[Artículo traducido] Abordaje del adulto mayor con fractura vertebral por fragilidad ósea.

Osteoporosis is a metabolic and systemic disease characterized by alterations at the level of bone tissue with loss of bone mineral density, changes in microarchitecture, mineralization and remodeling that determine greater bone fragility and risk of fracture.Falls in the elderly are a risk factor closely related to fragility fractures and numerous studies demonstrate this relationship.Vertebral fractures are a major cause of morbidity and mortality. The epidemiology differs from osteoporotic fractures at other skeletal sites, as only one-third are clinically recognized. In the elderly, the approach to osteoporotic vertebral fracture involves comprehensive evaluation of the patient since it is both a cause and a consequence of multiple geriatric syndromes. This fracture, in its acute phase and subsequently, can lead to destabilization of other organs and systems of the elderly, medical complications at different levels, functional deterioration, dependence, and even the need for institutionalization.Therefore, multiple assessment of patients with vertebral fractures is necessary, addressing not only the history and risk factors of osteoporosis, but also those factors that lead to falls, as well as a comprehensive geriatric assessment and the complications closely associated with it.In this chapter we address each of these aspects that are necessary in the individual and multidimensional approach to the elderly patient with vertebral fracture due to bone fragility.

Approach to the elderly patient with vertebral fracture due to bone fragility. / Abordaje del adulto mayor con fractura vertebral por fragilidad ósea.

Osteoporosis is a metabolic and systemic disease characterized by alterations at the level of bone tissue with loss of bone mineral density, changes in microarchitecture, mineralization and remodeling that determine greater bone fragility and risk of fracture. Falls in the elderly are a risk factor closely related to fragility fractures and numerous studies demonstrate this relationship. Vertebral fractures are a major cause of morbidity and mortality. The epidemiology differs from osteoporotic fractures at other skeletal sites, as only one-third are clinically recognized. In the elderly, the approach to osteoporotic vertebral fracture involves comprehensive evaluation of the patient, since it is both a cause and a consequence of multiple geriatric syndromes. This fracture, in its acute phase and subsequently, can lead to destabilization of other organs and systems of the elderly, medical complications at different levels, functional deterioration, dependence, and even the need for institutionalization. Therefore, it is important to carry out a multiple assessment of patients with vertebral fractures, addressing not only the history and risk factors of osteoporosis, but also those factors that lead to falls, as well as a comprehensive geriatric assessment and the complications closely associated with it. In this chapter we address each of these aspects that are necessary in the individual and multidimensional approach to the elderly patient with vertebral fracture due to bone fragility.

Enhancing ovarian cancer conventional chemotherapy through the combination with cannabidiol loaded microparticles.

In this work, we evaluated, for the first time, the antitumor effect of cannabidiol (CBD) as monotherapy and in combination with conventional chemotherapeutics in ovarian cancer and developed PLGA-microparticles as CBD carriers to optimize its anticancer activity. Spherical microparticles, with a mean particle size around 25 µm and high entrapment efficiency were obtained. Microparticles elaborated with a CBD:polymer ratio of 10:100 were selected due to the most suitable release profile with a zero-order CBD release (14.13 ± 0.17 µg/day/10 mg Mps) for 40 days. The single administration of this formulation showed an in vitro extended antitumor activity for at least 10 days and an in ovo antitumor efficacy comparable to that of CBD in solution after daily topical administration (≈1.5-fold reduction in tumor growth vs control). The use of CBD in combination with paclitaxel (PTX) was really effective. The best treatment schedule was the pre + co-administration of CBD (10 µM) with PTX. Using this protocol, the single administration of microparticles was even more effective than the daily administration of CBD in solution, achieving a ≈10- and 8- fold reduction in PTX IC50 respectively. This protocol was also effective in ovo. While PTX conducted to a 1.5-fold tumor growth inhibition, its combination with both CBD in solution (daily administered) and 10-Mps (single administration) showed a 2-fold decrease. These results show the promising potential of CBD-Mps administered in combination with PTX for ovarian cancer treatment, since it would allow to reduce the administered dose of this antineoplastic drug maintaining the same efficacy and, as a consequence, reducing PTX adverse effects.

Stability characteristics of cannabidiol for the design of pharmacological, biochemical and pharmaceutical studies.

Cannabidiol (CBD) is one of the most promising cannabinoids in therapeutics. Nevertheless, the reported stability testing has been carried out with plant extracts and not with CBD as a drug substance. The aim of this work was to evaluate the stability of CBD in solution. A High-Performance Liquid Chromatography (HPLC) analytical method, with CBD in ethanol, was previously validated for these stability studies. The resulting method was linear and proportional in a range of concentrations from 1 to 150 µg CBD/mL, as well as precise. It was also considered suitable to quantify CBD in aqueous medium as reported in accuracy studies. The stability of CBD was influenced by multiple factors. Temperature was one of the most critical parameters, with an activation energy of 92.19KJ/mol. At room temperature, CBD was highly unstable (t95 = 117.13 days). However, at 5 °C it was stable for at least 12 months. CBD was also sensitive to oxidation, with a short t95 of 1.77 days in oxidizing environments, as well as to light. The photolytic reaction seems to be oxidative. The solvent influences CBD stability, and the latter is more stable in ethanol than in aqueous medium. In fact, in simulated physiological conditions (pH 7.4 and 37 °C) 10% of CBD was degraded within 24 h. These studies indicate that CBD is highly unstable, and this should be taken into account in the development of in vitro and in vivo studies of CBD activity and in the pharmaceutical development of dosage forms.

CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer.

Cannabidiol (CBD) has emerged as a potential agent for breast cancer management. In this work, the potential use of cannabidiol in solution (CBDsol) and encapsulated in polymeric microparticles when combined with paclitaxel (PTX) and doxorubicin (DOX) in breast cancer treatment has been evaluated for the first time using MCF-7 and MDA-MB-231 cells. CBDsol, previously administered at suboptimal concentrations (cell death < 10%), enhanced the PTX and DOX effect in both breast cancer cells. The co-administration of CBDsol and PTX or DOX showed a synergistic effect. PLGA-502 was selected as the most suitable polymer to develop CBD-loaded microparticles. The developed formulation (CBD-Mps) was effective as monotherapy, showing extended antiproliferative activity for at least 10 days, and when combined with PTX or DOX. In fact, the use of CBD-Mps allows the combination of both, pre and co-administration strategies, with a single administration, also showing a significant increase in PTX and DOX antiproliferative activity. Finally, the anticancer effect of both CBDsol and CBD-Mps as monotherapy or in combination with PTX was also confirmed in ovo, usingMDA-MB-231-derived tumours. This data evidences the promising inclusion of CBD in conventional breast cancer chemotherapy and the use of CBD-Mps for the extended release of this cannabinoid, optimising the effect of the chemotherapeutic agents.

Current status of nanomedicine in the chemotherapy of breast cancer.

Despite the efforts that have been made in the field of breast cancer therapy, it is a leading cause of cancer death in women and a major health problem. The current treatments combine several strategies (surgery, radiotherapy, immunotherapy, hormone therapy, and chemotherapy) depending on cancer subtype and tumour stage. The use of chemotherapy is required in certain circumstances, like before or after surgery or in advanced stages of the disease. Chemotherapeutic regimens that include anthracyclines (e.g. doxorubicin), taxanes (e.g. paclitaxel), 5-fluorouracil and/or cyclophosphamide show, in general, a high toxicity that limit their clinical use. The use of targeted chemotherapy allows to get a selective location of the drug at tumour mass, decreasing the toxicity of these treatments. An increase of the antitumour efficacy can also be achieved. The use of nanocarriers containing anticancer drugs can be a good strategy to get targeted chemotherapy. In fact, several nanoformulations containing paclitaxel and doxorubicin have been approved or are under clinical trial for breast cancer therapy. The main advantage of these nanomedicines is their lower toxicity compared to conventional formulations, which can be attributed to the elimination of the solvents of the formulation (e.g. Cremophor-EL in paclitaxel conventional formulations) and the more selective location of the drug at tumour site (e.g. cardiotoxicity related to free doxorubicin). However, some adverse events (e.g. hand foot syndrome or infusion reactions) have been related to the administration of some nanomedicines, which have to be considered.

Diseño de Exoesqueleto con base en Cuatro Casos de Estudio de Rehabilitación de Miembro Superior / Design of an Exoskeleton based on Four Cases of Upper Limb Rehabilitation Study

Resumen: En este artículo se presenta un enfoque para rehabilitación pasiva de miembro superior mediante la formulación de cuatro casos de estudio haciendo un análisis de las patologías y los ejercicios que se aplican. Para llevar a cabo la experimentación en los casos propuestos se registraron los datos de las trayectorias de las articulaciones del brazo de un paciente realizando los ejercicios de rehabilitación con un terapeuta. Se diseñó el exoesqueleto ERMIS de siete grados de libertad para emular los movimientos anatómicos en el brazo durante la rehabilitación a partir de los requerimientos de los casos de estudio. Para validar el funcionamiento del exoesqueleto en los casos se simuló el modelo dinámico del ERMIS y se compararon los datos con los datos muestreados de los ejercicios. Al final se presentan los resultados obtenidos de los ejercicios realizados con el exoesqueleto, obteniendo en la precisión un desempeño promedio del 95% en los movimientos de hombro, codo y muñeca al emular la terapia con timón.

Abstract: This paper presents an approach for passive upper limb rehabilitation based on four case studies by analyzing the pathologies and exercises that are applied. To carry out the experimentation in the proposed cases, the data from the trajectories of the patient's arm articulations were registered, performing the rehabilitation exercises with a therapist. The ERMIS exoskeleton´s seven degrees of freedom was designed to emulate the anatomical movements in the arm during rehabilitation from the requirements of the case studies. To validate the exoskeleton performance in the study cases, the ERMIS's dynamic model was simulated and the data were compared with the sampled data of the exercises. At the end, the results obtained from exoskeleton exercises emulating rudder therapy, where shoulder, elbow and wrist movements were showed with an accuracy of 95%.

[Factors predicting failure in empirical antibiotic treatment]. / Factores predictores del fracaso al tratamiento antibiótico empírico.

Infections are one of the main causes of morbidity and mortality in the population. The choice of empirical treatment is one of the most common decisions facing the physician. This first decision has consequences in the prognosis of the patient and the costs associated with the process. This review attempts to summarize the aspects that can lead to failure of antibiotic treatment by considering microbiological and pharmacological aspects, patient profile and infectious focus control. In addition, a series of recommendations are established to minimize this risk, from the point of view of diagnostic accuracy, adequate severity stratification of the patient, knowledge of the pharmacokinetic and pharmacodynamic aspects of antibiotics and control of the infectious focus.

Phyto-, endo- and synthetic cannabinoids: promising chemotherapeutic agents in the treatment of breast and prostate carcinomas.

INTRODUCTION: The term 'cannabinoids' designates a family of compounds with activity upon cannabinoid receptors. Cannabinoids are classified in three groups: phytocannabinoids, endocannabinoids, and the synthetic analogues of both groups. They have become a promising tool in the treatment of cancer disease, not only as palliative agents, but also as antitumor drugs, due to their ability to inhibit the proliferation, adhesion, migration, invasion, and angiogenesis of tumour cells. Two of the cancers where they have shown high anticancer activity are breast and prostate tumours. Despite this potential clinical interest, several studies have also reported that cannabinoids can stimulate the proliferation of cancer cells at very low concentrations. Areas covered: The aim of this review is to evaluate the promising chemotherapeutic utility of phytocannabinoids, endocannabinoids, and synthetic cannabinoids in breast and prostate cancer. Expert opinion: Cannabinoids, in particular the non-psychoactive CBD, may be promising tools in combination therapy for breast and prostate cancer, due to their direct antitumor effects, their ability to improve the efficacy of conventional antitumor drugs and their usefulness as palliative treatment. Nevertheless, deeper studies to fully establish the mechanisms responsible for their antitumour and pro-tumour properties and their formulation in efficient delivery systems remain to be established.

Behavior in vitro of the dentin-enamel junction in human premolars submitted to high temperatures: prediction of the maximum temperature based on logistic regression analysis.

OBJECTIVE: The aim of the study was to provide scientific evidence that would permit DEJ separation to be used as a parameter to estimate the temperature to which burnt, carbonized or incinerated cadavers or human remains had been subjected. MATERIALS AND METHODS: A descriptive pseudo-experimental study was carried out in vitro using cone beam tomography to determine the physical behavior of the dentine-enamel junction in 60 human premolars submitted to high temperatures (200°C, 400°C, 600°C, 800°C and 1000°C). RESULTS: Spearman's concordance and correlation index was used to determine the relationship between longitudinal separation of the dentine-enamel junction (mm) and temperature (°C) and a simple linear regression model developed to show that once micro- and macrostructural changes are initiated in the enamel and dentine. CONCLUSIONS: The dentine-enamel junction begins to separate from the cervical towards the occlusal as temperature increases.

Trauma Ultrasound Training for Latin American Countries.

Objective: The Pan-American Trauma Society (PTS) developed a Trauma and Emergency Ultrasound Course (USET) in response to the requirement for trauma ultrasound training for low-and middle-income countries. The objective of this study was to evaluate the efficiency of this course. Method: Pre- and post-course tests were used. And interval estimation of proportions was calculated at 95% CI. Theoretical and practical pre- and post-course knowledge were assessed with the Wilcoxon Signed Rank test at 0.05 level of statistical significance. Result: Between 2005 and 2007, 114 students, including general surgeons, emergency medicine physicians, anesthesiologists, critical care physicians, and residents of these specialties, were trained in seven countries (Uruguay, Peru, Mexico, Venezuela, Aruba, Colombia, and Ecuador). The difference on complete knowledge ranked scores before and after the course was statistically significant (p<0.001). After the course, almost all participants (97.4%) demonstrated complete knowledge in final evaluation. Conclusion: The USET course is an effective approach for trauma ultrasound training. Specific training programs for trauma care providers that work in low-and middle-income countries are necessary and could be performed with low cost training programs.

Critical attributes of formulation and of elaboration process of PLGA-protein microparticles.

Low drug loading, burst effect during release and drug inactivation account for the main drawbacks of protein microencapsulation in poly(d,l-lactic-co-glycolic) acid (PLGA) matrix by the water-in oil-in water (W/O/W) solvent evaporation method. Thus, the current study was set to invest the critical attributes of formulation and of elaboration process which determine protein loading into microparticles as well as its further release, using albumin as protein model. NaCl concentration in the external aqueous phase, poly(vinyl alcohol) (PVA) concentration and mostly viscosity of both the internal aqueous phase and the organic phase were critical attributes for improving drug loading, with polymer molecular weight and hydrophobicity likewise directly related to albumin loading. In such a way, when using 0.5% PVA as internal aqueous phase the highest albumin loading was achieved. Optimized microparticles exhibited a sustained in vitro release of albumin over 130 days. The influence of the microencapsulation process on albumin stability and biological activity was evaluated by carrying out cell proliferation assays on PC12 cells with albumin released from microparticles. Such assay demonstrated that the microencapsulation procedure optimized in this study did not affect the biological stability of the microencapsulated protein.