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Jellyfish venoms are rich sources of toxins designed to capture prey or deter predators, but they can also elicit harmful effects in humans. In this study, an integrated transcriptomic and proteomic approach was used to identify putative toxins and their potential role in the venom of the scyphozoan jellyfish Chrysaora fuscescens. A de novo tentacle transcriptome, containing more than 23,000 contigs, was constructed and used in proteomic analysis of C. fuscescens venom to identify potential toxins. From a total of 163 proteins identified in the venom proteome, 27 were classified as putative toxins and grouped into six protein families: proteinases, venom allergens, C-type lectins, pore-forming toxins, glycoside hydrolases and enzyme inhibitors. Other putative toxins identified in the transcriptome, but not the proteome, included additional proteinases as well as lipases and deoxyribonucleases. Sequence analysis also revealed the presence of ShKT domains in two putative venom proteins from the proteome and an additional 15 from the transcriptome, suggesting potential ion channel blockade or modulatory activities. Comparison of these potential toxins to those from other cnidarians provided insight into their possible roles in C. fuscescens venom and an overview of the diversity of potential toxin families in cnidarian venoms.

The neurotoxic effects produced by a tentacle venom extract and a fraction were analyzed and correlated by in vivo and in vitro approaches. The tentacle venom extract exhibited a wide range of protein components (from 24 to >225 kDa) and produced tetanic reactions, flaccid paralysis, and death when injected into crabs. Two chromatography fractions also produced uncontrolled appendix movements and leg stretching. Further electrophysiological characterization demonstrated that one of these fractions potently inhibited ACh-elicited currents mediated by both vertebrate fetal and adult muscle nicotinic acetylcholine receptors (nAChR) subtypes. Receptor inhibition was concentration-dependent and completely reversible. The calculated IC50 values were 1.77 μg/μL for fetal and 2.28 μg/μL for adult muscle nAChRs. The bioactive fraction was composed of a major protein component at ~90 kDa and lacked phospholipase A activity. This work represents the first insight into the interaction of jellyfish venom components and muscle nicotinic receptors.

La presente sistematización surge en el marco del Programa Integral de Nutrición (PIN) del Programa Nacional de Asistencia Alimentaria (PRONAA) el cual se desarrolló mediante tres componentes: educativo, alimentario, y monitoreo y evaluación. Su objetivo general fue prevenir la malnutrición en niños y niñas hasta los 12 años, priorizando a los menores de 3 años en situación de vulnerabilidad nutricional, para mejorar su calidad de vida. En este trabajo de tesis se busca sistematizar la experiencia de la intervención educativa del componente educativo del PIN en la finalidad Familias, en el distrito de Santiago de Chocorvos, provincia de Huaytará, región Huancavelica, tomando como eje principal el rol que desempeñó el facilitador durante la ejecución de la intervención. Un primer aporte de esta investigación se refiere a que el componente educativo es un pilar fundamental de todo programa nutricional que busca desarrollar y fortalecer las capacidades de la población para mejorar su calidad de vida. Asimismo, es un componente básico en la dimensión familiar y comunal, el rol del facilitador, quien es el puente o el nexo entre el mundo concreto de los usuarios del programa y su necesidad de conectarse con otras realidades y programas del Estado.Otro alcance importante de la investigación se refiere al facilitador como pieza sustancial del engranaje organizativo de toda intervención educativa, y su proactividad para promover el trabajo articulado con diferentes sectores, a fin de potenciar los resultados que puede tener un programa con estas características. Además, la investigación tiene también como objetivo reconocer la cualidad de la facilitadora de desarrollar un trabajo articulado y que gracias a esa cualidad se contribuya a potenciar los resultados obtenidos. De esta manera, se puede afirmar que la facilitadora es una pieza importante del engranaje organizativo de la intervención educativa.

IntroductionThere are many challenges encountered in the health technology assessment (HTA) of treatments for the management of neurodegenerative diseases like Alzheimer’s disease. A recent example where such challenges were visible was the assessment of aducanumab, a medication developed for Alzheimer’s disease. As part of the Innovative Medicines Initiative (IMI) Neuronet project, a series of workshops were held to understand the gaps in neurodegenerative disease research and identify the key research priorities, from the perspective of different stakeholders, that can inform decision-making and enable timely access to effective and safe treatments.MethodsThree workshops were organised by Neuronet to consult with HTA and regulatory experts, people with dementia and their supporters, and academic and industry researchers. The first consultation was with the European Working Group of People with Dementia and their supporters, and their feedback was fed into the following two workshops which were conducted with HTA and regulatory experts, and with researchers. Discussions during the workshops were used to develop a summary of the gaps in research, and priorities from the perspective of each stakeholder group to be submitted to IMI to inform future research funding allocation.ResultsKey priorities that were highlighted from an HTA and regulatory perspective were the collection of longitudinal data to understand the natural history of the disease, the generation of data on long-term clinical outcomes and the use of trial endpoints that are relevant to clinical practice. There is also a need for disease-modifying treatments that is yet to be met in this disease area. Furthermore, the involvement of the public, particularly people with dementia and relevant organisations, in setting research priorities and informing study designs was highlighted as a priority by all stakeholders.ConclusionsThere are key priorities for future neurodegenerative research from an HTA and regulatory perspective to address current gaps and challenges. It is important to involve different stakeholders in priority setting and decision-making to produce relevant and satisfactory research outputs.

The Public Health Center Vaccine Survey (PHCVS) examines the knowledge, attitudes, and beliefs about seasonal influenza and H1N1 vaccinations in a largely low-income, urban, public health clinic population in Los Angeles County, USA. A cross-sectional survey of vulnerable individuals at risk for severe influenza infection was conducted in one of the nation's largest local public health jurisdictions. A total of 1541 clinic patients were recruited in the waiting rooms of five large public health centers in Los Angeles County from June to August, 2010. Among prospective respondents who met eligibility criteria, 92% completed the survey. The majority was black or Latino and most were between the ages of 18 and 44 years. More than half were unemployed; two-thirds had no health insurance; and nearly one-half reported having a high school education or less. About one-fifth reported they had received the H1N1 vaccine during the previous flu season. In comparative analyses, negative beliefs about vaccine safety and efficacy were highly predictive of H1N1 vaccination. Blacks were less likely than non-black respondents to report receiving the H1N1 vaccine (OR = 0.7, 95% CI = 0.6–1.0). Blacks were also less likely than other respondents to agree that vaccines can prevent disease (OR = 0.4, 95% CI = 0.3–0.5), that vaccines are safe (OR = 0.5, 95% CI = 0.4–0.6), and that they trust doctors/clinicians who recommend vaccines (OR = 0.5, 95% CI = 0.4–0.7). Study findings provide a useful risk profile of vulnerable groups in Los Angeles County, which may be generalizable to other urban jurisdictions in the United States. They also describe real world situations that can be used to forecast potential challenges that vaccine beliefs may pose to national as well as local influenza pandemic planning and response, especially for communities with limited access to these preventive services.

Background and aim of the studyGiven the lipolytic effect of GH and its potential role in determining adipose tissue distribution, we evaluated the expression of the GH hormone receptor (GHR) isoforms in patients with morbid obesity seeking associations with metabolic parameters.Methods262 morbidly obese subjects (mean age 42.5 ± 11 years, 75% women) underwent PCR-genotyping of the exon 3 GHR polymorphism. In 17 of these subjects, who proved to be heterozygous for the exon 3 genotype (+3/−3), subcutaneous and visceral adipose tissue was obtained during bariatric surgery; total RNA was extracted, reversely transcribed, and the different isoforms of the GHR (exon 3 containing and lacking flGHR as well as the trGHR) were PCR-amplified using specific primers.Results27% were +3/+3 homozygous, 20% −3/−3 homozygous and 53% were +3/−3 heterozygous. Compared to subjects homozygous for the +3 genotype, homozygous and heterozygous carriers of the −3 genotype were significantly heavier and tended to have a higher HOMA 2-IR. Expression of the flGHR and trGHR mRNA was demonstrated in all evaluated samples of subcutaneous and visceral adipose tissue from the 17 patients. The exon 3+ isoform was expressed in all adipose tissue samples, whereas only six subjects expressed the 3− isoform as well. The only distinctive feature of these six patients was a higher HbA1c.ConclusionsThe heterozygous GHR +3/−3 genotype is more prevalent in subjects with morbid obesity. Patients expressing the exon +3 and exon −3 isoforms in adipose tissue had a higher HbA1c, than those expressing only the exon −3 isoform.