Metabolic Disturbance of High-Saturated Fatty Acid Diet in Cognitive Preservation.

Aging continues to be the main cause of the development of Alzheimer's, although it has been described that certain chronic inflammatory pathologies can negatively influence the progress of dementia, including obesity and hyperlipidemia. In this sense, previous studies have shown a relationship between low-density lipoprotein receptor (LDLR) and the amyloid-beta (Aß) binding activity, one of the main neuropathological features of Alzheimer's disease (AD). LDLR is involved in several processes, including lipid transport, regulation of inflammatory response and lipid metabolism. From this perspective, LDLR-/- mice are a widely accepted animal model for the study of pathologies associated with alterations in lipid metabolism, such as familial hypercholesterolemia, cardiovascular diseases, metabolic syndrome, or early cognitive decline. In this context, we induced hyperlipidemia in LDLR-/- mice after feeding with a high-saturated fatty acid diet (HFD) for 44 weeks. LDLR-/--HFD mice exhibited obesity, hypertriglyceridemia, higher glucose levels, and early hepatic steatosis. In addition, HFD increased plasmatic APOE and ubiquitin 60S levels. These proteins are related to neuronal integrity and health maintenance. In agreement, we detected mild cognitive dysfunctions in mice fed with HFD, whereas LDLR-/--HFD mice showed a more severe and evident affectation. Our data suggest central nervous system dysfunction is associated with a well-established metabolic syndrome. As a late consequence, metabolic syndrome boots many behavioral and pathological alterations recognized in dementia, supporting that the control of metabolic parameters could improve cognitive preservation and prognosis.

A Simple, Safe, and Effective Method for Preparing Autologous Bio-Based Fibrin Glue for Ophthalmic Use.

This study proposes a method to prepare autologous bio-based fibrin glue (FG) for use in ophthalmic surgery. FGs containing three fibrinogen concentrations and a thrombin concentrate were prepared using human blood from five donors (FG1: physiological fibrinogen concentration; FG2 and FG3: concentrated fibrinogen). The adhesion strength was tested, and the clinical safety and efficacy were studied in rabbit eyes in conjunctival surgery. A commercial FG was used as a control. From each donor, 2 mL of FG was prepared, containing 1 mL of 3.49 ± 0.78 (FG1), 17.74 ± 4.66 (FG2), or 47.46 ± 9.36 mg/mL (FG3) of fibrinogen and 1 mL of 2248.12 ± 604.20 UI/mL of thrombin. The average adhesion strength increased with the fibrinogen concentration, from 1.49 ± 0.39 kPa (FG1) to 3.14 ± 1.09 kPa (FG3). FG1 showed poor results when used for autograft adhesion. In contrast, the conjunctival autografts were successfully grafted using FG2 and FG3, revealing equivalent adhesion properties compared with commercial FG, but with less inflammation. In conclusion, FGs could be prepared on demand within minutes from small volumes of human blood, using a method that results in FGs which exhibit good adhesion capacity and are also safe and effective in a preclinical study.

Polymerizable Skin Hydrogel for Full Thickness Wound Healing.

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 years, tissue-engineered skin grafts have been based on the in vitro culture of keratinocytes over different scaffolds, requiring between 3 to 4 weeks of tissue culture before being used clinically. In this study, we describe the development of a polymerizable skin hydrogel consisting of keratinocytes and fibroblast entrapped within a fibrin scaffold. We histologically characterized the construct and evaluated its use on an in vivo wound healing model of skin damage. Our results indicate that the proposed methodology can be used to effectively regenerate skin wounds, avoiding the secondary in vitro culture steps and thus, shortening the time needed until transplantation in comparison with other bilayer skin models. This is achievable due to the instant polymerization of the keratinocytes and fibroblast combination that allows a direct application on the wound. We suggest that the polymerizable skin hydrogel is an inexpensive, easy and rapid treatment that could be transferred into clinical practice in order to improve the treatment of skin wounds.

The Role of DNA Damage Response in Dysbiosis-Induced Colorectal Cancer.

The high incidence of colorectal cancer (CRC) in developed countries indicates a predominant role of the environment as a causative factor. Natural gut microbiota provides multiple benefits to humans. Dysbiosis is characterized by an unbalanced microbiota and causes intestinal damage and inflammation. The latter is a common denominator in many cancers including CRC. Indeed, in an inflammation scenario, cellular growth is promoted and immune cells release Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), which cause DNA damage. Apart from that, many metabolites from the diet are converted into DNA damaging agents by microbiota and some bacteria deliver DNA damaging toxins in dysbiosis conditions as well. The interactions between diet, microbiota, inflammation, and CRC are not the result of a straightforward relationship, but rather a network of multifactorial interactions that deserve deep consideration, as their consequences are not yet fully elucidated. In this paper, we will review the influence of dysbiosis in the induction of DNA damage and CRC.

Study on adherence to treatment with imatinib in chronic myeloid leukaemia and its association with therapeutic response / Estudio de adhesión a imatinib en la leucemia mieloide crónica y su relación con la respuesta terapéutica

Objective: To assess the level of adherence to treatment with imatinib in patients with chronic myeloid leukaemia and its association with therapeutic response. Materials and methods: Study conducted on October, 2013 - March, 2014, including patients diagnosed with Chronic Myeloid Leukaemia on treatment with imatinib in the hospital. Therapeutic adherence was assessed through the standard Morisky-Green Questionnaire and the medication dispensing record. Those patients who did not complete 6 months of treatment and/or did not complete the questionnaire were excluded. Therapeutic response was assessed following clinical guidelines. The descriptive analysis of variables and correlation was conducted through Pearsons’s Chi-Square Test. Results: The study included 31 patients. When assessing the level of association between response variables and therapeutic adherence: 1. The highest molecular response was reached by 68.4% of those patients with high adherence, and by 75% of those patients with intermediate adherence. 2. Complete molecular response was achieved by 57.9% of patients with high adherence, and by 58.3% of patients with intermediate adherence. No statistically significant differences were found in response variables between patients with high and intermediate therapeutic adherence. No association was observed between level of adherence and therapeutic response. Conclusions: We cannot confirm that a different level of therapeutic adherence might have an impact on response to imatinib, though this should be taken into account in cases of therapeutic failure or sub-optimal response (AU)

Objetivo: El objetivo es evaluar el grado de adhesión terapéutica a imatinib en pacientes con leucemia mieloide crónica y su relación con la respuesta terapéutica. Material y métodos: Estudio realizado en octubre 2013-marzo 2014 que incluye a pacientes diagnosticados de leucemia mieloide crónica en tratamiento con imatinib en el hospital. Se evaluó la adhesión terapéutica mediante el cuestionario estandarizado Morisky-Green y el registro de dispensaciones de medicación. Se excluyeron aquellos que no completaron 6 meses de tratamiento y/o no realizaron el cuestionario. La respuesta terapéutica se evaluó siguiendo guías clínicas. Se realizó el análisis descriptivo de variables y correlación mediante test Chi-cuadrado de Pearson. Resultados: Se incluyeron 31 pacientes. Al evaluar el grado de asociación entre variables de respuesta y adhesión terapéutica: 1. La respuesta molecular mayor fue alcanzada por el 68,4% de los pacientes con alta adhesión y por el 75% de los pacientes con adhesión media. 2. La respuesta molecular completa fue alcanzada por el 57,9% de los pacientes con alta adhesión y por el 58,3% de los pacientes con adhesión media. No se observaron diferencias estadísticamente significativas en las variables de respuesta entre pacientes con adhesión terapéutica alta y media. No se observó asociación entre el grado de adhesión y la respuesta terapéutica. Conclusiones: No podemos afirmar que el distinto grado de adhesión terapéutica influya en la respuesta al imatinib, aunque debería considerarse en casos de fallo terapéutico o respuesta subóptima (AU)

Study on adherence to treatment with imatinib in chronic myeloid leukaemia and its association with therapeutic response.

OBJECTIVE: To assess the level of adherence to treatment with imatinib in patients with chronic myeloid leukaemia and its association with therapeutic response. MATERIALS AND METHODS: Study conducted on October, 2013 - March, 2014, including patients diagnosed with Chronic Myeloid Leukaemia on treatment with imatinib in the hospital. Therapeutic adherence was assessed through the standard Morisky-Green Questionnaire and the medication dispensing record. Those patients who did not complete 6 months of treatment and/or did not complete the questionnaire were excluded. Therapeutic response was assessed following clinical guidelines. The descriptive analysis of variables and correlation was conducted through Pearsons's Chi-Square Test. RESULTS: The study included 31 patients. When assessing the level of association between response variables and therapeutic adherence: 1. The highest molecular response was reached by 68.4% of those patients with high adherence, and by 75% of those patients with intermediate adherence. 2. Complete molecular response was achieved by 57.9% of patients with high adherence, and by 58.3% of patients with intermediate adherence. No statistically significant differences were found in response variables between patients with high and intermediate therapeutic adherence. No association was observed between level of adherence and therapeutic response. CONCLUSIONS: We cannot confirm that a different level of therapeutic adherence might have an impact on response to imatinib, though this should be taken into account in cases of therapeutic failure or sub-optimal response.

Objetivo: El objetivo es evaluar el grado de adhesión terapéutica a imatinib en pacientes con leucemia mieloide crónica y su relación con la respuesta terapéutica. Material y métodos: Estudio realizado en octubre 2013-marzo 2014 que incluye a pacientes diagnosticados de leucemia mieloide crónica en tratamiento con imatinib en el hospital. Se evaluó la adhesión terapéutica mediante el cuestionario estandarizado Morisky-Green y el registro de dispensaciones de medicación. Se excluyeron aquellos que no completaron 6 meses de tratamiento y/o no realizaron el cuestionario. La respuesta terapéutica se evaluó siguiendo guías clínicas. Se realizó el análisis descriptivo de variables y correlación mediante test Chi-cuadrado de Pearson. Resultados: Se incluyeron 31 pacientes. Al evaluar el grado de asociación entre variables de respuesta y adhesión terapéutica: 1. La respuesta molecular mayor fue alcanzada por el 68,4% de los pacientes con alta adhesión y por el 75% de los pacientes con adhesión media. 2. La respuesta molecular completa fue alcanzada por el 57,9% de los pacientes con alta adhesión y por el 58,3% de los pacientes con adhesión media. No se observaron diferencias estadísticamente significativas en las variables de respuesta entre pacientes con adhesión terapéutica alta y media. No se observó asociación entre el grado de adhesión y la respuesta terapéutica. Conclusiones: No podemos afirmar que el distinto grado de adhesión terapéutica influya en la respuesta al imatinib, aunque debería considerarse en casos de fallo terapéutico o respuesta subóptima.