Persistent NRG1 Type III Overexpression in Spinal Motor Neurons Has No Therapeutic Effect on ALS-Related Pathology in SOD1G93A Mice.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons (MNs). Neuregulin-1 (NRG1) is a pleiotropic growth factor that has been shown to be potentially valuable for ALS when supplemented by means of viral-mediated gene therapy. However, these results are inconsistent with other reports. An alternative approach for investigating the therapeutic impact of NRG1 on ALS is the use of transgenic mouse lines with genetically defined NRG1 overexpression. Here, we took advantage of a mouse line with NRG1 type III overexpression in spinal cord α motor neurons (MN) to determine the impact of steadily enhanced NRG1 signalling on mutant superoxide dismutase 1 (SOD1)-induced disease. The phenotype of SOD1G93A-NRG1 double transgenic mice was analysed in detail, including neuropathology and extensive behavioural testing. At least 3 animals per condition and sex were histopathologically assessed, and a minimum of 10 mice per condition and sex were clinically evaluated. The accumulation of misfolded SOD1 (mfSOD1), MN degeneration, and a glia-mediated neuroinflammatory response are pathological hallmarks of ALS progression in SOD1G93A mice. None of these aspects was significantly improved when examined in double transgenic NRG1-SOD1G93A mice. In addition, behavioural testing revealed that NRG1 type III overexpression did not affect the survival of SOD1G93A mice but accelerated disease onset and worsened the motor phenotype.

Dry Needling of the Popliteus Muscle Validation by Ultrasound Imaging: A Cross-Sectional Observational Study.

Dry needling is a widely used technique for the treatment of painful syndromes in the musculature, however, its usefulness is of greater relevance in deep structures, such as the popliteus muscle, as it is more difficult to access. This muscle is heavily involved in knee pathology, being a source of pain and functional impairment, especially secondary to underlying pathologies. The method selected for the observation and study of the soft tissues, by means of imaging tests that do not use ionising radiation, is ultrasound. A cross-sectional observational study is proposed. It will be carried out in a healthy population, during the years 2021 and 2022, observing, by ultrasound, the results of the popliteal puncture technique, recorded by Mayoral del Moral et al. A popliteus muscle needle reach of 92% was achieved with this technique, in 48 of 50 patients. The results of the present cross-sectional observational study in living subjects, support that the popliteal puncture, described by Mayoral et al. is a reliable and safe approach, when performed with a 0.30 × 50 mm needle, and no adverse reactions or punctures of the vascular-nerve structures have been reported during the interventions.

Therapeutic attributes and applied aspects of biological macromolecules (polypeptides, fucoxanthin, sterols, fatty acids, polysaccharides, and polyphenols) from diatoms - A review.

Diatoms are ubiquitous, biologically widespread, and have global significance due to their unique silica cell wall composition and noteworthy applied aspects. Diatoms are being extensively exploited for environmental monitoring, reconstruction, and stratigraphic correlation. However, considering all the rich elements of diatoms biology, the current literature lacks sufficient information on the therapeutic attributes and applied aspects of biological macromolecules from diatoms, hampering added advances in all aspects of diatom biology. Diatoms offer numerous high-value compounds, such as fatty acids, polysaccharides, polypeptides, pigments, and polyphenols. Diatoms with a high content of PUFA's are targets of transformation into high-value products through microalgal technologies due to their wide application and growing market as nutraceuticals and food supplements. Diatoms are renewable biomaterial, which can be used to develop drug delivery systems due to biocompatibility, surface area, cost-effective ratio, and ease in surface modifications. Innovative approaches are needed to envisage cost-effective ways for the isolation of bioactive compounds, enhance productivity, and elucidate the detailed mechanism of action. This review spotlights the notable applications of diatoms and their biologically active constituents, such as fucoxanthin and omega 3 fatty acids, among others with unique structural and functional entities.

Prognostic Value of the Nutritional Risk Index in Candidates for Continuous Flow Left Ventricular Assist Device Therapy.

INTRODUCTION AND OBJECTIVES: Malnutrition has been shown to affect clinical outcomes in patients with heart failure. The aim of this study was to analyze the impact of preoperative nutritional status assessed by the nutritional risk index (NRI) on the prognosis of patients with a continuous-flow left ventricular assist device (cf-LVAD). METHODS: We performed a retrospective study of 279 patients who underwent cf-LVAD implantation between 2009 and 2015 in our center. Preoperative NRI was calculated and the patients were followed-up for 1 year. The association between preoperative NRI and postoperative clinical events was analyzed using multivariable logistic regression. RESULTS: The prevalence of severe (NRI <83.5), moderate (83.5 ≤ NRI <97.5) and mild (97.5 ≤ NRI <100) nutritional risk was 5.4%, 21.5%, and 9.3%. Mortality rates 1 year after cf-LVAD implantation in these 3 categories were 53.3%, 31.7%, 23.1% vs 18.0% (P <.001) in patients with a normal IRN. A normal preoperative NRI value was an independent predictor of lower risk of death from any cause during follow-up (aHR per 1 unit, 0.961; 95%CI, 0.941-0.981; P <.001) was and a predictor for a lower risk of postoperative infections (aOR, 0.968; 95%CI, 0.946-0.991; P=.007), respiratory failure (aOR, 0,961; 95%CI, 0.936-0.987; P=.004), and right heart failure (aOR, 0.963; 95%CI, 0.934-0.992; P=.014). CONCLUSIONS: Malnourished patients are at increased risk for postoperative complications and death after cf-LVAD implantation. Assessment of nutritional risk could improve patient selection and the early initiation of nutritional support.

Cardiac assessment of early breast cancer patients 18 years after treatment with cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy.

BACKGROUND: Epirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect. METHODS: We re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin-cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m(2)) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m(2))]. Eligible patients were those who were alive and free of disease and had no contra-indications to the proposed tests (cardiac evaluation). Cardiotoxicity was defined as asymptomatic systolic dysfunction (left ventricular ejection fraction (LVEF)< 50%, New York Heart Association (NYHA) Class I) or symptomatic heart failure (NYHA Class II-IV). Differences in cardiotoxicity between CMF and SDE/HDE were assessed using chi-square and Fisher Exact tests for binary variables and t-test and Wilcoxon test for continuous variables. RESULTS: Among the 777 patients, 20 cases of CHF were reported (CMF = 1, SDE = 5, HDE = 14; p < 0.001). Between September 2010 and June 2013, 82 patients (30%) out of 269 eligible patients accepted to participate in this substudy. Median follow-up was 18 years (range 15-24). Epirubicin-treated patients had significantly higher heart rate, more abnormal echocardiograms and LVEF by magnetic resonance imaging (MRI) compared to CMF-treated ones. A trend towards higher BNP was also observed in the SDE/HDE group (P = 0.08). No differences were observed in LVEF assessed by echocardiogram or troponin T levels. CONCLUSIONS: Participation rate in this substudy was lower than expected highlighting the complexity of re-calling patients several years after the initial BC diagnosis. After 18 years, epirubicin-treated patients had a lower LVEF by MRI, more abnormal echocardiograms, higher heart rates compared to patients treated with CMF. However, no major delayed cardiotoxicity was observed.

Reacciones adversas a medicamentos en el Hospital La Paz registradas en el conjunto mínimo básico de datos (CMBD) durante 2003 / Adverse drug reactions recorded in the Minimum Basic Data Set of the Hospital La Paz in 2003

Objetivo: Las reacciones adversas medicamentosas (RAM) son un problema de salud pública, cuya magnitud es difícil de cuantificar debido a su infranotificación. Nuestro objetivo fue identificar y describir las RAM registradas en el conjunto mínimo básico de datos (CMBD) del Hospital La Paz durante 2003.Pacientes y métodos: Estudio transversal. Se seleccionaron los episodios codificados, según la CIE-9-MC, como tales en los informes de alta de todos los pacientes hospitalizados durante 2003. Se describieron y analizaron las variables sociodemográficas, las categorías diagnósticas y los tipos de fármacos, entre otras. Resultados: De las 50.929 altas registradas en el CMBD, se detectaron 1.092 episodios con al menos una RAM (2,1 por ciento). De éstos, 217 (0,4 por ciento del total) tuvieron como causa principal del ingreso una RAM. Los servicios con mayor número de pacientes ingresados por esta causa fueron los de oncología médica y medicina interna. Hallamos diferencias significativas (p < 0,001) entre la estancia media de los pacientes ingresados por una RAM (8,1 días) y los que la presentaron durante su hospitalización (18,2 días). Conclusiones: El CMBD es una herramienta útil para la identificación, la cuantificación y el análisis de las RAM (AU)