dimerization.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Proteínas de Insetos/metabolismo , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/metabolismo , Biofilmes/efeitos dos fármacos , Defensinas/química , Defensinas/metabolismo , Defensinas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/fisiologia , Proteínas de Insetos/química , Proteínas de Insetos/farmacologia , Transdução de Sinais
3.
Mult Scler Relat Disord ; 35: 176-181, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31394405

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory, neurodegenerative disorder. Many studies are investigating the potential role of body fluid biomarkers as prognostic factors for early identification of patients presenting with clinical isolated syndrome (CIS) at high risk for conversion to MS or to recognize RRMS patients at high risk for progression. OBJECTIVES: To evaluate the correlation between levels of BAFF, chitinase 3-like 1 (CHI3L1), sCD163, Osteopontin (OPN), both on serum and cerebral spinal fluid (CSF), and the disease activity and progression. We also want to explore a possible relationship between serological and CSF biomarker's levels. PATIENTS AND METHODS: We enrolled 82 patients between June 2014 and June 2016. Seventy-one received a diagnosis of demyelinating disease of CNS (46 RRMS and 25 CIS), while 11 were affected by other neurological diseases. All patients underwent a neural axis MRI, lumbar puncture and blood samples. Levels of BAFF, CHI3L1, sCD163, OPN on serum and CSF were analyzed by Luminex xMAP system, with a kit 11-plex ad hoc. RESULTS: The CSF CHI3L1, sCD163 and OPN levels were significantly higher in MS patients than in controls. We did not find significant differences in serum CHI3L1, sCD163 and OPN levels, nor CSF or serum BAFF levels between patient and control groups. We found significantly higher CSF level of sCD163 and CHI3L1 in all patients' subgroups compared with controls, while OPN was higher in CIS and RR subgroups. We did not find significant differences for serum and CSF levels of all the markers between patients with or without clinical or radiological disease activity. CSF sCD163 and CHI3L1 levels was significant higher in CIS patients who converted to MS (p < 0.05). Using ROC curve analysis, CSF sCD163 resulted the best predictive factor. CSF CHI3L1 and OPN levels resulted useful independent predictors too. Combined ROCs of those three analytes demonstrated a better predictive value, with sCD163 and CHI3L1 resulting as the best combination. CONCLUSIONS: CSF sCD163 CHI3L1 and OPN levels were higher in MS patients whereas serum CHI3L1, sCD163 and OPN levels did not show differences compared with controls. This finding confirms the high CSF specificity with regards to the analysis of processes, inflammatory and non-inflammatory, that occur within the CNS.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Doenças Desmielinizantes/diagnóstico , Esclerose Múltipla/diagnóstico , Adulto , Antígenos CD/sangue , Antígenos CD/líquido cefalorraquidiano , Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos de Diferenciação Mielomonocítica/líquido cefalorraquidiano , Fator Ativador de Células B/sangue , Fator Ativador de Células B/líquido cefalorraquidiano , Biomarcadores/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Proteína 1 Semelhante à Quitinase-3/líquido cefalorraquidiano , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/líquido cefalorraquidiano , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Osteopontina/sangue , Osteopontina/líquido cefalorraquidiano , Prognóstico , Receptores de Superfície Celular/sangue
5.
Hum Exp Toxicol ; 37(10): 1069-1079, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29405765

RESUMO

The widespread industrial application of nanomaterials (NMs) has dramatically increased the likelihood of environmental and occupational exposure of humans to such xenobiotics. This issue, together with the increasing public health interest in understanding the effects of chemicals on endocrine system, encouraged to investigate the disruptive potential of NMs on the endocrine function. Therefore, the aim of this study was to evaluate the effects of palladium nanoparticles (Pd-NPs) on the female reproductive system of Wistar rats, intravenously exposed to different doses (0.12, 1.2, and 12 µg/kg), through the assessment of possible quantitative changes in the serum concentrations of several sex hormones. Our results demonstrated that the highest exposure doses significantly reduced the estradiol and testosterone concentrations, while increased the luteinizing hormone levels in treated animals compared to controls. Such alterations are indicative for an abnormal reproductive axis function. However, further investigations are needed to clarify the role of the different NP physicochemical properties in determining such effects, and possible underlining molecular mechanisms, as well as their relevance for the development of diseases in the female reproductive system. Overall, this may be helpful to define accurate risk assessment and management strategies to protect the health of the general and occupational populations exposed to Pd-NPs.


Assuntos
Disruptores Endócrinos/farmacologia , Genitália Feminina/efeitos dos fármacos , Hormônios Esteroides Gonadais/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Nanopartículas Metálicas , Paládio/farmacologia , Reprodução/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Genitália Feminina/fisiologia , Ratos Wistar , Medição de Risco
6.
Hum Exp Toxicol ; 37(3): 309-320, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28387145

RESUMO

Recently, palladium nanoparticles (PdNPs) have been increasingly used in many industrial sectors, and this has led to a significant release of nano-sized palladium particles into the environment. However, despite the increase in occupational and general population exposure, information on the potential adverse effects of these PdNPs is still limited and their impact on the immune system constitutes a major health concern. Therefore, the aim of this study was to investigate the potential adverse effects induced by subchronic intravenous administration of PdNPs on the immune system of female Wistar rats by evaluating alterations in Interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-10, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), Interferon (INF)-γ, and Tumor Necrosis Factor (TNF)-α serum levels. Exposed and control animals were randomly divided into five groups (0, 0.012, 0.12, 1.2, and 12 µg PdNPs per kg body weight) which were treated with repeated intravenous injections of vehicle or PdNPs (on day 1, 30, and 60). Subchronic exposure to PdNPs induced a decreasing trend in serum levels in most of the cytokines investigated, with the highest concentration (12 µg/kg) determining significant inhibitory effects. Overall, these results showed that PdNPs are able to alter cytokine serum levels in subchronically treated Wistar rats, suggesting a possible impact of these xenobiotics on the immune system after long-term exposures.


Assuntos
Citocinas/sangue , Sistema Imunitário/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Paládio/toxicidade , Animais , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Ratos Wistar , Fatores de Tempo , Testes de Toxicidade Subcrônica
7.
Toxicol In Vitro ; 42: 191-199, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28473196

RESUMO

Palladium nanoparticles have been increasingly used in catalytic processes, wastewater treatment, electronics, and biomedicine. However, recent evidence proved that these nanoparticles are able to induce adverse effects both in in vitro and in vivo models. Nevertheless, molecular mechanisms underlying the toxic effects are still poorly understood. Therefore, this study aimed to investigate the potential toxicological mechanisms of palladium nanoparticles assessing their effects on normal diploid rat fibroblast and lung carcinoma human epithelial cell lines. Several endpoints such as cell growth, cell cycle progression, DNA damage, induction of apoptosis, reactive oxygen species production and expression of cell cycle regulatory proteins were evaluated. Results showed that palladium nanoparticles inhibited cell growth in a dose- and time-dependent manner in both cell lines, although with a more evident action on fibroblasts. Interestingly, inhibition of cell growth was not associated with the induction of apoptosis. Cell cycle progression was arrested in the G0/G1 phase and DNA damage was evident in both cell lines even if only a slight increase in the intracellular reactive oxygen species levels was detected. These findings provide valuable insight into understanding the molecular mechanisms responsible of palladium nanoparticles toxicity whose identification is essential to define an adequate risk assessment process.


Assuntos
Células Epiteliais/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Pulmão/citologia , Nanopartículas Metálicas/toxicidade , Paládio/toxicidade , Células A549 , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Células Epiteliais/metabolismo , Fibroblastos/metabolismo , Humanos , Ratos , Espécies Reativas de Oxigênio/metabolismo
8.
Colorectal Dis ; 18(12): O436-O444, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27649390

RESUMO

AIM: The pathogenesis of cryptoglandular anal fistula (AF) is still under debate. Tissue inflammation could play a primary role. The pathological process of epithelial mesenchymal transition (EMT) might be involved but has never been investigated. METHOD: In a prospective pilot study, 12 patients with an AF had a fistulectomy. The excised track was divided into proximal (intrasphincteric) and distal (extrasphincteric) parts which were subjected to standard histopathological examination. The cytokines IL-8 and IL-1beta were analysed as markers of inflammation, while EMT was evaluated by expression of TGF-beta, Vimentin, Zeb-1, Snail and E-cadherin. The mRNA and protein expression of these molecules was investigated by real-time PCR (RT-PCR), Western blot analysis and immunohistochemistry and was compared with that of the normal adjacent tissue. RESULTS: Chronic inflammation and granulation tissue and a stratified epithelium were evident on standard histopathological examination. The cytokine IL-8 was more expressed in the proximal than the distal part of the track (fold increase 4.34 vs 3.60), while the reverse was found for IL-1beta (fold increase 1.33 vs 2.01); both were more intensely expressed compared with the normal anal mucosa. EMT was demonstrated, in both proximal and distal parts of the track, with an increase of TGF-beta, Vimentin, Zeb-1 and Snail and a mean decrease of E-cadherin. Western blot analysis and immunohistochemistry confirmed the protein expression. CONCLUSION: The study suggests that chronic inflammation is present in cryptoglandular fistulas. The inflammatory pattern might be different in the proximal than in the distal part of the fistula track. The cytokines IL-1beta and IL-8 could play a possible role in fistula formation. The study demonstrates for the first time the potential importance of EMT in the pathogenesis of cryptoglandular AF.


Assuntos
Mediadores da Inflamação/análise , Fístula Retal/patologia , Adulto , Canal Anal/química , Canal Anal/patologia , Canal Anal/cirurgia , Antígenos CD , Western Blotting , Caderinas/análise , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Interleucina-1beta/análise , Interleucina-8/análise , Masculino , Projetos Piloto , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Fístula Retal/metabolismo , Fístula Retal/cirurgia , Fatores de Transcrição da Família Snail/análise , Fator de Crescimento Transformador beta/análise , Vimentina/análise , Homeobox 1 de Ligação a E-box em Dedo de Zinco/análise
9.
Soft Matter ; 11(28): 5719-26, 2015 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-26083581

RESUMO

SW480 and SW620 colon carcinoma cell lines derive from primary tumour and lymph-node metastasis of the same patient, respectively. For this reason, these cells represent an ideal system to analyse phenotypic variations associated with the metastatic process. In this study we analysed SW480 and SW620 cytoskeleton remodelling by measuring the cells' mechanics and morphological properties using different microscopic techniques. We observed that different specialized functions of cells, i.e. the capacity to metastasize of elongated cells inside the primary tumour and the ability to intravasate and resist shear forces of the stream of cells derived from lymph node metastasis, are reflected in their mechanical properties. We demonstrated that, together with stiffness and adhesion between the AFM tip and the cell surface, cell shape, actin organization and surface roughness are strictly related and are finely modulated by colorectal cancer cells to better accomplish their specific tasks in cancer growth and invasion.


Assuntos
Neoplasias Colorretais/ultraestrutura , Citoesqueleto/ultraestrutura , Linfonodos/ultraestrutura , Invasividade Neoplásica/ultraestrutura , Linhagem Celular Tumoral , Forma Celular , Neoplasias Colorretais/química , Neoplasias Colorretais/patologia , Citoesqueleto/química , Humanos , Linfonodos/química , Metástase Linfática/patologia , Metástase Linfática/ultraestrutura , Fenômenos Mecânicos , Microscopia de Força Atômica , Invasividade Neoplásica/patologia , Propriedades de Superfície
10.
Rev. esp. geriatr. gerontol. (Ed. impr.) ; 48(6): 290-296, nov.-dic. 2013.
Artigo em Espanhol | IBECS | ID: ibc-116827

RESUMO

Los cambios demográficos y la realidad económica de los últimos años han condicionado una reorientación de las políticas sanitarias priorizando la atención a la cronicidad. Dada la concentración de costes en la atención hospitalaria de los pacientes con enfermedades crónicas, la reducción de las hospitalizaciones ha pasado a ser un objetivo preferente. Mientras tanto, constatamos que entre el objetivo paradigmático de abordaje eminentemente comunitario propuesto para estos pacientes y la realidad asistencial vigente, queda aún un largo recorrido que valdría la pena realizar paso a paso. Con la evidencia científica de la que disponemos en el momento actual: ¿Es razonable dar por sentado que hay un nivel adecuado de ingresos o que reducir el número de ingresos es necesariamente mejor para los pacientes? ¿Es posible definir operativamente y con la suficiente fiabilidad cuáles de los ingresos hospitalarios son evitables? ¿Es perjudicial para un paciente y para el sistema que una persona con enfermedades crónicas con altas necesidades de atención ingrese en un hospital? ¿No serán los ingresos hospitalarios evitables y los reingresos, indicadores de fragmentación de los sistemas de salud? Ante esta situación, un abordaje razonable requiere en primer lugar de un análisis crítico de las distintas realidades asistenciales (microsistemas) y de la revisión sistemática de la evidencia científica –rompiendo algunos tópicos si es preciso–. En segundo lugar es indispensable llevar este conocimiento a la práctica asistencial, con la necesidad absoluta de conciliar el «qué» y el «cómo», la visión individual con la visión poblacional, la enfermedad única con la multimorbilidad y, finalmente, el abordaje clínico con la planificación sanitaria (AU)


Demographic changes and the economic situation of the recent years have conditioned a turning point in health policies, which have decided to progressively prioritize chronicity care programs. Given that hospital costs were concentrated in attention to patients with chronic diseases, reduction on admissions is now a priority target.Meanwhile, we state that among the obviously community handling paradigmatic aim for those patients and the current care situation, there is a long way to do that should be done gradually. According to the current scientific evidence: Is it sensible to assume that there is a proper level of admissions or is it better for the patients to reduce the number of admissions? Is it possible to operationally and reliably define which hospital admissions are avoidable? Is it harmful to a patient and to the health care system to admit a patient with multiple chronic disease? Maybe are hospital admissions are avoidable and readmissions are indicators of a fragmented health care system?Given that situation, a reasonable approach requires firstly a critical analysis of the various realities of care (microsystems) and a systematic review of the scientific evidence-breaking, and rejecting some topics if necessary. Secondly, we should bring all this knowledge to clinical practice, conciliating «what» and the know-how, individual and population view, sole disease and multimorbidity, and finally clinical approach and health planning (AU)


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/epidemiologia , Doença Crônica/prevenção & controle , Doença Crônica/economia , Assistência Hospitalar , Custos e Análise de Custo/métodos , Custos Diretos de Serviços/tendências , /tendências , Doença Crônica/reabilitação , Doença Crônica/terapia , 17140 , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/organização & administração , Medicina Baseada em Evidências/normas , Estudos de Coortes
11.
Rev Esp Geriatr Gerontol ; 48(6): 290-6, 2013.
Artigo em Espanhol | MEDLINE | ID: mdl-24075488

RESUMO

Demographic changes and the economic situation of the recent years have conditioned a turning point in health policies, which have decided to progressively prioritize chronicity care programs. Given that hospital costs were concentrated in attention to patients with chronic diseases, reduction on admissions is now a priority target. Meanwhile, we state that among the obviously community handling paradigmatic aim for those patients and the current care situation, there is a long way to do that should be done gradually. According to the current scientific evidence: Is it sensible to assume that there is a proper level of admissions or is it better for the patients to reduce the number of admissions? Is it possible to operationally and reliably define which hospital admissions are avoidable? Is it harmful to a patient and to the health care system to admit a patient with multiple chronic disease? Maybe are hospital admissions are avoidable and readmissions are indicators of a fragmented health care system? Given that situation, a reasonable approach requires firstly a critical analysis of the various realities of care (microsystems) and a systematic review of the scientific evidence-breaking, and rejecting some topics if necessary. Secondly, we should bring all this knowledge to clinical practice, conciliating «what¼ and the know-how, individual and population view, sole disease and multimorbidity, and finally clinical approach and health planning.


Assuntos
Admissão do Paciente/estatística & dados numéricos , Idoso , Humanos
12.
Mar Pollut Bull ; 76(1-2): 365-9, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23998853

RESUMO

Total mercury (Hg tot) and methyl mercury (MeHg) were quantified in several specimens of Dicentrarchus labrax and Sparus aurata from the east basin of the Orbetello lagoon, central Italy. The size of each specimen was recorded to estimate body burdens (BBs); =Hg tot and MeHg were measured in fillets of both species. Hg tot and MeHg in S. aurata ranged between 0.355-1.58 and 0.341-1.53 µg/g wet weight (ww), respectively; in D. labrax, their ranges were 0.284-2.54 and 0.214-2.35 µg/g ww. Approximately 90% of the concentrations measured exceeded Hg tot regulatory maximum level of 0.5 µg/g ww; however, exceedance rate was different in the two species studied. No correlations between specimen size and Hg tot or MeHg BBs were detected in this study.


Assuntos
Monitoramento Ambiental , Peixes/metabolismo , Mercúrio/metabolismo , Compostos de Metilmercúrio/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Itália , Mercúrio/análise , Compostos de Metilmercúrio/análise , Água do Mar/química , Poluentes Químicos da Água/análise
13.
J Lab Clin Med ; 133(5): 461-8, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10235129

RESUMO

This study was designed to assess Q-T interval dispersion as a marker of electrical instability in subjects with anxiety. Recent observations have shown that the presence of anxiety symptoms increases the risk of sudden death. The Kawachi anxiety questionnaire identified 29 subjects (male/female ratio 13:16) who scored 0, 22 subjects (male/female ratio 14:8) who scored 1, and 37 subjects (male/female ratio 13:24) who scored 2 or more. In all subjects we measured electrocardiographic interlead QT dispersion and autonomic function through spectral analysis of R-R interval and blood pressure variabilities and left ventricular mass. Compared with subjects who scored 0, those reporting 2 or more symptoms showed increased heart rate-corrected QT dispersion (54.9+/-1.7 ms vs. 34.9+/-3.2 ms, P<.001), sympathetic modulation (normal logarithm low-frequency power/high-frequency power 0.59+/-0.1 vs. 0.12+/-0.04, P<.05), and left ventricular mass (120.7+/-3.5 g/m2 vs. 97.9+/-2.8 g/m2, P<.001). Probably because it augments sympathetic activity, anxiety causes left ventricular mass to increase and, like hypertension, increases heart rate-corrected Q-T interval dispersion. The consequent electrical instability could be the substrate responsible for inducing fatal ventricular arrhythmias.


Assuntos
Ansiedade/fisiopatologia , Sistema Nervoso Autônomo/fisiologia , Eletrocardiografia , Arritmias Cardíacas/etiologia , Pressão Sanguínea , Morte Súbita Cardíaca/etiologia , Feminino , Frequência Cardíaca , Ventrículos do Coração/fisiopatologia , Humanos , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Inquéritos e Questionários
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