Liquid biopsy approaches are powerful strategies that potentially allow the diagnosis and prognosis of a number of diseases. The field is continuously and rapidly growing, encouraging the discovery ...of novel predictory biomarkers. Antibodies are usually exploited in sensors to validate biomarker candidates. Unfortunately, the immobilization of antibodies on the surface of sensors represents a challenging task. Immobilization strategies need to be optimized for each antibody, representing a huge obstacle to overcome in the discovery of new biomarkers. Herein we propose a novel strategy for the immobilization of antibodies, based on the use of a streptavidin-binding aptamer. Using this approach it is possible to immobilize antibodies on the surface of sensors with no need for optimization, with the only requirement for antibody to be biotinylated. The proposed strategy potentially paves the way towards a straightforward immobilization of antibodies on biosensors, making their use in biomarker validation more accessible.
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•Immobilization of biotinylated antibodies through streptavidin binding aptamer.•Improvement in immunocapturing of extracellular vesicles.•Easy access to customization of antibody microarrays.
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bstract
We present a parton-level study of electro-weak production of vector-boson pairs at the Large Hadron Collider, establishing the sensitivity to a set of dimension-six operators in the ...Standard Model Effective Field Theory (SMEFT). Different final states are statistically combined, and we discuss how the orthogonality and interdependence of different analyses must be considered to obtain the most stringent constraints. The main novelties of our study are the inclusion of SMEFT effects in non-resonant diagrams and in irreducible QCD backgrounds, and an exhaustive template analysis of optimal observables for each operator and process considered. We also assess for the first time the sensitivity of vector-boson-scattering searches in semileptonic final states.
The parenteral administration of protein therapeutics is increasingly gaining importance for the treatment of human diseases. However, the presence of practically impermeable blood–brain barriers ...greatly restricts access of such pharmaceutics to the brain. Treating brain disorders with proteins thus remains a great challenge, and the slow clinical translation of these therapeutics may be largely ascribed to the lack of appropriate brain delivery system. Exploring new approaches to deliver proteins to the brain by circumventing physiological barriers is thus of great interest. Moreover, parallel advances in the molecular neurosciences are important for better characterizing blood–brain interfaces, particularly under different pathological conditions (e.g., stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease). This review presents the current state of knowledge of the structure and the function of the main physiological barriers of the brain, the mechanisms of transport across these interfaces, as well as alterations to these concomitant with brain disorders. Further, the different strategies to promote protein delivery into the brain are presented, including the use of molecular Trojan horses, the formulation of nanosystems conjugated/loaded with proteins, protein-engineering technologies, the conjugation of proteins to polymers, and the modulation of intercellular junctions. Additionally, therapeutic approaches for brain diseases that do not involve targeting to the brain are presented (i.e., sink and scavenging mechanisms).
Abstract Background Iliac branch device (IBD) technique has been introduced as an appealing and effective solution to avoid complications occurring during repair of aorto-iliac aneurysm with ...extensive iliac involvement. Nevertheless, no large series with long-term follow-up of IBD are available. The aim of this study was to analyse safety and long-term efficacy of IBD in a consecutive series of patients. Methods Between 2006 and 2011, 100 consecutive patients were enrolled in a prospective database on IBD. Indications included unilateral or bilateral common iliac artery aneurysms combined or not with abdominal aneurysms. Patients were routinely followed up with computed tomography. Data were reported according to the Kaplan–Meier method. Results There were 96 males, mean age 74.1 years. Preoperative median common iliac aneurysm diameter was 40 mm (interquartile range (IQR): 35–44 mm). Sixty-seven patients had abdominal aortic aneurysm >35 mm (IQR: 40–57 mm) associated with iliac aneurysm. Eleven patients presented hypogastric aneurysm. Twelve patients underwent isolated iliac repair with IBD and 88 patients received associated endovascular aortic repair. Periprocedural technical success rate was 95%, with no mortality. Two patients experienced external iliac occlusion in the first month. At a median follow-up of 21 months (range 1–60) aneurysm growth >3 mm was detected in four iliac (4%) arteries. Iliac endoleak (one type III and two distal type I) developed in three patients and buttock claudication in four patients. Estimated patency rate of internal iliac branch was 91.4% at 1 and 5 years. Freedom from any reintervention rate was 90% at 1 year and 81.4% at 5 years. No late ruptures occurred. Conclusions Long-term results show that IBD use can ensure persistent iliac aneurysm exclusion at 5 years, with low risk of reintervention. This technique can be considered as a first endovascular option in patients with extensive iliac aneurysm disease and favourable anatomy.
Summary Sickle cell disease (SCD) includes a group of heterogenous disorders that result in significant morbidities. HbSS is the most common type of SCD and HbSC is the second most common type of ...SCD. The prevalence of HbSC disease in the United States and United Kingdom is ~1 in 7174 births and 1 in 6174 births respectively. Despite its frequency, however, HbSC disease has been insufficiently studied and was historically categorized as a more ‘mild’ form of SCD. We conducted this study of HbSC disease as part of the NHLBI funded Sickle Cell Disease Implementation Consortium (SCDIC). The SCDIC registry included 2282 individuals with SCD, ages 15–45 years of whom 502 (22%) had HbSC disease. Compared with people with sickle cell anaemia (SCA), the study found that people with HbSC disease had a higher frequency of splenomegaly ( n (%) = 169 (33.7) vs. 392 (22.1)) and retinopathy ( n (%) = 116 (23.1) vs. 189 (10.6)). A Many people with HbSC also had avascular necrosis ( n (%) = 112 (22.3)), pulmonary embolism ( n (%) = 43 (8.6)) and acute chest syndrome ( n (%) = 228 (45.4)) demonstrating significant disease severity. HbSC disease is more clinically severe than was previously recognized and deserves additional evaluation and targeted treatments.
Background
The concordance of haemovigilance criteria developed for surveillance of transfusion‐associated circulatory overload (TACO) with its clinical diagnosis has not been assessed. In a pilot ...study to evaluate an electronic screening algorithm, we sought to examine TACO incidence and application of haemovigilance criteria in patients with post‐transfusion pulmonary oedema.
Study Design and Methods
From June to September 2014, all transfused adult inpatients at four academic hospitals were screened with an algorithm identifying chest radiographs ordered within 12 h of blood component release. Patients with post‐transfusion pulmonary oedema underwent case adjudication by an expert panel. TACO incidence was calculated, and clinical characteristics were compared with other causes of post‐transfusion pulmonary oedema.
Results
Among 4932 transfused patients, there were 3412 algorithm alerts, 50 cases of TACO and 47 other causes of pulmonary oedema. TACO incidence was 1 case per 100 patients transfused. TACO classification based on two sets of haemovigilance criteria (National Healthcare Safety Network and proposed revised International Society for Blood Transfusion) was concordant with expert panel diagnosis in 57% and 54% of reviewed cases, respectively. Although the majority of clinical parameters did not differentiate expert panel adjudicated TACO from other cases, improved oxygenation within 24 h of transfusion did (P = 0·01).
Conclusions
The incidence of TACO was similar to that observed in prior studies utilizing active surveillance. Case classification by haemovigilance criteria was frequently discordant with clinical diagnoses of TACO in patients with post‐transfusion pulmonary oedema. Improvements in oxygenation within 24 h of transfusion merit further evaluation in the diagnosis of TACO.
This paper presents a model-based fault detection (FD) and isolation scheme for rigid manipulators. A single fault acting on a specific actuator or on a specific sensor of the manipulator is detected ...(and, if possible, the exact location of the fault), and an estimation of the fault signal is performed. Input-signal estimator and output observers are considered in order to make the FD procedure possible. By using the suboptimal second-order sliding-mode (SOSM) algorithm to design the input laws of the observers, satisfactory stability properties of the observation error are established. The proposed algorithm is verified in simulation and experimentally on a COMAU SMART3-S2 robot manipulator.
Drug delivery to the brain is a challenge because of the many mechanisms that protect the brain from the entry of foreign substances. Numerous molecules which could be active against brain disorders ...are not clinically useful due to the presence of the blood-brain barrier. Nanoparticles can be used to deliver these drugs to the brain. Encapsulation within colloidal systems can allow the passage of nontransportable drugs across this barrier by masking their physicochemical properties. It should be noted that the status of the blood-brain barrier is different depending on the brain disease. In fact, in some pathological situations such as tumors or inflammatory disorders, its permeability is increased allowing very easy translocation of carriers. This chapter gathers the promising results obtained by using nanoparticles as drug delivery systems with the aim to improve the therapy of some CNS diseases such as brain tumor, Alzheimer's disease, and stroke. The data show that several approaches can be investigated: (1) carrying drug through a permeabilized barrier, (2) crossing the barrier thanks to receptor-mediated transcytosis pathway in order to deliver drug into the brain parenchyma, and also (3) targeting and treating the endothelial cells themselves to preserve locally the brain tissue. The examples given in this chapter contribute to demonstrate that delivering drugs into the brain is one of the most promising applications of nanotechnology in clinical neuroscience.
In vitro electrophysiological data suggest that interleukin‐1 may promote non‐rapid eye movement sleep by inhibiting spontaneous firing of wake‐active serotonergic neurons in the dorsal raphe nucleus ...(DRN). Interleukin‐1 enhances GABA inhibitory effects. DRN neurons are under an inhibitory GABAergic control. This study aimed to test the hypothesis that interleukin‐1 inhibits DRN serotonergic neurons by potentiating GABAergic inhibitory effects. In vitro intracellular recordings were performed to assess the responses of physiologically and pharmacologically identified DRN serotonergic neurons to rat recombinant interleukin‐1β. Coronal slices containing DRN were obtained from male Sprague–Dawley rats. The impact of interleukin‐1 on firing rate and on evoked post‐synaptic potentials was determined. Evoked post‐synaptic potentials were induced by stimulation with a bipolar electrode placed on the surface of the slice ventrolateral to DRN. Addition of interleukin‐1 (25 ng/mL) to the bath perfusate significantly decreased firing rates of DRN serotonergic neurons from 1.3 ± 0.2 Hz (before administration) to 0.7 ± 0.2 Hz. Electrical stimulation induced depolarizing evoked post‐synaptic potentials in DRN serotonergic neurons. The application of glutamatergic and GABAergic antagonists unmasked two different post‐synaptic potential components: a GABAergic evoked inhibitory post‐synaptic potentials and a glutamatergic evoked excitatory post‐synaptic potentials, respectively. Interleukin‐1 increased GABAergic evoked inhibitory post‐synaptic potentials amplitudes by 30.3 ± 3.8% (n = 6) without affecting glutamatergic evoked excitatory post‐synaptic potentials. These results support the hypothesis that interleukin‐1 inhibitory effects on DRN serotonergic neurons are mediated by an interleukin‐1‐induced potentiation of evoked GABAergic inhibitory responses.
Bioprobes immobilization methods that elevate the probes from the substrate are generally preferred in microarray technology because they prevent steric limitations during the hybridization of the ...target to probes. A versatile approach to control the thickness of a polymeric coating based on click chemistry to obtain covalently linked layer-by-layer coatings for surface functionalization is presented. By alternating cycles of coating using copolymers bearing click groups, the thickness of the film increases, while remaining functional and stable. Click chemistry reactions provide numerous advantages over standard conjugation procedures typically used in microarrays. They include: quantitative yields and insensitivity of the reaction to pH and hydrolysis. Moreover, click reactions do not interfere with organic groups naturally present in DNA, proteins and peptides such as amino and carboxyl groups allowing orthogonal and chemoselective probe immobilization. In addition to the formation of multilayers, click reactions allow to bind biomolecules to polymer chains generating so-called polymeric probes, which are then immobilized on microarray supports. In a microarray assay of clinical relevance, this methodology provides a miniaturized, tri-dimensional multilayer with higher density of capture probe, improved hybridization efficiency and sensitivity.
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