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Objective: Acute aortic dissection remains a serious emergency in the field of cardiovascular medicine and a challenge for cardiothoracic surgeons. In the present study, we seek to compare the outcomes of different surgical techniques in the repair of type A acute aortic dissection. Methods: Between April 2015 and May 2023, 213 patients (82 women, aged: 63.9 ± 13.3â years) with acute aortic dissection (205 type A and 8 non-A-non-B dissections) underwent surgical treatment in our department. A total of 45 patients were treated with the frozen elephant trunk (FET) technique supported by the Thoraflex™ Hybrid prosthesis, 33 received total aortic arch replacement (TAR)-standard or conventional elephant trunk-treatment, and 135 were treated with hemiarch replacement (HR). Aortic arch surgery was performed in most patients under moderate hypothermic (28°C on average) circulatory arrest, with selective antegrade cerebral perfusion through the right axillary artery. Results: The rates of early mortality were 17.8% (38 perioperative deaths) in the whole population, 8.9% in the FET group of patients, and 33% and 17% in the TAR and HR group of patients, respectively (P-value 0.025). The rate of spinal cord injury was 2.3% (five patients), and a paresis of recurrent laryngeal occurred in 3.7% of patients (seven patients, four were treated with FET). Permanent neurological dysfunction occurred in 27 patients (12.7%). After a mean follow-up of 3â years, the rate of mid-term mortality of discharged patients was 19.4% (34 deaths: 7 FET, 4 TAR, and 23 HR) and the overall mortality rate was 33.8% [72 deaths: 11 FET (24.4%); 15 TAR (45.4%); 46 HR (34.1%)]. A total of 8 patients (17.8%) in whom FET was applied received additional endovascular treatment in the descending aorta. Conclusions: In our institutional experience, we found that the frozen elephant trunk technique with a high-end Thoraflex Hybrid prosthesis proved its surgical suitability in the treatment of acute aortic dissection with favorable outcomes. The FET technique and our perioperative management led to comparable neurological outcomes and reduced mortality rates in these emergency cases.
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This report describes the understudied co-occurrence of temporomandibular joint ankylosis (TMJA) and extrahepatic portal vein obstruction (EHPVO), exploring a shared pathway involving hypercoagulability. TMJA is an acquired pathology where joint surfaces fuse, causing restricted mouth opening and facial asymmetry. Globally, TMJA is prevalent among 1.5 to 5 patients/million, with a higher incidence in developing countries. While trauma and infections often cause TMJA, the pathogenesis remains unclear in many cases. Recent literature notes a link between TMJA and EHPVO, a noncirrhotic vascular disorder causing portal hypertension and upper gastrointestinal bleeding in children. Prothrombotic disorders such as protein C and S deficiency may contribute to EHPVO, mirroring TMJA's association with hypercoagulability. This report focuses on an 11-year-old female diagnosed with TMJA, accompanied by a history of ear infection and concurrent EHPVO. We further presented clinical observations, surgical interventions, and outcomes alongside a literature review to understand the probable connection between EHPVO and TMJA.
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X-ray free-electron lasers (XFELs) deliver intense x-ray pulses that destroy the sample in a single shot by a Coulomb explosion. Experiments using XFEL pulse trains or the new generation of high-repetition rate XFELs require rapid sample replacement beyond those provided by the systems now used at low repletion-rate XFELs. We describe the development and characterization of a system based on a spinning disk to continuously deliver a solid sample into an XFEL interaction point at very high speeds. We tested our system at the Linac Coherent Light Source and European XFEL hard x-ray nano-focus instruments, employing it to deliver a 25 µm copper foil sample, which can be used as a gain medium for stimulated x-ray emission for the proposed x-ray laser oscillator.
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A surgical intervention for type A acute aortic dissection is the only effective method of treatment making it possible to prevent the development of life-threatening complications and to attain clinical recovery of the patient. Supracoronary replacement of the ascending aorta and the proximal portion of the aortic arch is considered to be the classical and most commonly used method of an open operative intervention. On the one hand, it is technically the simplest and shortest operation, and on the other, this surgical technique is often accompanied by long-term proximal and distal complications, and first of all those caused by a persistent false lumen. The accumulated surgical experience and contemporary operative techniques, as well as advances of intensive therapy in treatment of type A acute aortic dissection make it possible to currently perform more extensive primary resections in order to improve the remote results. Total aortic arch replacement, including the use of the 'frozen elephant trunk' technique leads to fast thrombosis of the false lumen, preventing progression of the disease of the thoracic aorta and promoting its positive remodelling. The article describes the perioperative therapeutic policy accepted and pursued in our medical facility, also presenting the authors' opinion on the role and place of the 'frozen elephant trunk' technique in rendering medical care for patients with type A acute aortic dissection.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/cirurgia , Aorta , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Humanos , Procedimentos Cirúrgicos VascularesRESUMO
This corrects the article DOI: 10.1103/PhysRevLett.120.265701.
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Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5'-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 Å resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds.
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Coenzimas/química , Cristalização , IMP Desidrogenase/química , Trypanosoma brucei brucei/enzimologia , Sequência de Aminoácidos , Animais , Sítios de Ligação , Domínio Catalítico , Clonagem Molecular , Guanosina Monofosfato , Modelos Moleculares , Conformação Proteica , Células Sf9 , Trypanosoma brucei brucei/genéticaRESUMO
The routine atomic resolution structure determination of single particles is expected to have profound implications for probing structure-function relationships in systems ranging from energy-storage materials to biological molecules. Extremely bright ultrashort-pulse X-ray sources - X-ray free-electron lasers (XFELs) - provide X-rays that can be used to probe ensembles of nearly identical nanoscale particles. When combined with coherent diffractive imaging, these objects can be imaged; however, as the resolution of the images approaches the atomic scale, the measured data are increasingly difficult to obtain and, during an X-ray pulse, the number of photons incident on the 2D detector is much smaller than the number of pixels. This latter concern, the signal 'sparsity', materially impedes the application of the method. An experimental analog using a conventional X-ray source is demonstrated and yields signal levels comparable with those expected from single biomolecules illuminated by focused XFEL pulses. The analog experiment provides an invaluable cross check on the fidelity of the reconstructed data that is not available during XFEL experiments. Using these experimental data, it is established that a sparsity of order 1.3 × 10-3â photons per pixel per frame can be overcome, lending vital insight to the solution of the atomic resolution XFEL single-particle imaging problem by experimentally demonstrating 3D coherent diffractive imaging from photon-sparse random projections.
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In this work, we monitor the onset of nonthermal melting in single-crystal silicon by implementing an x-ray pump-x-ray probe scheme. Using the ultrashort pulses provided by the Linac Coherent Light Source (SLAC) and a custom-built split-and-delay line for hard x rays, we achieve the temporal resolution needed to detect the onset of the transition. Our data show no loss of long-range order up to 150±40 fs from photoabsorption, which we interpret as the time needed for the electronic system to equilibrate at or above the critical nonthermal melting temperature. Once such equilibration is reached, the loss of long-range atomic order proceeds inertially and is completed within 315±40 fs from photoabsorption.
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Teneurin C-terminal associated peptide (TCAP) is an ancient paracrine signalling agent that evolved via lateral gene transfer from prokaryotes into an early metazoan ancestor. Although it bears structural similarity to corticotrophin-releasing hormone (CRH), it inhibits the in vivo actions of CRH. The TCAPs are highly expressed in neurones, where they induce rapid cytoskeletal rearrangement and are neuroprotective. Because these processes are highly energy-dependent, this suggests that TCAP has the potential to regulate glucose uptake because glucose is the primary energy substrate in brain, and neurones require a steady supply to meet the high metabolic demands of neuronal communication. Therefore, the objective of the present study was to assess the effect of TCAP-mediated glucose uptake in the brain and in neuronal cell models. TCAP-mediated 18 F-deoxyglucose (FDG) uptake into brain tissue was assessed in male wild-type Wistar rats by functional positron emission tomography. TCAP-1 increased FDG uptake by over 40% into cortical regions of the brain, demonstrating that TCAP-1 can significantly enhance glucose supply. Importantly, a single nanomolar injection of TCAP-1 increased brain glucose after 3 days and decreased blood glucose after 1 week. This is corroborated by a decreased serum concentration of insulin and an increased serum concentration of glucagon. In immortalised hypothalamic neurones, TCAP-1 increased ATP production and enhanced glucose uptake by increasing glucose transporter recruitment to the plasma membrane likely via AKT and mitogen-activated protein kinase/ERK phosphorylation events. Taken together, these data demonstrate that TCAP-1 increases glucose metabolism in neurones, and may represent a peptide signalling agent that regulated glucose uptake before insulin and related peptides.
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Encéfalo/efeitos dos fármacos , Glucose/metabolismo , Neurônios/efeitos dos fármacos , Peptídeos/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Glicemia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Linhagem Celular , Neuroimagem Funcional , Glucagon/sangue , Hipotálamo/citologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Insulina/sangue , Neurônios/citologia , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Tomografia por Emissão de Pósitrons , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
The structural investigation of noncrystalline, soft biological matter using x-rays is of rapidly increasing interest. Large-scale x-ray sources, such as synchrotrons and x-ray free electron lasers, are becoming ever brighter and make the study of such weakly scattering materials more feasible. Variants of coherent diffractive imaging (CDI) are particularly attractive, as the absence of an objective lens between sample and detector ensures that no x-ray photons scattered by a sample are lost in a limited-efficiency imaging system. Furthermore, the reconstructed complex image contains quantitative density information, most directly accessible through its phase, which is proportional to the projected electron density of the sample. If applied in three dimensions, CDI can thus recover the sample's electron density distribution. As the extension to three dimensions is accompanied by a considerable dose applied to the sample, cryogenic cooling is necessary to optimize the structural preservation of a unique sample in the beam. This, however, imposes considerable technical challenges on the experimental realization. Here, we show a route toward the solution of these challenges using ptychographic CDI (PCDI), a scanning variant of coherent imaging. We present an experimental demonstration of the combination of three-dimensional structure determination through PCDI with a cryogenically cooled biological sample--a budding yeast cell (Saccharomyces cerevisiae)--using hard (7.9 keV) synchrotron x-rays. This proof-of-principle demonstration in particular illustrates the potential of PCDI for highly sensitive, quantitative three-dimensional density determination of cryogenically cooled, hydrated, and unstained biological matter and paves the way to future studies of unique, nonreproducible biological cells at higher resolution.
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Saccharomyces cerevisiae/citologia , Tomografia/métodos , Difração de Raios X/métodos , Simulação por Computador , Elétrons , Congelamento , Imageamento Tridimensional/métodos , Modelos Teóricos , Fótons , Doses de Radiação , Difração de Raios X/instrumentação , Raios XRESUMO
PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES.
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Biodiversidade , Conservação dos Recursos Naturais/métodos , Ecossistema , Política Ambiental , Oceanos e Mares , Monitoramento Ambiental/métodos , Europa (Continente) , PressãoRESUMO
Intense femtosecond x-ray pulses from free-electron laser sources allow the imaging of individual particles in a single shot. Early experiments at the Linac Coherent Light Source (LCLS) have led to rapid progress in the field and, so far, coherent diffractive images have been recorded from biological specimens, aerosols, and quantum systems with a few-tens-of-nanometers resolution. In March 2014, LCLS held a workshop to discuss the scientific and technical challenges for reaching the ultimate goal of atomic resolution with single-shot coherent diffractive imaging. This paper summarizes the workshop findings and presents the roadmap toward reaching atomic resolution, 3D imaging at free-electron laser sources.
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Hinged ankle-foot orthoses are prescribed routinely for the treatment of ankle joint deficits, despite the conflicting outcomes and the little evidence on their functional efficacy. In particular, the axis of rotation of the hinge is positioned disregarding the physiological position and orientation. A multi-segment model was utilized to assess in vivo the effect of different positions for this axis on the kinematics of foot joints. A special custom-made hinged orthosis was manufactured via standard procedures for a young healthy volunteer. Four locations for the mechanical axis were obtained by a number of holes where two nuts and bolts were inserted to form the hinge: a standard position well above the malleoli, at the level of the medial malleolus, at the level of the lateral malleolus, and the physiological between the two malleoli. The shank and foot were instrumented with 15 reflective markers according to a standard protocol, and level walking was collected barefoot and with the orthosis in the four mechanical conditions. The spatio-temporal parameters observed in the physiological axis condition were the closest to normal barefoot walking. As expected, ankle joint rotation was limited to the sagittal plane. When the physiological axis was in place, rotations of the ankle out-of-sagittal planes, and of all other foot joints in the three anatomical planes, were found to be those most similar to the natural barefoot condition. These preliminary measures of intersegmental kinematics in a foot within an ankle-foot orthosis showed that only a physiological location for the ankle mechanical hinge can result in natural motion at the remaining joints and planes.
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Tornozelo/fisiologia , Articulações do Pé/fisiologia , Órtoses do Pé , Limitação da Mobilidade , Amplitude de Movimento Articular/fisiologia , Adulto , Tornozelo/fisiopatologia , Traumatismos do Tornozelo/fisiopatologia , Traumatismos do Tornozelo/reabilitação , Fenômenos Biomecânicos , Desenho de Equipamento , Feminino , Articulações do Pé/fisiopatologia , Humanos , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/métodos , Valores de Referência , Rotação , Análise Espaço-Temporal , Caminhada/fisiologiaRESUMO
A 45-year-old heart transplant recipient presented with fever, anorexia, asthenia, and lethargy. She had received heart transplantation only 5 weeks earlier for primary systemic amyloidosis with severe cardiac involvement. Serum sodium was low, and tacrolimus through level was high. Blood cultures and serology tests for infection were negative, and atypical pneumonia was suspected. Despite broad antibiotic, antiviral, and antifungal treatment, the patient clinical condition rapidly deteriorated and she died within three days of admission. Postmortem examination revealed a disseminated Toxoplasma gondii infection as a result of donor (+)/recipient(-) mismatch for Toxoplasma serology. Although very rare, toxoplasmosis in heart transplant recipient should be suspect in case of neurological deficit and respiratory symptoms. Prophylaxis treatment is recommended in case of mismatch.
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Diffractive imaging with free-electron lasers allows structure determination from ensembles of weakly scattering identical nanoparticles. The ultra-short, ultra-bright X-ray pulses provide snapshots of the randomly oriented particles frozen in time, and terminate before the onset of structural damage. As signal strength diminishes for small particles, the synthesis of a three-dimensional diffraction volume requires simultaneous involvement of all data. Here we report the first application of a three-dimensional spatial frequency correlation analysis to carry out this synthesis from noisy single-particle femtosecond X-ray diffraction patterns of nearly identical samples in random and unknown orientations, collected at the Linac Coherent Light Source. Our demonstration uses unsupported test particles created via aerosol self-assembly, and composed of two polystyrene spheres of equal diameter. The correlation analysis avoids the need for orientation determination entirely. This method may be applied to the structural determination of biological macromolecules in solution.
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The plasma dynamics of single mesoscopic Xe particles irradiated with intense femtosecond x-ray pulses exceeding 10(16) W/cm2 from the Linac Coherent Light Source free-electron laser are investigated. Simultaneous recording of diffraction patterns and ion spectra allows eliminating the influence of the laser focal volume intensity and particle size distribution. The data show that for clusters illuminated with intense x-ray pulses, highly charged ionization fragments in a narrow distribution are created and that the nanoplasma recombination is efficiently suppressed.
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AIM: Only a few papers with patients surviving more than 15 years after heart transplantation have been reported. Herein we report the characteristics of patients transplanted between 1984 and 1989 who are long-term survivors (>20 years). Survival after transplant, recipient and donor age and aetiology of heart failure were also compared with patients transplanted in the decades 1990-1999 and 2000-2009. METHODS: Our Heart Transplant Program Database and medical records of all cardiac transplants performed in our centre from July 1984 to 1989 were reviewed. Primary endpoint of the study was the long-term survival and secondary end points were the incidence of transplant-related complications over time. RESULTS: Forty-five transplants were performed in 1984-1989, 41 patients were male, median age was 46 years (IQR: 39-55), median donor age was 24 years (19-29) and mean graft ischemic time was 134±64 minutes. The actuarial survival of this cohort was 77.8%, 64.4%, 48.9%, 35.6% and 24.2% at 1, 5, 10, 15 and 20 years, respectively. Univariate Cox regression analysis revealed the female gender, the graft ischemic time, the recipient-donor gender mismatch, a diagnosis of diabetes and the number of acute rejection episodes during the first year post-transplant as significant risk factors adversely affecting long-term survival. Cardiac allograft vasculopathy is the main cause of death. The mean recipient and donor age and the graft ischemic time have progressively increased over time but survival has not changed. CONCLUSION: The long-term outcome of heart transplantation is noteworthy. The main limiting factor for survival is the allograft vasculopathy. Considering the tremendous advances in the immunosuppressive therapy and in the understanding of CAV pathophisyology, we can hope for even better results in the next years.
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Transplante de Coração/mortalidade , Sobreviventes/estatística & dados numéricos , Adulto , Distribuição de Qui-Quadrado , Feminino , Transplante de Coração/efeitos adversos , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The emergence of femtosecond diffractive imaging with X-ray lasers has enabled pioneering structural studies of isolated particles, such as viruses, at nanometer length scales. However, the issue of missing low frequency data significantly limits the potential of X-ray lasers to reveal sub-nanometer details of micrometer-sized samples. We have developed a new technique of dark-field coherent diffractive imaging to simultaneously overcome the missing data issue and enable us to harness the unique contrast mechanisms available in dark-field microscopy. Images of airborne particulate matter (soot) up to two microns in length were obtained using single-shot diffraction patterns obtained at the Linac Coherent Light Source, four times the size of objects previously imaged in similar experiments. This technique opens the door to femtosecond diffractive imaging of a wide range of micrometer-sized materials that exhibit irreproducible complexity down to the nanoscale, including airborne particulate matter, small cells, bacteria and gold-labeled biological samples.
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Elétrons , Imageamento Tridimensional/métodos , Lasers , Simulação por Computador , Microscopia Eletrônica de Transmissão , Fuligem/análise , Fatores de Tempo , Raios XRESUMO
The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology to climate science, yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate; visible light scattering provides insufficient resolution; and X-ray synchrotron studies have been limited to ensembles of particles. Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins, vibrational energy transfer by the hydrodynamic interaction of amino acids, and large-scale production of nanoscale structures by flame synthesis.
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Aerossóis/análise , Aerossóis/química , Fractais , Espectrometria de Massas , Movimento (Física) , Fuligem/análise , Fuligem/química , Aminoácidos/química , Elétrons , Lasers , Nanopartículas , Tamanho da Partícula , Proteínas/química , Solventes/química , Vibração , Difração de Raios XRESUMO
Magnesium/silicon carbide (Mg/SiC) multilayers have been fabricated with normal incidence reflectivity in the vicinity of 40% to 50% for wavelengths in the 25 to 50 nm wavelength range. However many applications, for example solar telescopes and ultrafast studies using high harmonic generation sources, desire larger bandwidths than provided by high reflectivity Mg/SiC multilayers. We investigate introducing a third material, Scandium, to create a tri-material Mg/Sc/SiC multilayer allowing an increase the bandwidth while maintaining high reflectivity.