Expanding the phenotypic and genotypic spectrum of Bietti crystalline dystrophy

Abstract: The rare form of retinal dystrophy, Bietti crystalline dystrophy, is associated with variations in CYP4V2, a member of the cytochrome P450 family. This study reports patients affected by typical and atypical Bietti crystalline dystrophy, expanding the spectrum of this disease. This is an observational case series of patients with a clinical and molecular diagnosis of Bietti crystalline dystrophy that underwent multimodal imaging. Four unrelated patients are described with two known variants, c.802‐8_810del17insGC and c.518T > G (p.Leu173Trp), and one novel missense variant, c.1169G > T (p.Arg390Leu). The patient with the novel homozygous variant had the most severe phenotype resulting in macular hole formation and retinal detachment in both eyes. To the best of our knowledge, there is no association of these features with Bietti crystalline dystrophy. Patient 1 was the youngest patient and had the mildest phenotype with crystals in the retina without chorioretinal atrophy and visual complaints. Patients 2 and 3 presented with fewer crystals and chorioretinal atrophy. These three patients presented a classic phenotype. The fourth patient presented with an atypical and severe phenotype. This study reveals a new genotype and new phenotype associated with this disorder. Keywords: bietti crystalline dystrophy; CYP4V2 protein; genetic testing; missense mutation; insertion‐deletion mutatio

Perfil de consumo de anticonceptivos orales en la ciudad de Córdoba, Argentina

Se agradece a los alumnos de 5º año de la carrera de Farmacia que cursaron la asignatura Practicanato en el año 2007 y a sus correspondientes Instructores de Prácticas Farmacéuticas.Objetivo: El objetivo de este trabajo fue analizar la oferta, demanda y costos de los anticonceptivos orales disponibles en Argentina, así como también caracterizar la población usuaria y la forma de uso de los anticonceptivos parte de los mismos. Material y Método: Se realizó un estudio descriptivo y observacional donde se trabajó con un procedimiento normalizado analizando dispensaciones en un total de 42 farmacias comunitarias de Córdoba (Argentina). Resultados: 90 son los anticonceptivos hormonales orales disponibles, 81 % de los cuales son combinados. Más del 80% de las ventas se concentren solo en 3 laboratorios productores siendo paradójicamente la combinación más costosa (Drospirenona-EtinilEstradiol) la más dispensada. En más del 60% de los casos el anticonceptivo fue adquirido sin receta médica y sin cobertura de la seguridad social, lo cual fue, generalmente, compensado con descuentos adicionales que provenían en su mayoría de la farmacia. A pesar de contar la población en estudio, en su mayoría, con un nivel educativo medio-alto y experiencia en el uso de anticonceptivos, se detectó desconocimiento en los parámetros de uso y actitudes a tomar ante olvidos. Conclusiones: A pesar de la amplia oferta de anticonceptivos orales, la demanda de los mismos en farmacias comunitarias de la ciudad de Córdoba está fuertemente concentrada en los anticonceptivos orales combinados de mayor precio de venta en el mercado, existiendo deficiencias en el conocimiento por parte de los paciente respecto al modo adecuado de uso, con una fuerte tendencia a la repetición de una prescripción o automedicación a utilizar combinaciones de 3ra o 4ta generación sin que las mismas sean las más recomendadas.Aim: The aim of this study was to describe the supply and demand of oral contraceptives available in Argentina, characterize the user population and how the patients use contraceptives. Materials and Methods: We worked with a normalized procedure, analyzing 713 dispensations in 42 community pharmacies in Córdoba (Argentina). Results: The 90 oral contraceptives available in the Argentine pharmaceutical market, 81% of which correspond to combined oral contraceptive. More than 80% of the sales are concentrated in only 3 laboratories. Among combined oral contraceptive, the combinations of Drosperinone-Ethinylestradiol, those with the highest average price, were also the ones most chosen by the users. In over 60% of the cases they were purchased without a prescription and without social security coverage. This was offset by additional discounts coming mostly from the pharmacy outlets. Although most of the study population had an acceptable level of education and experience in the use of contaceptives, a certain lack of knowledge in the parameters of use and in the attitude to adopt when missing the daily dose was detected. Conclusions: Despite the broad range of oral contraceptives, the demand in community pharmacies is heavily concentrated in the combined oral contraceptive with higher price in the market, existing deficiencies in the knowledge from the patient regarding the proper way to use and there is a strong trend self-medication and use combinations of 3rd or 4th generation without the appropriate indications

CD3e expression in HTLV-1-infected individuals is associated with proviral load and Tax expression

Financial support: FUNDHERP, CTC, INCTC, FAPESP, CNPq and CAPES

Comparação dos efeitos da ventilação mecânica não invasiva contínua e intermitente sobre parâmetros cardiorrespiratórios e modulação autonômica de indivíduos saudáveis

Modelo do estudo: Estudo transversal. Objetivo: Avaliar a influência da Ventilação Mecânica não Invasiva (VMNI) de forma contínua e intermitente sobre a modulação autonômica cardíaca e parâmetros cardiorrespiratórios em mulheres saudáveis. Métodos: Vinte voluntárias realizaram duas modalidades de VMNI: contínua por meio do CPAP e intermitente por meio do Reanimador de Muller. Inicialmente permaneceram em repouso em respiração espontânea por 20 minutos. Em seguida foram submetidas a 20 minutos de aplicação de VMNI com a técnica selecionada e por fim permaneceram 20 minutos em repouso em respiração espontânea. Os parâmetros cardiorrespiratórios e variabilidade da frequência cardíaca (VFC) foram mensurados em todos estes momentos. Resultados: Não houve diferenças significantes quando comparadas as duas técnicas. Observaram-se diferenças nos parâmetros cardiorrespiratórios e VFC quando analisadas individualmente. Menores valores de frequência cardíaca e frequência respiratória foram observados na modalidade contínua quando comparado os valores durante a ventilação com respiração espontânea (p<0,005). Em ambas técnicas observaram-se aumentos significantes de SpO2 durante a ventilação em comparação a respiração espontânea. Observou-se aumento da modulação parassimpática (RMSSD, HF ms2 e SD1) e da variabilidade global (SDNN, RR triangular e SD2) em ambas as técnicas quando comparado ventilação e respiração espontânea (p<0,005). Conclusão: Não houve diferença quando comparadas as duas modalidades de VMNI. Contudo, quando analisadas individualmente observam-se comportamento diferentes dos parâmetros cardiorrespiratórios e na modulação autonômicaStudy design: Cross-sectional study. Objective: To evaluate the influence of continuous and intermittent noninvasive mechanical ventilation (NIV) on cardiac autonomic modulation and cardiorespiratory parameters in healthy women. Methods: Twenty subjects performed two types of NIV: continuous through CPAP and intermittent through Müller Reanimator. Initially they remained at rest for 20 minutes in spontaneous breathing. Then volunteers were subjected to 20 minutes of NIV application with the selected technique and finally remained at rest for 20 minutes in spontaneous breathing. Cardiorespiratory parameters and heart rate variability (HRV) were measured in all these moments. Results: There were no significant differences when comparing the two techniques. Differences were observed in HRV and cardiorespiratory parameters when analyzed individually. Lower values of heart rate and respiratory rate were observed in continuous ventilation when compared to values during ventilation with spontaneous breathing (p <0.005). In both techniques we observed significant increases in SpO2 during ventilation compared to spontaneous breathing. We observed an increase in parasympathetic modulation (RMSSD, HF ms2 and SD1) and overall variability (SDNN, RR triangular and SD2) in both techniques when compared ventilation to spontaneous breathing (p <0.005). Conclusion: There was no difference comparing the two types of NIV. However, when analyzed individually we observe different behavior of cardiorespiratory parameters and autonomic modulatio

The administration of chitosan-tripolyphosphate-DNA nanoparticles to express exogenous SREBP1a enhances conversion of dietary carbohydrates into lipids in the liver of Sparus aurata

In addition to being essential for the transcription of genes involved in cellular lipogenesis, increasing evidence associates sterol regulatory element binding proteins (SREBPs) with the transcriptional control of carbohydrate metabolism. The aim of this study was to assess the effect of overexpression SREBP1a, a potent activator of all SREBP-responsive genes, on the intermediary metabolism of Sparus aurata, a glucose-intolerant carnivorous fish. Administration of chitosan-tripolyphosphate nanoparticles complexed with a plasmid driving expression of the N-terminal transactivation domain of SREBP1a significantly increased SREBP1a mRNA and protein in the liver of S. aurata. Overexpression of SREBP1a enhanced the hepatic expression of key genes in glycolysis-gluconeogenesis (glucokinase and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase), fatty acid synthesis (acetyl-CoA carboxylase 1 and acetyl-CoA carboxylase 2), elongation (elongation of very long chain fatty acids protein 5) and desaturation (fatty acid desaturase 2) as well as reduced nicotinamide adenine dinucleotide phosphate production (glucose-6-phosphate 1-dehydrogenase) and cholesterol synthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase), leading to increased blood triglycerides and cholesterol levels. Beyond reporting the first study addressing in vivo effects of exogenous SREBP1a in a glucose-intolerant model, our findings support that SREBP1a overexpression caused multigenic effects that favoured hepatic glycolysis and lipogenesis and thus enabled protein sparing by improving dietary carbohydrate conversion into fatty acids and cholesterol

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Global Spatial Risk Assessment of Sharks Under the Footprint of Fisheries

Effective ocean management and conservation of highly migratory species depends on resolving overlap between animal movements and distributions and fishing effort. Yet, this information is lacking at a global scale. Here we show, using a big-data approach combining satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively) and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of high-seas fishing effort. Results demonstrate an urgent need for conservation and management measures at high-seas shark hotspots and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real time, dynamic management

Geography and ecology shape the phylogenetic composition of Amazonian tree communities

AimAmazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types.LocationAmazonia.TaxonAngiosperms (Magnoliids; Monocots; Eudicots).MethodsData for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny.ResultsIn the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types.Main ConclusionNumerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions