Application of antisense conjugates for the treatment of myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies and can be potentially treated with antisense therapy decreasing mutant DMPK, targeting miRNAs or their binding sites or via a blocking mechanism for MBNL1 displacement from the repeats. Unconjugated antisense molecules are able to correct the disease phenotype in mouse models, but they show poor muscle penetration upon systemic delivery in DM1 patients. In order to overcome this challenge, research has focused on the improvement of the therapeutic window and biodistribution of antisense therapy using bioconjugation to lipids, cell penetrating peptides or antibodies. Antisense conjugates are able to induce the long-lasting correction of DM1 pathology at both molecular and functional levels and also efficiently penetrate hard-to-reach tissues such as cardiac muscle. Delivery to the CNS at clinically relevant levels remains challenging and the use of alternative administration routes may be necessary to ameliorate some of the symptoms experienced by DM1 patients. With several antisense therapies currently in clinical trials, the outlook for achieving a clinically approved treatment for patients has never looked more promising

El suicidio en Segovia (1992-1994).

Se registran los suicidios consumados, y las tentativas de suicidio que ingresaron en el Hospital General de Segovia entre 1992 y 1994. La tasa media anual de suicidios consumados es de 9,3 por diez mil habitantes y la de tentativas de 29,5, muy distintas a las recogidas en la Estadística del Suicidio del INE. Se establecen diferencias entre el suicidio consumado, suicidio frustrado y tentativas de suicidio (parasuicidio) considerando algunos factores asociados a las distintas conductas suicidas

El suicidio en Segovia (1992-1994).

Se registran los suicidios consumados, y las tentativas de suicidio que ingresaron en el Hospital General de Segovia entre 1992 y 1994. La tasa media anual de suicidios consumados es de 9,3 por diez mil habitantes y la de tentativas de 29,5, muy distintas a las recogidas en la Estadística del Suicidio del INE. Se establecen diferencias entre el suicidio consumado, suicidio frustrado y tentativas de suicidio (parasuicidio) considerando algunos factores asociados a las distintas conductas suicidas

Contribution of midgut bacteria to blood digestion and egg production in aedes aegypti (diptera: culicidae) (L.)

<p>Abstract</p> <p>Background</p> <p>The insect gut harbors a variety of microorganisms that probably exceed the number of cells in insects themselves. These microorganisms can live and multiply in the insect, contributing to digestion, nutrition, and development of their host.</p> <p>Recent studies have shown that midgut bacteria appear to strengthen the mosquito's immune system and indirectly enhance protection from invading pathogens. Nevertheless, the physiological significance of these bacteria for mosquitoes has not been established to date. In this study, oral administration of antibiotics was employed in order to examine the contribution of gut bacteria to blood digestion and fecundity in <it>Aedes aegypti</it>.</p> <p>Results</p> <p>The antibiotics carbenicillin, tetracycline, spectinomycin, gentamycin and kanamycin, were individually offered to female mosquitoes. Treatment of female mosquitoes with antibiotics affected the lysis of red blood cells (RBCs), retarded the digestion of blood proteins and reduced egg production. In addition, antibiotics did not affect the survival of mosquitoes. Mosquito fertility was restored in the second gonotrophic cycle after suspension of the antibiotic treatment, showing that the negative effects of antibiotics in blood digestion and egg production in the first gonotrophic cycle were reversible.</p> <p>Conclusions</p> <p>The reduction of bacteria affected RBC lysis, subsequently retarded protein digestion, deprived mosquito from essential nutrients and, finally, oocyte maturation was affected, resulting in the production of fewer viable eggs. These results indicate that <it>Ae. aegypti </it>and its midgut bacteria work in synergism to digest a blood meal.</p> <p>Our findings open new possibilities to investigate <it>Ae. aegypti</it>-associated bacteria as targets for mosquito control strategies.</p

Use of the checkerboard DNA-DNA hybridization technique for bacteria detection in Aedes aegypti (Diptera:Culicidae) (L.)

<p>Abstract</p> <p>Background</p> <p>Bacteria associated with insects can have a substantial impact on the biology and life cycle of their host. The checkerboard DNA-DNA hybridization technique is a semi-quantitative technique that has been previously employed in odontology to detect and quantify a variety of bacterial species in dental samples. Here we tested the applicability of the checkerboard DNA-DNA hybridization technique to detect the presence of <it>Aedes aegypti</it>-associated bacterial species in larvae, pupae and adults of <it>A. aegypti</it>.</p> <p>Findings</p> <p>Using the checkerboard DNA-DNA hybridization technique we could detect and estimate the number of four bacterial species in total DNA samples extracted from <it>A. aegypti </it>single whole individuals and midguts. <it>A. aegypti </it>associated bacterial species were also detected in the midgut of four other insect species, <it>Lutzomyia longipalpis, Drosophila melanogaster</it>, <it>Bradysia hygida </it>and <it>Apis mellifera</it>.</p> <p>Conclusions</p> <p>Our results demonstrate that the checkerboard DNA-DNA hybridization technique can be employed to study the microbiota composition of mosquitoes. The method has the sensitivity to detect bacteria in single individuals, as well as in a single organ, and therefore can be employed to evaluate the differences in bacterial counts amongst individuals in a given mosquito population. We suggest that the checkerboard DNA-DNA hybridization technique is a straightforward technique that can be widely used for the characterization of the microbiota in mosquito populations.</p

Chaotic asymptotic behaviour of the solutions of the Lighthill Whitham Richards equation

[EN] The phenomenon of chaos has been exhibited in mathematical nonlinear models that describe traffic flows, see, for instance (Li and Gao in Modern Phys Lett B 18(26-27):1395-1402, 2004; Li in Phys. D Nonlinear Phenom 207(1-2):41-51, 2005). At microscopic level, Devaney chaos and distributional chaos have been exhibited for some car-following models, such as the quick-thinking-driver model and the forward and backward control model (Barrachina et al. in 2015; Conejero et al. in Semigroup Forum, 2015). We present here the existence of chaos for the macroscopic model given by the Lighthill Whitham Richards equation.The authors are supported by MEC Project MTM2013-47093-P. The second and third authors are supported by GVA, Project PROMETEOII/2013/013Conejero, JA.; Martínez Jiménez, F.; Peris Manguillot, A.; Ródenas Escribá, FDA. (2016). Chaotic asymptotic behaviour of the solutions of the Lighthill Whitham Richards equation. 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Left ventricular non-compaction: clinical features and cardiovascular magnetic resonance imaging

Background: It is apparent that despite lack of family history, patients with the morphological characteristics of left ventricular non-compaction develop arrhythmias, thrombo-embolism and left ventricular dysfunction. METHODS: Forty two patients, aged 48.7 +/- 2.3 yrs (mean +/- SEM) underwent cardiovascular magnetic resonance (CMR) for the quantification of left ventricular volumes and extent of non-compacted (NC) myocardium. The latter was quantified using planimetry on the two-chamber long axis LV view (NC area). The patients included those referred specifically for CMR to investigate suspected cardiomyopathy, and as such is represents a selected group of patients. RESULTS: At presentation, 50% had dyspnoea, 19% chest pain, 14% palpitations and 5% stroke. Pulmonary embolism had occurred in 7% and brachial artery embolism in 2%. The ECG was abnormal in 81% and atrial fibrillation occurred in 29%. Transthoracic echocardiograms showed features of NC in only 10%. On CMR, patients who presented with dyspnoea had greater left ventricular volumes (both p < 0.0001) and a lower left ventricular ejection fraction (LVEF) (p < 0.0001) than age-matched, healthy controls. In patients without dyspnoea (n = 21), NC area correlated positively with end-diastolic volume (r = 0.52, p = 0.0184) and end-systolic volume (r = 0.56, p = 0.0095), and negatively with EF (r = -0.72, p = 0.0001). CONCLUSION: Left ventricular non-compaction is associated with dysrrhythmias, thromboembolic events, chest pain and LV dysfunction. The inverse correlation between NC area and EF suggests that NC contributes to left ventricular dysfunction

Parathyroid adenoma apoplexy as a temporary solution of primary hyperparathyroidism: a case report

<p>Abstract</p> <p>Introduction</p> <p>The natural history of patients with spontaneous parathyroid necrosis is unknown. In this case report we describe the clinical course, laboratory, radiographic, bone densitometry tests, parathyroid ultrasonography and scintigraphy examinations of a patient performed over a period of eight years after she first presented with a sudden episode of spontaneous resolution of primary hyperparathyroidism (PHPT).</p> <p>Case presentation</p> <p>A 24-year-old woman with a clinical history and laboratory and radiographic tests compatible with PHPT suffered a sudden episode of cervical pain and presented with clinical evidence of hypocalcemia. Biopsy of a cervical nodule revealed necrotic material compatible with ischemia of the parathyroid. The follow-up of the patient presented four distinct phases: the first, which lasted two years, was compatible with a period of bone hunger during which it was necessary to introduce calcitriol and calcium carbonate. During this period, the patient showed bone mass gain. The second phase was characterized by normalization of calcium and parathyroid hormone levels and its end was difficult to define. During the third phase there was a recurrence of hypercalcemia associated with elevated parathyroid hormone (PTH) levels and loss of bone mass. The last phase corresponded to the interval after parathyroidectomy, which was characterized by normalization of serum levels of calcium and PTH, as well as bone mass gain.</p> <p>Conclusion</p> <p>This case report indicates that spontaneous resolution of PHPT by adenoma necrosis is potentially temporary. Thus, in cases in which a conservative approach is chosen, clinical and laboratory follow-up is indispensable. Bone mass measurement is a useful tool in the follow-up of these cases. However, this option exposes the patient to a potential roller-coaster ride of bone mass gain and loss, whose long term consequences are still unknown.</p

Concept of finite limit of a function at a point: meanings and specific terms

In this paper, we present some results of an exploratory study performed with students aged 16-17. We investigate the different uses that these students make of terms such as ‘to approach’, ‘to tend’, ‘to reach’, ‘to exceed’ and ‘limit’ that describe the basic notions related to the concept of the finite limit of a function at a point. We use the interpretive framework of conceptual analysis to infer the meanings that students associate with these specific terms in connection with the effective use of terms in their answers.This study was performed with aid and financing from Fellowship FPU AP2010-0906 (MEC-FEDER), Projects EDU2009-11337 and EDU2012-33030 of the National Plan for R&D&R (MICIN), Subprogram EDUC and Group FQM-193 of the 3rd Andalusian Research Plan (PAIDI).This chapter is derived in part from an article published in International Journal of Mathematical Education in Science and Technology 05 Jul 2013, available online: http://www.tandfonline.com/10.1080/0020739X.2013.80588