Fostering collaborative research for rare genetic disease: The example of Niemann-Pick type C disease

Rare disease represents one of the most significant issues facing the medical community and health care providers worldwide, yet the majority of these disorders never emerge from their obscurity, drawing little attention from the medical community or the pharmaceutical industry. The challenge therefore is how best to mobilize rare disease stakeholders to enhance basic, translational and clinical research to advance understanding of pathogenesis and accelerate therapy development. Here we describe a rare, fatal brain disorder known as Niemann-Pick type C (NPC) and an innovative research collaborative known as Support of Accelerated Research for NPC (SOAR-NPC) which illustrates one pathway through which knowledge of a rare disease and its possible treatments are being successfully advanced. Use of the “SOAR” mechanism, we believe, offers a blueprint for similar advancement for many other rare disorders

Production of two novel laccase isoforms by a thermotolerant strain of Pycnoporus sanguineus isolated from an oil-polluted tropical habitat

A thermotolerant and halotolerant strain of Pycnoporus sanguineus was isolated from an oil-polluted site in a tropical area located in Veracruz, Mexico. This strain was able to grow at 47ºC and in culture medium containing 500 mM NaCl. The strain was also tolerant to the presence of 30,000 ppm of crude Maya oil. A 68-kDa protein purified submerged cultures exhibited laccase activity towards 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), guaiacol, syringaldazine and o-dianisidine, for which it presented the highest affinity (Km = 43 µM). Two-dimensional gel electrophoresis analysis showed that, unusual for laccases, the enzyme has two active isoforms, with isoelectric points of 7.00 and 7.08. The purified enzyme showed high thermostability, retaining 40% of its original activity after 3 h at 60ºC. This property seems to correlate with a long “shelf-life”, given that at 40ºC enzyme activity was only gradually lost over a 5-day period incubation. Both, the fungus and its laccase aer likely to have high potential for biotechnological applications

Efficiency Maximization of a Jet Pump for an Hydraulic Artificial Lift System

In science and engineering, mathematical modeling serves as a tool to understand processes and systems acting as a testing bed for several hypotheses. The selection of a specific model, as well as its variables and parameters, depends on the nature of the system under analysis and the acceptable simplifying assumptions. Therefore, it must allow for a good fit between both the hypothesis and the available data. Opposite to other design approaches based on experimental data or/and complex models, this work presents a simpler numerical design method for efficiency maximization of an Hydraulic Jet Pump (HJP) for oil-well extraction process, considering its hydraulic and geometric parameters. The design process consists in setting and solving a constrained non-linear optimization problem by taking into account the hydraulic model of the HJP in terms four design variables: throat area, nozzle area, injection flow, and injection pressure to the oil-well. The objective function of this case aims to maximize the HJP's efficiency avoiding to approach cavitation condition as well fulfilling technical constraints. A numerical technique, Differential Evolution Algorithm (DEA), has been implemented to solve the optimization problem. The proposed methodology leads to a solution set by considering only commercial geometries and feasible operating conditions for the HJP, which facilitates its practical implementation. A set of ten oil-wells with land production data, operating in the southeaster of Mexico, is used to compare and validate several Jet pump designs, i. e., through comparison with actual oil-well's operation condition.Peer Reviewe

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

Ponte et stratégie de la reproduction chez les femelles du tacaud Trisopterus luscus (Gadidés) du plateau continental de la Galice, nord-ouest de l'Espagne

[EN] Pouting, Trisopterus luscus is harvested commercially on the Galician shelf by the Spanish inshore artisanal fleet. In spite of a substantial decrease in pouting catches, fishery regulations are limited to size length restrictions. This study provides biological data including length-at-maturity based on histological methods, seasonal maturation, spawning and fecundity. A collection 443 females, from 17 to 42 cm in total length, were sampled from landings (December 2003 to December 2004). Pouting length-at-maturity was estimated as 19.2 cm on average. Pouting females in spawning condition were observed throughout the year and the number of developing oocytes ranged from 20 000 to 1 327 000. Peak spawning was observed between February and April, which correlated well with trends in gonadosomatic index, and inverse to condition factor and hepatosomatic index. Histological examination of the gonads revealed that pouting ovarian development organization is asynchronous, and fecundity is probably determinate.[FR] Le tacaud, Trisopterus luscus est pêché par la flotte artisanale espagnole. En dépit d'une diminution substantielle des captures de tacaud, la pêche est réglementée uniquement à partir d'une taille minimum commerciale. Cette étude fournit des données biologiques comprenant la taille à maturité sexuelle basée sur l'histologie, la maturation saisonnière, la ponte et la fécondité. Un échantillon de 443 femelles, de 17 à 42 cm longueur totale, est examiné à partir des débarquements durant une année (de décembre 2003 à décembre 2004). La taille moyenne à maturité sexuelle est estimée à 19,2 cm. Les femelles de tacaud en condition de ponte sont observée tout au long de l'année et le nombre d'ovocytes s'étend de 20 000 to 1 327 000 par individu. Les pics de ponte sont observés entre février et avril, ce qui est bien corrélé avec l'évolution du rapport gonado-somatique et inverse de celle du facteur de condition et du rapport hépato-somatique. L'étude histologique révèle que le développement ovarien chez le tacaud est asynchrone, et que la fécondité est probablement déterminée.Peer reviewe

Los CaCCs: proteínas multifuncionales, de la fisiología a la enfermedad

Los CaCCs son proteínas formadoras de poros que se ubican en la membrana celular. Los CaCCs permiten el paso de iones a través de la membrana, lo cual es clave para una adecuada realización de funciones celulares y para el desarrollo de algunas enfermedades. En este contexto, se brinda una reseña del papel fisiopatológico de los CaCCs. La metodología empleada fue hacer una extensa consulta en U.S. National Library of Medicine-PubMed.gov. Los resultados encontrados indican que, a pesar del papel fundamental que tienen los CaCCs en el desarrollo de enfermedades crónicas, en nuestro país se realiza poca investigación y difusión en este campo

Comprehensive sexual education program for the prevention of adolescent pregnancy in regular basic education students. Sechura 2022

This article: "Comprehensive Sexual Education Program for the Prevention of Adolescent Pregnancy in Regular Basic Education Students, Sechura, 2022", was investigated developing a qualitative approach of a descriptive type whose design is non-experimental, since the research problem is focuses on the following question: Is it possible to develop a comprehensive sexual education program to prevent adolescent pregnancy in students of Regular Basic Education - EBR in the province of Sechura? It should be noted that the situation regarding the problem of adolescent pregnancies constitutes a problem that affects the public health of our society; For this reason, I express my special interest in addressing this problem, since to contribute to its solution it has a lot to do with the educational issue.   The diagnosis made shows us that there is a wide misinformation on this subject, adolescents are unaware of the meaning of the term sexuality; They are also unaware of the dangers of having sex without proper protection. On the other hand, they are unaware of the use of contraceptive methods despite the fact that the vast majority of adolescents begin their sexual awakening between twelve and thirteen years of age. The research proposes the realization of an intervention program which will be applied extracurricularly, with the purpose of being able to generate significant changes in the community: students and parents. For the fulfillment of this effect, the committed participation of tutors and teachers is required, who will have the responsibility of being able to apply this proposal.El presente artículo : “Programa de Educación Sexual Integral para la Prevención del Embarazo Adolescente en Estudiantes de Educación Básica Regular, Sechura, 2022”, se investigó  desarrollando un enfoque cualitativo de tipo descriptivo cuyo diseño es no experimental, pues el problema de la investigación se centra en la siguiente interrogante: ¿Es posible desarrollar un programa de educación sexual integral para prevenir el embarazo adolescente en estudiantes de Educación Básica Regular – EBR en la provincia de Sechura? Cabe destacar que la situación respecto al problema de los embarazos adolescentes constituye un problema que afecta la salud pública de nuestra sociedad; por ello expreso mi especial interés en abordar este problema, ya que para aportar en su solución tiene que ver mucho con el tema educativo.  El diagnóstico realizado nos muestra que existe una amplia desinformación sobre este tema, los adolescentes desconocen el significado del término sexualidad; así como también no son conscientes de los peligros que encierra el hecho de mantener relaciones sexuales sin la debida protección. Por otra parte, desconocen del uso de los métodos anticonceptivos a pesar de que la gran mayoría de adolescentes inician su despertar sexual entre los doce y trece años de edad. La investigación propone la realización de un programa de intervención el cual se aplicará de manera extracurricular, con la finalidad de poder generar cambios significativos en la colectividad: estudiantes y padres de familia. Para el cumplimiento de tal efecto se requiere de la participación comprometida de los tutores y docentes quienes tendrán la responsabilidad de poder aplicar la presente propuesta

Forecasting Seizures in Dogs with Naturally Occurring Epilepsy

Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low-gamma (30-70 Hz), and high-gamma (70-180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring

Identification of the Rostral Migratory Stream in the Canine and Feline Brain

In the adult rodent brain, neural progenitor cells migrate from the subventricular zone of the lateral ventricle towards the olfactory bulb in a track known as the rostral migratory stream (RMS). To facilitate the study of neural progenitor cells and stem cell therapy in large animal models of CNS disease, we now report the location and characteristics of the normal canine and feline RMS. The RMS was found in Nissl-stained sagittal sections of adult canine and feline brains as a prominent, dense, continuous cellular track beginning at the base of the anterior horn of the lateral ventricle, curving around the head of the caudate nucleus and continuing laterally and ventrally to the olfactory peduncle before entering the olfactory tract and bulb. To determine if cells in the RMS were proliferating, the thymidine analog 5-bromo-2-deoxyuridine (BrdU) was administered and detected by immunostaining. BrdU-immunoreactive cells were present throughout this track. The RMS was also immunoreactive for markers of proliferating cells, progenitor cells and immature neurons (Ki-67 and doublecortin), but not for NeuN, a marker of mature neurons. Luxol fast blue and CNPase staining indicated that myelin is closely apposed to the RMS along much of its length and may provide guidance cues for the migrating cells. Identification and characterization of the RMS in canine and feline brain will facilitate studies of neural progenitor cell biology and migration in large animal models of neurologic disease