Abstract: 3D printing technologies enable medicine customization adapted to patients' needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid and locally applied or implanted medicines. 3D printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained release 3D-printed implants, stents and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines such as wound dressing, microneedles, and medicated contact lenses have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing tech-nique most suitable for each application and the type of pharmaceutical ink that should be devel-oped that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing (""Nanoprinting"") brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice.

Abstract: Reseña literaria de la novela “Lectura Fácil” de la escritora española Cristina Morales, ganadora del premio Herralde de Novela. Estableciendo conexiones con la escritora chilena Diamela Eltit, el cineasta argentino Gaspar Noé y la banda española Mecano, esta reseña indaga en las exploraciones de la autora en cuanto a feminismo, diversidad funcional, identidad, género, sistema económico, entre otros.

Abstract: Acute brain injuries are associated with high mortality rates and poor long-term functional outcomes. Measurement of cerebrospinal fluid (CSF) biomarkers in patients with acute brain injuries may help elucidate some ofthe pathophysiological pathways involved in the prognosis of these patients. We performed a systematic search and descriptive review using the MEDLINE database and the PubMed interface from inception up to June 29, 2021. Of the 39 studies that met our criteria, 30 reported that the biomarker concentration was associated with neurological outcome and 9 reported no association. In traumatic brain injury patients, increased extracellular concentrations of biomarkers related to neuronal cytoskeletal disruption, apoptosis and inflammation were associated with the severity of acute brain injury, early mortality and worse long-term functional outcome. Reduced concentrations of protein biomarkers related to impaired redox function were associated with increased risk of neurological deficit. In non-traumatic acute brain injury, concentrations of CSF protein biomarkers related to dysregulated inflammation and apoptosis were associated with a greater risk of vasospasm and a larger volume of brain ischemia. Resumen: Las lesiones cerebrales agudas se asocian con altas tasas de mortalidad y malos resultados funcionales a largo plazo. La medición de biomarcadores en el líquido cefalorraquídeo (LCR) en pacientes con lesiones cerebrales agudas puede ayudar a dilucidar algunas de las vías fisiopatológicas implicadas en el pronóstico de estos pacientes. Realizamos una búsqueda sistemática y revisión descriptiva utilizando la base de datos MEDLINE y la interfaz PubMed desde su inicio hasta el 29 de junio de 2021.De los 39 estudios que cumplieron con nuestros criterios de inclusión, 30 informaron que la concentración del biomarcador se asoció con el resultado neurológico y 9 no informaron ninguna asociación. En lesiones cerebrales traumáticas, el aumento de las concentraciones extracelulares de biomarcadores relacionados con la alteración del citoesqueleto neuronal, la apoptosis y la inflamación se asociaron con la gravedad de la lesión cerebral aguda, la mortalidad temprana y un peor resultado funcional a largo plazo. Las concentraciones reducidas de biomarcadores proteicos relacionados con la función redox deteriorada se asociaron con un mayor riesgo de déficit neurológico. En la lesión cerebral aguda no traumática, las concentraciones de biomarcadores proteicos del LCR relacionados con la inflamación desregulada y la apoptosis se asociaron con un mayor riesgo de vasoespasmo y un mayor volumen de isquemia cerebral.

Abstract: Quantitative analysis of ventricular cerebrospinal fluid (vCSF) proteins following acute brain injury (ABI) may help identify pathophysiological pathways and potential biomarkers that can predict unfavorable outcome. In this prospective proteomic analysis study, consecutive patients with severe ABI expected to require intraventricular catheterization for intracranial pressure (ICP) monitoring for at least 5 days and patients without ABI admitted for elective clipping of an unruptured cerebral aneurysm were included. vCSF samples were collected within the first 24 h after ABI and ventriculostomy insertion and then every 24 h for 5 days. Data-independent acquisition and sequential window acquisition of all theoretical spectra (SWATH) mass spectrometry were used to compare differences in protein expression in patients with ABI and patients without ABI and in patients with traumatic and nontraumatic ABI. We included 50 patients with ABI (SAH n = 23, TBI n = 15, intracranial hemorrhage n = 6, ischemic stroke n = 3, others n = 3) and 12 patients without ABI. There were significant differences in the expression of 255 proteins between patients with and without ABI (p < 0.01). There were intraday and interday differences in expression of seven proteins related to increased inflammation, apoptosis, oxidative stress, and cellular response to hypoxia and injury. Among these, glial fibrillary acidic protein expression was higher in patients with ABI with severe intracranial hypertension (ICH) (ICP ? 30 mm Hg) or death compared to those without (log 2 fold change: +2.4; p < 0.001), suggesting extensive primary astroglial injury or death. Dysregulated vCSF protein expression after ABI may be associated with an increased risk of severe ICH and death. Resumen: El análisis cuantitativo de las proteínas en el líquido cefalorraquídeo ventricular (vLCR) después de una lesión cerebral aguda (LCA) puede ayudar a identificar vías fisiopatológicas y posibles biomarcadores que pueden predecir un resultado desfavorable. En este estudio prospectivo de análisis proteómico, se incluyeron pacientes consecutivos con LCA grave que se esperaba que necesitaran cateterismo intraventricular cerebral para monitorizar la presión intracraneal (PIC) durante al menos 5 días y pacientes sin LCA ingresados para clipaje electivo de un aneurisma cerebral no roto. Las muestras de vCSF se recolectaron dentro de las primeras 24 h después de la inserción del ITB y la ventriculostomía y luego cada 24 h durante 5 días. Se utilizó la espectrometría de masas de adquisición independiente de datos y adquisición de ventana secuencial de todos los espectros teóricos (SWATH) para comparar las diferencias en la expresión de proteínas en pacientes con LCA y pacientes sin LCA y en pacientes con LCA traumática y no traumática. Se incluyeron 50 pacientes con LCA (HSA n = 23, TCE n = 15, hemorragia intracraneal n = 6, ictus isquémico n = 3, otros n = 3) y 12 pacientes sin LCA. Hubo diferencias significativas en la expresión de 255 proteínas entre pacientes con y sin LCA (p <0,01). Hubo diferencias intradía e interdía en la expresión de siete proteínas relacionadas con el aumento de la inflamación, la apoptosis, el estrés oxidativo y la respuesta celular a la hipoxia y las lesiones. Entre estos, la expresión de la proteína ácida fibrilar glial fue mayor en pacientes con LCA con hipertensión intracraneal (HIC) grave (PIC ? 30 mm Hg) o muerte en comparación con aquellos sin (cambio log 2 veces: + 2,4; p < 0,001), lo que sugiere una extensa Lesión astroglial primaria. La expresión desregulada de las proteínas en el vLCR después de una LCA puede estar asociada con un mayor riesgo de HIC grave y muerte.

Abstract: Patients with traumatic brain injury (TBI) are at an increased risk of developing chronic neurodegenerative diseases, including Alzheimer’s disease (AD), an association thought to be related to several factors, including altered production and clearance of apolipoprotein E (ApoE) and amyloid-? (A?). We previously reported decreased CSF expression of proteins related to cholesterol metabolism in patients with ABI, which may potentially lead to reduced neuro-steroid production, increased risk of neurodegenerative disease, and worse functional outcomes. In this post hoc analysis, ApoE (ApoEelisa), amyloid beta 1–40 (A?1–40), and amyloid beta 1–42 (A?1–42) concentrations were measured in vCSF taken from an external ventricular drain on Days 1–5 after non-traumatic ABI. The vCSF concentrations of ApoE were measured using a commercial enzyme linked immunosorbent assay (ELISA) test . The vCSF concentrations of A?1–40 and A?1–42 were also measured using a commercial ELISA test, with 50 ?l/patient (robotic pipette) per sample in duplicate using A?1–40 and A?1–42 monoclonal antibody, respectively. Day 1 ApoEelisa concentrations were significantly lower (p < 0.01) in patients with non-traumatic ABI than in control patients. vCSF A?1–40 (p < 0.001) and A?1–42 (p < 0.001) concentrations were also lower in the ABI patients. Day 1–5 ApoEswath protein expressions were significantly lower in patients with nontraumatic ABI than in controls (p < 0.0001). APLP1 values, but not those of APP or APLP2, were also significantly lower in non-traumatic ABI (p < 0.0001) throughout the 5-day period. These findings suggest that specific precursors of neurotoxic A? may be expressed in the early phase of nontraumatic ABI, such as that caused by vascular injury after ischemic or hemorrhagic strokes. Resumen: Los pacientes con lesión cerebral traumática (LCA traumática) tienen un mayor riesgo de desarrollar enfermedades neurodegenerativas crónicas, incluida la enfermedad de Alzheimer (EA), una asociación que se cree que está relacionada con varios factores, incluida la producción alterada y la eliminación de la apolipoproteína E (ApoE). y ?-amiloide (A?). Anteriormente informamos una disminución de la expresión en el LCR de proteínas relacionadas con el metabolismo del colesterol en pacientes con LCA, lo que potencialmente puede conducir a una reducción de la producción de neuroesteroides, un mayor riesgo de enfermedades neurodegenerativas y peores resultados funcionales. En este análisis post hoc, se midieron las concentraciones de ApoE (ApoEelisa), beta amiloide 1–40 (A?1–40) y beta amiloide 1–42 (A?1–42) en vCSF extraído de un drenaje ventricular externo en los días 1 a 5 después LCA no traumática. Las concentraciones de ApoE en vCSF se midieron utilizando una prueba comercial de ensayo inmunoabsorbente ligado a enzimas (ELISA). Las concentraciones de vCSF de A?1–40 y A?1–42 también se midieron utilizando una prueba ELISA comercial, con 50 ?l/paciente (pipeta robótica) por muestra por duplicado utilizando los anticuerpos monoclonales A?1–40 y A?1–42, respectivamente. Las concentraciones de ApoEelisa en el día 1 fueron significativamente más bajas (p <0,01) en pacientes con LCA no traumática que en pacientes de control. Las concentraciones de vCSF A?1–40 (p <0,001) y A?1–42 (p <0,001) también fueron más bajas en los pacientes con LCA. Las expresiones de la proteína ApoEswath de los días 1 a 5 fueron significativamente menores en pacientes con LCA no traumática que en los controles (p <0,0001). Los valores de APLP1, pero no los de APP o APLP2, también fueron significativamente más bajos en la LCA no traumática (p <0,0001) durante el período de 5 días. Estos hallazgos sugieren que precursores específicos de A? neurotóxico pueden expresarse en la fase temprana de una LCA no traumática, como la causada por una lesión vascular después de un accidente cerebrovascular isquémico o hemorrágico.

Abstract: The interaction of defects can lead to a phenomenon of erasure. During this process, a lower-dimensional object gets absorbed and dissolved by a higher-dimensional one. The phenomenon is very general and has a wide range of cosmological and fundamental implications. In particular, all types of strings, such as cosmic strings, QCD flux tubes, or fundamental strings, get erased when encountering a defect, either solitonic or a D-brane that deconfines their fluxes. This leads to a novel mechanism of cosmic string breakup, accompanied by gravitational and electromagnetic radiations. The arguments based on loss of coherence and the entropy count suggest that the erasure probability is very close to one, and strings never make it through the deconfining layer. We confirm this by a numerical simulation of the system, which effectively captures the essence of the phenomenon: a 2+1- dimensional problem of interaction between a Nielsen-Olesen vortex of a U(1) Higgs model and a domain wall, inside which the U(1) gauge group is un-Higgsed, and the magnetic flux is deconfined. In accordance with the entropy argument, in our simulation, the vortex never makes it across the wall.

Abstract: Vorticity has recently been suggested to be a property of highly-spinning black holes. The connection between vorticity and limiting spin represents a universal feature shared by objects of maximal microstate entropy, so-called saturons. Using QQ-ball-like saturons as a laboratory for black holes, we study the collision of two such objects and find that vorticity can have a large impact on the emitted radiation as well as on the charge and angular momentum of the final configuration. As black holes belong to the class of saturons, we expect that the formation of vortices can cause similar effects in black hole mergers, leading to macroscopic deviations in gravitational radiation. This could leave unique signatures detectable with upcoming gravitational-wave searches, which can thereby serve as a portal to macroscopic quantum effects in black holes. Note: ancillary video at https://youtu.be/t29WUvZM-io

Abstract: Black holes are considered exceptional due to their time evolution and information processing. However, it was proposed recently that these properties are generic for objects, the so-called saturons, that attain the maximal entropy permitted by unitarity. The present paper verifies this connection within a renormalizable SU(N) invariant theory. We show that the spectrum of the theory contains a tower of bubbles representing bound states of SU(N) Goldstones. Despite the absence of gravity, a saturated bound state exhibits a striking correspondence with a black hole: Its entropy is given by the Bekenstein-Hawking formula; semiclassically, the bubble evaporates at a thermal rate with a temperature equal to its inverse radius; the information retrieval time is equal to Page’s time. The correspondence goes through a trans-theoretic entity of the Poincaré Goldstone. The black hole–saturon correspondence has important implications for black hole physics, both fundamental and observational.

Abstract: In this work, we study the annihilation of a pair of ‘t Hooft-Polyakov monopoles due to confinement by a string. We analyze the regime in which the scales of monopoles and strings are comparable. We compute the spectrum of the emitted gravitational waves and find it to agree with the previously calculated pointlike case for wavelengths longer than the system width and before the collision. However, we observe that in a head-on collision, monopoles are never recreated. Correspondingly, not even once the string oscillates. Instead, the system decays into waves of Higgs and gauge fields. We explain this phenomenon by the loss of coherence in the annihilation process. Due to this, the entropy suppression makes the recreation of a monopole pair highly improbable. We argue that in a similar regime, analogous behavior is expected for the heavy quarks connected by a QCD string. There too, instead of restretching a long string after the first collapse, the system hadronizes and decays in a high multiplicity of mesons and glueballs. We discuss the implications of our results.

Abstract: We study the interactions between ’t Hooft-Polyakov magnetic monopoles and the domain walls formed by the same order parameter within an SU(2) gauge theory. We observe that the collision leads to the erasure of the magnetic monopoles, as suggested by Dvali et al. [Phys. Rev. Lett. 80, 2281 (1998)]. The domain wall represents a layer of vacuum with un-Higgsed SU(2) gauge symmetry. When the monopole enters the wall, it unwinds, and the magnetic charge spreads over the wall. We perform numerical simulations of the collision process and, in particular, analyze the angular distribution of the emitted electromagnetic radiation. As in the previous studies, we observe that erasure always occurs. Although not forbidden by any conservation laws, the monopole never passes through the wall. This is explained by entropy suppression. The erasure phenomenon has important implications for cosmology, as it sheds a very different light on the monopole abundance in postinflationary phase transitions and provides potentially observable imprints in the form of electromagnetic and gravitational radiation. The phenomenon also sheds light on fundamental aspects of gauge theories with coexisting phases, such as confining and Higgs phases.