Integrating a micro-mixing mechanism and on-line thermal processing for the large-scale ejection of polymeric liquid threads for producing ultrafine fibers.

Micro/nanofibers are structures that nowadays have a wide range of cutting-edge applications including energy generation and storage devices, smart textiles, cell growth, and tissue engineering. These fibrous materials are mostly produced from polymer solutions spun, under laminar flow conditions, into nanofibers by external forces. However, the turbulent interaction of gas-liquid interfaces offers an innovative approach for the high-throughput production of nanofibers. Here, we present Flow Blurring (FB), a solely pneumatic approach for the massive production of liquid threads of polymer solutions, which relies on a micro-mixing mechanism that triggers a turbulent motion capable of fragmenting a viscous flow. The as-ejected threads are subsequently processed thermally, on-line in a single-step, thus producing micro/nanofibers that form mats. The method operates with relatively large liquid flow rates, equivalent of a high production rate, and is thus suitable for industrial production of engineered nanomaterials. In this work, we used solutions of poly(vinyl alcohol) (PVA) to study its ejection and fragmentation dynamics through computational fluid dynamics (CFD) simulations. In addition, the physics underlying the regulation of the liquid flow rate in FB atomizers are proposed. Fibers with typical diameters in the range 400-800 nm were produced by online heating of the liquid threads. Liquid ejection experiments were performed under different operating conditions thus verifying the capability of the method for synthesizing submicrometer-sized fibers with high uniformity and production rates suitable for scaling up.

Micromixing with In-Flight Charging of Polymer Solutions in a Single Step Enables High-Throughput Production of Micro- and Nanofibers.

Controlled ejection of liquids at capillary scales is a ubiquitous phenomenon associated with significant advances in, for instance, molecular biology or material synthesis. In this work, we introduce a high-throughput approach, which relies on a micromixing mechanism to eject and fragment viscous liquids, for production of microfibers from poly(vinyl alcohol) solutions. First, filaments were generated pneumatically with a so-called flow-blurring atomizer and using liquid flow rates of up to ∼1 L/min. Subsequently, the filaments were ionized online by corona discharge and consecutively manipulated with an electric field created by disc electrodes. Such charging of the filaments and the effect of the electric field allowed for their ultrafast elongation and diameter reduction from 150 µm down to fibers of 500 nm, which after collection exhibited fabric-like texture. The approach presented herein is a general procedure with potential for scalability that, upon proper adaptation, may be extended to various polymeric materials.

On the Ejection of Filaments of Polymer Solutions Triggered by a Micrometer-Scale Mixing Mechanism.

Polymer filaments constitute precursor materials of so-called fiber mats, ubiquitous structures across cutting-edge technological fields. Thus, approaches that contribute to large-scale production of fibers are desired from an industrial perspective. Here, we use a robust liquid atomization device operated at relatively high flow rates, ~20 mL/min, as facilitating technology for production of multiple polymer filaments. The method relies on a turbulent, energetically efficient micro-mixing mechanism taking place in the interior of the device. The micro-mixing is triggered by radial implosion of a gas current into a liquid feeding tube, thus resulting in breakup of the liquid surface. We used poly(ethylene oxide) solutions of varying concentrations as test liquids to study their fragmentation and ejection dynamics employing ultra-high speed imaging equipment. Taking an energy cascade approach, a scaling law for filament diameter was proposed based on gas pressure, liquid flow rate and viscosity. We find that a filament dimensionless diameter, Df*, scales as a non-dimensional liquid flow rate Q* to the 1/5. The study aims to elucidate the underlying physics of liquid ejection for further applications in material production.

Sustained response to Rituximab in anti-AChR and anti-MuSK positive Myasthenia Gravis patients.

We report the results of treatment with Rituximab in six severe, non-responder MG patients. We treated three AChR+MG and three MuSK+MG patients, representing 2% and 20% of the respective groups of our series. Patients were assessed according to the Myasthenia Gravis Foundation of America (MGFA) recommendations. Antibody titers to AChR and MuSK, Ig levels, and IgG subclasses, were tested before treatment and during a follow-up of 9-22 months. All patients, one class V and five class IVB, improved dramatically, with no side effects. Antibody titers declined in all patients (p=0.006). The decline was significantly better in MuSK+MG patients at 9 months (p=0.046) and correlated with a more sustained clinical improvement. We did not find any significant changes in IgG4 that could explain the different outcome observed between these two groups.

Early diagnosis of amyotrophic lateral sclerosis mimic syndromes: pros and cons of current clinical diagnostic criteria.

OBJECTIVE: To describe the frequency and clinical characteristics of patients referred to a tertiary neuromuscular clinic as having amyotrophic lateral sclerosis (ALS) but who were re-diagnosed as having an ALS mimic syndrome, and to identify the reasons that led to the revision of the diagnosis. METHODS: We reviewed the final diagnosis of all patients prospectively registered in the Sant Pau-MND register from 1 January 2004 to 31 December 2015. A detailed clinical evaluation and a clinically-guided electrophysiological study were performed at first evaluation. RESULTS: Twenty of 314 (6.4%) patients included were re-diagnosed as having a condition other than ALS, in 18 cases already at first evaluation. An alternative specific diagnosis was identified in 17 of those 20, consisting of a wide range of conditions. The main finding leading to an alternative diagnosis was the result of the electrophysiological study. Fifty per cent did not fulfil the El Escorial revised criteria (EECr) for ALS. The most common clinical phenotype at onset in patients with ALS mimic syndromes was progressive muscular atrophy (PMA). CONCLUSIONS: Misdiagnosing ALS is still a common problem. Early identification of ALS mimic syndromes is possible based on atypical clinical features and a clinically-guided electrophysiological study. Patients should be attended in specialised centres. The application of EECr helps to identify ALS misdiagnoses.

Effects of 8-week, interval-based inspiratory muscle training and breathing retraining in patients with generalized myasthenia gravis.

STUDY OBJECTIVE: To assess the effect of interval-based inspiratory muscle training (IMT) combined with breathing retraining (BR) in patients with generalized myasthenia gravis (MG) in a partial home program. DESIGN: A randomized controlled trial with blinding of outcome assessment. SETTING: A secondary-care respiratory clinic. PATIENTS: Twenty-seven patients with generalized MG were randomized to a control group or a training group. INTERVENTIONS: The training group underwent interval-based IMT associated with BR (diaphragmatic breathing [DB] and pursed-lips breathing [PLB]) three times a week for 8 weeks. The sessions included 10 min each of DB, interval-based IMT, and PLB. Interval-based IMT consisted of training series interspersed with recovery time. The threshold load was increased from 20 to 60% of maximal inspiratory pressure (P(Imax)) over the 8 weeks. MEASUREMENTS AND RESULTS: Lung function, respiratory pattern, respiratory muscle strength, respiratory endurance, and thoracic mobility were measured before and after the 8 weeks. The training group improved significantly compared to control group in P(Imax) (p = 0.001), maximal expiratory pressure (P(Emax)) [p = 0.01], respiratory rate (RR)/tidal volume (V(T)) ratio (p = 0.05), and upper chest wall expansion (p = 0.02) and reduction (p = 0.04). Significant differences were seen in the training group compared to baseline P(Imax) (p = 0.001), P(Emax) (p = 0.01), maximal voluntary ventilation (p = 0.02), RR/V(T) ratio (p = 0.003), Vt (p = 0.02), RR (p = 0.01), total time of RR (p = 0.01), and upper chest wall expansion (p = 0.005) and reduction (p = 0.005). No significant improvement was seen in lower chest wall or lung function. CONCLUSIONS: The partial home program of interval-based IMT associated with BR is feasible and effective in patients with generalized MG. Improvements in respiratory muscle strength, chest wall mobility, respiratory pattern, and respiratory endurance were observed.

["Seronegative" myasthenia gravis and antiMuSK positive antibodies: description of Spanish series]. / Miastenia gravis "seronegativa" y anticuerpos antiMuSK positivos: descripción de una serie española.

BACKGROUND AND OBJECTIVE: Recently, the presence of antibodies to a muscle-specific tyrosine kinase (MuSK) has been reported in some patients with seronegative generalized myasthenia gravis. Our objective was to describe a group of patients who were positive for anti-MuSK antibodies. PATIENTS AND METHOD: Detection of antibodies using a radioimmunoassay was performed in the serum of 26 patients with generalized myasthenia gravis. We identified 9 patients with anti-MuSK antibodies (MuSK+). Clinical and therapeutic data from these patients were reviewed. RESULTS: Eight of nine patients were women aged between 20 and 40 years. Clinically, all of them showed prevalent bulbar signs, initially or during the progression of the disease. 77% of patients showed ocular involvement and 44% had symptoms of fatigability involving limbs. None of them improved upon thymectomy. Response to acetylcholinesterase inhibitors was variable. All of them responded to immunotherapy, although 30% required polytherapy. CONCLUSIONS: The study of anti-MuSK antibodies defines a subgroup of patients, 34,61% in our series, with seronegative generalized myasthenia. This group is characterized by an homogenous clinical presentation with prevalent bulbar symptoms. The knowledge of the immunopathogenic mechanisms of anti-MuSK antibodies will allow a better understanding of both the variable response to acetylcholinesterase inhibitors and the absence of response to thymectomy in these patients.

Comprehensive care of amyotrophic lateral sclerosis patients: a care model.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that presents with muscle weakness, causing progressive difficulty in movement, communication, eating and ultimately, breathing, creating a growing dependence on family members and other carers. The ideal way to address the problems associated with the disease, and the decisions that must be taken, is through multidisciplinary teams. The key objectives of these teams are to optimise medical care, facilitate communication between team members, and thus to improve the quality of care. In our centre, we have extensive experience in the care of patients with ALS through an interdisciplinary team whose aim is to ensure proper patient care from the hospital to the home setting. In this article, we describe the components of the team, their roles and our way of working.

Amyotrophic lateral sclerosis in Catalonia: a population based study.

Our objective was to determine the incidence and clinical-epidemiological characteristics of an ALS cohort patient in Catalonia (Spain). We conducted a population based registry for a three-year period (1999-2001) in Catalonia (6,361,365 inhabitants) using several sources of information. The original El Escorial diagnostic criteria (1994) for ALS were applied for the classification of patients. New cases diagnosed between 1 January 1999 and 31 December 2001 were 215 (118 males and 97 females), with an annual crude incidence rate of 1.4/100,000 (95% CI 1.3-1.8). This rate showed a peak age between 75 and 79 years. The incidence rate was 1.6 (95% CI 1.5-2.2) in males and 1.2 (95% CI 1.1-1.7) in females. Prevalence at the end of the period was 5.4/100,000 of the total population. Median age at onset was 64.3 years. Onset of symptoms was bulbar or generalized in 38% of cases. Mean disease duration at diagnosis was 11.0 months. Median time of survival from onset was 30.8 months. In conclusion, ALS incidence in Catalonia is within the range of other countries across Europe with different geographic, environmental and socioeconomic situations. However, as in other studies conducted in the Mediterranean area, Catalonia incidence is in the lower range of rates in Europe.

Atención integral a pacientes con esclerosis lateral amiotrófica: un modelo asistencial / Comprehensive Care of Amyotrophic Lateral Sclerosis Patients: A Care Model

La esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa devastadora que se manifiesta por debilidad muscular y produce dificultades progresivas de movilización, comunicación, alimentación y, en última instancia, respiración, creando una dependencia creciente de familiares y de otros cuidadores. La manera ideal de afrontar los problemas derivados de la enfermedad y las decisiones necesarias es a través de equipos multidisciplinarios. Los objetivos fundamentales de estos equipos son optimizar la atención médica, facilitar la comunicación entre los miembros del equipo y consecuentemente mejorar la calidad asistencial. En nuestro centro tenemos una larga experiencia en la atención a pacientes con ELA a través de un equipo interdisciplinario cuya pretensión es asegurar la correcta asistencia del paciente desde el hospital hasta el propio domicilio. En este artículo mostramos los componentes del equipo, sus funciones y nuestro modo de trabajo (AU)

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that presents with muscle weakness, causing progressive difficulty in movement, communication, eating and ultimately, breathing, creating a growing dependence on family members and other carers. The ideal way to address the problems associated with the disease, and the decisions that must be taken, is through multidisciplinary teams. The key objectives of these teams are to optimise medical care, facilitate communication between team members, and thus to improve the quality of care. In our centre, we have extensive experience in the care of patients with ALS through an interdisciplinary team whose aim is to ensure proper patient care from the hospital to the home setting. In this article, we describe the components of the team, their roles and our way of working (AU)

Miastenia gravis «seronegativa» y anticuerpos antiMuSK positivos: descripción de una serie española / «Seronegative» myasthenia gravis and antiMuSK positive antibodies: description of Spanish series

Fundamento y objetivo: Recientemente se ha descrito que un subgrupo de pacientes con miastenia gravis generalizada seronegativa tienen anticuerpos frente a la molécula tirosincinasa muscular específica (AcMuSK). Nuestro objetivo es describir nuestra serie de pacientes con miastenia generalizada y AcMuSK positivo. Pacientes y método: Mediante radioinmunoanálisis se determinaron los anticuerpos en el suero de 26 pacientes con miastenia generalizada seronegativa. Se identificaron 9 pacientes con AcMuSK, cuyos datos clínicos y terapéuticos se revisaron. Resultados: De los 9 pacientes, 8 eran mujeres de entre 20 y 40 años. Todos presentaron debilidad bulbar grave, bien inicialmente o durante la evolución. El 77% presentó también clínica ocular y un 44%, fatigabilidad leve en las extremidades. Ninguno mejoró tras la timectomía. La respuesta a anticolinesterásicos fue variable. Todos respondieron a inmunoterapia, aunque un 30% precisó politerapia. Conclusiones: Los AcMuSK distinguen a un subgrupo de pacientes, el 34,61% en esta serie, con miastenia generalizada seronegativa que presentan una clínica homogénea con debilidad de predominio bulbar. Conocer los mecanismos inmunopatológicos de los AcMuSK permitirá entender la variabilidad de respuesta a los anticolinesterásicos, así como la falta de respuesta a la timectomía, en estos pacientes

Background and objective: Recently, the presence of antibodies to a muscle-specific tyrosine kinase (MuSK) has been reported in some patients with seronegative generalized myasthenia gravis. Our objective was to describe a group of patients who were positive for anti-MuSK antibodies. Patients and method: Detection of antibodies using a radioimmunoassay was performed in the serum of 26 patients with generalized myasthenia gravis. We identified 9 patients with anti-MuSK antibodies (MuSK+). Clinical and therapeutic data from these patients were reviewed. Results: Eight of nine patients were women aged between 20 and 40 years. Clinically, all of them showed prevalent bulbar signs, initially or during the progression of the disease. 77% of patients showed ocular involvement and 44% had symptoms of fatigability involving limbs. None of them improved upon thymectomy. Response to acetylcholinesterase inhibitors was variable. All of them responded to immunotherapy, although 30% required polytherapy. Conclusions: The study of anti-MuSK antibodies defines a subgroup of patients, 34,61% in our series, with seronegative generalized myasthenia. This group is characterized by an homogenous clinical presentation with prevalent bulbar symptoms. The knowledge of the immunopathogenic mechanisms of anti-MuSK antibodies will allow a better understanding of both the variable response to acetylcholinesterase inhibitors and the absence of response to thymectomy in these patients