An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach

Diagnóstico del deterioro de la piedra en el patrimonio construido. Datos y perspectivas

Stone and other materials used for the construction of historic buildings, memorial statues, gravestones and similar are exposed to weathering and polluting agents and, therefore, progressive decay. Such deterioration, whether physical, chemical or biological, involves mineral phases and their interrelationships (structure and texture).A review of the analytical procedures applied in scientific research on stone damage has revealed the need for appropriate tools and tests (each with a specific scope, depending on the extant damage) to identify decay processes and apply the correct “therapy”, i.e. temporary and/or permanent protection (cleaning, protection, reinforcement, repair and/or replacement). A number of case histories of famous components of the Italian built heritage are discussed in the context of the use of integrated methodologies for researching decay in different kinds of stone.La piedra y otros materiales utilizados para construir edificios históricos, estatuas conmemorativas, lápidas, etc. sufren la acción de los agentes atmosféricos y contaminantes y, por tanto, a una degradación progresiva. En dicha degradación, ya sea física, química o biológica, intervienen las fases minerales de la piedra y sus correspondientes interrelaciones (estructura y textura).Un análisis de los procedimientos analíticos aplicados en la investigación científica sobre los daños en la piedra ha puesto de manifiesto la necesidad de herramientas y pruebas adecuadas (cada una con un objetivo concreto, según el daño existente) para identificar los procesos de degradación y aplicar la «terapia» adecuada; es decir, una protección provisional o definitiva (limpieza, protección, refuerzo, reparación o sustitución).Se comentan varios casos prácticos relacionados con conocidos elementos del patrimonio construido italiano en el contexto del empleo de metodologías integradas para la investigación de la degradación en distintos tipos de piedra

Freeze/thaw stress induces organelle remodeling and membrane recycling in cryopreserved human mature oocytes

Purpose: Our aim was to evaluate the ultrastructure of human metaphase II oocytes subjected to slow freezing and fixed after thawing at different intervals during post-thaw rehydration. Methods: Samples were studied by light and transmission electron microscopy. Results: We found that vacuolization was present in all cryopreserved oocytes, reaching a maximum in the intermediate stage of rehydration. Mitochondria-smooth endoplasmic reticulum (M-SER) aggregates decreased following thawing, particularly in the first and intermediate stages of rehydration, whereas mitochondria-vesicle (MV) complexes augmented in the same stages. At the end of rehydration, vacuoles and MV complexes both diminished and M-SER aggregates increased again. Cortical granules (CGs) were scarce in all cryopreserved oocytes, gradually diminishing as rehydration progressed. Conclusions: This study also shows that such a membrane remodeling is mainly represented by a dynamic process of transition between M-SER aggregates and MV complexes, both able of transforming into each other. Vacuoles and CG membranes may take part in the membrane recycling mechanism

Potentially Toxic Elements (PTEs) in Cultivated Soils from Lombardy (Northern Italy): Spatial Distribution, Origin, and Management Implications

This work aims to quantify the contribution of agricultural practices to diffuse pollution in cultivated soils. Two samples (the first from the top layer and the second from a depth of about 100 cm) were retrieved from about 1000 soil profiles and analyzed for their potentially toxic elements (PTEs) content (Cd, Cu, Ni, Pb, Zn, Mn). In addition, we collected dedicated soil profiles for three specific types of land use and agronomic practice, namely vine-, cereal- and rice-growing areas. Baseline concentrations and distribution maps were produced. Statistical data treatment, coupled with the results of the dedicated soil profiles, enabled the identification of precise pollution sources and processes. In cultivated soils, PTEs contents prove to be generally well below the Italian regulatory limits, with the exception of Cu in vineyard soils, due to the long-lasting use of Cu-based pesticides. South of Milan and in other urban areas, we attribute the top soil enrichment in Cd, Cu, Pb, and Zn to industrial activities and urban settlement. Ni sporadically exceeds regulatory standards, but its association with Mn and its depth distribution point to a natural origin, mostly due to the occurrence of serpentine. The project demonstrates that although agriculture, especially in the form of vineyards and of intensive cultivation, certainly contributes to pollution, such contribution is exceeded by that deriving from industry and road traffic

Patient semi-specific computational modeling of electromagnetic stimulation applied to neuroprotective treatments in acute ischemic stroke

Neuroprotective effects of pulsed electromagnetic fields (PEMFs) have been demonstrated both in vivo and in vitro. Moreover, preliminary clinical studies have been conducted and suggested PEMFs as a possible alternative therapy to treat acute ischemic stroke. In this work, we show that it’s possible to build-up a patient semi-specific head model, where the 3D reconstruction of the ischemic lesion of the patient under treatment is inserted in the head of the human body model “Duke” (v.1.0, Zurich MedTech AG). The semi-specific model will be used in the randomized, placebo-controlled, double-blind study currently ongoing. Three patients were modelled and simulated, and results showed that each ischemic lesion experiences a magnetic flux density field comparable to the one for which biological effects have been attested. Such a kind of dosimetric analysis reveals a reliable tool to assess the correlation between levels of exposure and the beneficial effect. Thus, once the on-going double blind study is complete it will prove if PEMFs treatment triggers a clinical effect, and we will then be able to characterize a dose-response curve with the methodology arranged in this study

An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach

Effect of electric current stimulation in combination with external fixator on bone healing in a sheep fracture model

Biophysical stimulations with electric and electromagnetic fields have been demonstrated to accelerate the bone-healing rate. This study has been designed to investigate the effects of electricity directly connected with the central pins of an external fixator in an experimental osteotomy model in sheep. Thirty mg/kg of tetracycline chloride were administered on the 30th and on the 45th day after surgery for histomorphometric studies. Plain radiographs were obtained in standard projections every 15 days after surgery and were analyzed with a software program (Corel Photo-Paint Pro X2, Corel Corporation, Ottawa, Canada). The specimens obtained after 60 days were examined with histological analysis. The results show that biophysical treatment with alternating electricity in combination with external fixator enhances new-bone formation. The translational value of this study, due to the similarities between ovine and human species, suggests that this treatment could be useful in speeding the bone-healing rate both in animals and humans

Low-Intensity Pulsed Ultrasound in the Treatment of Nonunions and Fresh Fractures: A Case Series

It is estimated that approximately 5% to 10% of fractures will evolve into nonunions. Nonunions have a significant impact on patient quality of life and on socioeconomic costs. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive therapy widely used within the orthopedic community to accelerate the healing of fresh fractures, to minimize delayed healing, and to promote healing of nonunions. In this case series, 46 nonunions and 19 fresh fractures were treated with LIPUS for at least three months or until fracture healing. Bone healing was assessed both at a radiological and a functional level. Of the nonunions healed, 89% had a mean healing time of 89 ± 53 days. In the group of fresh fractures, the healing percentage was 95% with a mean healing time of 46 ± 28 days. LIPUS treatment is proven to be safe and well tolerated; there were no adverse events related to the use of the device, even in the presence of internal fixations and infections. LIPUS therapy should be considered a low-risk option both as an adjunct to surgery or as a standalone therapy in the management of nonunion and fresh fractures

Electromagnetic fields counteract IL-1β during chondrogenesis in synovial bovine mesenchymal progenitor cells

Objective. Mesenchymal stem cells (MSCs) isolated from synovium and from synovial fluid, have shown a chondrogenesis potential suggesting that synovium is an excellent source of MSCs for cartilage regeneration. Electromagnetic fields (EMFs) display several effects on cartilage: increase the synthesis of proteoglycans (PGs), prevents the catabolic effect of the pro-inflammatory cytokine interleukin-1β (IL-1β), appear useful for the treatment of osteoarthritis. Our goal was to evaluate if the chondrogenic differentiation of synovial bovine mesenchymal progenitor cells, may be influenced by EMFs. Further, as chondrogenic differentiation of MSCs could be altered in an inflammatory environment and EMFs can counteract IL-1β activity, we also evaluated the role of EMFs during chondrogenic differentiation in the presence of IL-1β. Design. Synovial fluid was aspirated from the metacarpophalangeal joints of bovine. Synovial cells at the 3rd passage were centrifuged to obtain pellet cultures. Pellets were cultured in chondrogenic medium alone (control) or supplemented with 10 ng/ml TGF-β3 and/or 50 ng/ml IL-1β. The pellets were unexposed or exposed to EMF (75 Hz, 1.5 mT) (Igea, Carpi, Italy), during the whole period in culture (34 days). Alcian blue for sulphated glycosaminoglycans and immunostaining for type II collagen, were performed. PG synthesis was measured by radioactive 35S-sulphate incorporation. Results. Pellets cultured in the presence of TGF-β3 exhibited positive staining for type II collagen and Alcian blue, compared to control, indicating chondrogenic differentiation of synovial bovine mesenchymal progenitor cells. In the presence of IL-1β, type II collagen and Alcian blue staining dramatically decreased compared to TGF-β3 treatment alone. When pellets treated with both TGF-β3 and IL-1β were exposed to EMF, the histochemical staining for type II collagen and Alcian blue increased compared to EMF-unexposed pellets, suggesting that EMF might counteract the IL-1β effect. Biochemical analysis on PG synthesis confirmed histochemical data. Conclusions. The presence of inflammatory cytokines, such as IL-1β in human joints, may explain why existing methods of cartilage engineering repair strategies, that rely on the in situ differentiation of MSCs, fail to provide a reliably successful. Results of this study support the hypothesis that EMF treatment may favour chondrogenic differentiation in inflammatory conditions, suggesting a possible strategy for improving the clinical outcome of cartilage repair procedures