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The treatment of Gustilo-Anderson type III open femoral fracture with large segmental bone defect remains a challenge for orthopedic trauma surgeons. The aims of management are first to prevent the risk of infection and then to reconstruct the bone loss with correct alignment and length. The induced membrane technique (or Masquelet technique) was initially described for tibia nonunion but became over the years an established procedure to treat any kind of large bone defect. The case of a 22-year old male who sustained an open femoral shaft fracture with a circumferential 7-cm bone defect after a car accident is presented. Given the critical size of the bone loss, we chose to manage this patient using a modified-Masquelet technique, in which we stabilized the fracture by an intramedullary femoral nail and filled only the lateral side of the defect with a cement spacer. He went on to have a full and successful union of his fracture 16-weeks after the second stage surgery. The final functional outcomes were excellent allowing the patient to resume all activities without restriction.
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Articular fractures of the distal humerus are rare, and even rarer are fractures involving the trochlea and capitellum in a single fragment, with no associated comminution. These fractures are classified as 2a according to the Dubberley classification and are rarely described in the literature. Two cases of Dubberley 2a fractures were treated at our hospital. The first case, involving a 68-year-old patient, was treated with a medial and a lateral approach, combined with posteroanterior fixation using 3 Herbert screws. In the 2nd case, a 16-year-old male was treated with a single lateral approach, permitting fixation with two Herbert screws. One of the two screws is inserted into the bone at the edge of the cartilage, with an anteroposterior trajectory that leaves the cartilage intact. We opted mainly for posteroanterior screw fixation in subchondral bone, which is less damaging to articular cartilage and soft tissues and has already demonstrated its reliability. No associated lesions were found, and no complications were encountered. Results were excellent, with Mayo Elbow Performance Index (MEPI) scores of 95 and 100 respectively. Herbert screw fixation therefore appears to be an option of choice for these fractures, although comparative studies are needed to evaluate the different treatments available.
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INTRODUCTION: Software to predict the impact of aging on physical appearance is increasingly popular. But it does not consider the complex interplay of factors that contribute to skin aging. OBJECTIVES: To predict the +15-year progression of clinical signs of skin aging by developing Causal Bayesian Belief Networks (CBBNs) using expert knowledge from dermatologists. MATERIAL AND METHODS: Structures and conditional probability distributions were elicited worldwide from dermatologists with experience of at least 15 years in aesthetics. CBBN models were built for all phototypes and for ages ranging from 18 to 65 years, focusing on wrinkles, pigmentary heterogeneity and facial ptosis. Models were also evaluated by a group of independent dermatologists ensuring the quality of prediction of the cumulative effects of extrinsic and intrinsic skin aging factors, especially the distribution of scores for clinical signs 15 years after the initial assessment. RESULTS: For easiness, only models on African skins are presented in this paper. The forehead wrinkle evolution model has been detailed. Specific atlas and extrinsic factors of facial aging were used for this skin type. But the prediction method has been validated for all phototypes, and for all clinical signs of facial aging. CONCLUSION: This method proposes a skin aging model that predicts the aging process for each clinical sign, considering endogenous and exogenous factors. It simulates aging curves according to lifestyle. It can be used as a preventive tool and could be coupled with a generative AI algorithm to visualize aging and, potentially, other skin conditions, using appropriate images.
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Envejecimiento de la Piel , Humanos , Teorema de Bayes , Cara , Envejecimiento , FrenteRESUMEN
BACKGROUND: NCTF®135HA is a bio-revitalizing solution containing hyaluronic acid designed to compensate for skin dehydration, fatigue, and fine wrinkles associated with endogenous and environmental aging. METHODS: We conducted a randomized, active-controlled study to evaluate the efficacy and tolerability of NCTF®135HA injections on the face (crow's feet), neck, and décolleté regions. Subjects were randomly assigned (3:1) to receive three NCTF®135HA treatment sessions plus twice-daily anti-aging moisturizer cream or cream alone (control). The primary outcome was the reduction in superficial wrinkles between baseline and Day (D)75 in the three areas, assessed by profilometric measures, clinical scoring, subjective changes, and tolerability. RESULTS: 146 subjects were randomized to NCTF®135HA (n = 107) or control (n = 38). At D75 and D120, NCTF®135HA significantly reduced wrinkles in all three areas and improved facial radiance scores compared with the control. Skin hydration significantly increased 7 d after the last NCTF®135HA injection. Self-esteem scales showed statistically significant improvements at D75 and D120 in subjects treated with NCTF®135HA versus baseline. Most adverse events were mild, resolved within 48 h, and were related to the injection procedure. CONCLUSION: NCTF®135HA is an effective and well-tolerated treatment to reduce the skin signs of aging. The results are significantly superior to a routine anti-aging cream alone.(Funded by Laboratories FILLMED; ID-RCB number: 2018-A03167-48; clinicaltrials.gov number: NCT05609617).
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Ácido Hialurónico , Envejecimiento de la Piel , Humanos , Estudios Prospectivos , Piel , Resultado del Tratamiento , RejuvenecimientoRESUMEN
Some patients present at an advanced stage of their fingertip infection with an extension of the infection in anatomical spaces or into fragile structures. One hundred and twenty-five patients have been operated on for a finger infection. Forty-one patients (33%) have been treated at the "complication" stage, while 84 cases (67%) were considered "non-complicated". The delay between initial injury and the surgical treatment was 12 days in the "non-complicated" group versus 30 in the "complication" group (p < 0.001). Osteitis (39% of the complications), and flexor sheath infection (37%) were the most frequent complications. Prescribing preoperative antibiotics increases the risk of being in the "complicated" group at p = 0.09. One hundred and thirteen patients (90.4%) were cured of their infection after a single operation. Neither the cause of infection, nor the type of germ or associated diabetes increased the risk of complication in our series. A better education of the first interveners (general practitioner or emergency doctor) in hand infection care could reduce the rate of complication allowing a faster access to hand surgeons.
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Dedos , Mano , Antibacterianos/uso terapéutico , Humanos , Enfermedad Iatrogénica/epidemiologíaRESUMEN
In this Letter, we demonstrate how harmonic oscillator equations can be integrated in a neural network to improve the spectral response prediction for an optical system. We use the optical properties of a one-dimensional nanoslit array for a practical implementation of the study. This method allows to build more generalizable relations between the input parameters of the array and its optical properties, showing a 20-fold improvement for parameters outside the range used for the training. We also show how this model generates the output spectrum from phenomenological relationships between the input parameters and the output spectrum, indicating how it grasps the physical mechanisms of the optical response of the structure.
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INTRODUCTION: The Masquelet technique based on induced membrane is performed in two stages, first with generally an external fixator which is more and more relayed by an internal fixator. The aim of this study is to assess the results of stabilization by using intramedullary nailing from the first stage. PATIENTS AND METHODS: Nine patients were treated for a bone defect concerning 8 femurs and one tibia. The mean size of bone defect was 9.25 cm. It was secondary to a fracture (6 case) with bone defect and two septic and aseptic pseudarthrosis. In all cases the nailing was performed at the first stage of Masquelet. Prior to cement delivery, the site was thoroughly cleaned with iterative excisions as needed. Blood count control, normal CRP and negative culture were required before cement delivery. The cement was placed around the nail and encased the bony extremity. In the second stage, after removal of the cement, the defect was fulfilled by a mixture of cortico-cancellous autogenous graft taken from the iliac crest and phosphocalcic bone substitute. The nail was not changed in any patient. In post operative the mobilization of the above and underlying joints was immediate. RESULTS: No sepsis was detected before the second time. Early weight bearing was allowed on average at the end of the 2 nd month. Total bearing without support was allowed at a mean of 5.5 months. All patients have consolidated. One patient had a shortening of 2.35 cm. The mean follow-up was 46.1 months. The average period to effective return to work was 21 months. CONCLUSION: The nailing performed at the first stage of the induced membrane technique (IMT) gives good results. This modification does not seem to increase the risk of infection. These good results deserve to be confirmed by other studies to confirm the interests of associating nailing to IMT from the first stage.
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The first phase of this study showed that ART FILLER Universal filler (AFU; FILORGA Laboratories) and ART FILLER Fine lines (AFFL) were non-inferior to JUVÉDERM Ultra 3 (Allergan) and FIRST LINES PureSense (Teoxane), respectively. The clinical benefits of AFU and AFFL on nasolabial folds and crow's feet persisted until at least Day 180. This article reports results from an open-label extension phase that assessed the tolerability and efficacy of AFU and AFFL for up to 18 months based on clinical evaluation and ultrasound high-frequency imaging. METHODS: Eligible subjects were enrolled at D180 and assessed on D270, D360, and D540. The primary outcome measured was local tolerability. Secondary outcomes measured included: proportion of subjects in whom the severity of nasolabial folds and crow's feet remained at least 1 point below the baseline measurement (Lemperle scale); general safety; Global Aesthetic Improvement Scale scores by subjects and investigators; wrinkle volumes; and skin thickness by high-frequency ultrasound. RESULTS: Adverse events were consistent with the product information and the initial study. No serious adverse events were recorded. In exploratory analyses, wrinkle correction with AFU and AFFL is sustained for at least 18 months: 48.4% and 98.3% of subjects respectively still showed at least a 1-point decrease in the mean Lemperle score compared with the baseline. The benefits were sustained irrespective of whether subjects received additional injections. Modifications in wrinkle volume and skin thickness at D540 were statistically significant compared with the baseline. CONCLUSION: AFU and AFFL were well tolerated and, in exploratory analyses, showed a sustained efficacy for at least 18 months.
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The lamellar-to-sponge phase transition of fluorescently labelled large unilamellar vesicles (LUVs) of the non-ionic surfactant triethylene glycol mono n-decyl ether (C10E3) was investigated in situ by confocal laser scanning microscopy (CLSM). Stable dispersions of micrometer-sized C10E3 LUVs were prepared at 20 °C and quickly heated at different temperatures close to the lamellar-to-sponge phase transition temperature. Phase transition of the strongly fluctuating individual vesicles into micrometre-sized sponge phase droplets was observed to occur via manyfold multilamellar morphologies with increasing membrane confinement through inter- and intra- lamellar fusion. The very low bending rigidity and lateral tension of the C10E3 bilayer were supported by quantitative image analysis of a stable fluctuating membrane using both flicker noise spectroscopy and spatial autocorrelation function.
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The diffusion of adequate peptide through an enzyme-embedded host hydrogel leads to the in situ start-up and growth of an interpenetrated fibrous network. Based on the enzyme-assisted self-assembly concept, both chemistry and mechanical features of the hybrid hydrogel can be tuned.
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Fosfatasa Alcalina/metabolismo , Difusión , Hidrogeles/metabolismo , Péptidos/metabolismo , Hidrogeles/química , Estructura Molecular , Tamaño de la Partícula , Péptidos/química , Polietilenglicoles/química , Polietilenglicoles/metabolismo , Propiedades de SuperficieRESUMEN
OBJECTIVE: To study the effect on pain of per-cutaneous cementoplasty for painful extraspinal bone metastasis. METHOD: 43 patients with extraspinal bone metastasis were included between April 2006 and October 2014 in this retrospective monocenter study. The primary endpoint was pain level measured on a 0-10 numeric rating scale at week 1 after cementoplasty as compared with pre-cementoplasty. Secondary endpoints were long-term pain level and impact on quality of life and disability. RESULTS: Mean pain score was 4.2 (SD ±3.6) before cementoplasty and 1.09 (SD ±2.4) at week 1 (pâ¯=â¯0.005) (nâ¯=â¯31 patients). At 22 months after cementoplasty, quality of life and disability improved (according to the patient global assessment) for 47.6% and 52.2% of patients (nâ¯=â¯21patients). We did not find a predictor of good response. Cement leakage was the most common adverse event. CONCLUSION: Percutaneous cementoplasty of extraspinal bone metastasis is a rapidly efficient treatment with few adverse events. Its efficacy persists over time, with a benefit for disability and quality of life. Although this technique is only palliative, it should be considered in this situation.
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BACKGROUND: This study aims to describe the cardiovascular manifestations in children with autosomal dominant polycystic kidney disease (ADPKD) and detect their relation with kidney disease and type of gene mutation. METHODS: Twenty-one patients (7 to 19 years old) were included. Cardiovascular evaluation involved blood pressure (BP), indexed left ventricular mass (LVMI), pulse wave velocity (PWV), and carotid intima media thickness (cIMT) measurement. Patients were classified according to percentile reference values of these parameters in healthy children. The 95th percentile was the highest level of normal values. Glomerular filtration rate (GFR) and microalbuminuria were also measured. RESULTS: Antihypertensive treatment, large LVMI, high PWV, and increased cIMT were observed in 6 (28.6%), 2 (9.5%), 4 (19%), and 8 (38.1%) patients respectively. Antihypertensive treatment was not associated with either high PWV or increased cIMT. Linear correlation was noticed between LVMI and PWV (r2 = 0.243, p = 0.023) and also between LVMI and cIMT (r2 = 0.203, p = 0.041). The median age of patients with high PWV, increased cIMT, and large LVMI was 9.5, 13, and 18 years old. GFR was normal in all patients. Patients with increased cIMT presented higher levels of urine microalbumin to creatinine ratio (p = 0.025). Genetic mutation was available in 18 patients. Antihypertensive treatment was more frequent in patients without PKD1 missense mutation (p = 0.044). CONCLUSIONS: High PWV and increased cIMT indicating arterial stiffness and hypertrophic vasculopathy may be present in children with ADPKD regardless BP status, and prior to GFR decline, suggesting that vascular disease precedes chronic kidney disease in ADPKD.
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Hipertensión/diagnóstico , Hipertrofia Ventricular Izquierda/diagnóstico , Riñón Poliquístico Autosómico Dominante/complicaciones , Adolescente , Adulto , Albuminuria/diagnóstico , Albuminuria/etiología , Albuminuria/fisiopatología , Antihipertensivos/uso terapéutico , Presión Sanguínea/fisiología , Grosor Intima-Media Carotídeo , Niño , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Ventrículos Cardíacos/patología , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/etiología , Hipertensión/orina , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/patología , Masculino , Mutación Missense , Tamaño de los Órganos , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/fisiopatología , Riñón Poliquístico Autosómico Dominante/orina , Análisis de la Onda del Pulso , Canales Catiónicos TRPP/genética , Rigidez Vascular , Adulto JovenRESUMEN
PURPOSE: Currently the screening for lung cancer for risk groups is based on Computed Tomography (CT) or low dose CT (LDCT); however, the lung cancer death rate has not decreased significantly with people undergoing LDCT. We aimed to develop a simple reliable blood test for early detection of all types of lung cancer based on the immunogenicity of aberrant forms of BARD1 that are specifically upregulated in lung cancer. METHODS: ELISA assays were performed with a panel of BARD1 epitopes to detect serum levels of antibodies against BARD1 epitopes. We tested 194 blood samples from healthy donors and lung cancer patients with a panel of 40 BARD1 antigens. Using fitted Lasso logistic regression we determined the optimal combination of BARD1 antigens to be used in ELISA for discriminating lung cancer from healthy controls. Random selection of samples for training sets or validations sets was applied to validate the accuracy of our test. RESULTS: Fitted Lasso logistic regression models predict high accuracy of the BARD1 autoimmune antibody test with an AUC = 0.96. Validation in independent samples provided and AUC = 0.86 and identical AUCs were obtained for combined stages 1-3 and late stage 4 lung cancers. The BARD1 antibody test is highly specific for lung cancer and not breast or ovarian cancer. CONCLUSION: The BARD1 lung cancer test shows higher sensitivity and specificity than previously published blood tests for lung cancer detection and/or diagnosis or CT scans, and it could detect all types and all stages of lung cancer. This BARD1 lung cancer test could therefore be further developed as i) screening test for early detection of lung cancers in high-risk groups, and ii) diagnostic aid in complementing CT scan.
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Autoanticuerpos/sangre , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Proteínas Supresoras de Tumor/inmunología , Ubiquitina-Proteína Ligasas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Neoplasias Pulmonares/inmunología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Spiral drawing is one of the standard tests used to assess tremor severity for the clinical evaluation of medical treatments. Tremor severity is estimated through visual rating of the drawings by movement disorders experts. Different approaches based on the mathematical signal analysis of the recorded spiral drawings were proposed to replace this rater dependent estimate. The objective of the present study is to propose new numerical methods and to evaluate them in terms of agreement with visual rating and reproducibility. METHODS: Series of spiral drawings of patients with essential tremor were visually rated by a board of experts. In addition to the usual velocity analysis, three new numerical methods were tested and compared, namely static and dynamic unraveling, and empirical mode decomposition. The reproducibility of both visual and numerical ratings was estimated, and their agreement was evaluated. RESULTS: The statistical analysis demonstrated excellent agreement between visual and numerical ratings, and more reproducible results with numerical methods than with visual ratings. CONCLUSIONS: The velocity method and the new numerical methods are in good agreement. Among the latter, static and dynamic unravelling both display a smaller dispersion and are easier for automatic analysis. SIGNIFICANCE: The reliable scores obtained through the proposed numerical methods allow considering that their implementation on a digitized tablet, be it connected with a computer or independent, provides an efficient automatic tool for tremor severity assessment.
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Computadoras de Mano , Diagnóstico por Computador/métodos , Temblor Esencial/diagnóstico , Temblor Esencial/fisiopatología , Destreza Motora/fisiología , Adulto , Anciano , Computadoras de Mano/normas , Diagnóstico por Computador/normas , Femenino , Escritura Manual , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND: There are requirements for long-term, objective comparisons of hyaluronic acid (HA) dermal fillers. OBJECTIVE: To compare efficacy and tolerability of ART FILLER Universal (AFU) and ART FILLER Fine lines (AFFL) with the existing HA fillers for the treatment of nasolabial folds and crow's feet. MATERIALS AND METHODS: Prospective, randomized, rater- and patient-blind, split-face comparison of AFU with JUVEDERM Ultra 3 (JUV) and AFFL with FIRST LINES PureSense (FLPS). The severity of nasolabial folds and crow's feet was assessed by independent blinded evaluators using the Lemperle scale at baseline, day (D) 30/D45, D90, and D180. Tolerability, Global Aesthetic Improvement Scale (GAIS), wrinkle volumes, and skin thickness and density were also measured at D30/D45, D90, and D180. RESULTS: At D30 and D180 respectively, 61 and 57 patients were assessed. Scores for nasolabial folds and crow's feet showed statistically significant improvements at D30, D90, and D180. AFU and AFFL were noninferior to JUV and FLPS, respectively. Most patients showed GAIS improvements, maintained until at least D180 and significant increases of collagen synthesis in crow's feet and nasolabial folds. Treatments were well tolerated. CONCLUSION: AFU and AFFL are noninferior to comparators. The methodology used represents a novel approach to augment existing clinical assessment of HA fillers.
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Rellenos Dérmicos/administración & dosificación , Ácido Hialurónico/administración & dosificación , Envejecimiento de la Piel , Adulto , Anciano , Técnicas Cosméticas , Rellenos Dérmicos/uso terapéutico , Ojo , Femenino , Humanos , Ácido Hialurónico/uso terapéutico , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Surco Nasolabial , Estudios Prospectivos , Método Simple Ciego , PielRESUMEN
INTRODUCTION: Spinocerebellar ataxia 13 (SCA13) is a rare autosomal dominant cerebellar ataxia. To our knowledge, its association to movement disorders has never been described. We aimed at reporting 8 new SCA13 cases with a focus on movement disorders especially myoclonus. METHODS: We performed a detailed neurological examination and neurophysiological recording in 8 patients consecutively diagnosed with SCA13 between December 2013 and October 2015 and followed up in two French tertiary centers. RESULTS: We identified mild subcortical myoclonus in all patients, with a homogenous clinical and electrophysiological pattern. Myoclonus ataxia was very slowly progressive, like the other symptoms of the disease, whatever the age of onset. Patients with R423H mutation had an earlier age of onset than patients with R420H mutation. CONCLUSIONS: Myoclonus appears to be frequent in SCA13. SCA13 should be considered facing non-progressive autosomal dominant myoclonus ataxia, and polymyographic recording should be included in the diagnosis work.
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Ataxinas/genética , Mutación/genética , Mioclonía/etiología , Ataxias Espinocerebelosas/congénito , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Electroencefalografía , Electromiografía , Salud de la Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mioclonía/genética , Examen Neurológico , Ataxias Espinocerebelosas/complicaciones , Ataxias Espinocerebelosas/genética , Adulto JovenRESUMEN
Previous reports have shown that expression of BARD1δ, a deletion-bearing isoform of BARD1, correlates with tumor aggressiveness and progression. We show that expression of BARD1δ induces cell cycle arrest in vitro and in vivo in non-malignant cells. We investigated the mechanism that leads to proliferation arrest and found that BARD1δ overexpression induced mitotic arrest with chromosome and telomere aberrations in cell cultures, in transgenic mice, and in cells from human breast and ovarian cancer patients with BARD1 mutations. BARD1δ binds more efficiently than BARD1 to telomere binding proteins and causes their depletion from telomeres, leading to telomere and chromosomal instability. While this induces cell cycle arrest, cancer cells lacking G2/M checkpoint controls might continue to proliferate despite the BARD1δ-induced chromosomal instability. These features of BARD1δ may make it a genome permutator and a driver of continuous uncontrolled proliferation of cancer cells.
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Neoplasias de la Mama/metabolismo , Proliferación Celular , Neoplasias Ováricas/metabolismo , Homeostasis del Telómero , Telómero/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Empalme Alternativo , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Inestabilidad Cromosómica , Femenino , Puntos de Control de la Fase G2 del Ciclo Celular , Regulación Neoplásica de la Expresión Génica , Mutación de Línea Germinal , Células HEK293 , Humanos , Ratones Endogámicos C57BL , Ratones Transgénicos , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Unión Proteica , Isoformas de Proteínas , Complejo Shelterina , Transducción de Señal , Telómero/genética , Telómero/patología , Proteínas de Unión a Telómeros/metabolismo , Proteína 2 de Unión a Repeticiones Teloméricas/metabolismo , Factores de Tiempo , Transfección , Proteínas Supresoras de Tumor/genética , Ubiquitina-Proteína Ligasas/genética , Regulación hacia ArribaRESUMEN
Precise spatial and temporal control of pressure stimulation at the nanometer scale is essential for the fabrication and manipulation of nano-objects, and for exploring single-molecule behaviour of matter under extreme conditions. However, state-of-the-art nano-mechanical transducers require sophisticated driving hardware and are currently limited to moderate pressure regimes. Here we report a gold plasmonic bowtie (AuBT) nano-antennas array that can generate extreme pressure stimulus of â¼100 GPa in the ps (10-12 s) time scale with sub-wavelength resolution upon irradiation with ultra-short laser pulses. Our method leverages the non-linear interaction of photons with water molecules to excite a nano-plasma in the plasmon-enhanced near-field and induce extreme thermodynamic states. The proposed method utilizes laser pulses, which in contrast to micro- and nano-mechanical actuators offers simplicity and versatility. We present time-resolved shadowgraphic imaging, electron microscopy and simulation data that suggest that our platform can efficiently create cavitation nano-bubbles and generate intense pressure in specific patterns, which can be controlled by the selective excitation of plasmon modes of distinct polarizations. This novel platform should enable probing non-invasively the mechanical response of cells and single-molecules at time and pressure regimes that are currently difficult to reach with other methods.
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Ureases are metalloenzymes that catalyze the hydrolysis of urea to ammonia and carbon dioxide. Jack bean (Canavalia ensiformis) produces three isoforms of urease (Canatoxin, JBU and JBURE-II). Canatoxin and JBU display several biological properties independent of their ureolytic activity, such as neurotoxicity, exocytosis-inducing and pro-inflammatory effects, blood platelets activation, insecticidal and antifungal activities. The Canatoxin entomotoxic activity is mostly due to an internal peptide, named pepcanatox, released upon the hydrolysis of the protein by insect cathepsin-like digestive enzymes. Based on pepcanatox sequence, Jaburetox-2Ec was produced in Escherichia coli. JBU and its peptides were shown to permeabilize membranes through an ion channel-based mechanism. Here we studied the JBU and Jaburetox-2Ec interaction with platelet-like multilamellar liposomes (PML) using Dynamic Light Scattering and Small Angle X-ray Scattering techniques. We also analyzed the interaction of JBU with giant unilamellar vesicles (GUVs) using Fluorescence Microscopy. The interaction of vesicles with JBU led to a slight reduction of hydrodynamic radius, and caused an increase in the lamellar repeat distance of PML, suggesting a membrane disordering effect. In contrast, Jaburetox-2Ec decreased the lamellar repeat distance of PML membranes, while also diminishing their hydrodynamic radius. Fluorescence microscopy showed that the interaction of GUVs with JBU caused membrane perturbation with formation of tethers. In conclusion, JBU can interact with PML, probably by inserting its Jaburetox "domain" into the PML external membrane. Additionally, the interaction of Jaburetox-2Ec affects the vesicle's internal bilayers and hence causes more drastic changes in the PML membrane organization in comparison with JBU.
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Canavalia/enzimología , Liposomas/metabolismo , Péptidos/metabolismo , Ureasa/metabolismo , Dispersión Dinámica de Luz , Microscopía Fluorescente , Dispersión del Ángulo Pequeño , Difracción de Rayos XRESUMEN
SEE MUTHURAMAN ET AL DOI101093/AWW164 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects.