Advanced CMOS manufacturing of superconducting qubits on 300 mm wafers.

The development of superconducting qubit technology has shown great potential for the construction of practical quantum computers1,2. As the complexity of quantum processors continues to grow, the need for stringent fabrication tolerances becomes increasingly critical3. Utilizing advanced industrial fabrication processes could facilitate the necessary level of fabrication control to support the continued scaling of quantum processors. However, at present, these industrial processes are not optimized to produce high-coherence devices, nor are they a priori compatible with the approaches commonly used to make superconducting qubits. Here we demonstrate superconducting transmon qubits manufactured in a 300 mm complementary metal-oxide-semiconductor (CMOS) pilot line using industrial fabrication methods, with resulting relaxation and coherence times exceeding 100 µs. We show across-wafer, large-scale statistics of coherence, yield, variability and ageing that confirm the validity of our approach. The presented industry-scale fabrication process, which uses only optical lithography and reactive-ion etching, has a performance and yield in line with conventional laboratory-style techniques utilizing metal lift-off, angled evaporation and electron-beam writing4. Moreover, it offers the potential for further upscaling through three-dimensional integration5 and more process optimization. This result marks the advent of an alternative and new, large-scale, truly CMOS-compatible fabrication method for superconducting quantum computing processors.

Osteogenic-angiogenic coupled response of cobalt-containing mesoporous bioactive glasses in vivo.

The incorporation of cobalt ions into the composition of bioactive glasses has emerged as a strategy of interest for bone regeneration purposes. In the present work, we have designed a set of bioactive mesoporous glasses SiO2-CaO-P2O5-CoO (Co-MBGs) with different amounts of cobalt. The physicochemical changes introduced by the Co2+ ion, the in vitro effects of Co-MBGs on preosteoblasts and endothelial cells and their in vivo behaviour using them as bone grafts in a sheep model were studied. The results show that Co2+ ions neither destroy mesoporous ordering nor inhibit in vitro bioactive behaviour, exerting a dual role as network former and modifier for CoO concentrations above 3 % mol. On the other hand, the activity of Co-MBGs on MC3T3-E1 preosteoblasts and HUVEC vascular endothelial cells is dependent on the concentration of CoO present in the glass. For low Co-MBGs concentrations (1mg/ml) cell viability is not affected, while the expression of osteogenic (ALP, RUNX2 and OC) and angiogenic (VEGF) genes is stimulated. For Co-MBGs concentration of 5 mg/ml, cell viability decreases as a function of the CoO content. In vivo studies show that the incorporation of Co2+ ions to the MBGs improves the bone regeneration activity of these materials, despite the deleterious effect that this ion has on bone-forming cells for any of the Co-MBG compositions studied. This contradictory effect is explained by the marked increase in angiogenesis that takes place inside the bone defect, leading to an angiogenesis-osteogenesis coupling that compensates for the partial decrease in osteoblast cells. STATEMENT OF SIGNIFICANCE: The development of new bone grafts implies to address the need for osteogenesis-angiogenesis coupling that allows bone regeneration with viable tissue in the long term. In this sense the incorporation of cobalt ions into the composition of bioactive glasses has emerged as a strategy of great interest in this field. Due to the potential cytotoxic effect of cobalt ions, there is an important controversy regarding the suitability of their incorporation in bone grafts. In this work, we address this controversy after the implantation of cobalt-doped mesoporous bioactive glasses in a sheep model. The incorporation of cobalt ions in bioactive glasses improves the bone regeneration ability of these bone grafts, due to enhancement of the angiogenesis-osteogenesis coupling.

Conditional performance factors in padel players: a mini review.

Introduction: Padel's global growth highlights its technical complexity. The first publications focus on the physical aspects of padel, using methods that evaluate players' endurance, strength, speed, and range of motion, while the quantification of load, using internal and external indicators, is crucial for performance optimization, whilst taking into account athletes' profiles and levels. Therefore, the objective entailed analyzing the scientific literature about the conditional demands in competition within padel players from different levels. Methods: Data was collected from various databases and after the selection process, the information was analyzed in mini review. Results: The mini review shows that the conditional demands are categorized into internal and external load to try to obtain reference values that may define the demands of padel based on the competitive level and sex. Regarding the internal load, the heart rate (HR)% of the padel players from different levels is around 70%-80% of the HR Max. Regarding the external load, in femalés categories, a greater number of strokes are made per point which entails a longer duration in the points. Conclusions: Padel research usually analyses physical demands using internal and external loading. HR% values (70%-80% HR Max) are consistent across studies. There is variation between variables such as strokes per point, and contextual factors affect the metrics. Further exploration is vital to obtain comprehensive benchmarks and understand the demands of this sport.

[Translated article] Design and comparison of bone substitutes. Study of in vivo behaviour in a rabbit model.

AIM: To compare the in vivo bone formation capacity of of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxiapatite and the other one on bioactive mesoporous glass. MATERIALS AND METHODS: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite scaffold, and with bioactive mesoporous glass scaffold. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. RESULTS: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than the autograft group. CONCLUSION: Both scaffolds seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.

Desing and comparison of bone substitutes. Study of in vivo behavior in a rabbit model. / Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo.

AIM: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. MATERIALS AND METHODS: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. RESULTS: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. CONCLUSION: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.

Intensification of Hydrogen Production by a Co-culture of Syntrophomonas wolfei and Rhodopseudomonas palustris Employing High Concentrations of Butyrate as a Substrate.

The purpose of this study is to present an effective form of developing a sequential dark (DF) and photo (PF) fermentation using volatile fatty acids (VFAs) and nitrogen compounds as bonding components between both metabolic networks of microbial growing in each fermentation. A simultaneous (co-)culture of Syntrophomonas wolfei (with its ability to consume butyrate and produce acetate) and Rhodopseudomonas palustris (that can use the produced acetate as a carbon source) performed a syntrophic metabolism. The former bacteria consumed the acetate/butyrate mixture reducing the butyrate concentration below 2.0 g/L, permitting Rhodopseudomonas palustris to produce hydrogen. Considering that the inoculum composition (Syntrophomonas wolfei/Rhodopseudomonas palustris) and the nitrogen source (yeast extract) define the microbial biomass specific productivity and the butyrate consumption, a response surface methodology defined the best inoculum design and yeast extract (YE) yielding to the highest biomass concentration of 1.1 g/L after 380.00 h. A second culture process (without a nitrogen source) showed the biomass produced in the previous culture process yields to produce a total cumulated hydrogen concentration of 3.4 mmol. This value was not obtained previously with the pure strain Rhodopseudomonas palustris if the culture medium contained butyrate concentration above 2.0 g/L, representing a contribution to the sequential fermentation scheme based on DF and PF.

Antibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus.

Osteomyelitis is a hard-to-treat infection of the bone and bone marrow that is mainly caused by Staphylococcus aureus, with an increasing incidence of methicillin-resistant S. aureus (MRSA). Owing to the aggressiveness of these bacteria in colonizing and destroying the bone, systemic antibiotic treatments fail to eradicate the infection. Instead, it normally entails surgery to remove the dead or infected bone. In this work, we report bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis. The nanoparticles have been engineered with a functional gelatine/colistin coating able to hamper premature release from the mesopores while effectively disaggregating the bacterial biofilm. Because antibiotic resistance is a global emergency, we have designed two sets of identical nanoparticles, carrying each of them a clinically relevant antibiotic, that have demonstrated to have synergistic effect. The bone-targeted nanoparticles have been thoroughly evaluated in vitro and in vivo, obtaining a notable reduction of the amount of bacteria in the bone in just 24 h after only one dose, and paving the way for localized, nanoparticle-mediated treatment of MRSA-caused osteomyelitis. STATEMENT OF SIGNIFICANCE: In this work, we propose the use of bone-targeted mesoporous silica nanoparticles to address S. aureus-caused osteomyelitis that render synergistic therapeutic effect via multidrug delivery. Because the bacterial biofilm is responsible for an aggressive surgical approach and prolonged antibiotic treatment, the nanoparticles have been functionalized with a functional coating able to both disaggregate the biofilm, hamper premature antibiotic release and protect the intact bone. These engineered nanoparticles are able to effectively target bone tissue both in vitro and in vivo, showing high biocompatibility and elevated antibacterial effect.

Engineering Symmetry-Selective Couplings of a Superconducting Artificial Molecule to Microwave Waveguides.

Tailoring the decay rate of structured quantum emitters into their environment opens new avenues for nonlinear quantum optics, collective phenomena, and quantum communications. Here, we demonstrate a novel coupling scheme between an artificial molecule comprising two identical, strongly coupled transmon qubits and two microwave waveguides. In our scheme, the coupling is engineered so that transitions between states of the same (opposite) symmetry, with respect to the permutation operator, are predominantly coupled to one (the other) waveguide. The symmetry-based coupling selectivity, as quantified by the ratio of the coupling strengths, exceeds a factor of 30 for both waveguides in our device. In addition, we implement a Raman process activated by simultaneously driving both waveguides, and show that it can be used to coherently couple states of different symmetry in the single-excitation manifold of the molecule. Using that process, we implement frequency conversion across the waveguides, mediated by the molecule, with efficiency of about 95%. Finally, we show that this coupling arrangement makes it possible to straightforwardly generate spatially separated Bell states propagating across the waveguides. We envisage further applications to quantum thermodynamics, microwave photodetection, and photon-photon gates.

[Prognosis of patients assisted in the emergency unit by the 'TIA protocol' in a third-level hospital at 90 days]. / Pronóstico de pacientes atendidos en urgencias mediante 'protocolo AIT' en un hospital de tercer nivel a los 90 días.

INTRODUCTION: Care models developed for the rapid management of patients with transient ischaemic attack (TIA) are safe, effective and reduce recurrence rates. The aim is to determine the prevalence of cardiovascular events at 90 days. PATIENTS AND METHODS: An observational, analytical, cross-sectional study was conducted. Adult male and female patients seen in the emergency department using the 'TIA protocol' between January 2016 and December 2019 were analysed. Data were collected on clinical variables, complementary tests, treatment and cardiovascular events (stroke/TIA, acute coronary syndrome or death due to cardiovascular causes) at 90 days. The study was approved by the Research Ethics Committee of Aragon. RESULTS: The TIA protocol was performed on 163 out of 591 patients diagnosed with TIA in the emergency department. Brain CT and neurosonology scans were performed in 100% and a 24-hour Holter-electrocardiogram was carried out in 52.1%; atrial fibrillation (AF) was detected in 3.6% of them. An MRI brain scan was performed in 78.4% and acute ischaemic injury was seen in diffusion sequences (DWI+) in 13.5%. The prevalence of cardiovascular events at 90 days was 4.9% (8): stroke, 3.1% (five TIAs); acute coronary syndrome, 0.6% (one); and death from cardiovascular causes, 1.2% (two). Major adverse cardiovascular events were significantly associated with a history of ischaemic heart disease (p = 0.014). Cardiovascular death was associated with a history of AF (p = 0.008), anticoagulants at discharge (p = 0.007) and no antiplatelet therapy at discharge (p = 0.012), and there was a tendency towards an association with a history of type 2 diabetes mellitus (p = 0.05). CONCLUSIONS: Rapid TIA protocols allow early care and avoid hospital admissions, without increasing the incidence of cardiovascular events or recurrence of stroke or TIA at 90 days.

TITLE: Pronóstico de pacientes atendidos en urgencias mediante 'protocolo AIT' en un hospital de tercer nivel a los 90 días.Introducción. Los modelos asistenciales desarrollados para el manejo rápido de pacientes con accidente isquémico transitorio (AIT) son seguros, eficaces y disminuyen las tasas de recurrencia. El objetivo es conocer la prevalencia de eventos cardiovasculares a 90 días. Pacientes y métodos. Estudio observacional, analítico y transversal. Se analiza a pacientes adultos de ambos sexos atendidos en urgencias mediante el 'protocolo AIT' entre enero de 2016 y diciembre de 2019. Se recogen variables clínicas, pruebas complementarias, tratamiento y eventos cardiovasculares (ictus/AIT, síndrome coronario agudo o muerte por causa cardiovascular) a los 90 días. El estudio fue aprobado por el Comité Ético de Investigación de Aragón. Resultados. Se realizó el protocolo AIT a 163 de 591 pacientes diagnosticados de AIT en urgencias. Se realizó una tomografía computarizada cerebral y una neurosonología al 100%, y un Holter-electrocardiograma de 24 horas al 52,1%, y se detectó fibrilación auricular (FA) en el 3,6%. Se hizo una resonancia magnética cerebral al 78,4%, y se demostró lesión isquémica aguda en secuencias de difusión (DWI+) en un 13,5%. La prevalencia de eventos cardiovasculares a los 90 días fue del 4,9% (8): ictus, el 3,1% (cinco AIT); síndrome coronario agudo, el 0,6% (uno), y muerte por causa cardiovascular, el 1,2% (dos). Los eventos adversos cardiovasculares mayores se asociaron de forma significativa al antecedente de cardiopatía isquémica (p = 0,014). La muerte por causa cardiovascular se asoció al antecedente de FA (p = 0,008), anticoagulación al alta (p = 0,007) y no antiagregación al alta (p = 0,012), y hubo una tendencia a la asociación con antecedente de diabetes mellitus de tipo 2 (p = 0,05). Conclusiones. Los protocolos AIT de actuación rápida permiten una atención precoz y evitan ingresos hospitalarios, sin implicar un incremento en la incidencia de eventos cardiovasculares o recurrencia de ictus o AIT a los 90 días.

Social determinants in the access to health care for Chagas disease: A qualitative research on family life in the "Valle Alto" of Cochabamba, Bolivia.

INTRODUCTION: Chagas disease is caused by the Trypanosoma cruzi infection. It is a neglected tropical disease with considerable impact on the physical, psychological, familiar, and social spheres. The Valle Alto of Cochabamba is a hyperendemic region of Bolivia where efforts to control the transmission of the disease have progressed over the years. However, many challenges remain, above all, timely detection and health-care access. METHODS: Following the Science Shop process, this bottom-up research emerged with the participation of the civil society from Valle Alto and representatives of the Association of Corazones Unidos por el Chagas from Cochabamba. The aim of this study is to explore the social determinants in the living realities of those affected by Chagas disease or the silent infection and how families in the Valle Alto of Cochabamba cope with it. An interdisciplinary research team conducted a case study of the life stories of three families using information from in-depth interviews and performed a descriptive qualitative content analysis and triangulation processes. FINDINGS: Findings provide insights into social circumstances of the research subjects' lives; particularly, on how exposure to Trypanosoma cruzi infection affects their daily lives in terms of seeking comprehensive health care. Research subjects revealed needs and shared their experiences, thus providing an understanding of the complexity of Chagas disease from the socioeconomic, sociocultural, political, and biomedical perspectives. Results enlighten on three dimensions: structural, psychosocial, and plural health system. The diverse perceptions and attitudes toward Chagas within families, including the denial of its existence, are remarkable as gender and ethnocultural aspects. Findings support recommendations to various stakeholders and translation materials. CONCLUSIONS: Intersectional disease management and community involvement are essential for deciding the most appropriate and effective actions. Education, detection, health care, and social programs engaging family units ought to be the pillars of a promising approach.

A bio-degradable synthetic membrane to treat superficial and deep second degree burn wounds in adults and children - 4 year experience.

INTRODUCTION: A new bio-degradable synthetic membrane was recently introduced to treat second degree burns in adults and pediatric patients. OBJECTIVE: To assess complications and outcomes using this absorbable synthetic membrane to treat second degree burns. METHODS: 229 burn patients, 138 pediatric, with superficial and deep second -degree wounds, treated with the absorbable synthetic membrane (Suprathel®, Polymedics, Denkendorf, Germany) were included in this study. Patients were treated under anesthesia or moderate sedation. The wound bed was prepared by using either rough debridement or dermabrasion excision. After hemostasis, the membrane was applied to the wound with an outer layer dressing of fatty gauze, bridal veil, absorptive gauze and an ACE® wrap. The outer dressing was removed every one to four days, depending on exudate, in order to closely follow the wound through the translucent membrane and fatty gauze layers. After complete epithelialization, the dressing separated and could be removed. The study focused on the need for subsequent grafting, healing time, patient pain level, hypertrophic scarring and rate of infection. RESULTS: All wounds in this study that were treated with Suprathel® healed without grafting. The average TBSA (Total Body Surface Area) was 8.9% (1%-60%). Average time to healing was 13.7 days for ≥ 90% epithelialization with 11.9 days for pediatric patients versus 14.7 days for adults. Throughout the treatment period, the average pain level was 1.9 on a 10-point scale. 27 patients developed hypertrophic scarring in some areas (11.7%). Average Length of stay (LOS) was 6.9 days. The rate of infection was 3.8% (8/229). Failure or progression to full thickness in part of the wounds was 5.2% (12/229). CONCLUSION: In treating second degree burn wounds, this membrane provides a simple, effective solution alternative with good outcomes and less pain than conventional and previously studied treatment options in the same institution. Fewer dressing changes and easier overall management of the wounds contribute to its favorable profile.

ZnO-mesoporous glass scaffolds loaded with osteostatin and mesenchymal cells improve bone healing in a rabbit bone defect.

The use of 3D scaffolds based on mesoporous bioactive glasses (MBG) enhanced with therapeutic ions, biomolecules and cells is emerging as a strategy to improve bone healing. In this paper, the osteogenic capability of ZnO-enriched MBG scaffolds loaded or not with osteostatin (OST) and human mesenchymal stem cells (MSC) was evaluated after implantation in New Zealand rabbits. Cylindrical meso-macroporous scaffolds with composition (mol %) 82.2SiO2-10.3CaO-3.3P2O5-4.2ZnO (4ZN) were obtained by rapid prototyping and then, coated with gelatin for easy handling and potentiating the release of inorganic ions and OST. Bone defects (7.5 mm diameter, 12 mm depth) were drilled in the distal femoral epiphysis and filled with 4ZN, 4ZN + MSC, 4ZN + OST or 4ZN + MSC + OST materials to evaluate and compare their osteogenic features. Rabbits were sacrificed at 3 months extracting the distal third of bone specimens for necropsy, histological, and microtomography (µCT) evaluations. Systems investigated exhibited bone regeneration capability. Thus, trabecular bone volume density (BV/TV) values obtained from µCT showed that the good bone healing capability of 4ZN was significantly improved by the scaffolds coated with OST and MSC. Our findings in vivo suggest the interest of these MBG complete systems to improve bone repair in the clinical practice.

Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cells.

There is an urgent need of biosynthetic bone grafts with enhanced osteogenic capacity. In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2-15%CaO-5%P2O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1-600 µm) and big channels (∼1000 µm), were prepared. These MBG scaffolds with or without osteostatin were evaluated in hMCSs cultures. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications. STATEMENT OF SIGNIFICANCE: Mesoporous bioactive glasses (MBGs) are bioceramics whose unique properties make them excellent materials for bone tissue engineering. Physico-chemical characterization of MBGs as scaffolds made by rapid prototyping, doped with zinc (potential osteogenic, angiogenic and bactericidal ion) and loaded with osteostatin (osteogenic peptide) are described. These Zn-MBGs scaffolds showed 3D hierarchical meso-macroporous structure that enables to host and release osteostatin. When decorated with human mesenchymal stem cells (hMSCs), MBGs scaffoldsenriched with both zinc and osteostatin exhibited a synergistic effect to enhance hMSCs growth, and also hMSCs osteogenic differentiationwithout addition of other osteoblastic differentiation factors to the culture medium. This novel strategy has a great potential for use in bone tissue engineering.

Assessment of pasteurisation of edible insects using enzymatic tests (activity of alkaline phosphatase and lactoperoxidase) applied in dairy products.

Industrialising edible insects goes along with quality control and hazard analysis and critical control points. One of those steps is assessing heat treatment. For the present contribution, the potential of enzymatic heat assessment tests used in the dairy industry (alkaline phosphatase and lactoperoxidase) to detect heat treatment in several insect species ( Acheta domesticus, Gryllus assimilis, Gryllus bimaculatus, Locusta migratoria, Schistocerca gregaria, Chilecomadia moorei, Galleria mellonella, Bombyx mori, Pachnoda marginata, Tenebrio molitor, Zophobas atratus, Apis mellifera, and Hermetia illucens) was evaluated. Insect material was homogenised, diluted, and the enzymatic tests (Lactognost®, Peroxtesmo®) were carried with these liquids as if they were milk. All species but C. moorei, B. mori, P. marginata, and A. mellifera showed alkaline phosphatase activity in raw samples and none in heated (10 min at 100 ℃) ones, while only G. mellonella, T. molitor, and Z. atratus reacted accordingly with lactoperoxidase. In trial 2 focusing only on alkaline phosphatase activity, inactivation of the enzyme after 5, 10, and 15 min of heating occurred species specific within a range of 60-86 ℃, i.e. within ordinary pasteurisation schemes. Thus and for the time being, heat treatment in many edible insect species can be assessed using alkaline phosphatase activity test kits. In contrast to milk samples, positive results may display bluish or greenish colours, and the time until a reliable reading is possible is extended to 1-1.5 h (24 h in the case of Gryllidae).

[Lacosamide associated with high-degree block in a patient with trigeminal neuralgia]. / Lacosamida asociada a bloqueo de alto grado en un paciente con neuralgia del trigemino.

INTRODUCTION: Lacosamide is an antiepileptic drug whose exact mechanism of action remains unknown. It acts by increasing the slow inactivation of the voltage-dependent sodium channels of the cell membranes. It is indicated in the treatment of focal seizures with or without secondary generalisation and is occasionally used as adjunct treatment in neuropathic pain. Although the most frequent side effects are mild (dizziness, diplopia, blurred vision, headache, tremor, etc.), others such as supraventricular tachyarrhythmias, changes in repolarisation, atrioventricular blocks and even cardiac arrest or sudden death have been reported. CASE REPORT: A 74-year-old male, diagnosed with classic trigeminal neuralgia treated with 200 mg/12 h of carbamazepine, who visited due to a worsening of the pain in the trigeminal V1-V2 region. On the sixth day after admission, after adjusting the carbamazepine treatment to a descending regime, 400 mg/24 h of eslicarbazepine and 100 mg/12 h of intravenous lacosamide, he presented a complete atrioventricular block with extreme bradycardia that required the placement of a pacemaker. CONCLUSIONS: Voltage-dependent sodium channel blockade mainly affects non-sinusal cardiac tissue. An alteration in the atrioventricular or infrahisian node is more consistent with its mechanism of action. Other cases of atrioventricular block in this kind of polytherapy have been reported. Precaution is advised in the concomitant use of antiepileptic drugs, above all among those that prolong the PR interval, and they should be contraindicated in patients with a history of atrioventricular block, ischaemic heart disease or heart failure. Before starting, a baseline electrocardiogram and regular electrocardiographic monitoring are advised during the first few weeks.

TITLE: Lacosamida asociada a bloqueo de alto grado en un paciente con neuralgia del trigemino.Introduccion. La lacosamida es un farmaco antiepileptico cuyo mecanismo de accion exacto se desconoce. Actua aumentando la inactivacion lenta de los canales de sodio dependientes del voltaje de las membranas celulares. Indicado en el tratamiento de crisis focales con o sin generalizacion secundaria, ocasionalmente se emplea como tratamiento coadyuvante en el dolor neuropatico. Aunque los efectos adversos mas frecuentes son leves (mareo, diplopia, vision borrosa, cefalea, temblor…), se han descrito taquiarritmias supraventriculares, cambios en la repolarizacion, bloqueos auriculoventriculares e incluso parada cardiaca o muerte subita. Caso clinico. Varon de 74 años, diagnosticado de neuralgia del trigemino clasica en tratamiento con 200 mg/12 h de carbamacepina, que acude por reagudizacion del dolor en el territorio trigeminal V1-V2. El sexto dia de ingreso, tras ajustar el tratamiento con carbamacepina en pauta descendente, 400 mg/24 h de eslicarbacepina y 100 mg/12 h de lacosamida intravenosa, presenta bloqueo auriculoventricular completo con bradicardia extrema que precisa la implantacion de un marcapasos definitivo. Conclusiones. El bloqueo de canales de sodio dependientes del voltaje afecta predominantemente al tejido cardiaco no sinusal. Una alteracion en el nodo auriculoventricular o infrahisiano es mas congruente con su mecanismo de accion. Existen mas casos comunicados de bloqueo auriculoventricular en este tipo de politerapia. Se recomienda precaucion en el uso concomitante de farmacos antiepilepticos, sobre todo entre los que prolonguen el intervalo PR, asi como su contraindicacion en pacientes con antecedentes de bloqueo auriculoventricular, cardiopatia isquemica o insuficiencia cardiaca. Antes de su inicio, se aconseja realizar un electrocardiograma basal y monitorizacion electrocardiografica regular durante las primeras semanas.

Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains.

OBJECTIVES: Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain. METHODS: We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells. RESULTS: We showed that both N- and C-terminal PTHrP peptides at 100 nM decreased reactive oxygen species production and forkhead box protein O activation following hydrogen peroxide (H2O2)-induced oxidation, which was related to decreased lipid oxidative damage and caspase-3 activation in these cells. This was associated with their ability to restore the deleterious effects of H2O2 on cell growth and alkaline phosphatase activity, as well as on the expression of various osteoblast differentiation genes. The addition of Rp-cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium salt (a cyclic 3',5'-adenosine monophosphate antagonist) and calphostin C (a protein kinase C inhibitor), or a PTH type 1 receptor antagonist, abrogated the effects of N-terminal PTHrP, whereas protein phosphatase 1 (an Src kinase activity inhibitor), SU1498 (a vascular endothelial growth factor receptor 2 inhibitor), or an anti osteostatin antiserum, inhibited the effects of C-terminal PTHrP. CONCLUSION: These findings indicate that the antioxidant properties of PTHrP act through its N- and C-terminal domains and provide novel insights into the osteogenic action of PTHrP.Cite this article: S. Portal-Núñez, J. A. Ardura, D. Lozano, I. Martínez de Toda, M. De la Fuente, G. Herrero-Beaumont, R. Largo, P. Esbrit. Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains. Bone Joint Res 2018;7:58-68. DOI: 10.1302/2046-3758.71.BJR-2016-0242.R2.

A novel visible light responsive nanosystem for cancer treatment.

A novel singlet-oxygen sensitive drug delivery nanocarrier able to release its cargo after exposure to visible (Vis) light from a common lamp is presented. This nanodevice is based on mesoporous silica nanoparticles (MSN) decorated with porphyrin-caps grafted via reactive oxygen species (ROS)-cleavable linkages. In the presence of Vis light porphyrin-nanocaps produce singlet oxygen molecules that break the sensitive-linker, which triggers pore uncapping and therefore allows the release of the entrapped cargo (topotecan, TOP). This new system takes advantage of the non-toxicity and greater penetration capacity of Vis radiation and a double antitumor effect due to the drug release and the ROS production. In vitro tests with HOS osteosarcoma cancer cells reveal that TOP is able to be released in a controlled fashion inside the tumor cells. This research work constitutes a proof of concept that opens up promising expectations in the search for new alternatives for the treatment of cancer.

Evaluation of bacterial adherence of clinical isolates of Staphylococcus sp. using a competitive model: An in vitro approach to the "race for the surface" theory.

OBJECTIVES: Implant-related infection is one of the most devastating complications in orthopaedic surgery. Many surface and/or material modifications have been developed in order to minimise this problem; however, most of the in vitro studies did not evaluate bacterial adhesion in the presence of eukaryotic cells, as stated by the 'race for the surface' theory. Moreover, the adherence of numerous clinical strains with different initial concentrations has not been studied. METHODS: We describe a method for the study of bacterial adherence in the presence of preosteoblastic cells. For this purpose we mixed different concentrations of bacterial cells from collection and clinical strains of staphylococci isolated from implant-related infections with preosteoblastic cells, and analysed the minimal concentration of bacteria able to colonise the surface of the material with image analysis. RESULTS: Our results show that clinical strains adhere to the material surface at lower concentrations than collection strains. A destructive effect of bacteria on preosteoblastic cells was also detected, especially with higher concentrations of bacteria. CONCLUSIONS: The method described herein can be used to evaluate the effect of surface modifications on bacterial adherence more accurately than conventional monoculture studies. Clinical strains behave differently than collection strains with respect to bacterial adherence.Cite this article: M. Martinez-Perez, C. Perez-Jorge, D. Lozano, S. Portal-Nuñez, R. Perez-Tanoira, A. Conde, M. A. Arenas, J. M. Hernandez-Lopez, J. J. de Damborenea, E. Gomez-Barrena, P. Esbrit, J. Esteban. Evaluation of bacterial adherence of clinical isolates of Staphylococcus sp. using a competitive model: An in vitro approach to the "race for the surface" theory. Bone Joint Res 2017;6:315-322. DOI: 10.1302/2046-3758.65.BJR-2016-0226.R2.

[Analysis of factors associated with multiple pregnancies in assisted reproduction treatment complex]. / Análisis de los factores asociados con embarazos múltiples en tratamientos de reproducción asistida compleja.

BACKGROUND: Today, advances in technology provide the best success rates in the reproductive medicine field. One of the biggest concerns about it, is the high risk of achieving multiple pregnancies, which may carry greater health risks for both; the mother and fetuses. Besides that, multiple pregnancies are considered a complication or an adverse effect of assisted reproduction treatments. OBJECTIVES: To compare the factors associated with multiple pregnancy in patients who underwent complex assisted reproduction techniques. MATERIAL AND METHODS: A retrospective and transversal case control study was rolled to compare the factors associated with multiple pregnancy rates, these results were correlated using a logistic regression model. RESULTS: a total of 1063 cases were reviewed, we obtained a pregnancy rate of 35.9%, and a multiple pregnancy rate of 31.5%. We found positive statistical association between patient age, total number of oocytes obtained, total embryos transferred, total vitrified embryos per cycle, total serum cuantitative B-GCH level, endometrial thickness in milimeters, and the Honest of a multiple pregnancy. In the logistic regression model, we found statistical association between the number of embryos transferred, number of embryos obtained, embryo quality, total vitrified embryos and the risk for multiple pregnancies. CONCLUSIONS: The total number of embryos transferred in a cycle of a complex assisted reproduction, is the most important factor for the onset of multiple pregnancies. The age of patients, the number of oocytes, total number of embryos obtained, the number of embryos transferred, the quality of embryos transferred and the number of frozen embryos per cycle, correlate significantly with more risk for multiple pregnancies.