Patient access to gene therapy medicinal products : a comprehensive review

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Background Gene therapies have the potential to be a curative approach to a large number of genetic diseases. However, granting of a positive marketing authorisation does not equal patient access to therapy. Objectives The purpose of this paper is to identify a full set of hurdles potentially preventing patient access to gene therapies based on the available literature. Methods A review of the literature using systematic approach in two distinct databases was performed by identifying relevant, peer-reviewed publications, between 2012 and 2018. Results Seven major topics were identified as potential patient access hurdles, namely affordability, assessment of value, development of therapy, ethical/social factors, evidence generation, operational implementation and regulatory hurdles. From these, 25 additional subthemes were further identified. The most frequently mentioned obstacle in the literature is related to the affordability aspect especially focusing on high cost of therapy (84%) and therapy payment/reimbursement (51%). Importantly, the evidence generation focusing on limited trial outcomes (81%) seems as a strong obstacle in patient access to these therapies. Conclusions A growing number of gene therapies are expected to be developed and made available to patients and healthcare professionals. Improvement of patient access to gene therapies can only be achieved by understanding all hurdles, in a complete and integrated fashion, so that strategies are timely established to ensure gene therapies’ benefits are provided to patients and to the society.info:eu-repo/semantics/publishedVersio

Historical demography and spatial genetic structure of the subterranean rodent <i>Ctenomys magellanicus</i> in Tierra del Fuego (Argentina)

Ctenomys (tuco-tuco) is the most numerous genus of South American subterranean rodents and one of the most genetically diverse clades of mammals known. In particular, the genus constitutes a very interesting model for evolutionary studies of genetic divergence and conservation. Ctenomys magellanicus is the southernmost species of the group and the only one living in Isla Grande de Tierra del Fuego (Argentina). This species presents two chromosomal forms (Cm34 and Cm36) fragmented into demes distributed from the north region (steppe) to the south region (ecotone) of the island, respectively; no hybrids or overlapping areas were detected. To study the historical demography and the spatial genetic structure of the C.magellanicus population we used mitochondrial DNA (mtDNA) (D-loop and cytochrome b) and microsatellite loci. Nine mtDNA haplotypes were identified, three of them belonging to the north and the other six to the south. Shared haplotypes between regions were not detected. mtDNA and microsatellite genotypes showed a marked pattern of population structure with low values of genetic flow between regions. The south is made up of small populations or isolated demes making up an endogamic metapopulation with unique alleles and haplotypes. Also, the results suggest a northward expansion process starting from an ancestral haplotype from the south. That population might have lived at a refuge through the adverse Pleistocene environmental conditions that took place at Tierra del Fuego. Results of this study are relevant to the conservation of C.magellanicus, suggesting that each region (north and south) might be considered as an Evolutionarily Significant Unit.Centro Regional de Estudios Genómico

Atividade física e aptidão física em crianças de etnia cigana e não cigana: um estudo em crianças de ambos os géneros

La escuela y la familia asumen un papel preponderante en la adquisición de un estilo de vida activo en los niños, en particular la escuela, que permite el acceso equitativo a la AF a través de la Educación Física (EF), independientemente del estatuto socioeconómico (ESE) de las familias, ya que es sabido que tiene una relación inversa con la AF (Serrano, 2004; Zahner y col., 2006). Los estudios realizados con adolescentes revelaron que el 80% de los que tenían sobrepeso pertenecían a grupos minoritarios. Por otro lado, los niños de grupos étnicos minoritarios son también quienes más juegan con los padres (Niederer y col., 2009). En nuestro estudio, se hace una evaluación de estos factores, asociados al pueblo gitano. Conocidos como un pueblo habilidoso y ritmado, muy ligado a la cultura circense y flamenca, aunque también asociado a un ESE más bajo (Costa, 2006). Objetivo: Evaluar la AF y los niveles de aptitud física (ApF), en niños de etnia gitana (EG) y no gitanos (NG), con edades comprendidas entre 6 y 10 años.The school and the family assume a preponderant role in the acquisition of an active lifestyle in children, in particular the school, which allows equitable access to PhA through Physical Education (PhE), regardless of the socio-economic status (SES) of families, since it is known that it has an inverse relationship with PhA (Serrano, 2004; Zahner et al., 2006). Studies involving adolescents revealed that 80% of those who were overweight belonged to minority groups. On the other hand, children from ethnic minority groups are also the ones who most play with parents (Niederer et al., 2009). In our study, an assessment is made of these factors, associated with the Roma people. Known as a skilled and rhythmic people, closely linked to the circus and flamenco culture, although also associated with a lower SES (Costa, 2006). Objective: To evaluate the PhA and the levels of physical fitness (PhF), in children of gypsy ethnicity (GE) and non-gypsies (NG), with ages between 6 and 10 years.A escola e a família assumem um papel preponderante na aquisição de um estilo de vida ativo das crianças, nomeadamente a escola, que permite o acesso equitativo à AF através da Educação Física (EF), independentemente do estatuto socioeconómico (ESE) das famílias, que é sabido que tem uma relação inversa com a AF (Serrano, 2004; Zahner e col., 2006). Estudos realizados com adolescentes revelaram que 80% dos que tinham excesso de peso eram pertencentes a grupos minoritários. Por outro lado, as crianças de grupos étnicos minoritários são também quem mais brinca com os pais (Niederer e col., 2009). No nosso estudo, é feita uma avaliação destes fatores, associados ao povo cigano. Conhecidos como sendo um povo habilidoso e ritmado, muito ligado à cultura circense e flamenga, embora também associado a um ESE mais baixo (Costa, 2006). Objetivo: Avaliar a AF e os níveis de aptidão física (ApF), em crianças de etnia cigana (EC) e não cigana (NC), com idades compreendidas entre 6 e 10 anos.peerReviewe

Biofuels and high value added products from the yeast Rhodosporidium toruloides NCYC 921: Strategies towards a true cost-effective and environmentally sustainable integrated multiproduct driven biorefinery [Poster]

Single-cell oils (SCO) have been considered a promising source of 3rd generation biofuels mainly in the final form of biodiesel. However, its high production costs have been a barrier towards the commercialization of this commodity. The fast growing yeast Rhodosporidium toruloides NCYC 921 has been widely reported as a potential SCO producing yeast. In addition to its well-known high lipid content (that can be converted into biodiesel), is rich in high value added products such as carotenoids with commercial interest. The process design and integration may contribute to reduce the overall cost of biofuels and carotenoid production and is a mandatory step towards their commercialization. The present work addresses the biomass disruption, extraction, fractionation and recovery of products with special emphasis on high added valued carotenoids (beta-carotene, torulene, torularhodin) and fatty acids directed to biodiesel. The chemical structure of torularhodin with a terminal carboxylic group imposes an additional extra challenge in what concern its separation from fatty acids. The proposed feedstock is fresh biomass pellet obtained directly by centrifugation from a 5L fed-batch fermentation culture broth. The use of a wet instead of lyophilised biomass feedstock is a way to decrease processing energy costs and reduce downstream processing time. These results will contribute for a detailed process design. Gathered data will be of crucial importance for a further study on Life-Cycle Assessment (LCA)

Historical demography and spatial genetic structure of the subterranean rodent <i>Ctenomys magellanicus</i> in Tierra del Fuego (Argentina)

Ctenomys (tuco-tuco) is the most numerous genus of South American subterranean rodents and one of the most genetically diverse clades of mammals known. In particular, the genus constitutes a very interesting model for evolutionary studies of genetic divergence and conservation. Ctenomys magellanicus is the southernmost species of the group and the only one living in Isla Grande de Tierra del Fuego (Argentina). This species presents two chromosomal forms (Cm34 and Cm36) fragmented into demes distributed from the north region (steppe) to the south region (ecotone) of the island, respectively; no hybrids or overlapping areas were detected. To study the historical demography and the spatial genetic structure of the C.magellanicus population we used mitochondrial DNA (mtDNA) (D-loop and cytochrome b) and microsatellite loci. Nine mtDNA haplotypes were identified, three of them belonging to the north and the other six to the south. Shared haplotypes between regions were not detected. mtDNA and microsatellite genotypes showed a marked pattern of population structure with low values of genetic flow between regions. The south is made up of small populations or isolated demes making up an endogamic metapopulation with unique alleles and haplotypes. Also, the results suggest a northward expansion process starting from an ancestral haplotype from the south. That population might have lived at a refuge through the adverse Pleistocene environmental conditions that took place at Tierra del Fuego. Results of this study are relevant to the conservation of C.magellanicus, suggesting that each region (north and south) might be considered as an Evolutionarily Significant Unit.Centro Regional de Estudios Genómico

The impact of exercise training on liver transplanted familial amyloidotic polyneuropathy (FAP) patients

Liver transplantation is nowadays the only effective answer to adjourn the outcome of functional limitations associated with familial amyloidotic polyneuropathy (FAP), a neurodegenerative disease characterized by sensory and motor polyneuropathies. Nevertheless, there is a detrimental impact associated with the after-surgery period on the fragile physical condition of these patients. Exercise training has been proven to be effective on reconditioning patients after transplantation. However, the effects of exercise training in liver transplanted FAP patients have not been scrutinized yet

Body composition, muscle strength, functional capacity, and physical disability risk in liver transplanted familial amyloidotic polyneuropathy patients

Abstract: Background: Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease leading to sensory and motor polyneuropathies, and functional limitations. Liver transplantation is the only treatment for FAP, requiring medication that negatively affects bone and muscle metabolism. The aim of this study was to compare body composition, levels of specific strength, level of physical disability risk, and functional capacity of transplanted FAP patients (FAPTx) with a group of healthy individuals (CON). Methods: A group of patients with 48 FAPTx (28 men, 20 women) was compared with 24 CON individuals (14 men, 10 women). Body composition was assessed by dual-energy X-ray absorptiometry, and total skeletal muscle mass (TBSMM) and skeletal muscle index (SMI) were calculated. Handgrip strength was measured for both hands as was isometric strength of quadriceps. Muscle quality (MQ) was ascertained by the ratio of strength to muscle mass. Functional capacity was assessed by the six-minute walk test. Results: Patients with FAPTx had significantly lower functional capacity, weight, body mass index, total fat mass, TBSMM, SMI, lean mass, muscle strength, MQ, and bone mineral density. Conclusion: Patients with FAPTx appear to be at particularly high risk of functional disability, suggesting an important role for an early and appropriately designed rehabilitation program

Estimación del tamaño muestral para estudios de variabilidad morfológica in situde Lippia integrifolia (Verbenaceae) en el Parque Nacional Talampaya, La Rioja (Argentina)

Lippia integrifolia “incayuyo” is an aromatic and medicinal shrub of economic importance, distributed from Bolivia to northwestern and central Argentina. It has shown a wide variation between individuals of the same species, which could be the result of interaction with the environment and / or be genetically determined. On the basis of this variability, characterization studies are needed for further agronomic evaluations, plant breeding, selection, conservation and reproduction of specimen with desirable characteristics. The aim of this study is to determine, using two estimation methods, the minimum number of individuals to be assessed that represents in situ morphological variability of a population of L. integrifolia. From a preliminary sampling conducted in the Parque Nacional Talampaya, in which 11 morphometric characters were registered in L. integrifolia, a parametric and a nonparametric estimation of the Minimum Sample Size was performed. Based on the morphometric characters evaluated here it is recommended a minimum sample size in between 35-40 individuals, determined by the characters that showed greater variability, with which the morphological variability of the species would be guaranteedLippia integrifolia“incayuyo” es un arbusto aromático y medicinal de interés económico cuya distribución abarca desde Bolivia hasta el noroeste y centro de Argentina. Presenta una amplia variabilidad intraespecífica, la cual podría ser el resultado de la interacción con el ambiente y/o estar determinada genéticamente. Debido a esta variabilidad, estudios de caracterización son necesarios para posteriores evaluaciones agronómicas, mejoramiento genético, selección,reproducción y conservación de ejemplares con características deseables. El objetivo de este trabajo es determinar, utilizando dos métodos de estimación, el número de individuos mínimo a relevar in situque representen la variabilidad morfológica de una población de L. integrifolia. A partir de un muestreo preliminar realizado en el Parque Nacional Talampaya en el que se registraron 11 caracteres morfométricos en L. integrifolia, se realizó una estimación paramétrica y una no paramétrica del Tamaño Muestral Mínimo. Sobre la base de los caracteres morfométricos aquí evaluados se recomienda un tamaño de muestra mínimo de entre 35 a 40 ejemplares, determinado por los caracteres que mostraron mayor variabilidad, con el cual se garantizaría poder captar la variabilidad morfológica de la especie

APLICACIÓN DE BUENAS PRÁCTICAS DE MANUFACTURA Y DETERMINACIÓN DE AGENTES CONTAMINANTES EN HAMBURGUESAS EXPENDIDAS EN SALTA (ARGENTINA)

El objetivo fue determinar agentes contaminantes (microorganismos patógenos y oxidación lipídica) en hamburguesas expendidas en la ciudad de Salta, República Argentina. Se observó planta física, condiciones higiénicas de instalaciones, equipos y personal en 25 establecimientos habilitados (al azar). Se tomaron 25muestras de emparedados de hamburguesas (pan, carne picada y moldeada, huevo, tomate, lechuga y aderezos) en bolsas estériles. Se realizó: Recuento Total de Aerobios Mesófilos, Coliformes, Enterobacterias, Staphylococcus aureus, Escherichia coli (O157: H7) e Índice de Peróxidos (IP) y Malonilaldehído (MDA). Estadísticamente se realizaron pruebas no paramétricas (Rho de Sperman); Programa SPSS 7.0. El 60% de los locales presentaban instalaciones, equipos y baños en buenas condiciones según normas vigentes (80/96 Reglamento MERCOSUR). Entre el 56 al 68% tenían mínimas condiciones de higiene en todos los sectores de la fábrica: 52% no contaba con programa de saneamiento o desinfección según lo exigido por organismos competentes. El 40% del personal no vestían uniforme completo ni limpio; el 56% sin libreta sanitaria y el 80% sin cursos de capacitación en BPM. Los hábitos indeseables fueron observados en el 88% de los casos, con conductas de trabajo regulares (40%) y contaminación cruzada (90 %). Recuento Total Positivo 95% de las muestras (103 a 107 UFC/g); 60% conColiformes (102 a 8 x 105 UFC/g), 10% con Enterobacterias (103 a 6 x 103 UFC/g) y 35% con Sthaphilococcus aureus (3 x 102 a 104 UFC/g) excediendo límites permitidos para consumo. E. coli negativa (100%). El 20% con IP mayor a10mEqO2 / Kg (10,44 a 14,53); el 92% con contenido de MDA inferior a 0,5 (0,154 a 0,451). Correlación altamente significativa entre análisis microbiológicos y libreta sanitaria, cursos de capacitación, conductas y contaminación cruzada. La aplicación de BPM fue insuficiente, lo cual se refleja en la calidad higiénico sanitaria de los productos analizados ya que recuentos elevados indican materias primas contaminadas, tratamientos no satisfactorios y condiciones inadecuadas de almacenamiento. Peróxidos y MDA excedieron los límites permitidos constituyendo peligros potenciales para la salud de los consumidores.Palabras Clave: hamburguesas, microorganismos patógenos, Índice de Peróxidos, Malonilaldehído, E. coli.hamburgers, pathogenic microorganisms , Index of Peroxides, Malonilaldehyd, E. col

The Me and the Us of Emotions: a cluster-randomized controlled trial of the feasibility and efficacy of a compassion-based social–emotional learning program for children

There are well-established benefits of social and emotional learning (SEL) programs for children within educational contexts. Combining social–emotional skills and compassion abilities has been seldomly done, and it may be valuable at individual and societal levels, for resilient, empathetic, and inclusive societies. This study explored the feasibility and efficacy of a program designed to promote socioemotional and compassion skills in children attending the 3rd and 4th grades, by using in-class dynamics complemented with serious games. This program, named “The Me and the Us of Emotions,” is part of the Gulbenkian Knowledge Academies 2020 and consists of 10 group sessions embedded in the school curriculum. Using a cluster-randomized controlled trial design, school classes were allocated to intervention (classes, n = 8; children, n = 163) and control groups (classes, n = 6; children, n = 132). During the program, facilitators assessed adherence to the sessions’ plan, attendance, dosage (i.e., how many sessions were delivered), and participant responsiveness. Children completed self-report measures of social–emotional skills and emotional climate at pre-, post-intervention, 3-month, and 6-month follow-ups. Results indicate that the program is feasible, with high adherence, high attendance rate, and participant responsiveness. Results also indicate empathy, soothing, and drive feelings to change from pre-intervention to all other assessment moments, for the intervention group only. Moreover, cooperation and threat changed over time for participants in both the control and the intervention groups. The current study offers empirical support for the feasibility and utility of a compassion-based social–emotional learning program on promoting children’s empathy, and emotions of soothing and vitality in the school context. Thus, these findings contribute to recent research on the potential added value of compassion practices within an SEL program