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The purpose of this study was to assess the main clinical predictors and microbiological features of ventilator-associated pneumonia (VAP) in the Intensive Care Unit (ICU) environment. This work is a retrospective analysis over one year from September 2010 to September 2011. Patients' risk factors, causes of admission, comorbidities and respiratory specimens collected in six Italian ICUs were reviewed. Incidence and case fatality rate of VAP were evaluated. After stratification for VAP development, univariate and multivariate analyses were performed to assess the impact of patients' conditions on the onset of this infection. A total of 1,647 ICU patients (pts) were considered. Overall, 115 patients (6.9 %) experienced at least one episode of VAP. The incidence rate for VAP was 5.82/1,000 pts-days, with a case fatality rate of 44.3 %. Multivariate analysis showed that admission for neurological disorders (aIRR 4.12, CI 1.24-13.68, p = 0.02) and emergency referral to ICU from other hospitals (aIRR 2.11, CI 1.03-4.31, p = 0.04) were associated with higher risk of VAP, whereas a tendency to a higher risk of infection was detected for admission due to respiratory disease, cardiac disease, trauma and for having obesity or renal failure. A total of 372 microbiological isolates from respiratory specimens were collected in VAP patients. The most common species were Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, showing high resistance rates to carbapenems. Neurological disorders and emergency referral at the admission into the ICU are significantly associated with the onset of VAP. A high incidence of multi-drug resistant Gram- species was detected in the respiratory specimens.
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Bactérias/classificação , Bactérias/isolamento & purificação , Candida/isolamento & purificação , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais , Humanos , Incidência , Unidades de Terapia Intensiva , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Pneumonia Associada à Ventilação Mecânica/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Xylella fastidiosa is a xylem-limited, Gram-negative phytopathogen responsible for economically relevant crop diseases. Its genome was thus sequenced in an effort to characterize and understand its metabolism and pathogenic mechanisms. However, the assignment of the proper functions to the identified open reading frames (ORFs) of this pathogen was impaired due to a lack of sequence similarity in the databases. In the present work, we used small-angle X-ray scattering and in silico modeling approaches to characterize and assign a function to a predicted LysR-type transcriptional regulator in the X. fastidiosa (XfLysRL) genome. XfLysRL was predicted to be a homologue of BenM, which is a transcriptional regulator involved in the degradation pathway of aromatic compounds. Further functional assays confirmed the structural prediction because we observed that XfLysRL interacts with benzoate and cis,cis-muconic acid (also known as 2E,4E-hexa-2,4-dienedioic acid; hereafter named muconate), both of which are co-factors of BenM. In addition, we showed that the XfLysRL protein is differentially expressed during the different stages of X. fastidiosa biofilm formation and planktonic cell growth, which indicates that its expression responds to a cellular signal that is likely related to the aromatic compound degradation pathway. The assignment of the proper function to a protein is a key step toward understanding the cellular metabolic pathways and pathogenic mechanisms. In the context of X. fastidiosa, the characterization of the predicted ORFs may lead to a better understanding of the cellular pathways that are linked to its bacterial pathogenicity.
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Proteínas de Bactérias/química , Modelos Moleculares , Espalhamento a Baixo Ângulo , Difração de Raios X/métodos , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Benzoatos/química , Benzoatos/metabolismo , Benzoatos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Simulação por Computador , Eletroforese em Gel de Poliacrilamida , Dados de Sequência Molecular , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Ácido Sórbico/análogos & derivados , Ácido Sórbico/química , Ácido Sórbico/metabolismo , Ácido Sórbico/farmacologia , Xylella/genética , Xylella/metabolismo , Xylella/fisiologiaRESUMO
Dynein light chains mediate the interaction between the cargo and the dynein motor complex during retrograde microtubule-mediated transport in eukaryotic cells. In this study, we expressed and characterized the recombinant human dynein light chain Rp3 and developed a modified variant harboring an N-terminal DNA-binding domain (Rp3-Db). Our approach aimed to explore the retrograde cell machinery based on dynein to enhance plasmid DNA (pDNA) traffic along the cytosol toward the nucleus. In the context of non-viral gene delivery, Rp3-Db is expected to simultaneously interact with DNA and dynein, thereby enabling a more rapid and efficient transport of the genetic material across the cytoplasm. We successfully purified recombinant Rp3 and obtained a low-resolution structural model using small-angle X-ray scattering. Additionally, we observed that Rp3 is a homodimer under reducing conditions and remains stable over a broad pH range. The ability of Rp3 to interact with the dynein intermediate chain in vitro was also observed, indicating that the recombinant Rp3 is correctly folded and functional. Finally, Rp3-Db was successfully expressed and purified and exhibited the ability to interact with pDNA and mediate the transfection of cultured HeLa cells. Rp3-Db was also capable of interacting in vitro with dynein intermediate chains, indicating that the addition of the N-terminal DNA-binding domain does not compromise its function. The transfection level observed for Rp3-Db is far superior than that reported for protamine and is comparable to that of the cationic lipid Lipofectamine™. This report presents an initial characterization of a non-viral delivery vector based on the dynein light chain Rp3 and demonstrates the potential use of modified human light chains as gene delivery vectors.
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Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Técnicas de Transferência de Genes , Transporte Biológico , Expressão Gênica , Células HeLa , Humanos , Modelos Moleculares , Plasmídeos , Conformação Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Electron backscatter diffraction (EBSD) was used in Conservation Science for characterization of ancient materials collected from works of art. The results demonstrate the feasibility of EBSD analysis on heterogeneous matrices as very small samples of paint layers collected from paintings. Two reference pigments were selected from those used by artists to investigate the relationship existing between EBSD pattern quality and properties of the investigated material (i.e., average atomic number, density, and Mohs hardness). The technique was also tested to investigate the pigment phases on two real samples collected from Romanino's Santa Giustina altarpiece, an oil on wood painting dated 1514 (Civic Museum, Padova, Italy). Results show for the first time the acquisition of EBSD patterns from painting samples mounted in resin, i.e., painting cross sections, opening a new powerful tool to elucidate the pigment phases avoiding large sampling on works of arts and to further study the complex mechanisms of pigment deterioration.
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Treatment of pregnant women with antiphospholipid syndrome (APS) should be set apart from that from thrombotic APS patients. Patients with a history of pregnancy morbidity but no vascular thrombosis are usually treated with a prophylactic dose of heparin plus low-dose aspirin; whereas, those with previous vascular thrombosis alone or associated with previous pregnancy morbidity, are commonly treated with a therapeutic dose of heparin generally combined with low-dose aspirin. However, in about 20% of pregnant APS women these regimens fail. In this context, we conducted a case-control study on a large multicentre cohort of conventionally treated pregnancies to verify whether specific laboratory profiles and/or clinical characteristics are predictive of unsuccessful pregnancy outcome during conventional treatments. Multivariate analysis showed that pregnancy failure during conventional therapies was independently associated with a history of both thrombosis and pregnancy morbidity, the presence of systemic lupus erythematosus (SLE) or other systemic autoimmune diseases and triple antiphospholipid antibody positivity. With the aim to discover the most effective and safe treatments in high-risk pregnant APS women a large-scale multicentre study focusing on the effect of treatments on pregnancy outcome in women with APS and further risk factors for pregnancy failure has been designed.
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Síndrome Antifosfolipídica/prevenção & controle , Complicações na Gravidez/prevenção & controle , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Fatores de Risco , Prevenção SecundáriaRESUMO
The diagnosis of catheter-related bloodstream infections (CRBSIs) in febrile patients with indwelling central venous catheters (CVCs) needs improvement. To diagnose CRBSIs more efficiently, we have developed a novel culture approach using the catheter tips removed from febrile patients. CVCs and blood cultures from 1,070 patients with only CVC-related infections were obtained over a period of 3 years (January 2009 to December 2011). The CVCs were evaluated by a semi-quantitative catheter culture method according to Maki's method and by our novel method, which is based on the use of the HB&L UROQUATTRO™ system (Alifax, Padova, Italy). Using our new method, 571 (571/1,070) of the infections were confirmed as CRBSIs. The remaining 487 patients had infections that were associated with hematologic malignancies, neutropenia, prior exposure to antibiotics, and a decreased CVC removal rate. Twelve samples were identified as false-positives. The percentage of patients with CRBSIs confirmed using the HB&L UROQUATTRO™ system was 53.36 % versus 34.95 % (p-value 0.004) using Maki's method (374/1,070 CVC Maki-positive samples). Our results indicate that our new culture method allows for an improved CRBSI diagnosis rate. A significant number of tip cultures (18.41 %) tested positive for CRBSIs using our system but were negative when tested using Maki's method. Moreover, the use of the HB&L UROQUATTRO™ system allowed us to significantly reduce diagnosis time; a negative CRBSI diagnosis could be made within 6 h and a positive diagnosis could be made within 22-28 h.
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Infecções Relacionadas a Cateter/diagnóstico , Cateteres Venosos Centrais/efeitos adversos , Técnicas Microbiológicas/métodos , Sepse/diagnóstico , Erros de Diagnóstico/estatística & dados numéricos , Humanos , Fatores de TempoRESUMO
In this paper, we propose an analytical methodology for attributing provenance to natural lapis lazuli pigments employed in works of art, and for distinguishing whether they are of natural or synthetic origin. A multitechnique characterization of lazurite and accessory phases in lapis lazuli stones from Afghan, Siberian and Chilean quarries, on the pigments obtained by their purification, and on synthetic ultramarine pigments was performed. According to the results obtained, infrared spectroscopy is not a suitable technique for distinguishing the provenance of lapis lazuli, but a particular absorbance band makes it relatively easy to determine whether it is of natural or synthetic origin. On the other hand, EDS elemental composition and XRD patterns show the presence of specific mineral phases associated with specific lapis lazuli sources, and can be used to distinguish the provenance of the stones as well as-albeit to a lesser extent-the corresponding purified blue pigments. In contrast, FEG-SEM observations clearly show different stone textures depending on their provenance, although these distinctive features do not persist in the corresponding pigments. PCA analyses of EDS data allow Afghan lapis lazuli stone to be distinguished from Chilean and Siberian ones, and can distinguish between the pigments resulting from their purification as well as synthetic blue ones. Although this methodology was developed using a limited number of samples, it was tested on lapis lazuli pigments collected from three paintings (from the fourteenth to sixteenth centuries) in order to perform a preliminary validation of the technique, and based on the results, the provenance of the blue pigments employed in those artworks is proposed. Finally, upon analytically monitoring the process of purifying lapis lazuli to obtain the corresponding pigments, it was found that ion-exchange reactions occur between the alkali modifiers of silicate/aluminosilicate phases and free carboxylic acids present in the doughy mixture of natural terpenes and ground stone, namely pastello. These reactions favor (i) the retention of silicate phases in the organic mixture and (ii) the selective extraction of lazurite due to the formation of Brønsted acidic sites [Al(OH)Si], which are responsible for its high hydrophilicity in comparison to the one of the other species present in the lapis lazuli stone.
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The OxyR oxidative stress transcriptional regulator is a DNA-binding protein that belongs to the LysR-type transcriptional regulators (LTTR) family. It has the ability to sense oxidative species inside the cell and to trigger the cell's response, activating the transcription of genes involved in scavenging oxidative species. In the present study, we have overexpressed, purified and characterized the predicted OxyR homologue (orf xf1273) of the phytopathogen Xylella fastidiosa. This bacterium is the causal agent of citrus variegated chlorosis (CVC) disease caused by the 9a5c strain, resulting in economic and social losses. The secondary structure of the recombinant protein was analyzed by circular dichroism. Gel filtration showed that XfoxyR is a dimer in solution. Gel shift assays indicated that it does bind to its own predicted promoter under in vitro conditions. However, considering our control experiment we cannot state that this interaction occurs in vivo. Functional complementation assays indicated that xfoxyR is able to restore the oxidative stress response in an oxyr knockout Escherichia coli strain. These results show that the predicted orfxf1273 codes for a transcriptional regulator, homologous to E. coli OxyR, involved in the oxidative stress response. This may be important for X. fastidiosa to overcome the defense mechanisms of its host during the infection and colonization processes.
Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Estresse Oxidativo , Proteínas Repressoras , Xylella/genética , Sequência de Bases , Dicroísmo Circular , Clonagem Molecular , Ensaio de Desvio de Mobilidade Eletroforética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Dados de Sequência Molecular , Plantas/metabolismo , Plantas/microbiologia , Regiões Promotoras Genéticas/fisiologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Homologia de Sequência , Transcrição Gênica/fisiologia , Xylella/metabolismo , Xylella/patogenicidadeRESUMO
OBJECTIVES: Current guidelines for the treatment of patients with obstetric antiphospholipid syndrome (APS) recommend low dose aspirin (LDA) and prophylactic doses of low molecular weight heparin (LMWH). Most clinicians use a fixed dosage of LMWH in pregnant APS women despite the fact that there are no clinical trials establishing that fixed doses are more efficacious than adjusted ones in preventing pregnancy complications. The efficacy and safety of adjusted single daily doses of LMWH (nadroparin) combined with LDA have thus been evaluated in 33 consecutive pregnancies in women with diagnosed obstetric APS. METHODS: LMWH doses were augmented as the pregnancies progressed and maternal/foetal weight increased. 70-80-90 U/Kg doses ranging between 3800 and 6650 U were administered daily during the first, second and third trimesters, respectively. LDA (100 mg/day) was also prescribed. RESULTS: Pregnancy outcome was successful in 97% of the patients studied, who delivered, between the 29th and 41st weeks of gestation (mean 37.4 ±2.1 SD), 32 infants with a mean birth weight of 3084 g ± 514 SD. One woman (3%) experienced a spontaneous abortion at the 8th week of gestation. CONCLUSIONS: The high live birth rate, the satisfactory mean gestational age and weight at birth and the absence of major pregnancy/neonatal-associated complications indicate that adjusted, once daily doses of LMWH together with LDA could be an efficacious treatment option for pregnant APS patients with no history of thrombosis.
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Aborto Espontâneo/prevenção & controle , Síndrome Antifosfolipídica/tratamento farmacológico , Aspirina/uso terapêutico , Fibrinolíticos/uso terapêutico , Nadroparina/uso terapêutico , Complicações Hematológicas na Gravidez/prevenção & controle , Adulto , Estudos de Coortes , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Idade Gestacional , Humanos , Nascido Vivo , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Estudos RetrospectivosRESUMO
The main object of this study is the treatment of polymeric (PVC, PC) surfaces with the aim of inducing enhanced superhydrophilic characteristics together with nanohardness features; this would allow polymeric surfaces to have longer durability and prevent the accumulation of dirt on the surface which could disable the proper use of these polymeric surfaces. Indeed plastic surfaces are difficult substrates to be covered effectively and functionalized, mainly due to their high sensitivity to heat treatments and irradiation in the UV-Vis range together with their inert behavior. Their functionalization is achieved through the deposition of ceramic coatings such as titania (TiO2), on the polymeric surfaces via PECVD (Plasma Enhanced Chemical Vapor Deposition) at low temperatures. Characterizations are carried out by contact angle analysis for the superhydrophilic characteristics, and by nanoindentation analysis for the tribological features. A cold PECVD discontinuous method allowed us to improve nanohardness, reaching a value of 1.39 GPa which is nearly ten times higher than that of the uncoated polymeric substrate, and seems a promising solution for improving uniformity of the coatings. Superhydrophilic behavior of the activated TiO2 surfaces showed contact angle values lower than 10 degrees.
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Currently, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus, represents the greatest global health threat. Most people infected by the virus present mild to moderate respiratory symptoms and recover with supportive treatments. However, certain susceptible hosts develop an acute respiratory distress syndrome (ARDS), associated with an inflammatory "cytokine storm", leading to lung damage. Despite the current availability of different COVID-19 vaccines, the new emerging SARS-CoV-2 genetic variants represent a major concern worldwide, due to their increased transmissibility and rapid spread. Indeed, it seems that some mutations or combinations of mutations might confer selective advantages to the virus, such as the ability to evade the host immune responses elicited by COVID-19 vaccines. Several therapeutic approaches have been investigated but, to date, a unique and fully effective therapeutic protocol has not yet been achieved. In addition, steroid-based therapies, aimed to reduce inflammation in patients with severe COVID-19 disease, may increase the risk of opportunistic infections, increasing the hospitalization time and mortality rate of these patients. Hence, there is an unmet need to develop more effective therapeutic options. Here, we discuss the potential use of natural immunomodulators such as Thymosin α1 (Tα1), all-trans retinoic acid (ATRA), and lactoferrin (LF), as adjunctive or preventive treatment of severe COVID-19 disease. These agents are considered to be multifunctional molecules because of their ability to enhance antiviral host immunity and restore the immune balance, depending on the host immune status. Furthermore, they are able to exert a broad-spectrum antimicrobial activity by means of direct interactions with cellular or molecular targets of pathogens or indirectly by increasing the host immune response. Thus, due to the aforementioned properties, these agents might have a great potential in a clinical setting, not only to counteract SARS-CoV-2 infection, but also to prevent opportunistic infections in critically ill COVID-19 patients.
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Tratamento Farmacológico da COVID-19 , COVID-19/imunologia , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Humanos , Fatores Imunológicos/farmacologia , Lactoferrina/imunologia , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Tretinoína/imunologia , Tretinoína/farmacologia , Tretinoína/uso terapêuticoRESUMO
The beamline for advanced dichroism of the Istituto Officina dei Materiali-Consiglio Nazionale delle Ricerche, operating at the Elettra synchrotron in Trieste (Italy), works in the extreme ultraviolet-soft x-ray photon energy range with selectable light polarization, high energy resolution, brilliance, and time resolution. The beamline offers a multi-technique approach for the investigation of the electronic, chemical, structural, magnetic, and dynamical properties of materials. Recently, one of the three end stations has been dedicated to experiments based on electron transfer processes at the solid/liquid interfaces and during photocatalytic or electrochemical reactions. Suitable cells to perform soft x-ray spectroscopy in the presence of liquids and reagent gases at ambient pressure were developed. Here, we present two types of static cells working in transmission or in fluorescence yield and an electrochemical flow cell that allows us to carry out cyclic voltammetry in situ and electrodeposition on a working electrode and to study chemical reactions under operando conditions. Examples of x-ray absorption spectroscopy measurements performed under ambient conditions and during electrochemical experiments in liquids are presented.
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BACKGROUND: There seems to be a clear correlation between antibodies against domain I (anti-DI) of ß2Glycoprotein I and severe clinical profiles in antiphospholipid syndrome (APS) patients. We investigated the clinical significance of anti-DI antibodies in a cohort of aPL carriers. METHODS: One hundred and five carriers persistently positive for IgG anti-ß2Glycoprotein 1 antibodies (a-ß2GPI) and/or IgG anticardiolipin (aCL) and/or lupus anticoagulants (LAC) were tested for the presence of anti-DI antibodies using the QUANTA Flash® Beta2GPI-Domain I chemiluminescence immunoassay. RESULTS: Anti-DI antibodies were detected in 44 aPL carriers (41.9%) and they were significantly associated to triple aPL positivity (LAC plus IgG a-ß2GPI plus IgG aCL antibodies). Isolated LAC and a-ß2GPI antibodies were significantly associated to anti-DI negative aPL carriers. During a 82.2â¯month mean follow-up, ten aPL carriers (9.5%) developed a first thrombotic event so becoming APS patients. Anti-DI antibodies, triple aPL positivity, thromboembolic risk factors and autoimmune disorders significantly prevailed in carriers becoming APS. Logistic regression analysis showed that anti-DI positivity was an independent risk factor for thrombosis. CONCLUSIONS: Anti-DI antibody positivity can be considered a new risk factor predictive of the first thrombotic event in aPL carriers, instead, negative anti-DI may be useful to identify low-risk aPL carriers.
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Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , beta 2-Glicoproteína I/análise , Adulto , Idoso , Anticorpos Antifosfolipídeos/análise , Estudos de Coortes , Feminino , Humanos , Imunoensaio , Modelos Logísticos , Luminescência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , beta 2-Glicoproteína I/imunologiaRESUMO
Even with good surveillance programmes, hospital-acquired infections (HAIs) are not always recognized and this may lead to an outbreak. In order to reduce this risk, we propose a model for prompt detection of HAIs, based on the use of a real-time epidemiological information system called VIGI@ct (bioMèrieux, Las Balmas, France) and on the rapid confirmation or exclusion of the genetic relationship among pathogens using fluorescent amplified length fragment polymorphism (f-AFLP) microbial fingerprinting. We present the results of one year's experience with the system, which identified a total of 306 suspicious HAIs. Of these, 281 (92%) were 'confirmed' by clinical evidence, 16 (5%) were considered to be simple colonization and the latter nine (3%) were archived as 'not answered' because of the absence of the physician's cooperation. There were seven suspected outbreaks; of these, f-AFLP analysis confirmed the clonal relationship among the isolates in four cases: outbreak 1 (four isolates of Pseudomonas aeruginosa), outbreak 2 (three Escherichia coli isolates), outbreak 6 (two Candida parapsilosis isolates) and outbreak 7 (30 ESbetaL-producing Klebsiella pneumoniae subsp. pneumoniae). Based on our results, we conclude that the combination of VIGI@ct and f-AFLP is useful in the rapid assessment of an outbreak due to Gram-positive or Gram-negative bacteria and yeasts.
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Técnicas de Tipagem Bacteriana/métodos , Infecção Hospitalar/diagnóstico , Surtos de Doenças/prevenção & controle , Controle de Infecções/métodos , Sistemas Computadorizados de Registros Médicos , Infecção Hospitalar/prevenção & controle , Genótipo , Humanos , Unidades de Terapia Intensiva , Itália , Polimorfismo de Fragmento de Restrição , Vigilância de Evento SentinelaRESUMO
Digital ulcers (DU) at the hands are one of the more frequent and severe complications in systemic sclerosis. Data on their prevalence and distribution in the different subsets of disease are variable in the literature. We studied the frequency of DU in a cohort of 333 scleroderma patients followed in the last 10 years in our Unit. DU have been recorded in 133 patients (39,9%), more frequently in males, in patients with cutaneous diffuse form of disease and in patients with anti-Scl70 ANA specificity. Complications of DU have been observed in 12,3% of cases. Surgery of the hands has been required in 8,7% of patients. The more effective treatment of DU are i.v. prostanoids, performed usually in day hospital, with high costs for the National Health Service. Recently the efficacy of bosentan, an oral receptor antagonist of endothelin, has been demonstrated, thus opening new perspectives in the treatment of DU in systemic sclerosis.
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Dedos/patologia , Esclerodermia Difusa/complicações , Úlcera Cutânea/etiologia , Adulto , Idoso , Autoanticorpos/imunologia , Bosentana , Centrômero/imunologia , Estudos de Coortes , DNA Topoisomerases Tipo I , Antagonistas dos Receptores de Endotelina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/imunologia , Prevalência , Prostaglandinas/uso terapêutico , Esclerodermia Difusa/imunologia , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/epidemiologia , Úlcera Cutânea/cirurgia , Sulfonamidas/uso terapêuticoRESUMO
OBJECTIVE: In order to investigate the potential role of hyperhomocysteinemia as an additional risk factor for thrombotic events, we studied its prevalence in patients with primary antiphospholipid syndrome (APS) and evaluated its association with different clinical features. METHODS: We enrolled 29 patients without any current evidence of underlying connective tissue disorder and fulfilling the Sapporo preliminary classification criteria for APS. RESULTS: Ten (34,4%) patients showed mild hyperhomocysteinemia (18,34 micromol/L +/- 2,04 DS). Nine had history of cerebrovascular disease, isolated (3 cases) or more often (6 cases) in association with other APS features. All patients, but one, showed multiple ischemic cerebral lesions. Seven of the 10 patients with hyperhomocysteinemia had multiple antiphospholipid antibody positivity and presented more frequently (6 cases) multi-site vascular involvement. CONCLUSIONS: The frequency of hyperhomocysteinemia in patients with primary APS is not negligible and appears to be associated with cerebral microangiopathic disease, multiple antiphospholipid antibody positivity and the simultaneous involvement of different vascular districts. For this reason and because hyperhomocysteinemia can be easily corrected with safe and relatively inexpensive therapeutic interventions, we advocate the measurement of homocysteinemia in every patient affected by APS and possibly in subjects with positive antiphospholipid antibody without a history of thrombosis.
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Síndrome Antifosfolipídica/epidemiologia , Hiper-Homocisteinemia/complicações , Adulto , Idoso , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/imunologia , Estudos de Coortes , Feminino , Humanos , Hiper-Homocisteinemia/epidemiologia , Hiper-Homocisteinemia/imunologia , Trombose Intracraniana/epidemiologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
OBJECTIVE: To study the incidence and the features of congenital heart block (CHB) in patients with undifferentiated connective tissue disease (UCTD) and primary Sjögren's syndrome (pSS). METHODS: We studied 81 pregnancies of 41 women attending the Outpatients' Clinic of the Rheumatology Unit of University Hospital of Padova from July 1989 to March 2004. Twenty five of these (61%) were affected with UCTD and 16 (39%) with pSS. Serologic inclusion criteria was anti-Ro/La positivity, assessed by counterimmunoelectrophoresis and ELISA. RESULTS: CHB was found in 2 out of the 46 (4.3%) pregnancies followed by our Staff and in 2 out of the 35 (5.7%) included in the retrospective part of the study. In 3 cases CHB was a 3rd degree block, causing pregnancy termination in 2. The only 2nd degree block was identified in one patient at the 22nd week of gestation and treated with dexamethasone and plasma-exchange. All of the women were positive to 52 kd and 60 kd Ro autoantibodies. CHB mothers had higher titer antibodies to 52 kd Ro protein than did the mothers with healthy infants (P = 0.026). Electrocardiographic abnormalities at birth were found in 3 out of 29 asymptomatic infants. One presented sinus bradycardia, the second abnormalities of ventricular repolarization, both regressed spontaneously, while the third ventricular extrasystoles which continue even now at 5 months. CONCLUSIONS: These results showed that in UCTD and pSS there is a higher incidence of CHB than that reported in Systemic Lupus Erythematosus. Electrocardiographic screening in all infants born to mothers with anti-Ro/La antibodies would seem an important measure to identify those with irreversible heart conduction abnormalities.
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Doenças do Tecido Conjuntivo/complicações , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/complicações , Complicações na Gravidez , Síndrome de Sjogren/complicações , Adulto , Feminino , Bloqueio Cardíaco/epidemiologia , Humanos , Gravidez , Prevalência , Estudos Prospectivos , Estudos RetrospectivosRESUMO
OBJECTIVE: This study aimed to evaluate the sensitivity and specificity of the anti-β2-glycoprotein I (GPI) antibodies for pregnancy morbidity in the antiphosoplipid syndrome (APS). METHODS: 335 women were recruited and on the basis of their clinical features were subdivided into 2 groups homogenous for number and age. The first (study) group contained the women whose pregnancy complications satisfied the classification criteria for APS. The second (control) group was made up of women with pregnancy complications not included in the classification criteria for APS. Anti-β2-GPI, anticardiolipin antibodies (aCL) and lupus anticoagulants (LA) were determined in all of these women. RESULTS: The only antiphospholipid antibodies occurring with a significant frequency (p=0,00) in the women with pregnancy criteria for APS were the IgG anti-β2-GPI and the IgG aCL present respectively in 23,92% and in 27,60% of the women. Its association was found to be significant (p=0,000). The distribution of the different levels of positivity of the IgG and IgM anti-β2-GPI in the patients of the study and control groups was not significantly different. The highest sensitivity for pregnancy complications was that of the IgG aCL and of the IgG anti-β2-GPI whose difference was not statistically significant. The comparison of the specificity of the IgG and IgM anti-β2-GPI with that of the IgG and IGM aCL was not statistically significant. CONCLUSIONS: The importance of determining the IgG anti-β2-GPI as part of routine laboratory testing of women with pregnancy complications typical of APS was confirmed. Together with IgG aCL these antibodies have proved to be the most sensitive and specific markers of pregnancy complications in APS.
Assuntos
Anticoagulantes/sangue , Síndrome Antifosfolipídica/imunologia , Complicações na Gravidez/imunologia , beta 2-Glicoproteína I/imunologia , Adulto , Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Fatores Imunológicos/sangue , Inibidor de Coagulação do Lúpus/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Sensibilidade e EspecificidadeRESUMO
The emerging fields of graphene-based magnetic and spintronic devices require a deep understanding of the interface between graphene and ferromagnetic metals. This paper reports a detailed investigation at the nanometer level of the Fe-graphene interface carried out by angle-resolved photoemission, high-resolution photoemission from core levels, near edge X-ray absorption fine structure, scanning tunnelling microscopy and spin polarized density functional theory calculations. Quasi-free-standing graphene was grown on Pt(111), and the iron film was either deposited atop or intercalated beneath graphene. Calculations and experimental results show that iron strongly modifies the graphene band structure and lifts its π band spin degeneracy.
RESUMO
A highly spread polymorphism flanking the 3. Calpha1 human IG heavy chain gene was identified. This polymorphism allowed the detection of an internal duplication within the 3' flanking region of both Calpha1 and Calpha2. This region has a regulatory function with four enhancer structures also present at the 3' end of the human Calpha2 as well as in that of mouse and rat single Calpha genes. The 5682-bp sequence of clone lambdapl8 described here starts 3' of Calpha1 and presents three open reading frames; one of them contains part of the tandem repeats with the 20-bp consensus described previously that is expressed in a poly(A)+ RNA and found in three dbEST clones of the human tonsillar cDNA library. Here, we demonstrate that in the CLF1 B lymphoblastoid cell line, this transcript is associated with polysomes. We also discuss the possibility of the presence of a new regulatory gene that does not encode an immunoglobulin and maps in the human IG heavy chain gene cluster.